{ "bpc-157": { "name": "BPC-157", "full_name": "Body Protection Compound 157", "aliases": [ "BPC-157 acetate", "PL 14736", "Bepecin", "Pentadecapeptide BPC 157", "Arg-BPC-157 (stable version)" ], "categories": [ "recovery-healing" ], "tagline": "A 15-amino-acid fragment of the gastric body-protection compound, the most widely self-administered healing peptide for tendon, ligament, muscle, and gut injuries.", "status": "Research chemical / not FDA-approved. Tested in a handful of small human trials under the name PL 14736 (rectal enemas for ulcerative colitis); most other human use is off-label self-administration.", "origin": "A fragment of a larger gastric-juice protein called Body Protection Compound. It occurs naturally in the human GI tract, and older Croatian tissue-distribution work found it expressed at low levels in lung, kidney, and skin too.", "mechanism": "It doesn't bind classical receptors: dopamine, serotonin, histamine, adrenergic, muscarinic, and adenosine receptors have all been screened and show no affinity. Its effects instead run through upregulated growth-factor receptor expression (including growth hormone receptor in tendon fibroblasts), nitric-oxide modulation, and strong pro-angiogenic signaling. In animal models it consistently speeds fibroblast activity, blood vessel formation, and collagen organization at injury sites while suppressing scar tissue.", "research_summary": "The published evidence base is large, over 200 papers, but almost entirely rodent and in-vitro. Repeated findings include faster healing of tendon, ligament, muscle, and nerve transections; faster healing of skin incisions, burns, and GI fistulas; protection against and healing of gastric ulcers; and a strong anti-inflammatory effect across multiple models. Human data is limited to Phase I/II trials of a rectal enema formulation (PL 14736) in healthy volunteers and ulcerative colitis patients in the early 2000s: well tolerated, with a statistically significant improvement in disease-activity scores versus placebo, and essentially no systemic absorption from the rectal route. No modern human dosing, efficacy, or long-term safety trials exist for the injectable or oral forms people use. One red flag: essentially every animal study on BPC-157 reports a positive result, which points to publication bias. Treat individual studies as suggestive, not proof. One in-vitro plasma-stability study found roughly 36% of BPC-157 still intact after 60 minutes, implying a plasma half-life in the range of 40 minutes \u2014 short, consistent with why community protocols favor frequent small doses over infrequent large ones.", "reported_benefits": [ "Faster recovery from tendon, ligament and muscle strains reported anecdotally and in animal studies", "Reduced joint and connective-tissue pain in long-standing injuries", "Improved gut symptoms (reflux, IBD-type symptoms, leaky-gut complaints) reported by oral users", "General anti-inflammatory effect described by long-term users" ], "dosing_protocols": [ { "route": "Subcutaneous injection (most commonly used for systemic/peripheral healing)", "protocol": "A frequently cited compounding-pharmacy protocol is 300 mcg once daily for 30 days. A very common self-administered pattern in online communities is 250 mcg injected subcutaneously into belly fat, twice daily. Conservative starting point: 100 mcg once daily, increasing slowly while watching for reactions." }, { "route": "Oral (capsules or reconstituted drops)", "protocol": "500 mcg, twice daily is a commonly reported oral dose. The 'stable' arginine-salt version (Arg-BPC-157) survives low stomach pH far better than the acetate salt and is generally preferred for oral use, though orally dosed BPC-157 is too large a molecule to be meaningfully absorbed intact \u2014 any systemic effect from oral dosing is unproven and the community consensus is that oral use is mainly reported to help local GI complaints, not peripheral joint or tendon injuries." }, { "route": "Local/near-injury injection", "protocol": "Some experienced users inject near (not into) an injury site on the theory of a local concentration effect; mainstream practice is simple subcutaneous injection into abdominal fat, which is easier, safer, and has the deepest anecdotal track record." } ], "side_effects": [ "Injection-site irritation, stinging, occasional bruising", "Drowsiness / increased sleep need reported in the first 1-2 weeks by some users", "Rare reports of headache or lightheadedness", "No established maximum tolerated human dose; animal toxicology found no lethal dose up to very high doses, but this has not been replicated in modern controlled human trials" ], "safety_notes": "Legal status is grey-market in most countries: possessing the research chemical is typically not illegal, but it's sold 'not for human consumption' and falls outside any regulatory framework. No long-term human safety data exists for the doses and routes people use. People with active cancer should be cautious: BPC-157's strong pro-angiogenic activity is exactly what makes it good at healing tissue, and in theory could also feed a tumor's blood supply. This hasn't been directly studied.", "community_notes": "One of the most discussed peptides in self-experimentation communities (notably r/Peptides), with unusually consistent reporting: people using injectable BPC-157 on stalled tendon, ligament, or joint injuries report it 'restarting' healing within days to a few weeks, often alongside noticeably increased sleepiness the first week. Users with connective tissue disorders (EDS/HSD) who stack it with GH secretagogues like CJC-1295/Ipamorelin report stronger, more durable results than BPC-157 alone. Oral users consistently report GI benefit but are far less confident about peripheral joint or tendon benefit; the community's strong prior is that injection is needed for systemic connective-tissue effects, while oral is a cheaper option purely for gut issues.", "related": [ "tb-500", "ghk-cu", "kpv", "ara-290", "ipamorelin" ], "citations": [ { "title": "Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study", "authors_year": "Bi\u00e7er et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42542926/" }, { "title": "Peptide Supplements and Their Therapeutic Applications in Sports Medicine", "authors_year": "Tewari et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42578445/" }, { "title": "From Regeneration to Analgesia: The Role of BPC-157 in Tissue Repair and Pain Management", "authors_year": "Yuan et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41898733/" }, { "title": "Regeneration or Risk? A Narrative Review of BPC-157 for Musculoskeletal Healing", "authors_year": "McGuire et al. 2025", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/40789979/" } ], "mixing_notes": { "clinic_combos": [ "cjc-1295", "cjc-1295-dac", "epithalon", "ghk-cu", "ghrp-6", "hexarelin", "ipamorelin", "kpv", "mgf", "pe-22-28", "pinealon", "selank", "semax", "tb-500", "tesamorelin", "thymalin", "thymosin-alpha-1" ], "anecdotal_combos": [ "hcg", "igf-1-lr3" ], "reported_avoid": [ "ara-290", "mots-c", "nad" ] } }, "tb-500": { "name": "TB-500 / Thymosin Beta-4", "full_name": "Thymosin Beta-4 (full sequence) \u2014 products sold as 'TB-500' may contain either the full 43-amino-acid T\u03b24 or just its Frag 17-23 fragment", "aliases": [ "TB-500", "TB4", "Thymosin \u03b24", "Frag 17-23" ], "categories": [ "recovery-healing" ], "tagline": "A naturally occurring wound-response peptide released by platelets, used for muscle, tendon and neurological healing, often stacked with BPC-157.", "status": "Research chemical for the self-administered market. The active molecule (T\u03b24) has gone through legitimate pharmaceutical development under RegeneRx as RGN-259 (eye drops, completed Phase III), RGN-352 (systemic injection, completed Phase I) and RGN-137 (topical gel, Phase II) \u2014 but none of these are approved, marketed drugs.", "origin": "Thymosin Beta-4 is a 43-amino-acid peptide present in nearly all human cells, especially platelets and white blood cells, released at wound sites as part of the natural clotting and repair cascade. 'TB-500' is a commercial name that's ambiguous: some vendors sell the full T\u03b24 sequence, others sell only its Frag 17-23 region (LKKTETQ), the piece responsible for actin-binding and cell-migration effects. Check what a specific product actually contains before assuming.", "mechanism": "Different regions of the T\u03b24 sequence do different jobs: amino acids 1-4 are anti-inflammatory and anti-fibrotic; 1-15 is anti-apoptotic/cytoprotective; 17-23 drives actin binding, cell migration, angiogenesis and dermal wound healing (and triggers mast-cell degranulation); 40-43 supports cardiac cell migration after ischemic injury. TB4 binds free actin monomers (G-actin) rather than a conventional receptor, effectively expanding the pool of building blocks cells use to rebuild cytoskeletal structure during repair.", "research_summary": "A 2015 meta-analysis found broad applicability across tissue regeneration, post-heart-attack cardiac repair, stroke and neurological recovery, kidney/liver repair, and bone/ligament/spinal cord injury in animal models. Human data is more substantial than for most research peptides: RGN-259 eye drops completed Phase III trials for dry eye and neurotrophic keratitis with statistically significant symptom improvement and no adverse events. RGN-352 systemic IV dosing was tested up to single doses of 1260 mg and repeated daily dosing for 14 days (cumulative ~18.9 g in one subject) with no dose-limiting toxicity, no cardiovascular/respiratory signal, and no cancers at 6-month follow-up; headache was the only adverse event, occurring equally in placebo. Pharmacokinetics show a short half-life (under 1-2 hours even at high doses) and dose-independent clearance, so TB4 doesn't meaningfully accumulate with daily dosing at the doses studied.", "reported_benefits": [ "Faster recovery from muscle strains and tears", "Reduced muscle spasticity / tightness (notably reported by people with hypermobility disorders)", "Support for tendon and ligament healing, often paired with BPC-157", "Reported improvements in flexibility, which some users find beneficial and others find undesirable (increased joint laxity)" ], "dosing_protocols": [ { "route": "Subcutaneous injection \u2014 loading protocol", "protocol": "A widely circulated protocol: 5 mg twice weekly (e.g. Monday/Thursday) for 5 weeks, then 5 mg once weekly for 2 more weeks (total ~35 mg over 7 weeks)." }, { "route": "Subcutaneous injection \u2014 daily lower-dose protocol", "protocol": "Alternative protocols use smaller daily doses: roughly 450-750 mcg per day for 20-30 days. Because T\u03b24's half-life is short and it doesn't accumulate systemically, both large-infrequent and small-frequent dosing schemes appear in the literature with good animal results; there's no head-to-head human comparison." }, { "route": "Post-injury / acute dosing", "protocol": "Some practitioners use a short course of higher daily dosing (e.g. ~1.5 mg/day for about a week) immediately after an acute injury or surgery, on the theory of mimicking the natural post-injury T\u03b24 spike, then tapering to a lower maintenance dose." } ], "side_effects": [ "Injection site irritation", "Possible mast-cell activation from the Frag 17-23 region \u2014 a concern for people with MCAS", "Theoretical proliferative/metastasis-promoting risk, since T\u03b24 overexpression is associated with several cancer types at the cellular level (no data yet on whether exogenous dosing carries this risk in humans) \u2014 TB4 is generally considered contraindicated for anyone with active or recent cancer" ], "safety_notes": "Human injection safety data (RGN-352 Phase I) is reassuring at doses far higher than self-experimenters typically use: no dose-limiting toxicity, no cancer signal at 6-month follow-up. But that was a short trial in healthy volunteers, not a long-term study, and the theoretical cancer-proliferation concern from cell-biology data means anyone with a personal or strong family history of cancer should weigh that risk carefully and ideally talk to a physician.", "community_notes": "Frequently stacked with BPC-157: BPC for connective tissue and gut, TB4 for muscle, systemic inflammation and flexibility. People with Ehlers-Danlos/hypermobility spectrum disorders report mixed results on flexibility; most find reduced muscle spasticity helpful, a minority report an unwanted increase in joint hypermobility during use. Community also disputes what's actually being sold as 'TB-500': cheaper vials are more likely the smaller Frag 17-23 fragment rather than full T\u03b24. That's not necessarily a scam (Frag 17-23 delivers more molecules per mg and covers the muscle/actin-binding effects), but buyers should know which one they're getting if they want T\u03b24's broader immune and cardiac-repair activity too. Separately, some in the EDS/HSD community flag that TB-500's active sequence includes a region known to activate mast cells, and suggest starting low for anyone with Mast Cell Activation Syndrome (MCAS) or a history of mast-cell reactivity.", "related": [ "bpc-157", "ghk-cu", "kpv" ], "variant_note": "Sometimes sold as 'TB-500 Frag' or 'Thymosin Beta-4 Fragment' \u2014 a shorter fragment of the same parent protein, marketed as a cheaper alternative. It is not established as pharmacologically equivalent to full TB-500/T\u03b24, and independent evidence for the fragment specifically is essentially absent; treat fragment products as a distinct, far less characterized compound rather than an interchangeable substitute.", "citations": [ { "title": "Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study", "authors_year": "Bi\u00e7er et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42542926/" }, { "title": "Peptide Supplements and Their Therapeutic Applications in Sports Medicine", "authors_year": "Tewari et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42578445/" }, { "title": "Engineered Tandem Thymosin Peptide Promotes Corneal Wound Healing", "authors_year": "Nguyen et al. 2025", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41235866/" }, { "title": "Thymosin \u03b24 and Actin: Binding Modes, Biological Functions and Clinical Applications", "authors_year": "Ying et al. 2023", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/36464872/" } ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "ghk-cu", "ipamorelin", "ll-37", "mt-1", "mt-2", "pinealon", "selank", "semax", "thymalin", "thymosin-alpha-1" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "kpv": { "name": "KPV", "full_name": "Lysine-Proline-Valine (C-terminal tripeptide fragment of alpha-MSH)", "aliases": [ "KPV tripeptide", "\u03b1-MSH(11-13)" ], "categories": [ "recovery-healing" ], "tagline": "A tiny 3-amino-acid fragment of alpha-MSH studied mainly for gut and skin inflammation, popular among self-experimenters with IBD-type symptoms.", "status": "Research chemical, no clinical approval. Preclinical (rodent, cell-culture) evidence only for the isolated tripeptide.", "origin": "KPV is the C-terminal three amino acids of alpha-melanocyte-stimulating hormone (alpha-MSH), a peptide with well-established anti-inflammatory and immune-modulating effects. KPV retains alpha-MSH's anti-inflammatory activity without the pigmentation (skin-darkening) effects that come from alpha-MSH's action on melanocortin receptors.", "mechanism": "KPV works partly independent of the classical melanocortin receptors, directly inhibiting NF-kB signaling, a central pathway driving inflammatory cytokine production. This gives it broad anti-inflammatory activity in gut epithelium and skin without the receptor-mediated side effects (tanning, appetite/libido changes) seen with full alpha-MSH analogs like Melanotan II.", "research_summary": "Rodent studies show KPV reduces colonic inflammation in colitis models, improves epithelial barrier integrity, and has topical anti-inflammatory and antimicrobial effects on skin, including activity against Staph aureus in some in-vitro work. No human clinical trials exist for KPV as an isolated compound; it's an academic compound of interest for IBD and dermatology, still firmly preclinical.", "reported_benefits": [ "Reduced GI inflammation and bloating reported by users with IBD-type or leaky-gut symptoms", "Topical use reported for inflammatory skin conditions (acne, eczema-type flares)", "Often used alongside BPC-157 for combined gut-healing protocols" ], "dosing_protocols": [ { "route": "Oral capsules/drops", "protocol": "Commonly reported range in self-experimentation communities is 200-500 mcg, once or twice daily, often cycled in blocks of a few weeks." }, { "route": "Subcutaneous injection", "protocol": "Less commonly injected than BPC-157/TB-500; when used, doses in the low hundreds of mcg per day are typical among self-experimenters, frequently combined with BPC-157 in the same syringe." }, { "route": "Topical", "protocol": "Compounded topical creams (skin conditions) are the other common route; no standardized concentration exists outside individual compounding pharmacy formulations." } ], "side_effects": [ "Limited human safety data \u2014 most reported issues are generic to peptide self-injection (site irritation)", "No known pigmentation or libido effects (unlike full-length alpha-MSH analogs)" ], "safety_notes": "There's essentially no human trial data for isolated KPV, so dosing and long-term safety rest entirely on extrapolation from animal work and community reporting. One of the least-studied compounds in this wiki.", "community_notes": "Popular in gut-health and autoimmune-adjacent corners of the peptide community as a companion to BPC-157, particularly for people who feel oral BPC-157 alone isn't enough for inflammatory GI symptoms. Reports are generally positive but sparse compared to BPC-157/TB-500, and much of the online protocol information traces back to a small number of vendor blog posts rather than independent user reporting.", "related": [ "bpc-157", "ara-290" ], "citations": [ { "title": "Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis", "authors_year": "Xiao et al. 2017", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28143741/" }, { "title": "Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases", "authors_year": "Brzoska et al. 2008", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/18612139/" }, { "title": "Critical role of PepT1 in promoting colitis-associated cancer and therapeutic benefits of the anti-inflammatory PepT1-mediated tripeptide KPV in a murine model", "authors_year": "Viennois et al. 2016", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/27458604/" }, { "title": "Self-Cross-Linked Hydrogel of Cysteamine-Grafted \u03b3-Polyglutamic Acid Stabilized Tripeptide KPV for Alleviating TNBS-Induced Ulcerative Colitis in Rats", "authors_year": "Sun et al. 2021", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/34547895/" } ], "mixing_notes": { "clinic_combos": [ "bpc-157", "ghk-cu" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "ara-290": { "name": "ARA-290", "full_name": "Cibinetide", "aliases": [ "ARA-290", "Cibinetide", "PH-BSP" ], "categories": [ "recovery-healing" ], "tagline": "A non-hematopoietic EPO fragment developed for neuropathic pain and small-fiber nerve repair, without EPO's blood-thickening effects.", "status": "Clinical-stage investigational drug (further along than most peptides in this wiki) \u2014 tested in several placebo-controlled human trials for small fiber neuropathy and diabetic neuropathy, but not yet an approved medication.", "origin": "Derived from erythropoietin (EPO), the hormone that drives red blood cell production. EPO's neuroprotective, anti-inflammatory, and nerve-repair effects run through a separate receptor complex (the innate repair receptor) from the one that stimulates red blood cells. ARA-290 was engineered to hit only the repair pathway, giving EPO-like tissue protection without raising red blood cell count or blood viscosity.", "mechanism": "Binds the innate repair receptor, distinct from the classical EPO receptor, triggering anti-inflammatory and cytoprotective signaling in nerve and vascular tissue. Trials have shown it increases corneal small-nerve-fiber density, a direct, measurable marker of nerve regeneration.", "research_summary": "Multiple placebo-controlled human trials exist. A double-blind trial in sarcoidosis patients with small fiber neuropathy (4 mg subcutaneous daily for 28 days) showed symptom improvement and increased corneal nerve fiber density versus placebo. Separate trials in type 2 diabetes patients with neuropathic symptoms showed improved metabolic control and symptom scores, with dose-ranging work across 1 mg, 4 mg, and 8 mg groups. It's one of the better-studied compounds in peptide communities, with real dose-response human data, a rarity here.", "reported_benefits": [ "Reduced neuropathic pain (burning, tingling, numbness from small fiber neuropathy)", "Reported benefit for some autonomic nervous system symptoms (dysautonomia) in community anecdotes, though this indication is not clinically validated", "Interest from the EDS/HSD community for small-fiber neuropathy that often accompanies connective tissue disorders" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Clinical trial dosing used 4 mg once daily for 28 days as the primary studied protocol; other trial arms used 1 mg and 8 mg daily. There is no established chronic/maintenance dosing outside trial contexts, and self-experimenters generally try to mirror the 4 mg daily trial protocol for a similar duration." } ], "side_effects": [ "Generally well tolerated in trials with no major red flags reported", "Does not raise red blood cell count or blood pressure the way EPO itself can \u2014 this was the whole design goal and trial data supports it" ], "safety_notes": "One of the more reassuring safety profiles here, backed by real placebo-controlled human dosing data. But trials ran only 28 days in specific patient populations (sarcoidosis, diabetic neuropathy); long-term use in healthy people or off-label indications like dysautonomia hasn't been studied.", "community_notes": "Less mainstream than BPC-157/TB-500, but draws strong interest from people with small fiber neuropathy, POTS/dysautonomia, and EDS/HSD, where standard treatment is mostly symptom management rather than repair. Cost and sourcing difficulty temper enthusiasm, and anecdotal reports of benefit are sparser than for the popular healing peptides.", "related": [ "bpc-157", "kpv" ], "citations": [ { "title": "Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain", "authors_year": "Culver et al. 2017", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28475703/" }, { "title": "ARA 290 for treatment of small fiber neuropathy in sarcoidosis", "authors_year": "van Velzen et al. 2014", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/24555851/" }, { "title": "The erythropoietin-derived peptide ARA290 reverses mechanical allodynia in the neuritis model", "authors_year": "Pulman et al. 2012", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/23262243/" }, { "title": "Corneal nerve fiber size adds utility to the diagnosis and assessment of therapeutic response in patients with small fiber neuropathy", "authors_year": "Brines et al. 2018", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/29549285/" } ], "mixing_notes": { "clinic_combos": [], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "bpc-157", "cjc-1295", "cjc-1295-dac", "dsip", "epithalon", "ghk-cu", "ghrp-2", "ghrp-6", "hcg", "hexarelin", "hgh-somatropin", "humanin", "igf-1-lr3", "ipamorelin", "kisspeptin", "kpv", "ll-37", "mgf", "mots-c", "mt-1", "mt-2", "nad", "p21", "pe-22-28", "pinealon", "pt-141", "selank", "semax", "tb-500", "tesamorelin", "thymalin", "thymosin-alpha-1" ] } }, "ghk-cu": { "name": "GHK-Cu", "full_name": "Glycyl-L-Histidyl-L-Lysine \u2014 Copper Complex", "aliases": [ "Copper peptide", "GHK-Copper", "Copper tripeptide-1" ], "categories": [ "anti-aging", "recovery-healing" ], "tagline": "A naturally occurring copper-binding tripeptide found in human plasma. The best-studied skin peptide, also investigated for wound healing, hair and connective tissue.", "status": "Widely used as a cosmetic ingredient (topical, well-studied and legal essentially everywhere) and separately used off-label as an injectable/subcutaneous compound in the self-experimentation community, which is far less studied.", "origin": "First isolated from human blood plasma. Naturally circulating GHK declines substantially with age, from around 200 ng/mL at age 20 to about 80 ng/mL by age 60, part of why it's of interest for anti-aging use. Also found in saliva and urine.", "mechanism": "GHK-Cu regulates a large number of genes involved in tissue remodeling, collagen and elastin synthesis, antioxidant enzyme production, and anti-inflammatory signaling. It promotes fibroblast and keratinocyte activity, stimulates angiogenesis, and scavenges free radicals directly. In hair follicle studies it enlarges follicle size and increases blood vessel formation around follicles.", "research_summary": "Topically, GHK-Cu has a genuinely deep evidence base: decades of dermatology and wound-healing literature support improved skin firmness, reduced fine lines, faster wound healing and reduced hyperpigmentation. Gene-expression studies from Pickart and colleagues show GHK-Cu resets expression of over 4,000 genes toward a more youthful pattern in some analyses, an early-stage systems-biology finding, not a validated anti-aging therapy. Systemic/injectable use is far less studied in humans; most injectable dosing information circulating online is extrapolated from topical/animal data, not dedicated injection trials.", "reported_benefits": [ "Topical: improved skin firmness, texture and fine lines; faster healing of cuts, post-procedure skin; reduced hyperpigmentation", "Injectable (anecdotal): reported support for connective tissue repair alongside BPC-157/TB-500 stacks; reported hair density improvements when combined with topical minoxidil-style protocols", "Interest in immune modulation and antioxidant support from systemic research" ], "dosing_protocols": [ { "route": "Topical (cosmetic)", "protocol": "Commercial skincare products typically use 1-5% GHK-Cu-containing formulations or specific copper-peptide serums; this is the best-supported route." }, { "route": "Subcutaneous injection (self-experimentation, not clinically established)", "protocol": "Community-reported doses vary widely, roughly 1-2 mg per day in longer runs, or shorter 'cycles' around 20 mg total spread over 1-2 weeks. Because true injection dose-response data doesn't exist in humans, treat any specific number as a community convention, not a validated dose." } ], "side_effects": [ "Topical: generally very well tolerated; can transiently increase skin sun-sensitivity due to increased cell turnover \u2014 sunscreen use recommended during treatment", "Injectable: local injection-site reactions reported; systemic safety data at self-experimentation doses is essentially absent" ], "safety_notes": "Topical GHK-Cu is one of the safest and best-studied compounds in this wiki. Injectable/systemic use is different: popular in self-experimentation stacks, but without the same evidence backing as the topical form, and dosing is folk convention.", "community_notes": "Frequently added in small doses to BPC-157/TB-500 healing stacks and to hair-loss protocols alongside minoxidil/finasteride. Also popular as a standalone topical anti-aging ingredient outside the injectable-peptide community, showing up in mainstream skincare marketing. Community sentiment on injectable use is generally positive but far less confident and detailed than for BPC-157 or TB-500: people describe it as a nice addition, not a primary driver of results. Reported personal dosing patterns vary widely, from roughly 1 mg/day as a baseline addition to a stack, up to occasional higher-dose cycles around 20 mg \u2014 none of it standardized, and mostly folded into other peptides' protocols rather than run alone.", "related": [ "bpc-157", "tb-500", "epithalon" ], "variant_note": "Sometimes sold as plain 'GHK' (without copper already bound) rather than the copper-complexed GHK-Cu described on this page. GHK requires copper binding in vivo to exert its characteristic effects, so uncomplexed GHK is a meaningfully different product with a thinner evidence base than the copper complex.", "citations": [ { "title": "Peptide Supplements and Their Therapeutic Applications in Sports Medicine", "authors_year": "Tewari et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42578445/" }, { "title": "GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration", "authors_year": "Pickart et al. 2015", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/26236730/" }, { "title": "The human tri-peptide GHK and tissue remodeling", "authors_year": "Pickart 2008", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/18644225/" }, { "title": "Augmented Skin Beneficial Effects of Thermus Thermophilus and Bacillus Subtilis Mixed-Culture Ferment Extract by Tripeptide GHK-Cu", "authors_year": "Wang et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42573538/" } ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "ipamorelin", "kpv", "tb-500", "thymalin" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "epithalon": { "name": "Epithalon", "full_name": "Epithalon / Epitalon (Ala-Glu-Asp-Gly)", "aliases": [ "Epitalon", "Epithalone", "AEDG peptide" ], "categories": [ "anti-aging", "longevity", "bioregulators" ], "tagline": "A synthetic tetrapeptide based on a natural pineal-gland extract, studied by Russian researchers for telomerase activation, sleep and immune aging.", "status": "Research chemical, no clinical approval anywhere. Human data comes mostly from a small body of Russian-language research (limited peer review by Western standards) plus animal studies.", "origin": "Synthetic analog of Epithalamin, a peptide complex extracted from calf pineal glands. Developed by Vladimir Khavinson's group in St. Petersburg starting in the 1980s as part of a broader program on peptide bioregulators.", "mechanism": "Proposed to activate telomerase in some cell types (extending telomere length in vitro in several Khavinson studies), regulate melatonin secretion via the pineal gland, and modulate the hypothalamic-pituitary axis. Also proposed to increase lymphocyte interferon-gamma production, relevant because declining interferon-gamma is linked to immune aging.", "research_summary": "The core human evidence comes from decades of Khavinson's work, including reports of extended lifespan in elderly cohorts given pineal/thymus peptide bioregulator courses and improved markers of biological aging. The research has real limitations by current standards: small cohorts, limited blinding detail, mostly published in Russian-language journals, and no independent replication in large Western randomized trials. Animal telomerase-activation data is stronger than the human longevity claims. Treat Epithalon as an interesting, under-replicated hypothesis, not an established longevity intervention.", "reported_benefits": [ "Reported improvement in sleep quality and depth", "Anecdotal reports of improved skin appearance and energy over multi-week cycles", "Interest as part of broader 'peptide bioregulator' anti-aging stacks" ], "dosing_protocols": [ { "route": "Subcutaneous injection \u2014 classic 'course' protocol", "protocol": "The traditional Khavinson-derived protocol is 5-10 mg per day for 10-20 days, done as a single annual or biannual course rather than continuous daily use \u2014 the theory being pulsed exposure rather than constant dosing." }, { "route": "Subcutaneous injection \u2014 lower dose variant", "protocol": "Some self-experimenters use lower daily doses (around 1 mg/day) for a similar 10-20 day course." } ], "side_effects": [ "Generally reported as well tolerated with few acute side effects", "Long-term human safety data at self-administered doses does not exist" ], "safety_notes": "The gap between Epithalon's marketing as a telomere/longevity peptide and the underlying human evidence is large. Treat the anti-aging framing skeptically: what's actually been shown is telomerase activity in some cell-culture and animal work, plus older, methodologically limited human cohort research from a single group.", "community_notes": "A staple of longevity stacks, usually run as an annual or twice-yearly short course rather than continuously. Sleep improvement is the most consistently reported subjective effect. Skepticism about how much of Khavinson's telomere/lifespan story translates to modern self-administered use is common even within the community.", "related": [ "thymosin-alpha-1", "mots-c", "ghk-cu", "nad", "dsip" ], "variant_note": "Sometimes sold as 'N-Acetyl Epitalon Amidate' rather than plain Epithalon (Epitalon/Epithalone). The acetylated, amidated form is marketed as more stable in solution; it has not been independently studied to the same degree as the parent tetrapeptide, and community reports of equivalence are anecdotal.", "citations": [ { "title": "Morphofunctional and molecular bases of pineal gland aging", "authors_year": "Khavinson and Lin'kova 2012", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/22567846/" }, { "title": "Normalizing effect of the pineal gland peptides on the daily melatonin rhythm in old monkeys and elderly people", "authors_year": "Korkushko et al. 2007", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/17969590/" }, { "title": "The influence of melatonin and epithalon on blood leukocyte count and leukocyte alkaline phosphatase in rats under different lighting conditions during ontogenesis", "authors_year": "Uzenbaeva et al. 2008", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/19432172/" }, { "title": "Effect of a synthetic pineal tetrapeptide (Ala-Glu-Asp-Gly) on melatonin secretion by the pineal gland of young and old rats", "authors_year": "Djeridane et al. 2003", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/12809170/" } ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "dsip", "ghk-cu", "ghrp-2", "ghrp-6", "ipamorelin", "pe-22-28", "pinealon", "selank", "semax", "tb-500", "tesamorelin", "thymalin", "thymosin-alpha-1" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "thymosin-alpha-1": { "name": "Thymosin Alpha-1", "full_name": "Thymosin \u03b11 (T\u03b11)", "aliases": [ "TA-1", "T\u03b11", "Zadaxin (brand name)" ], "categories": [ "anti-aging", "longevity", "bioregulators" ], "tagline": "A naturally occurring immune-regulating peptide, approved as a prescription drug (Zadaxin) in dozens of countries for chronic hepatitis B/C and as an immune adjuvant, one of the few peptides here with real regulatory approval somewhere in the world.", "status": "Approved prescription drug (as Zadaxin) in roughly 35 countries for chronic hepatitis B/C, certain cancers as adjunct therapy, and immune support, though not FDA-approved in the United States. Widely used off-label/self-administered for general immune modulation.", "origin": "First isolated from the thymus gland in 1972, a naturally occurring 28-amino-acid peptide fragment involved in T-cell maturation and immune regulation.", "mechanism": "Modulates the immune system in both directions: it can boost an underactive response (helpful in chronic infection) while dampening an overactive one (of interest in some autoimmune contexts), largely through effects on dendritic cell maturation, T-cell differentiation and cytokine signalling, including toll-like receptor pathways.", "research_summary": "Genuinely well studied relative to most peptides in this wiki, including real RCTs: shown to improve outcomes in chronic hepatitis B and C (part of why it holds drug approval in multiple countries), studied as an adjuvant in several cancer types and for improving vaccine response in immunocompromised populations, and investigated for cystic fibrosis and various chronic/recurrent infections, including some COVID-19-era research for severe cases. One of the more legitimately evidence-backed compounds discussed in self-experimentation circles, even though it isn't FDA-approved domestically.", "reported_benefits": [ "Reduced frequency/severity of recurrent infections reported by long-term users", "Used by some with autoimmune conditions seeking immune 'rebalancing' rather than pure suppression or pure stimulation", "General immune support during illness or high-stress/high-training periods" ], "dosing_protocols": [ { "route": "Subcutaneous injection \u2014 standard protocol", "protocol": "The approved Zadaxin dosing (in countries where it's licensed) is 1.6 mg subcutaneously, twice weekly. Self-experimenters largely mirror this." }, { "route": "Acute illness / short-term immune support", "protocol": "Some users increase frequency to 2-3x per week during an active infection or high-risk exposure period, then return to twice-weekly maintenance." } ], "side_effects": [ "Generally well tolerated in the clinical literature backing its drug approval abroad", "Mild injection-site reactions reported", "As an immune modulator, caution is warranted for people on immunosuppressant therapy or with autoimmune conditions \u2014 effects on an already-dysregulated immune system are harder to predict" ], "safety_notes": "One of the better safety profiles in this wiki given genuine drug-approval-grade trial data, though most of that data comes from specific patient populations (chronic hepatitis, cancer adjuvant use) rather than healthy people using it prophylactically.", "community_notes": "Popular among people who get frequent colds/infections, and within the EDS/HSD and chronic-illness communities as a general immune-support peptide. Regarded as one of the 'more legitimate' peptides because of its overseas drug approval, a common talking point when comparing evidence quality across peptides.", "related": [ "epithalon", "ara-290", "kpv" ], "citations": [ { "title": "Safety and efficacy of Thymosin \u03b11 in the treatment of hepatitis B virus-related acute-on-chronic liver failure: a randomized controlled trial", "authors_year": "Chen et al. 2022", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/35616850/" }, { "title": "Combination of entecavir with thymosin alpha-1 in HBV-related compensated cirrhosis: a prospective multicenter randomized open-label study", "authors_year": "Wu et al. 2018", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/30063860/" }, { "title": "A multicenter, randomized, observation-controlled clinical trial to evaluate the efficacy and safety of thymalfasin adjuvant therapy in patients with HBV-related HCC after curative resection - first announcement of the protocol", "authors_year": "Qiu et al. 2015", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/26094695/" }, { "title": "Thymosin alpha 1 - Reimagine its broader applications in the immuno-oncology era", "authors_year": "Mao 2023", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/36871535/" } ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "ipamorelin", "ll-37", "mgf", "pinealon", "selank", "semax", "tb-500", "thymalin" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "nad": { "name": "NAD+", "full_name": "Nicotinamide Adenine Dinucleotide (technically a coenzyme/dinucleotide, not a peptide)", "aliases": [ "NAD+", "NAD", "often discussed alongside precursors NMN and NR" ], "categories": [ "longevity" ], "tagline": "Cellular coenzyme central to energy metabolism and DNA repair. Not actually a peptide, but a fixture of longevity peptide clinics and stacks.", "status": "NAD+ itself is used clinically (IV infusion clinics) and sold as an injectable/subcutaneous product in the wellness/longevity space; its precursors NMN and NR are sold as oral supplements. Not FDA-approved as a therapeutic for any anti-aging indication.", "origin": "NAD+ is a coenzyme in every living cell, essential for redox reactions in energy metabolism (glycolysis, the citric acid cycle, oxidative phosphorylation) and as a substrate for DNA-repair enzymes (PARPs) and signaling enzymes (sirtuins, central to several longevity theories).", "mechanism": "Cellular NAD+ declines measurably with age, linked to reduced mitochondrial function, impaired DNA repair, and reduced sirtuin activity. Restoring it, directly or via precursors NMN/NR that the body converts to NAD+, is theorized to support mitochondrial and metabolic health. Whether raising NAD+ alone meaningfully changes the human aging trajectory is unresolved.", "research_summary": "Mouse studies show NMN or NR supplementation can improve metabolic health markers, mitochondrial function, and in some studies lifespan. Human trials of NMN and NR are more numerous than for most compounds in this wiki: NAD+ levels reliably rise with supplementation, and some metabolic markers (insulin sensitivity, blood pressure, physical performance) improve modestly in some but not all trials. Results are mixed, effect sizes small. Direct IV or subcutaneous NAD+ has far less rigorous human data than the oral precursor route; most 'NAD+ IV therapy' clinic use isn't backed by controlled trials, and self-reported effects (energy, mental clarity, less hangover-like fatigue) are the main evidence.", "reported_benefits": [ "Reported increase in energy and mental clarity, especially with IV/injectable administration", "Interest for supporting recovery from alcohol use, chronic fatigue, and long-COVID-type fatigue in wellness-clinic marketing (not clinically validated for these uses)", "Long-term interest as part of general metabolic-health/longevity stacks alongside exercise and caloric-restriction-mimetic strategies" ], "dosing_protocols": [ { "route": "IV infusion (clinic setting)", "protocol": "Typical clinic protocols range from 250 mg to 1000+ mg per infusion, sometimes over several hours due to infusion-rate-related side effects (flushing, chest tightness at faster rates); frequency varies from weekly to monthly." }, { "route": "Subcutaneous injection (self-administered)", "protocol": "Community-reported doses are much lower than IV, commonly in the 50-100 mg range per injection, a few times per week, partly because subcutaneous NAD+ injection is reported to be quite uncomfortable/stinging at higher concentrations." }, { "route": "Oral precursors (NMN/NR)", "protocol": "Typical studied oral doses are 250-1000 mg/day for NMN and 300-1000 mg/day for NR \u2014 these are the routes with the most actual human trial data." } ], "side_effects": [ "IV/injection: flushing, chest or throat tightness (especially with fast IV infusion rates), nausea", "Subcutaneous injection is frequently reported as painful/stinging", "Oral NMN/NR: generally very well tolerated, mild GI upset in some" ], "safety_notes": "Direct NAD+ injection causes more acute discomfort (flushing, chest tightness) than the oral precursor route, and has thinner human safety data despite heavy marketing in longevity clinics. For raising NAD+ with the best evidence-to-risk ratio, the oral precursor route (NMN/NR) is the better-supported option; IV/injectable NAD+ is more about acute subjective effects than proven long-term benefit.", "community_notes": "A fixture of longevity clinics and stacks, often bundled with anti-aging peptides like Epithalon. Community opinion splits between people reporting strong subjective energy benefits from IV/injectable NAD+ and a growing skeptical contingent pointing to the thin controlled-trial evidence for the injectable route, favoring oral NMN/NR as the better-studied way to raise NAD+.", "related": [ "epithalon", "mots-c", "humanin" ], "citations": [ { "title": "Safety and efficacy of long-term nicotinamide mononucleotide supplementation on metabolism, sleep, and nicotinamide adenine dinucleotide biosynthesis in healthy, middle-aged Japanese men", "authors_year": "Yamaguchi et al. 2024", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/38191197/" }, { "title": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "authors_year": "Katayoshi et al. 2023", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/36797393/" }, { "title": "Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin", "authors_year": "Vreones et al. 2022", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/36515353/" }, { "title": "Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin-resistant men", "authors_year": "Dollerup et al. 2019", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/31710095/" } ], "mixing_notes": { "clinic_combos": [ "humanin", "mots-c" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "bpc-157", "cjc-1295", "cjc-1295-dac", "dsip", "epithalon", "ghk-cu", "ghrp-2", "ghrp-6", "hcg", "hexarelin", "hgh-somatropin", "igf-1-lr3", "ipamorelin", "kisspeptin", "kpv", "ll-37", "mgf", "mt-1", "mt-2", "p21", "pe-22-28", "pinealon", "pt-141", "selank", "semax", "tb-500", "tesamorelin", "thymalin", "thymosin-alpha-1" ] } }, "mots-c": { "name": "MOTS-c", "full_name": "Mitochondrial Open Reading Frame of the 12S rRNA-c", "aliases": [ "MOTS-c" ], "categories": [ "longevity", "fitness-muscle" ], "tagline": "Mitochondrial-derived peptide encoded in mitochondrial DNA, studied for metabolic regulation and exercise-mimetic effects.", "status": "Research chemical, no clinical approval. Human evidence is essentially nonexistent; almost all data is from rodent studies.", "origin": "Discovered in 2015. Unusual among peptides here: it's encoded not by nuclear DNA but within the mitochondrial genome, in the 12S ribosomal RNA region, and appears to signal mitochondrial status to the rest of the cell and body.", "mechanism": "In animal studies, MOTS-c activates AMPK, the energy-sensing pathway also triggered by exercise and caloric restriction, and moves to the nucleus under metabolic stress to regulate genes for glucose metabolism and antioxidant response. This exercise-mimetic mechanism drives interest in it for metabolic health and longevity.", "research_summary": "Mouse studies show MOTS-c can prevent age-dependent and diet-induced insulin resistance, improve exercise capacity, and in some studies extend healthspan markers in older mice. Circulating MOTS-c in humans declines with age and rises with exercise, the correlational basis for its 'exercise-in-a-vial' reputation. No published human interventional trials of injected MOTS-c exist. Early-stage, more hypothesis than validated therapy.", "reported_benefits": [ "Reported by users as supporting exercise capacity and recovery", "Interest for metabolic health/insulin sensitivity support", "Often stacked with other longevity peptides (Epithalon, NAD+) despite having a distinct, muscle/metabolism-focused mechanism" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Common community-reported protocol is roughly 5-10 mg per week, split across 2-3 injections, often cycled in blocks of several weeks with breaks. No human dose-finding trial exists, so treat any specific number as convention, not evidence-based dosing." } ], "side_effects": [ "Injection-site reactions reported", "No systematic human safety data exists at any dose" ], "safety_notes": "One of the least human-validated compounds in this wiki. The mouse mechanism is genuinely interesting to metabolic-disease researchers, but there's a large gap between promising mouse data and a known-safe, known-effective human compound.", "community_notes": "Popular in longevity stacks alongside Epithalon and NAD+, usually framed around metabolic health and exercise capacity rather than tissue repair. Discussion skews speculative and mechanism-focused rather than experience-report-focused, unlike BPC-157, reflecting how new and understudied it is.", "related": [ "nad", "epithalon", "humanin" ], "citations": [ { "title": "The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance", "authors_year": "Lee et al. 2015", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/25738459/" }, { "title": "The mitochondrial-derived peptide MOTS-c is a regulator of plasma metabolites and enhances insulin sensitivity", "authors_year": "Kim et al. 2019", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/31293078/" }, { "title": "Mitochondrial-derived peptides and exercise", "authors_year": "Woodhead and Merry 2021", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/34520826/" }, { "title": "Exercise-Induced Muscle-Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging", "authors_year": "Tero-Vescan et al. 2025", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/40872612/" } ], "mixing_notes": { "clinic_combos": [ "humanin", "nad" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "bpc-157", "cjc-1295", "cjc-1295-dac", "dsip", "epithalon", "ghk-cu", "ghrp-2", "ghrp-6", "hcg", "hexarelin", "hgh-somatropin", "igf-1-lr3", "ipamorelin", "kisspeptin", "kpv", "ll-37", "mgf", "mt-1", "mt-2", "p21", "pe-22-28", "pinealon", "pt-141", "selank", "semax", "tb-500", "tesamorelin", "thymalin", "thymosin-alpha-1" ] } }, "humanin": { "name": "Humanin", "full_name": "Humanin (HN)", "aliases": [ "HN", "HNG (Humanin analog S14G)" ], "categories": [ "longevity" ], "tagline": "A mitochondrial-derived peptide originally discovered for neuroprotection against Alzheimer's-related cell death, now explored in metabolic and longevity research.", "status": "Research chemical, no clinical approval. Human interventional data is essentially absent; most evidence is cell-culture and rodent-based.", "origin": "Discovered in 2001 in surviving neurons from Alzheimer's disease patients, encoded (like MOTS-c) within mitochondrial DNA. Circulating Humanin levels, like MOTS-c, tend to decline with age.", "mechanism": "In preclinical work, Humanin protects cells against a range of stressors by inhibiting apoptotic pathways, and shows insulin-sensitizing and anti-inflammatory effects. It signals partly through a receptor complex shared with other cytoprotective pathways.", "research_summary": "The evidence is mostly preclinical: cell-culture protection against amyloid-beta toxicity (the original Alzheimer's finding), rodent studies showing improved insulin sensitivity and reduced oxidative stress markers, and correlational human data linking higher circulating Humanin to healthier metabolic profiles and, in some cohort studies, to longevity in centenarian populations. No published human interventional trials exist for exogenous Humanin or its more potent synthetic analog HNG.", "reported_benefits": [ "Interest for cognitive/neuroprotective support, though this is extrapolated from cell and animal data rather than demonstrated in humans", "Included in some metabolic-health-focused longevity stacks", "Correlational human data linking naturally higher levels to healthier aging is a talking point, though this doesn't establish that raising levels artificially replicates the benefit" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Not a well-established self-experimentation compound compared to MOTS-c or Epithalon; where it is used, community-reported doses are in the low single-digit mg per week range for the synthetic HNG analog, split across a few injections. Evidence behind any specific number is essentially absent." } ], "side_effects": [ "No systematic human safety or side-effect data exists" ], "safety_notes": "One of the least practically useful entries here for anyone looking for dosing guidance grounded in real human data. It's included because it comes up often in longevity-peptide discussions, not because a mature protocol exists.", "community_notes": "Discussed far less often than MOTS-c in self-experimentation forums, usually mentioned alongside other mitochondrial-derived peptides in longevity-stack theorizing rather than carrying its own body of user reports.", "related": [ "mots-c", "nad", "epithalon" ], "citations": [ { "title": "Detailed characterization of neuroprotection by a rescue factor humanin against various Alzheimer's disease-relevant insults", "authors_year": "Hashimoto et al. 2001", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/11717357/" }, { "title": "Mechanisms of neuroprotection by a novel rescue factor humanin from Swedish mutant amyloid precursor protein", "authors_year": "Hashimoto et al. 2001", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/11327724/" }, { "title": "Neuroprotective Action of Humanin and Humanin Analogues: Research Findings and Perspectives", "authors_year": "Karachaliou and Livaniou 2023", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/38132360/" }, { "title": "The Molecular Structure and Role of Humanin in Neural and Skeletal Diseases, and in Tissue Regeneration", "authors_year": "Zhu et al. 2022", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/35372353/" } ], "mixing_notes": { "clinic_combos": [ "mots-c", "nad" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290" ] } }, "semaglutide": { "name": "Semaglutide", "full_name": "Semaglutide (GLP-1 receptor agonist)", "aliases": [ "Ozempic (diabetes brand)", "Wegovy (weight-loss brand)", "Rybelsus (oral brand)" ], "categories": [ "fat-loss" ], "tagline": "Long-acting GLP-1 receptor agonist that kicked off the modern GLP-1 weight-loss era. FDA-approved for type 2 diabetes and chronic weight management.", "status": "FDA-approved prescription medication (Ozempic for type 2 diabetes, Wegovy for chronic weight management, Rybelsus as an oral tablet). Widely available by prescription; also present in the grey/compounded market, which carries additional quality-control risk.", "origin": "A synthetic analog of human GLP-1, modified with a fatty-acid side chain that binds albumin, extending its half-life from the native hormone's few minutes to about a week and allowing once-weekly injection.", "mechanism": "Activates GLP-1 receptors in the pancreas (glucose-dependent insulin secretion, glucagon suppression), the brain (appetite suppression via hypothalamic and brainstem centers, reduced food reward), and the gut (delayed gastric emptying, longer satiety after meals).", "research_summary": "One of the most rigorously studied drugs in this wiki: large RCTs (STEP for weight loss, SUSTAIN for diabetes) enrolling thousands of patients. STEP trials showed average weight loss around 15% of body weight over 68 weeks in non-diabetic participants at the 2.4 mg/week dose, versus roughly 2-3% with placebo. The SELECT cardiovascular outcomes trial showed fewer major adverse cardiovascular events in overweight/obese patients with existing cardiovascular disease. Long-term data beyond a few years is still accumulating, and weight regain after stopping is well documented: most trial participants regained a substantial portion of lost weight within a year of stopping.", "reported_benefits": [ "Substantial, well-documented weight loss in clinical trial populations", "Improved glycemic control in type 2 diabetes", "Reduced cardiovascular event risk in at-risk patients (per SELECT trial)", "Reported reduction in 'food noise' / compulsive eating thoughts, widely discussed in user communities" ], "dosing_protocols": [ { "route": "Subcutaneous injection, once weekly (standard prescribed titration)", "protocol": "Standard titration starts at 0.25 mg/week for 4 weeks, then increases roughly every 4 weeks (0.5 mg \u2192 1 mg \u2192 1.7 mg \u2192 2.4 mg for Wegovy) to reduce GI side effects; maintenance dose depends on indication and tolerability." } ], "side_effects": [ "Nausea, vomiting, diarrhea or constipation, especially during dose escalation \u2014 the most common reason people stop", "Rare but serious: pancreatitis, gallbladder disease, risk of thyroid C-cell tumors (boxed warning based on rodent data; human relevance unconfirmed but the warning stands)", "Loss of lean muscle mass alongside fat mass is a well-documented concern, making resistance training and adequate protein intake important during treatment", "Not recommended in personal/family history of medullary thyroid carcinoma or MEN 2 syndrome" ], "safety_notes": "A real, extensively trialed prescription drug with a comparatively well-characterized safety profile versus the research-chemical peptides elsewhere in this wiki. Main practical risks for most users are GI side effects during titration and muscle loss if not paired with resistance training and enough protein. Compounded (non-brand) semaglutide sold outside the regulated pharmacy supply chain carries real quality and dosing-accuracy risk and has drawn FDA warnings.", "community_notes": "The most widely discussed weight-loss peptide by a wide margin. Community reporting consistently points to 'food noise' reduction as the most distinctive subjective effect, more than simply feeling less hungry. Slow dose titration to manage nausea, plus strength training and protein intake to preserve muscle during the cut, come up constantly. Weight regain after stopping is a recurring topic; many long-term users treat it as ongoing maintenance rather than a finite course.", "related": [ "tirzepatide", "retatrutide", "tesamorelin" ], "citations": [ { "title": "Once-Weekly Semaglutide in Adults with Overweight or Obesity", "authors_year": "Wilding et al. 2021", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/33567185/" }, { "title": "Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension", "authors_year": "Wilding et al. 2022", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/35441470/" }, { "title": "Changes in Glucose Metabolism and Glycemic Status With Once-Weekly Subcutaneous Semaglutide 2.4 mg Among Participants With Prediabetes in the STEP Program", "authors_year": "Perreault et al. 2022", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/35724304/" }, { "title": "Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5", "authors_year": "Kushner et al. 2020", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/32441473/" } ], "mixing_caution": "This chart's source flags GLP-1/GIP/glucagon-receptor drugs as broadly avoided in combination with other research peptides across the board \u2014 not a peptide-specific interaction, more a general caution against stacking incretin drugs with anything else. Treat any combination here as unverified." }, "tirzepatide": { "name": "Tirzepatide", "full_name": "Tirzepatide (dual GIP/GLP-1 receptor agonist)", "aliases": [ "Mounjaro (diabetes brand)", "Zepbound (weight-loss brand)" ], "categories": [ "fat-loss" ], "tagline": "A dual GIP/GLP-1 receptor agonist that generally outperforms semaglutide for weight loss in head-to-head trials. FDA-approved for type 2 diabetes and chronic weight management.", "status": "FDA-approved prescription medication (Mounjaro for type 2 diabetes, Zepbound for chronic weight management).", "origin": "A single synthetic peptide engineered to activate both the GIP and GLP-1 receptors, combining two incretin hormone pathways in one molecule, with a fatty-acid modification giving it a once-weekly half-life similar to semaglutide.", "mechanism": "GLP-1 receptor activation provides the same appetite-suppression, gastric-emptying-delay and glucose-control effects as semaglutide. Added GIP receptor activation appears to enhance insulin sensitivity and may directly affect fat cell metabolism, thought to explain tirzepatide's larger average weight-loss effect in trials.", "research_summary": "The SURMOUNT trial program showed average weight loss around 20-22% of body weight at the highest studied dose (15 mg/week) over 72 weeks in non-diabetic participants, meaningfully larger than semaglutide's ~15% in comparable trial designs. A head-to-head trial (SURMOUNT-5) found tirzepatide produced significantly more weight loss than semaglutide directly. Visceral fat reduction, measured via DXA scan substudies, showed roughly 40% reduction in visceral fat mass over the ~72-week SURMOUNT trial period.", "reported_benefits": [ "Larger average weight loss than semaglutide in head-to-head and cross-trial comparison", "Strong visceral fat reduction specifically (measured via imaging in trial substudies)", "Improved glycemic control in type 2 diabetes, generally considered at least as effective as semaglutide for this indication" ], "dosing_protocols": [ { "route": "Subcutaneous injection, once weekly (standard prescribed titration)", "protocol": "Starting dose 2.5 mg/week for 4 weeks, then increasing in 2.5 mg increments roughly every 4 weeks as tolerated, up to a maximum studied/approved dose of 15 mg/week." } ], "side_effects": [ "Similar GI side-effect profile to semaglutide: nausea, diarrhea, vomiting, constipation, most pronounced during dose escalation", "Same boxed warning regarding thyroid C-cell tumor risk based on rodent data", "Lean mass loss alongside fat loss, same caveat as semaglutide regarding resistance training and protein intake", "Not recommended with personal/family history of medullary thyroid carcinoma or MEN 2" ], "safety_notes": "Like semaglutide, this is a properly trialed, FDA-approved medication with a comparatively well-characterized safety profile versus most entries in this wiki. Requires sustained treatment (72+ weeks in trials) to reach full visceral-fat-reduction effect; the compounded/grey-market version carries the same quality-control caveats as compounded semaglutide.", "community_notes": "Generally reported as more potent than semaglutide for both appetite suppression and weight loss, sometimes at the cost of more pronounced GI side effects during titration. A frequent discussion point is trading off tirzepatide's stronger effect against semaglutide's gentler side-effect profile for people sensitive to GI symptoms.", "related": [ "semaglutide", "retatrutide" ], "citations": [ { "title": "Tirzepatide Once Weekly for the Treatment of Obesity", "authors_year": "Jastreboff et al. 2022", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/35658024/" }, { "title": "Tirzepatide for Obesity Treatment and Diabetes Prevention", "authors_year": "Jastreboff et al. 2024", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/39536238/" } ], "mixing_caution": "This chart's source flags GLP-1/GIP/glucagon-receptor drugs as broadly avoided in combination with other research peptides across the board \u2014 not a peptide-specific interaction, more a general caution against stacking incretin drugs with anything else. Treat any combination here as unverified." }, "retatrutide": { "name": "Retatrutide", "full_name": "Retatrutide (triple GIP/GLP-1/glucagon receptor agonist)", "aliases": [ "LY3437943", "Triple-G agonist" ], "categories": [ "fat-loss" ], "tagline": "Investigational triple-hormone-receptor agonist with the largest weight-loss effect of any GLP-1-class compound tested so far. Not FDA-approved.", "status": "Investigational \u2014 in Phase 3 clinical trials as of this writing, not yet FDA-approved for any indication. Available through research-chemical/grey-market channels despite lacking approval, which carries significant additional risk versus using a regulated, approved drug.", "origin": "Developed by Eli Lilly. A single synthetic peptide engineered to hit three receptors at once: GLP-1, GIP, and glucagon. The first 'triple agonist' in this class to reach late-stage trials.", "mechanism": "Combines GLP-1 and GIP receptor activity (as in tirzepatide) with glucagon receptor agonism, which raises energy expenditure and drives lipolysis in the liver. That stacks a metabolic-rate effect on top of the appetite suppression the other GLP-1-class drugs already provide.", "research_summary": "A Phase 2 trial in the New England Journal of Medicine reported average weight loss around 24% of body weight at the highest dose (12 mg/week) at 48 weeks, the largest effect size reported for this class at time of publication. Weight loss was still trending down, not plateaued, at trial's end, suggesting more loss with continued treatment. Phase 3 trials are underway to confirm long-term efficacy and safety at scale; longer-term glucagon-receptor effects are still being worked out.", "reported_benefits": [ "Largest average weight-loss effect reported for any GLP-1-class compound in trials to date", "Added metabolic-rate/energy-expenditure component beyond pure appetite suppression, due to glucagon receptor activity", "Trial data suggests effect had not plateaued by 48 weeks, unlike some comparator trials" ], "dosing_protocols": [ { "route": "Subcutaneous injection, once weekly (as studied in trials)", "protocol": "Phase 2 trial dosing escalated up to 12 mg/week; because this drug is not yet approved, there is no standardized prescribing protocol, and self-sourced dosing is based on extrapolating from trial data rather than an established, regulated titration schedule." } ], "side_effects": [ "GI side effects similar to but potentially more pronounced than semaglutide/tirzepatide given the added glucagon receptor activity, including nausea, diarrhea and reduced appetite", "Increased heart rate has been observed in trials, thought related to glucagon receptor activation \u2014 a distinguishing safety signal versus the dual/single agonists", "Long-term safety data does not yet exist at the scale available for semaglutide or tirzepatide" ], "safety_notes": "This is an investigational drug, not an approved medication. Anyone using it outside a trial is taking a compound with an unestablished long-term human safety profile, sourced through channels with zero regulatory quality control. Take the heart-rate signal seen in trials seriously: it's mechanistically distinct from the other GLP-1-class drugs.", "community_notes": "Big buzz in weight-loss and longevity circles as the 'next generation' GLP-1 drug on the strength of its trial results. But access is entirely grey-market research-chemical sourcing since it isn't FDA-approved, a meaningfully different risk than prescribed semaglutide or tirzepatide. Weigh that against just waiting for approval or using what's already approved.", "related": [ "tirzepatide", "semaglutide" ], "citations": [ { "title": "Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial", "authors_year": "Jastreboff et al. 2023", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/37366315/" }, { "title": "The power of three: Retatrutide's role in modern obesity and diabetes therapy", "authors_year": "Abdul-Rahman et al. 2024", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/39515565/" } ], "mixing_caution": "This chart's source flags GLP-1/GIP/glucagon-receptor drugs as broadly avoided in combination with other research peptides across the board \u2014 not a peptide-specific interaction, more a general caution against stacking incretin drugs with anything else. Treat any combination here as unverified." }, "aod-9604": { "name": "AOD-9604", "full_name": "Anti-Obesity Drug 9604 (a modified fragment of human growth hormone, amino acids 176-191)", "aliases": [ "AOD-9604", "hGH Fragment 176-191" ], "categories": [ "fat-loss" ], "tagline": "A growth hormone fragment engineered to isolate the fat-burning effect and drop HGH's blood sugar and tissue growth effects. Trialed for obesity, never reached market.", "status": "Failed to reach approval as an obesity drug after Phase IIb trials showed insufficient efficacy versus placebo; sold today only as a research chemical, with no clinical approval anywhere.", "origin": "Australian biotech Metabolic Pharmaceuticals isolated the C-terminal fragment of human growth hormone (amino acids 176-191), the piece responsible for GH's lipolytic activity, and dropped the rest of the molecule that drives growth and blood-sugar effects.", "mechanism": "Meant to stimulate lipolysis and block lipogenesis in adipose tissue, mimicking one piece of GH's action without touching IGF-1, bone/tissue growth, or insulin resistance.", "research_summary": "Early studies, including some human work, suggested a modest fat-metabolism effect, enough to advance it to Phase IIb obesity trials. Those trials, the most rigorous human data that exists for this compound, found no statistically significant weight-loss benefit over placebo, and development for obesity was dropped. It hasn't been meaningfully re-investigated since.", "reported_benefits": [ "Marketed by research-chemical vendors as supporting fat loss, but this is not supported by the compound's own Phase IIb trial results", "Some anecdotal reports of mild fat-loss support when stacked with a caloric deficit and other compounds, difficult to disentangle from those other interventions" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Community-reported doses commonly range 250-500 mcg/day; there is no validated effective human dose because the compound failed its efficacy trials at the doses tested." } ], "side_effects": [ "Reported as generally well tolerated in trials (this was not the reason development stopped \u2014 lack of efficacy was)", "Limited independent safety data outside the original manufacturer's trials" ], "safety_notes": "This compound went through real Phase IIb human obesity trials and didn't beat placebo. That's a worse evidence situation than most research peptides, which simply haven't been tested rigorously at all. Read continued marketing for fat loss in that light.", "community_notes": "Still sold and discussed occasionally, but enthusiasm has cooled as the failed trial results became more widely known. Overshadowed now by tesamorelin, which has real approved-drug evidence for visceral fat, and by the GLP-1 drugs, which have far stronger trial results.", "related": [ "tesamorelin", "semaglutide" ], "citations": [ { "title": "The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice", "authors_year": "Heffernan et al. 2001", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/11713213/" }, { "title": "Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment", "authors_year": "Heffernan et al. 2001", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/11673763/" }, { "title": "Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone", "authors_year": "Ng et al. 2000", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/11146367/" } ], "mixing_notes": { "clinic_combos": [], "anecdotal_combos": [], "reported_avoid": [ "ara-290", "cjc-1295", "cjc-1295-dac", "dsip", "epithalon", "ghk-cu", "ghrp-2", "ghrp-6", "hcg", "hexarelin", "hgh-somatropin", "humanin", "igf-1-lr3", "kisspeptin", "kpv", "ll-37", "mgf", "mots-c", "mt-1", "mt-2", "nad", "p21", "pe-22-28", "pinealon", "pt-141", "selank", "semax", "tb-500", "thymalin", "thymosin-alpha-1" ] } }, "tesamorelin": { "name": "Tesamorelin", "full_name": "Tesamorelin (a growth hormone releasing hormone / GHRH analog)", "aliases": [ "Egrifta" ], "categories": [ "fat-loss", "fitness-muscle" ], "tagline": "FDA-approved GHRH analog specifically approved for reducing visceral fat in HIV-associated lipodystrophy, used off-label more broadly for visceral fat reduction and as a growth-hormone secretagogue.", "status": "FDA-approved prescription drug (Egrifta) for reduction of excess visceral fat in HIV-associated lipodystrophy. Used off-label for general visceral fat reduction and GH-axis support.", "origin": "A synthetic analog of GHRH, stabilized against enzymatic breakdown to extend its action compared to native GHRH.", "mechanism": "Stimulates the pituitary to release the body's own growth hormone in a pulsatile, physiological pattern rather than injecting synthetic HGH directly. That raises IGF-1 and has been shown to reduce visceral adipose tissue, the metabolically dangerous fat around internal organs, more than subcutaneous fat.", "research_summary": "The pivotal trials supporting FDA approval were conducted in HIV-associated lipodystrophy patients and showed a statistically significant reduction in visceral adipose tissue (measured by CT scan) versus placebo, along with improved triglycerides. Since the mechanism (raising endogenous GH/IGF-1) isn't HIV-specific, tesamorelin is used off-label in the general population for visceral fat reduction, and by some in longevity/performance medicine as a 'cleaner' GH-axis stimulator than exogenous HGH, since it preserves the pituitary's natural pulsatile release and negative feedback control.", "reported_benefits": [ "Clinically demonstrated visceral fat reduction (in its approved indication population)", "Reported improvements in sleep quality and body composition among off-label users", "Considered by some GH-axis-focused practitioners to be gentler/more physiological than direct HGH injection because it preserves the body's own feedback regulation" ], "dosing_protocols": [ { "route": "Subcutaneous injection, daily", "protocol": "The FDA-approved dose is 2 mg once daily, injected subcutaneously in the abdomen, typically at bedtime; this is also the dose most commonly used off-label." } ], "side_effects": [ "Injection-site reactions", "Joint pain, swelling or fluid retention (edema) \u2014 a known class effect of raising GH/IGF-1", "Increased blood glucose has been observed in trials \u2014 caution advised for people with insulin resistance or diabetes", "Contraindicated in active malignancy given IGF-1's growth-promoting effects" ], "safety_notes": "A real, FDA-approved drug with a genuine efficacy trial behind its specific indication, firmer ground than most 'GH secretagogue' research peptides. Watch for the known GH-axis side effects (fluid retention, joint discomfort, blood sugar effects), particularly if you have pre-diabetes or diabetes.", "community_notes": "Popular in longevity and physique-focused communities specifically for visceral fat reduction, often discussed as a more evidence-backed alternative to peptide-only GH secretagogue stacks (CJC-1295/Ipamorelin) because it has actual placebo-controlled human trial data behind it, even though that data comes from a specific patient population rather than healthy adults.", "related": [ "semaglutide", "cjc-1295", "ipamorelin" ], "citations": [ { "title": "Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data", "authors_year": "Falutz et al. 2010", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/20554713/" }, { "title": "Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation", "authors_year": "Falutz et al. 2008", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/18690162/" }, { "title": "Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin", "authors_year": "Stanley et al. 2012", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/22495074/" } ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "ipamorelin" ], "anecdotal_combos": [], "reported_avoid": [ "ara-290", "mots-c", "nad" ] } }, "cjc-1295": { "name": "CJC-1295 / Mod-GRF (1-29)", "full_name": "Modified Growth Hormone Releasing Factor (1-29), with or without Drug Affinity Complex (DAC)", "aliases": [ "Mod-GRF (1-29)", "CJC-1295 without DAC", "CJC-1295 with DAC" ], "categories": [ "fitness-muscle" ], "tagline": "A modified GHRH analog for boosting growth hormone release, almost always stacked with a GHRP like Ipamorelin. The 'without DAC' version (Mod-GRF) sees far more use than the long-acting DAC version.", "status": "Research chemical, not FDA-approved for any indication. GHRH analogs as a class have approved relatives (e.g. tesamorelin) but CJC-1295/Mod-GRF specifically has not gone through human drug trials.", "origin": "A synthetically modified fragment of growth hormone releasing hormone (GHRH). The DAC version has a Drug Affinity Complex attached that binds serum albumin, extending half-life from minutes to roughly a week. The far more commonly used version without DAC, technically Mod-GRF 1-29, behaves like a short-acting GHRH lasting about 30 minutes, which better suits the pulsatile dosing pattern users are trying to replicate.", "mechanism": "GHRH analogs increase the number and sensitivity of pituitary cells that respond to a co-administered GHRP like Ipamorelin, amplifying the GH pulse those compounds produce. The two classes are meant to be used together, not alone, since they act on complementary parts of the GH release pathway.", "research_summary": "Human data is limited mostly to older, small pharmacokinetic and pharmacodynamic studies of the underlying GHRH(1-29) sequence, not dedicated trials of the modified compounds sold today. The DAC-bearing long-acting version has drawn more safety concern in self-experimentation circles: prolonged, less-controllable elevation of GH/IGF-1 and a higher rate of reported adverse reactions than the short-acting Mod-GRF version. Most experienced users and harm-reduction guides now favor Mod-GRF over CJC-1295 with DAC.", "reported_benefits": [ "Improved sleep quality (commonly reported, consistent with GH's normal role in sleep architecture)", "Modest reported improvements in recovery and body composition when combined with a GHRP and resistance training", "Considered a cost-effective way to amplify the GH pulse from a GHRP like Ipamorelin rather than a strong standalone compound" ], "dosing_protocols": [ { "route": "Subcutaneous injection (Mod-GRF, without DAC) \u2014 the generally preferred version", "protocol": "Commonly cited compounding-pharmacy protocol: 200 mcg once daily, 5x/week, paired with a GHRP. Many experienced self-experimenters use notably lower doses \u2014 around 100 mcg or less \u2014 arguing that higher doses increase GH only marginally further while adding cost and side-effect risk. Nobody in harm-reduction-focused communities recommends exceeding 100 mcg per injection." }, { "route": "Timing", "protocol": "Standard advice is to inject in a fasted state (2-3 hours after eating, avoiding food for 30 minutes after), commonly before bed and/or immediately on waking, to align with the body's natural pulsatile GH release windows and avoid insulin blunting the GH pulse." } ], "side_effects": [ "Flushing, hot skin, itchiness reported especially at higher doses \u2014 treated by cautious users as an early warning sign to reduce dose, not a benign sign of 'working'", "Heart palpitations reported at higher doses \u2014 a stop-and-reassess signal", "Water retention / mild edema, joint discomfort \u2014 general GH-axis class effects", "The DAC (long-acting) version specifically has more reports of allergic-type reactions in self-experimentation communities than Mod-GRF" ], "safety_notes": "Since no dedicated human trials of these modified compounds exist, dosing is community convention, not established pharmacology. The harm-reduction-minded corner of the community has shifted toward lower doses and the shorter-acting Mod-GRF version, based on accumulated adverse-reaction reports at higher doses and with the DAC version.", "community_notes": "Almost always discussed and used paired with Ipamorelin or another GHRP, rather than alone. Widely seen as one of the 'gateway' GH-secretagogue combos, and a frequent subject of debate over optimal (generally lower-than-marketed) dosing.", "related": [ "ipamorelin", "sermorelin", "mk-677", "tesamorelin" ], "variant_note": "Not to be confused with 'CJC-1295 with DAC' (see the separate page for that long-acting, albumin-binding variant) \u2014 the two are pharmacokinetically distinct compounds with different half-lives and dosing frequency, despite the similar name.", "citations": [ { "title": "Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults", "authors_year": "Teichman et al. 2006", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/16352683/" }, { "title": "Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog", "authors_year": "Ionescu and Frohman 2006", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/17018654/" }, { "title": "A new era of doping? Use of peptide and peptide-analog drugs in recreational and professional sport and bodybuilding: a critical review", "authors_year": "Coutinho et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41880199/" } ], "mixing_notes": { "clinic_combos": [ "bpc-157", "epithalon", "ghk-cu", "ghrp-6", "hexarelin", "ipamorelin", "mgf", "pe-22-28", "pinealon", "selank", "semax", "tb-500", "tesamorelin", "thymalin", "thymosin-alpha-1" ], "anecdotal_combos": [ "igf-1-lr3" ], "reported_avoid": [ "aod-9604", "ara-290", "hgh-somatropin", "mots-c", "nad" ] } }, "ipamorelin": { "name": "Ipamorelin", "full_name": "Ipamorelin (a Growth Hormone Releasing Peptide / GHRP)", "aliases": [ "NNC 26-0161" ], "categories": [ "fitness-muscle" ], "tagline": "One of the most selective growth hormone secretagogues available. It stimulates GH release without the cortisol, prolactin or appetite spikes of older GHRPs, and is almost always paired with a GHRH analog like CJC-1295/Mod-GRF.", "status": "Research chemical, not FDA-approved for any indication.", "origin": "A pentapeptide developed in the 1990s specifically to be a more selective ghrelin-receptor agonist than earlier growth hormone releasing peptides like GHRP-6 or Hexarelin.", "mechanism": "Binds the ghrelin/growth hormone secretagogue receptor in the pituitary, triggering release of stored growth hormone. Its selectivity means it does this without meaningfully raising ACTH, cortisol, prolactin, or other pituitary hormones that earlier-generation GHRPs also stimulate, the main reason it largely replaced GHRP-6 and GHRP-2 in self-experimentation use.", "research_summary": "Preclinical and early pharmacology studies established its GH-releasing selectivity and potency relative to older GHRPs, but like CJC-1295, no large-scale modern human efficacy trial exists for the doses and chronic use patterns common in self-experimentation. The broader GH-axis literature (physiological GH pulses, collagen synthesis, body composition) is used to infer likely effects, but this is extrapolation, not direct trial evidence for Ipamorelin at self-administered doses.", "reported_benefits": [ "Improved sleep depth/quality, widely reported and consistent with GH's normal physiological role in sleep", "Improved recovery from training", "Modest reported improvements in body composition (more fat loss, better muscle retention) over months of consistent use combined with training", "Considered gentler / fewer side effects than older GHRPs like GHRP-6, notably without the strong hunger-stimulating effect GHRP-6 is known for" ], "dosing_protocols": [ { "route": "Subcutaneous injection, paired with a GHRH analog", "protocol": "A commonly cited compounding-pharmacy protocol is 200 mcg once daily, 5x/week, paired with Mod-GRF/CJC-1295. Some self-experimenters use up to 200-300 mcg, up to 3x/day spaced 4+ hours apart. A more conservative, cost-effective approach favored by parts of the harm-reduction community caps doses around 100-125 mcg, arguing that higher doses increase GH release only marginally further." }, { "route": "Timing", "protocol": "Same fasted-state, pre-bed and/or on-waking timing logic as CJC-1295/Mod-GRF \u2014 insulin can blunt the GH pulse, so injecting away from meals is standard advice." } ], "side_effects": [ "Allergic-type reactions have been anecdotally reported, though generally considered rare and more associated with high doses or with the co-administered GHRH", "Mild injection-site reactions", "Water retention / mild joint discomfort possible as part of the general GH-axis effect", "Users are advised to start at a low dose specifically to screen for individual reaction sensitivity before committing to a regular protocol" ], "safety_notes": "Considered one of the gentler GH secretagogues by the self-experimentation community, but gentler than GHRP-6 is a relative, community-derived judgment, not a conclusion from controlled human trials. As with CJC-1295, start low and watch for flushing, itching or palpitations as a signal to reduce dose.", "community_notes": "The default GHRP choice in most modern GH-secretagogue stacks, almost always paired with CJC-1295/Mod-GRF. Sleep quality improvement is the most consistently and confidently reported effect, more so than body-composition change, which users describe as modest and cumulative over months.", "related": [ "cjc-1295", "sermorelin", "mk-677", "bpc-157" ], "citations": [ { "title": "Ipamorelin, the first selective growth hormone secretagogue", "authors_year": "Raun et al. 1998", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/9849822/" }, { "title": "Efficacy of ipamorelin, a novel ghrelin mimetic, in a rodent model of postoperative ileus", "authors_year": "Venkova et al. 2009", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/19289567/" } ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "ghk-cu", "pe-22-28", "pinealon", "selank", "semax", "tb-500", "tesamorelin", "thymalin", "thymosin-alpha-1" ], "anecdotal_combos": [], "reported_avoid": [ "ara-290", "mots-c", "nad" ] } }, "sermorelin": { "name": "Sermorelin", "full_name": "Sermorelin (GHRH 1-29, the natural-sequence growth hormone releasing hormone fragment)", "aliases": [ "GRF 1-29", "Geref (discontinued brand)" ], "categories": [ "fitness-muscle" ], "tagline": "The original, FDA-approved GHRH analog (its approved brand was later discontinued), the natural-sequence precursor that CJC-1295/Mod-GRF are modified versions of.", "status": "Was FDA-approved (as Geref) for diagnostic testing of growth hormone deficiency and as a treatment for GH deficiency in children; the branded product was discontinued for commercial reasons, not safety. Now mainly available through compounding pharmacies (often prescribed off-label by anti-aging/hormone clinics) or research-chemical vendors.", "origin": "The first 29 amino acids of the naturally occurring 44-amino-acid GHRH molecule, the shortest fragment found to retain full GH-releasing activity.", "mechanism": "Same mechanism as the modified GHRH analogs: binds GHRH receptors in the pituitary, stimulating release of stored growth hormone in a pulsatile, physiological pattern. Preserves the body's natural negative-feedback regulation, unlike direct HGH injection.", "research_summary": "Because it held actual FDA approval, sermorelin has more legitimate human clinical trial history behind it than most GH secretagogues discussed in self-experimentation circles, including diagnostic pharmacokinetic data and pediatric GH-deficiency treatment trials. Its short half-life, a few minutes, versus modified analogs like CJC-1295 with DAC, is generally seen as an advantage for preserving physiological pulsatility, not a downside.", "reported_benefits": [ "Improved sleep quality", "Used in anti-aging/hormone-optimization clinics specifically for adults with low-normal IGF-1 as a 'gentler' alternative to direct HGH therapy", "Considered by some clinicians a reasonable starting point for GH-axis support given its approval history, even though current off-label use for aging/body composition isn't itself trial-validated" ], "dosing_protocols": [ { "route": "Subcutaneous injection, nightly", "protocol": "A commonly used clinical/off-label dose is 200-300 mcg injected subcutaneously at bedtime, daily, aiming to align with the largest natural nighttime GH pulse." } ], "side_effects": [ "Injection-site reactions", "Flushing, headache reported in some users, generally at higher doses", "Same general GH-axis caveats as other secretagogues: fluid retention, joint discomfort possible with sustained elevated GH/IGF-1" ], "safety_notes": "Among the more reassuring GH secretagogues given its genuine (if now discontinued as a branded product) FDA approval history. Current off-label adult use for body composition/anti-aging isn't the indication that approval was based on.", "community_notes": "Often recommended by hormone-optimization clinics as a first step before GHRP combinations. Some in self-experimentation communities view it as 'safer by reputation' than compounds that never went through any approval process, even though day-to-day self-administered use isn't itself clinically validated.", "related": [ "cjc-1295", "ipamorelin", "mk-677" ], "citations": [ { "title": "Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency", "authors_year": "Prakash and Goa 1999", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/18031173/" }, { "title": "Pharmacokinetics of growth hormone-releasing hormone(1-29)-NH2 and stimulation of growth hormone secretion in healthy subjects after intravenous or intranasal administration", "authors_year": "Wilton et al. 1993", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/8329825/" }, { "title": "The relative roles of continuous growth hormone-releasing hormone (GHRH(1-29)NH2) and intermittent somatostatin(1-14)(SS) in growth hormone (GH) pulse generation: studies in normal and post cranial irradiated individuals", "authors_year": "Achermann et al. 1999", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/10594518/" } ] }, "mk-677": { "name": "MK-677 (Ibutamoren)", "full_name": "Ibutamoren (not a peptide \u2014 an orally active small-molecule ghrelin receptor agonist, included here because it's routinely grouped with GH-secretagogue peptides)", "aliases": [ "Ibutamoren", "Ibutamoren Mesylate", "Nutrobal" ], "categories": [ "fitness-muscle" ], "tagline": "Orally active ghrelin mimetic that raises growth hormone and IGF-1 without injections. Not actually a peptide, but a fixture of GH-secretagogue discussions.", "status": "Was investigated by pharmaceutical companies (Merck and others) for GH deficiency, sarcopenia and hip fracture recovery in the elderly, but never received FDA approval for any indication and development was discontinued. Sold today only as a research chemical/grey-market product.", "origin": "A small synthetic molecule, not a peptide, developed as an orally bioavailable ghrelin receptor agonist. The appeal: a daily pill instead of daily injections for GH-axis stimulation.", "mechanism": "Activates the same ghrelin/GH secretagogue receptor as injectable GHRPs like Ipamorelin, but produces a sustained GH/IGF-1 elevation over roughly 12-24 hours per dose instead of the sharper, shorter pulse from injectables. Because it mimics ghrelin, the hunger hormone, it reliably increases appetite \u2014 a plus for some users, a problem for others.", "research_summary": "Human trial data is more substantial than for most research peptides. Studies in the elderly showed increased lean body mass and improved some muscle function markers, with the clearest benefit in people who actually had low GH to begin with \u2014 a caveat for younger, GH-replete users expecting the same results. A hip fracture trial was stopped early over safety concerns: increased congestive heart failure and edema in the treatment group. That trial is a big part of why it never reached approval.", "reported_benefits": [ "Increased appetite (often deliberately used for this reason during muscle-gain phases)", "Improved sleep quality, commonly and consistently reported", "Reported improvements in skin, hair and nail quality with extended use, attributed to sustained IGF-1 elevation", "Reported strength/recovery benefits, more consistently in older or lower-baseline-GH individuals per the available trial data" ], "dosing_protocols": [ { "route": "Oral, once daily", "protocol": "Commonly cited doses range from 10-25 mg once daily, typically taken at night given its sedating/sleep-promoting effect and to align with nighttime GH release; many self-experimenters start at the lower end (10 mg) to assess tolerance, particularly for blood-sugar and water-retention effects before increasing." } ], "side_effects": [ "Increased appetite/hunger \u2014 often significant and sometimes unwanted", "Water retention, mild edema, especially in the hands/feet/face \u2014 a known dose-related effect", "Elevated blood glucose / reduced insulin sensitivity reported with sustained use \u2014 worth monitoring, especially for anyone with pre-diabetes", "The hip-fracture trial safety signal (increased heart failure/edema rates) is a genuine red flag, particularly for anyone with existing cardiovascular disease", "Lethargy or grogginess reported by some users the morning after dosing" ], "safety_notes": "MK-677 has real human efficacy data, unusual for this class, but the same trial history includes a safety signal serious enough to halt a study: increased heart failure and edema in hip fracture patients. That's one of the most clearly documented risk signals in this wiki, especially relevant for anyone with existing cardiovascular risk factors.", "community_notes": "Popular because it's oral, no injections, and reliably improves sleep and appetite, which appeals to people trying to gain muscle. Water retention and blood sugar effects get discussed often. The community generally knows about the cardiovascular signal from the discontinued hip-fracture trial, though not everyone treats it with real caution.", "related": [ "ipamorelin", "cjc-1295", "igf-1-lr3" ], "citations": [ { "title": "Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial", "authors_year": "Nass et al. 2008", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/18981485/" }, { "title": "Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects", "authors_year": "Chapman et al. 1996", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/8954023/" }, { "title": "Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure", "authors_year": "Svensson et al. 1998", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/9467542/" } ] }, "igf-1-lr3": { "name": "IGF-1 LR3", "full_name": "Long R3 Insulin-like Growth Factor 1 (a modified, longer-acting analog of IGF-1)", "aliases": [ "IGF-1 LR3", "Long R3 IGF-1" ], "categories": [ "fitness-muscle" ], "tagline": "A modified, long-acting version of IGF-1, the growth factor downstream of growth hormone that directly drives muscle cell proliferation. Used in bodybuilding circles for localized and systemic muscle growth.", "status": "Research chemical, not FDA-approved for any indication. Native IGF-1 (mecasermin) is an approved drug for a rare pediatric growth-failure condition, but the modified LR3 analog discussed here has no approval of its own.", "origin": "Native IGF-1 mediates most of growth hormone's downstream tissue-building effects, but has a very short half-life (minutes) because it's rapidly bound and cleared by IGF-binding proteins. LR3 carries an amino acid substitution and an added 13-amino-acid extension that dramatically reduces binding to those clearance proteins, extending the functional half-life to many hours.", "mechanism": "Binds the IGF-1 receptor, directly stimulating satellite cell proliferation and differentiation, the process by which muscle fibers gain new nuclei and grow. Unlike GH secretagogues, which work upstream by increasing the body's own hormone release, IGF-1 LR3 works downstream, delivering the growth signal directly. Some bodybuilders inject it locally near a specific muscle group aiming for localized hypertrophy, though whether meaningful localization occurs versus rapid systemic distribution is disputed.", "research_summary": "Native IGF-1's biology is extremely well studied in growth hormone deficiency and general physiology, but the modified LR3 analog has essentially no dedicated human clinical trial data. It exists almost entirely as a bodybuilding/self-experimentation compound, not a researched pharmaceutical candidate. Unlike tesamorelin, where the underlying biology and the product in use are both studied, here the biology (IGF-1's role in muscle growth) is established but the specific product and dosing patterns are not tested in controlled human trials.", "reported_benefits": [ "Reported increases in muscle fullness/pump during use, sometimes described as more pronounced and immediate than GH secretagogues", "Interest for localized muscle growth via site-specific injection, though this specific claim is more folklore than established pharmacology", "Sometimes used short-term around intense training blocks rather than continuously" ], "dosing_protocols": [ { "route": "Subcutaneous or intramuscular injection", "protocol": "Community-reported doses are typically very low \u2014 commonly 20-50 mcg per day \u2014 reflecting IGF-1's high potency; doses are often kept short-term (a few weeks) rather than continuous, partly due to concerns about hypoglycemia and receptor downregulation with longer use." } ], "side_effects": [ "Hypoglycemia (low blood sugar) is a well-documented risk given IGF-1's insulin-like receptor cross-activity \u2014 this is one of the more acutely dangerous side effects discussed in this wiki and requires blood glucose awareness, especially combined with fasting or low-carb dieting", "Injection site reactions, and with intramuscular use, more significant local soreness", "Theoretical organ growth (organomegaly) concern with prolonged high-dose use, extrapolated from IGF-1's known growth-promoting physiology", "Theoretical cancer-growth-promotion concern given IGF-1's role in cell proliferation signalling \u2014 a reason it's generally considered contraindicated for anyone with active or recent cancer" ], "safety_notes": "The hypoglycemia risk is real and distinct from most other compounds here: IGF-1 cross-reacts with the insulin receptor at high enough local concentrations, and self-experimenters have reported acute low-blood-sugar episodes. This is a genuinely different, more acute risk profile than the GH secretagogues it's often grouped with.", "community_notes": "Popular in bodybuilding-adjacent corners of the peptide community for its rapid, visible pump and fullness effect, generally used in short cycles rather than continuously. Discussion centers on hypoglycemia risk management, keeping fast-acting carbohydrate on hand, avoiding fasted use, more than for most other compounds here, reflecting real awareness of this specific danger.", "related": [ "mk-677", "cjc-1295", "ipamorelin" ], "citations": [ { "title": "Revolutionary decellularized Alstroemeria stem-based nerve conduit integrated with GelMA and controlled IGF-1 LR3 release for enhanced rat sciatic nerve regeneration", "authors_year": "Yavuz et al. 2025", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41015370/" }, { "title": "Provisional Treatment of Volumetric Muscle Loss With Insulin-like Growth Factor 1 Releasing Muscle Void Fillers", "authors_year": "Clark et al. 2025", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41418663/" }, { "title": "Insulin-like growth factor-I and analogues increase growth in artificially-reared neonatal pigs", "authors_year": "Dunshea et al. 2002", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/12067429/" } ], "mixing_notes": { "clinic_combos": [], "anecdotal_combos": [ "bpc-157", "cjc-1295" ], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "pt-141": { "name": "PT-141 (Bremelanotide)", "full_name": "Bremelanotide", "aliases": [ "PT-141", "Vyleesi (FDA-approved brand, for women)" ], "categories": [ "sexual-health" ], "tagline": "A melanocortin-receptor agonist that acts on the brain's sexual-arousal pathways rather than on blood flow directly \u2014 FDA-approved as Vyleesi for hypoactive sexual desire disorder in premenopausal women, used off-label by men for erectile/libido support.", "status": "FDA-approved prescription drug (Vyleesi) for acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. Used off-label, including by men, and also available through the grey/research-chemical market outside a prescription.", "origin": "A synthetic analog of alpha-MSH engineered specifically for activity at melanocortin 4 receptors (MC4R) in the brain, which govern sexual arousal, distinct from the pigmentation-related MC1R pathway.", "mechanism": "Unlike PDE5 inhibitors (sildenafil, tadalafil), which work locally by increasing blood flow to genital tissue, bremelanotide acts centrally on melanocortin receptors in the neural arousal pathway. That's why it's framed as addressing 'desire' rather than mechanical erectile function, and why it treats a condition, HSDD, that PDE5 inhibitors don't touch.", "research_summary": "The RECONNECT trials that supported Vyleesi's FDA approval were conducted in premenopausal women with HSDD and showed statistically significant improvement in desire and reduction in distress versus placebo, though the effect size was modest and placebo response was meaningful too, typical for this trial category. Male sexual-function research on bremelanotide is smaller in scale, mostly from earlier-stage development, including erectile dysfunction trials before development pivoted to the female HSDD indication. It showed improved erectile response, but that's not the compound's approved use in men.", "reported_benefits": [ "Increased subjective sexual desire/arousal, the primary effect in its approved female indication", "Reported improved erectile response in men (off-label use), sometimes combined with PDE5 inhibitors for complementary mechanisms", "Effect is described by users as psychological/arousal-focused rather than purely mechanical" ], "dosing_protocols": [ { "route": "Subcutaneous injection (approved autoinjector dose)", "protocol": "The approved Vyleesi dose is 1.75 mg, self-injected at least 45 minutes before anticipated sexual activity, with a maximum of one dose per 24 hours and no more than 8 doses per month." }, { "route": "Off-label / self-sourced use (commonly lower doses than the approved autoinjector)", "protocol": "Community-reported doses are often lower than the approved 1.75 mg autoinjector dose, commonly in the 0.5-1.5 mg range, adjusted based on side-effect tolerance (particularly nausea), taken roughly an hour before activity." } ], "side_effects": [ "Nausea is the most common and often dose-limiting side effect \u2014 frequently reported and can be significant", "Flushing, headache", "Transient increase in blood pressure and decrease in heart rate observed in trials \u2014 worth caution for anyone with cardiovascular disease", "Skin/gum darkening has been reported with frequent, prolonged use, related to melanocortin receptor activity on pigmentation pathways" ], "safety_notes": "Nausea is common enough that many users experiment with the lowest effective dose instead of the full approved autoinjector amount. Blood pressure and heart rate effects warrant caution for anyone with cardiovascular conditions, and should be discussed with a physician even for off-label male use.", "community_notes": "Widely discussed as an alternative or complement to PDE5 inhibitors, specifically because it works on desire and arousal rather than blood flow. Some men report using both together for a more complete effect. Nausea management, via lower doses or timing around meals, is the most common practical topic in user communities.", "related": [ "oxytocin", "kisspeptin" ], "variant_note": "Occasionally discussed alongside PSK/other melanocortin-pathway variants sold under adjacent names; PT-141 (bremelanotide) itself is the only form with FDA approval (as Vyleesi, for HSDD in women) and the only form with real human trial data.", "citations": [ { "title": "Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials", "authors_year": "Kingsberg et al. 2019", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/31599840/" }, { "title": "Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder", "authors_year": "Simon et al. 2019", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/31599847/" }, { "title": "Responder Analyses from a Phase 2b Dose-Ranging Study of Bremelanotide", "authors_year": "Althof et al. 2019", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/31277966/" } ], "mixing_notes": { "clinic_combos": [ "ghrp-2", "kisspeptin", "pinealon", "semax" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "oxytocin": { "name": "Oxytocin", "full_name": "Oxytocin (a naturally occurring neuropeptide hormone)", "aliases": [ "Pitocin/Syntocinon (FDA-approved brands for labor/postpartum indications)" ], "categories": [ "sexual-health" ], "tagline": "The 'bonding hormone' \u2014 an FDA-approved drug for labor induction and postpartum hemorrhage, explored off-label for social bonding, sexual intimacy and anxiety.", "status": "FDA-approved prescription drug (as Pitocin/Syntocinon) for labor induction/augmentation and postpartum hemorrhage control. Off-label and research-chemical use for social/sexual/anxiety purposes is not an approved indication.", "origin": "A naturally occurring neuropeptide hormone produced in the hypothalamus and released by the posterior pituitary. Classically known for childbirth (uterine contractions) and lactation (milk let-down), more recently studied for social bonding, trust, and attachment.", "mechanism": "Acts on oxytocin receptors throughout the brain, especially regions involved in social cognition and reward, and peripherally on uterine smooth muscle. The 'bonding hormone' label comes from behavioral neuroscience research showing oxytocin administration increases trust, in-group bonding, eye contact, and emotional empathy in experimental settings, alongside its role in orgasm and post-intimacy bonding physiology.", "research_summary": "Intranasal oxytocin has a large academic literature on social cognition, trust, autism-spectrum social behavior, and anxiety. The field has also faced a real replication crisis: several high-profile early findings, increased trust especially, failed to replicate cleanly in larger, more rigorous follow-up studies. Honest read: real biological effects on social/bonding behavior exist, but the magnitude and reliability in typical adults is weaker than early 2000s-2010s media coverage suggested.", "reported_benefits": [ "Reported increased feelings of closeness/bonding with a partner, especially around intimacy", "Some report anxiolytic (anxiety-reducing) and socially 'softening' effects", "Explored (with mixed trial results) for social difficulties in autism spectrum contexts, though this remains an active and unsettled research area, not an established treatment" ], "dosing_protocols": [ { "route": "Intranasal spray (most common self-administered route)", "protocol": "Community and research-context doses commonly range from 10-40 IU, taken 15-45 minutes before an intended social or intimate context; research studies most commonly use 24 IU or 40 IU intranasal doses." } ], "side_effects": [ "Generally well tolerated at studied doses", "Nasal irritation with intranasal use", "Theoretical concern about blunting rather than enhancing some social responses in certain contexts/doses per some of the more nuanced recent research \u2014 the effect isn't simply 'more is better' in all social situations" ], "safety_notes": "Oxytocin's approved uses are obstetric (labor, postpartum bleeding), at doses and routes very different from intranasal self-administration for social or sexual purposes. Off-label users are relying on the separate, more mixed academic literature on intranasal effects, not the approval that put it on the market.", "community_notes": "Popular as a couples' intimacy aid, sometimes used alongside PT-141. Reports of a subjective 'warmth' or closeness effect are common, but consistent with the replication concerns, some users report no noticeable effect at all. Response varies a lot between individuals and contexts.", "related": [ "pt-141", "kisspeptin" ], "citations": [ { "title": "Does intranasal oxytocin reduce symptoms of mental disorders? A meta-analysis of clinical trials", "authors_year": "Bonnieux et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42134427/" }, { "title": "A key gene modulating oxytocin efficacy in autism: genome-wide discovery and verification in randomized controlled trials datasets", "authors_year": "Kuwabara et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41904269/" }, { "title": "The role of the oxytocinergic system in oral microbiome composition in children with autism: evidence from a randomized controlled trial of intranasal oxytocin", "authors_year": "Evenepoel et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41876480/" }, { "title": "Biological modulators of treatment outcome during psychiatric care: The interplay between inflammation and oxytocin", "authors_year": "Sedoff et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42156189/" } ] }, "kisspeptin": { "name": "Kisspeptin", "full_name": "Kisspeptin (KP-10 and related fragments, encoded by the KISS1 gene)", "aliases": [ "KP-10", "Metastin (older name)" ], "categories": [ "sexual-health" ], "tagline": "The master upstream regulator of the reproductive hormone axis, more recently studied for direct effects on sexual and emotional brain processing, not just downstream hormone levels.", "status": "Research/investigational compound. Not FDA-approved for any indication, though it has been used in legitimate clinical research settings (including UK academic trials on sexual response and reproductive hormone stimulation) more than most 'research chemical' peptides.", "origin": "The peptide product of the KISS1 gene, discovered originally in cancer-metastasis-suppression research (hence its older name metastin) before its essential role triggering puberty and regulating the reproductive hormone axis was identified.", "mechanism": "Kisspeptin neurons in the hypothalamus sit directly upstream of GnRH neurons: kisspeptin release triggers GnRH release, which drives LH/FSH release from the pituitary and ultimately testosterone/estrogen production. Beyond this classic reproductive-axis role, functional brain imaging studies from Imperial College London show kisspeptin administration modulates activity in brain regions tied to sexual and romantic processing directly, effects beyond downstream hormone stimulation.", "research_summary": "One of the more legitimately academically researched compounds in the sexual-health category, with published human trials, including controlled fMRI studies, showing kisspeptin administration increases sexual and romantic brain activity in men, and separately increases LH pulsatility in reproductive-axis research. Also studied as a potential fertility-treatment adjunct for triggering ovulation in IVF protocols. None of this has translated into an approved, marketed drug; it remains a research and early clinical-trial compound.", "reported_benefits": [ "Research-documented increase in reproductive hormone axis activity (LH, and downstream testosterone/estrogen)", "Academic research (not yet self-experimentation-community-level evidence) suggesting direct effects on sexual/romantic brain processing", "Interest in fertility contexts (IVF ovulation triggering) is a genuine, ongoing area of clinical research" ], "dosing_protocols": [ { "route": "Subcutaneous injection (self-experimentation, extrapolated from research protocols)", "protocol": "Research studies commonly use kisspeptin doses in the range of a few hundred nanomoles to low micrograms-per-kg, given as single doses or short infusions in controlled research settings \u2014 very different from the community-sourced 'daily dosing' patterns common for other peptides, since kisspeptin's research use has mostly been in acute, single-administration study designs rather than chronic self-dosing protocols." } ], "side_effects": [ "Generally well tolerated in the research trials conducted to date", "Because it sits at the top of the reproductive hormone cascade, theoretical concern about disrupting normal hormonal feedback loops with chronic/frequent dosing outside a controlled research context \u2014 this hasn't been well studied" ], "safety_notes": "Kisspeptin's research pedigree is unusually strong for a peptide discussed in self-experimentation spaces, but nearly all of it used acute, single-dose or short-infusion protocols in controlled clinical settings, not the ongoing, self-directed daily/weekly dosing typical of self-experimentation. That mismatch between how it's been studied and how it's actually used off-label matters.", "community_notes": "Less mainstream than PT-141 in self-experimentation communities. Interest tends to come from people who've read the Imperial College London fMRI research rather than from a large base of self-reported user experience, the opposite pattern from something like BPC-157: the academic research is ahead of the community-use track record.", "related": [ "pt-141", "oxytocin" ], "citations": [ { "title": "Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy", "authors_year": "Abbara et al. 2015", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/26192876/" }, { "title": "A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial", "authors_year": "Abbara et al. 2017", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28854728/" }, { "title": "The direct and indirect effects of kisspeptin-54 on granulosa lutein cell function", "authors_year": "Owens et al. 2018", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/29206944/" } ], "mixing_notes": { "clinic_combos": [ "pinealon", "pt-141" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "semax": { "name": "Semax", "full_name": "Semax (a synthetic ACTH(4-10) analog)", "aliases": [ "Semax", "N-Acetyl Semax Amidate" ], "categories": [ "nootropics-cognitive" ], "tagline": "Russian-developed nootropic peptide, approved as a prescription drug in Russia for stroke recovery and cognitive/attention support. Widely used off-label elsewhere as a nasal-spray nootropic.", "status": "Approved prescription drug in Russia (for ischemic stroke, optic nerve atrophy, and ADHD-type attention difficulties). Not approved in the US, EU, or most other countries; used there as a research chemical/off-label nasal spray.", "origin": "Developed by Russian researchers at the Institute of Molecular Genetics, Russian Academy of Sciences, in the 1980s. Derived from a fragment of ACTH but modified to remove ACTH's hormonal (adrenal-stimulating) activity while keeping its CNS effects.", "mechanism": "Increases brain-derived neurotrophic factor (BDNF) expression in animal studies, modulates dopaminergic and serotonergic signalling, and shows neuroprotective and antioxidant effects in stroke and hypoxia models. It doesn't act like a stimulant; effects are described as neuroplasticity and neuroprotection support rather than acute energizing.", "research_summary": "Russian clinical trials, the basis for its drug approval, studied it in ischemic stroke patients, showing improved neurological outcome scores in some trials versus standard care, and in children with attention difficulties. This evidence, like Epithalon's, comes largely from a research tradition with less rigorous international peer review and independent replication than Western regulatory standards require, so weight it accordingly even with genuine drug approval in its country of origin.", "reported_benefits": [ "Reported improvements in focus, mental clarity and motivation, commonly described by users as smoother/less jittery than stimulants", "Reported mood-lifting effect by some users", "Interest for post-concussion or general cognitive-recovery support, extrapolating from its stroke-recovery research" ], "dosing_protocols": [ { "route": "Intranasal spray", "protocol": "Commonly reported doses are 200-600 mcg per dose (a few sprays), once to a few times per day; because tolerance/desensitization is reported by some users with continuous daily use, many self-experimenters cycle it (e.g. several days on, then a break) rather than dosing continuously long-term." } ], "side_effects": [ "Generally reported as well tolerated at typical nasal-spray doses", "Nasal irritation from the spray itself", "Some users report reduced subjective effect with continuous daily use, prompting cycling protocols", "Long-term safety data at self-administered doses outside Russian clinical trial contexts is limited" ], "safety_notes": "The Russian drug-approval status is a genuine point in its favor relative to purely speculative research peptides, but comes from a regulatory tradition with less overlap with FDA/EMA-style trial and review standards, worth more independent scrutiny from Western readers.", "community_notes": "One of the more popular 'Russian peptide' nootropics, often discussed alongside Selank as a complementary pair: Semax for focus/motivation, Selank for anxiolytic/calming. Reports of diminishing effect with continuous use are common enough that cycling is standard practice, not a niche precaution.", "related": [ "selank", "dsip" ], "variant_note": "Sometimes sold as 'NA-Semax amidate' (N-acetyl, amidated form) rather than the original Semax sequence. The amidate modification is intended to improve stability, and community reports treat it as roughly interchangeable in effect, but it has not been independently studied to the same extent as the parent compound.", "citations": [ { "title": "[The efficacy of semax in the treatment of patients at different stages of ischemic stroke]", "authors_year": "Gusev et al. 2018", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/29798983/" }, { "title": "[The effect of semax and its C-end peptide PGP on expression of the neurotrophins and their receptors in the rat brain during incomplete global ischemia]", "authors_year": "Stavchanski\u012d et al. 2011", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/22295573/" }, { "title": "Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action", "authors_year": "Shadrina et al. 2009", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/19662538/" } ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "ghrp-2", "ghrp-6", "hexarelin", "ipamorelin", "ll-37", "mgf", "pt-141", "tb-500", "thymalin", "thymosin-alpha-1" ], "anecdotal_combos": [ "dsip", "p21" ], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "selank": { "name": "Selank", "full_name": "Selank (a synthetic analog of the endogenous immunomodulatory peptide tuftsin)", "aliases": [ "Selank" ], "categories": [ "nootropics-cognitive" ], "tagline": "Russian-developed anxiolytic peptide, approved as a prescription drug in Russia for anxiety and mixed anxiety-depressive disorders. Used off-label elsewhere as a calming nasal-spray nootropic.", "status": "Approved prescription drug in Russia for generalized anxiety disorder and mixed anxiety-depressive states. Not approved in the US, EU, or most other countries.", "origin": "Comes from the same Russian research tradition as Semax. Selank is a synthetic peptide based on tuftsin, a naturally occurring immunomodulatory peptide, modified for stability and CNS activity.", "mechanism": "Modulates GABAergic and serotonergic signalling, which drives its anxiolytic effect, without the sedation or dependence risk of benzodiazepines. Like Semax, it's been shown in animal studies to influence BDNF expression and carries mild immunomodulatory effects, a holdover from its tuftsin origin.", "research_summary": "The Russian trials behind its drug approval studied generalized anxiety disorder and mixed anxiety-depression, generally reporting anxiolytic effects comparable to reference anxiolytics but with a better side-effect and dependence profile. As with Semax, this evidence comes from a research and regulatory tradition with less independent international replication than Western-standard trials.", "reported_benefits": [ "Reported reduction in anxiety and stress reactivity without the sedation typically associated with benzodiazepines", "Reported improved focus under stress (calm-but-alert effect, distinct from a sedative)", "Often used situationally (before a stressful event) rather than as a continuous daily regimen" ], "dosing_protocols": [ { "route": "Intranasal spray", "protocol": "Commonly reported doses are 250-750 mcg per dose, taken as needed for acute anxiety/stress, or once to twice daily for ongoing use; similar to Semax, some users cycle it rather than using continuously, though reported tolerance/desensitization concerns are generally described as less pronounced than with Semax." } ], "side_effects": [ "Generally reported as well tolerated", "Nasal irritation from the spray formulation", "Limited independent (non-Russian-trial) human safety data" ], "safety_notes": "Genuine drug-approval status in Russia counts for something, but the trial base behind it has less international independent replication than Western regulatory review typically demands. Treat it as more evidence-backed than a typical research chemical, less so than an FDA/EMA-approved medication.", "community_notes": "Often paired with Semax: Selank for calm/anxiety, Semax for focus/motivation. Popular as a non-sedating alternative to benzodiazepines for situational anxiety, like before public speaking or other high-stress events.", "related": [ "semax", "dsip" ], "variant_note": "Sometimes sold as 'Selank amidate' rather than the original Selank sequence. As with Semax's amidate variant, this is a stability-oriented modification with a thinner independent evidence base than the parent peptide, though community reports treat it as similar in effect.", "citations": [ { "title": "[Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia]", "authors_year": "Zozulia et al. 2008", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/18454096/" } ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "ipamorelin", "ll-37", "pinealon", "tb-500", "thymalin", "thymosin-alpha-1" ], "anecdotal_combos": [ "dsip", "p21" ], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "dsip": { "name": "DSIP", "full_name": "Delta Sleep-Inducing Peptide", "aliases": [ "DSIP" ], "categories": [ "nootropics-cognitive" ], "tagline": "A short peptide first isolated from the brains of sleeping rabbits, explored for sleep, stress and pain modulation. Human evidence for an actual sleep-inducing effect is thin, despite the name.", "status": "Research chemical, no clinical approval anywhere. Human trial data is sparse and dated.", "origin": "First isolated in 1977 from rabbit blood during electrically induced slow-wave (delta) sleep, hence the name. Later research found DSIP has a wider range of physiologic and endocrine roles than sleep induction alone.", "mechanism": "Proposed to modulate ACTH levels, inhibit somatostatin secretion (relevant to GH-release timing, since somatostatin blocks GH release), normalize blood pressure, and alter pain perception, alongside its namesake but weakly proven role in delta-wave sleep.", "research_summary": "The human evidence that DSIP reliably induces or deepens delta-wave sleep is older and weaker than most people assume. Studies from the 1970s-80s produced mixed results, and no rigorous, modern, large-scale human sleep trial has followed. Most claims in wellness/peptide marketing trace back to this limited older literature.", "reported_benefits": [ "Reported improvement in sleep onset or depth by some users, though response is described as inconsistent between individuals", "Reported reduction in stress reactivity", "Sometimes included in stacks with Epithalon for a broader 'sleep and recovery' framing" ], "dosing_protocols": [ { "route": "Subcutaneous injection, before bed", "protocol": "Commonly reported doses are 100-300 mcg, injected 30-60 minutes before intended sleep; given inconsistent reported response, many users treat it as worth a short trial period rather than an assumed-effective compound." } ], "side_effects": [ "Generally reported as well tolerated at typical self-administered doses", "Limited modern human safety data" ], "safety_notes": "The name promises more than the evidence supports. User reports are more mixed and inconsistent than Ipamorelin's sleep effect, which has a more consistent reporting pattern in the GH-secretagogue community.", "community_notes": "A lower-confidence addition to sleep/recovery stacks. Discussed less often and with more mixed reviews than the GH secretagogues or Epithalon.", "related": [ "epithalon", "semax", "selank" ], "citations": [ { "title": "Delta Sleep-Inducing Peptide Recovers Motor Function in SD Rats after Focal Stroke", "authors_year": "Tukhovskaya et al. 2021", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/34500605/" }, { "title": "DSIP-Like KND Peptide Reduces Brain Infarction in C57Bl/6 and Reduces Myocardial Infarction in SD Rats When Administered during Reperfusion", "authors_year": "Tukhovskaya et al. 2021", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/33918965/" }, { "title": "Secreted peptides crossing the blood-brain barrier and DSIP fusion peptide efficacy in PCPA-induced insomnia mouse models", "authors_year": "Mu et al. 2024", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/39444618/" }, { "title": "Phosphorylated delta sleep inducing peptide restores spatial memory and p-CREB expression by improving sleep architecture at high altitude", "authors_year": "Roy et al. 2018", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/30107169/" } ], "mixing_notes": { "clinic_combos": [ "epithalon" ], "anecdotal_combos": [ "selank", "semax" ], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "cagrilintide": { "name": "Cagrilintide", "full_name": "NN2640 (long-acting amylin receptor agonist)", "aliases": [ "long-acting amylin analog", "amylin agonist" ], "categories": [ "fat-loss", "fitness-muscle" ], "tagline": "Long-acting amylin agonist that adds synergistic weight loss on top of GLP-1 drugs.", "status": "Investigational (Phase 3) | Pending FDA approval", "origin": "Novo Nordisk built cagrilintide as a long-acting amylin receptor agonist derived from human amylin, the pancreatic hormone co-secreted with insulin. Lipidation technology extends its half-life for once-weekly dosing, unlike first-generation amylin analogs that needed daily injections. Development accelerated after Phase 2/3 data showed enhanced efficacy combined with semaglutide in the fixed-dose CagriSema.", "mechanism": "Activates amylin receptors (AMYR) and calcitonin receptors (CTR) in the hindbrain and hypothalamus, suppressing appetite, slowing gastric emptying, and driving satiation through neural circuits distinct from GLP-1 agonism. Combined with a GLP-1 agonist, activation in complementary brain regions produces additive satiety.", "research_summary": "Meta-analyses of Phase 2/3 trials show cagrilintide monotherapy produces about 6% body weight reduction; the CagriSema combination adds 7-10% weight loss beyond semaglutide alone. Adverse events are mostly gastrointestinal and dose-related, with no unexpected safety signals so far. Trials run 12-52 weeks; there's no data on safety or durability beyond 1-2 years.", "citations": [ { "title": "Maximizing weight loss with cagrisema: a systematic review and GRADE-assessed meta-analysis of randomized controlled trials", "authors_year": "Khan et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42608559/" }, { "title": "Co-agonism of GLP-1R and CTR/AMYR in the lateral dorsal tegmental nucleus produces additive effects on homeostatic and motivated feeding", "authors_year": "Sanchez-Navarro et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42603595/" } ], "reported_benefits": [ "weight loss (6-10% body weight reduction)", "reduced waist circumference", "improved glycemic control in diabetic subsets", "reduced hunger and food motivation" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Once-weekly: escalation from 0.25 mg to target maintenance doses of 2.0-2.4 mg (monotherapy) or 2.4 mg when combined with semaglutide (CagriSema)." } ], "side_effects": [ "nausea (dose-dependent)", "vomiting", "diarrhea", "gastric reflux", "injection site reactions", "fatigue" ], "safety_notes": "GI adverse events are the limiting factor: grade 3 nausea/vomiting hits 5-20% of users at higher doses. Caution advised for anyone with a pancreatitis history. No major cardiac, renal, or hepatic signals so far, but safety beyond 2 years isn't established.", "community_notes": "Anecdotal reports describe it as a potent satiety agent, more nausea-inducing than GLP-1 monotherapy alone. It's not available outside trials, and black-market sourcing brings potency variance and purity concerns.", "related": [ "semaglutide", "tirzepatide", "mazdutide", "survodutide" ] }, "mazdutide": { "name": "Mazdutide", "full_name": "LY3305677 (dual glucagon and GLP-1 receptor agonist)", "aliases": [ "LY3305677", "GCG/GLP-1 dual agonist" ], "categories": [ "fat-loss", "longevity" ], "tagline": "Dual GLP-1/glucagon agonist in Phase 3 trials showing 15-20% weight loss with metabolic benefits beyond weight reduction.", "status": "Investigational (Phase 3) | Positive Phase 2 data", "origin": "Developed by Eli Lilly and Innovent Biologics as a once-weekly subcutaneous GLP-1/glucagon dual agonist. Moved from Phase 1 through Phase 2 US trials to Phase 3 in Chinese populations, with 15-20% weight loss.", "mechanism": "Near-equipotent agonist at GLP-1 and glucagon receptors (GCGR). GLP-1R activation suppresses appetite; GCGR activation raises hepatic and peripheral lipid oxidation and energy expenditure. The glucagon component may preferentially mobilize visceral and hepatic fat.", "research_summary": "Phase 2 US trial: 10-16 mg produced 15.6-18.1% weight loss at week 32 vs -0.9% for placebo. Phase 3 China data show up to 20.1% weight loss. GI adverse events are dose-limiting, worst at 16 mg (20% discontinuation). Cardiovascular safety is still being evaluated in ongoing outcomes trials.", "citations": [ { "title": "Efficacy and safety of mazdutide in adults with obesity or overweight: a US-based, multicentre, phase 2, randomised, placebo-controlled clinical trial", "authors_year": "Hsia et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42628555/" } ], "reported_benefits": [ "weight loss (15-20% body weight reduction)", "reduced waist circumference", "improved glycemic control", "preferential visceral/hepatic fat loss", "potential kidney protection" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Once-weekly: dose escalation from 3 mg to maintenance of 10 mg or 16 mg depending on tolerability." } ], "side_effects": [ "nausea", "vomiting", "diarrhea", "constipation", "abdominal pain", "increased heart rate", "fatigue" ], "safety_notes": "GI toxicity is dose-limiting at 16 mg. Heart rate rises at all doses. Cardiovascular outcomes trial ongoing. No teratogenicity data; not studied in pregnancy.", "community_notes": "Access for self-experimenters is limited since it's still a Phase 3 drug. Trial participants report more weight loss and stronger appetite suppression than semaglutide alone.", "related": [ "semaglutide", "tirzepatide", "survodutide", "retatrutide" ], "mixing_caution": "This chart's source flags GLP-1/GIP/glucagon-receptor drugs as broadly avoided in combination with other research peptides across the board \u2014 not a peptide-specific interaction, more a general caution against stacking incretin drugs with anything else. Treat any combination here as unverified." }, "survodutide": { "name": "Survodutide", "full_name": "BI 456906 (dual glucagon and GLP-1 receptor agonist)", "aliases": [ "BI 456906", "GLP-1/GCGR dual agonist" ], "categories": [ "fat-loss", "longevity" ], "tagline": "Boehringer Ingelheim's GLP-1/glucagon dual agonist in Phase 3, showing 17-22% weight loss with a cardiovascular outcomes trial underway.", "status": "Investigational (Phase 3) | Cardiovascular outcomes trial ongoing", "origin": "Developed by Boehringer Ingelheim as a once-weekly subcutaneous GLP-1/glucagon receptor dual agonist. In Phase 3 following positive Phase 2 dose-finding trials in obesity, with multiple regional Phase 3 trials active including a dedicated cardiovascular outcomes trial.", "mechanism": "Selective dual agonist of GLP-1R and GCGR with balanced activity at both, combining appetite suppression with hepatic lipogenesis inhibition and higher energy expenditure. Preclinical and early clinical data suggest it preferentially reduces visceral and hepatic adiposity.", "research_summary": "Phase 2/3 data show survodutide 3.6-4.8 mg produces 17-22% body weight reductions over 52 weeks, with reported liver-fat reductions of 60-80% in some cohorts. Heart-rate elevation is observed and under formal cardiovascular evaluation. GI adverse events are dose-limiting but typically mild-to-moderate. Evidence is limited to 52-76 weeks of exposure.", "citations": [ { "title": "Survodutide for Obesity in Chinese Adults: Phase 3 Randomized Trial Design and Baseline Characteristics (SYNCHRONIZE-CN)", "authors_year": "Ji et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42599381/" } ], "reported_benefits": [ "weight loss (17-22% body weight reduction)", "improved glycemic control", "preferential visceral and liver-fat reduction", "potential cardioprotection (under investigation)" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Once-weekly: gradual escalation to maintenance at 3.6 or 4.8 mg over 4-8 weeks." } ], "side_effects": [ "nausea", "vomiting", "diarrhea", "constipation", "fatigue", "increased heart rate", "potential QTc prolongation (under investigation)" ], "safety_notes": "GI tolerability improves with slower dose escalation. Heart-rate elevation is consistent across dual agonists and under formal evaluation. Cardiovascular outcomes and safety remain the key open Phase 3 question.", "community_notes": "Biohacker access is limited since it's a Phase 3 drug. Scattered anecdotal trial-participant reports suggest efficacy similar to or better than mazdutide with slightly better liver-fat reduction.", "related": [ "mazdutide", "semaglutide", "tirzepatide", "retatrutide" ], "mixing_caution": "This chart's source flags GLP-1/GIP/glucagon-receptor drugs as broadly avoided in combination with other research peptides across the board \u2014 not a peptide-specific interaction, more a general caution against stacking incretin drugs with anything else. Treat any combination here as unverified." }, "liraglutide": { "name": "Liraglutide", "full_name": "GLP-1 receptor agonist (Saxenda for weight loss, Victoza for diabetes)", "aliases": [ "Saxenda", "Victoza", "NN2211" ], "categories": [ "fat-loss", "longevity" ], "tagline": "First-generation GLP-1 receptor agonist, FDA-approved for weight loss (Saxenda) and diabetes (Victoza) with well-established safety and efficacy.", "status": "FDA-approved (2014 for diabetes, 2016 for weight loss)", "origin": "Developed by Novo Nordisk as a once-daily subcutaneous GLP-1 receptor agonist, derived from human GLP-1 with a single amino-acid substitution and lipid modification for extended pharmacokinetics. Approved as Victoza (2010, diabetes) and Saxenda (2014, chronic weight management). The longest-marketed GLP-1 agonist.", "mechanism": "Activates GLP-1 receptors distributed through the brain, pancreatic islets, and GI tract. Central GLP-1R activation suppresses appetite; peripheral activation stimulates glucose-dependent insulin secretion and suppresses glucagon. Slows gastric emptying. Glucose-dependent signaling minimizes hypoglycemia risk.", "research_summary": "Evaluated in thousands of published studies. Pivotal SCALE obesity trials demonstrated 4.5-6% body weight reduction vs placebo at 56 weeks. The LEADER cardiovascular outcomes trial showed reduced major adverse cardiovascular events and mortality in type 2 diabetes. Long-term safety data span 15+ years; the most common adverse events are gastrointestinal and generally diminish with time.", "citations": [ { "title": "Assessing the Association Between GLP-1 Receptor Agonists and Diabetic Foot Complications Using Real-World Pharmacovigilance Database and Mendelian Randomization", "authors_year": "Zhang et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42726083/" } ], "reported_benefits": [ "weight loss (4.5-6% body weight reduction vs placebo)", "improved glycemic control", "reduced cardiovascular events and mortality", "improved lipid profiles" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Saxenda: 0.6 mg once-daily, escalating weekly to 3.0 mg maintenance. Victoza: 0.6 mg once-daily, escalating to 1.2-1.8 mg maintenance." } ], "side_effects": [ "nausea (30-40% mild)", "vomiting", "diarrhea", "constipation", "headache", "decreased appetite" ], "safety_notes": "GI adverse events typically resolve within 2-4 weeks. Pancreatitis risk is uncommon; causality debated. Rodent-only medullary thyroid carcinoma signal; contraindicated with personal/family MTC or MEN2A/2B history. Pregnancy category C.", "community_notes": "The most widely used GLP-1 agonist for self-experimentation; forums report modest but reliable 4-6% weight loss with pronounced early nausea that improves, and better tolerability than tirzepatide at lower doses.", "related": [ "semaglutide", "tirzepatide" ], "mixing_caution": "This chart's source flags GLP-1/GIP/glucagon-receptor drugs as broadly avoided in combination with other research peptides across the board \u2014 not a peptide-specific interaction, more a general caution against stacking incretin drugs with anything else. Treat any combination here as unverified." }, "adipotide": { "name": "Adipotide", "full_name": "CKGGRAKDC-GG-D-KLAKLAK-2 (proapoptotic peptide targeting adipose vasculature)", "aliases": [ "FTPP", "peptide CKGGRAKDC-KLAKLAK-2" ], "categories": [ "fat-loss" ], "tagline": "Proapoptotic peptide that kills off adipose-tissue blood vessels; pulled from development after it damaged kidneys in human trials.", "status": "Discontinued (Phase 1 nephrotoxicity) | Research chemical only", "origin": "Arrowhead Research built it as a targeted anti-angiogenesis strategy for obesity: an RGD homing motif binds integrin-expressing endothelial cells in white adipose tissue, fused to a proapoptotic KLAKLAK-2 domain. Efficacy in obese primates led to Phase 1 human trials in 2012, discontinued in 2019 for dose-limiting nephrotoxicity.", "mechanism": "The RGD sequence binds integrin-expressing endothelial cells in adipose vasculature; the KLAKLAK domain then permeabilizes the membrane and triggers apoptosis. Killing the vessels starves adipocytes of oxygen and shrinks fat tissue directly, with no appetite or glucose pathway involved.", "research_summary": "In obese rhesus monkeys, 0.43 mg/kg/day for 28 days produced about 11% body weight loss and improved insulin sensitivity. Phase 1 human trials hit dose-limiting renal toxicity: elevated creatinine and BUN, acute tubular injury. Development was abandoned, and no human efficacy data beyond preliminary reports was ever published.", "citations": [ { "title": "Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium", "authors_year": "Kim et al. 2012", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/22733798/" } ], "reported_benefits": [ "weight loss in preclinical primate models (11% over 28 days)", "weight-independent metabolic improvements in animal models" ], "dosing_protocols": [ { "route": "Intravenous or subcutaneous injection", "protocol": "Preclinical primate studies used 0.43 mg/kg/day; no validated human dose exists." } ], "side_effects": [ "acute kidney injury", "elevated serum creatinine", "elevated BUN", "acute tubular necrosis", "fatigue" ], "safety_notes": "Caused dose-limiting renal toxicity in humans and was discontinued in 2019. There's no antidote or reversal strategy. Self-experimentation risks acute renal failure.", "community_notes": "Cited in biohacker circles as a cautionary tale, not a protocol. Black-market 'adipotide' is often misidentified or contaminated. Not recommended.", "related": [] }, "aicar": { "name": "AICAR", "full_name": "5-aminoimidazole-4-carboxamide ribonucleoside (AMPK activator, small molecule nucleoside)", "aliases": [ "AICA ribonucleoside", "AMP-mimetic" ], "categories": [ "fitness-muscle", "fat-loss", "anti-aging" ], "tagline": "AMPK activator marketed as 'exercise in a pill.' WADA-banned in sport, not FDA-approved for anything.", "status": "Research chemical | WADA-banned | Not FDA-approved", "origin": "A nucleoside derivative first used as a research tool for studying AMPK signaling. A 2008 mouse study showing improved exercise endurance without any actual training turned it into an 'exercise mimetic.' Not FDA-approved; WADA banned it from competition in 2009.", "mechanism": "Mimics AMP to directly activate AMPK, the cell's energy sensor. That triggers fatty-acid oxidation and mitochondrial biogenesis via PGC-1-alpha, reproducing some of the metabolic adaptations of aerobic exercise.", "research_summary": "Rodent studies show improved glucose tolerance, reduced hepatic steatosis, and better endurance without exercise. Human trial data is sparse, no large registered trials have been completed, and oral bioavailability is poor (under 5%). No long-term human safety data exists.", "citations": [], "reported_benefits": [ "improved glucose tolerance and insulin sensitivity (animal/cell studies)", "enhanced mitochondrial biogenesis (theoretical)", "improved endurance in mice" ], "dosing_protocols": [ { "route": "Intraperitoneal, intravenous (no validated human route)", "protocol": "Animal studies use 500 mg/kg IP or IV; community biohacker protocols report 50-100 mg/day oral or 0.5-1 mg/kg subcutaneous, unvalidated." } ], "side_effects": [ "nausea (anecdotal)", "gastrointestinal upset", "potential gout exacerbation (elevated uric acid)", "fatigue or malaise" ], "safety_notes": "No human toxicology data exists and it's not FDA-approved. It elevates uric acid and can trigger gout or acute kidney injury in predisposed people. Black-market purity is unverifiable.", "community_notes": "Discussed as an exercise mimetic in longevity forums. Reports range from modest weight loss and better endurance to nothing noticeable. Even fans admit the preclinical data is strong and the human data is nonexistent.", "related": [] }, "5-amino-1mq": { "name": "5-Amino-1MQ", "full_name": "5-amino-1-methylquinolinium (NNMT inhibitor, small molecule)", "aliases": [ "5-A1MQ", "NNMT inhibitor" ], "categories": [ "fat-loss", "longevity", "anti-aging" ], "tagline": "NNMT inhibitor that redirects nicotinamide into NAD+ synthesis. Popular in biohacker circles, backed by zero human trials.", "status": "Research chemical | Not FDA-approved", "origin": "Inhibits nicotinamide N-methyltransferase (NNMT), the enzyme that diverts nicotinamide away from NAD+ synthesis. Mouse studies from 2015-2020 showed NNMT inhibition improves metabolic markers, and the compound moved into biohacker circles around 2021. No regulatory approval anywhere.", "mechanism": "Blocking NNMT redirects nicotinamide into the NAD+ salvage pathway. More NAD+ drives sirtuin and PARP activity, which preclinical work ties to mitochondrial biogenesis, metabolic flexibility, reduced fibrosis, and immune modulation.", "research_summary": "Mouse models show improved insulin sensitivity, higher energy expenditure, and less hepatic steatosis. No published human trials exist, and human pharmacokinetics and dose-response are unknown.", "citations": [ { "title": "A Bisubstrate Inhibitor of NNMT Suppresses Myofibroblast Reprogramming to Mitigate Skin Fibrosis", "authors_year": "Saba et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42716212/" } ], "reported_benefits": [ "potential weight loss via increased energy expenditure (animal models)", "improved insulin sensitivity (preclinical)", "increased NAD+ bioavailability (theoretical)" ], "dosing_protocols": [ { "route": "Oral capsule or powder; subcutaneous (anecdotal)", "protocol": "No human-validated dose. Community protocols (unvalidated) range 50-250 mg once or twice daily orally." } ], "side_effects": [ "potential gastrointestinal upset (anecdotal)", "potential nausea (anecdotal)", "unknown long-term effects" ], "safety_notes": "No human trials or toxicology data exist; safety in people is unknown. NNMT has other jobs in the cell, so chronic inhibition could impair methylation capacity. Sourced product purity is unverified.", "community_notes": "Discussed as a NAD+ restoration tool alongside NMN, NR, and metformin. Users report more energy and better body composition, but it's all unblinded and self-reported.", "related": [ "nad" ] }, "hgh-somatropin": { "name": "Somatropin", "full_name": "Recombinant human growth hormone, 191-amino acid", "aliases": [ "rHGH", "rhGH", "synthetic human growth hormone", "HGH 191AA" ], "categories": [ "fitness-muscle", "anti-aging", "recovery-healing" ], "tagline": "FDA-approved recombinant growth hormone for deficiency, widely used off-label for performance and body composition.", "status": "FDA-approved (GHD treatment) | Off-label use widespread", "origin": "Recombinant human growth hormone produced via genetic engineering starting in the 1980s, replacing cadaver-derived pituitary extracts. Now available in daily and long-acting pegylated/fusion formulations.", "mechanism": "Binds growth hormone receptor (GHR) on target tissues, promoting IGF-1 production in the liver (endocrine) and peripheral tissues (autocrine/paracrine). Stimulates lipolysis, amino acid uptake, protein synthesis in muscle, and bone mineral density.", "research_summary": "Long-acting GH formulations show non-inferiority to daily GH in height velocity and similar safety. Approved for childhood and adult GHD. Off-label performance use is common but carries risks including hyperglycemia, insulin resistance, and carpal tunnel syndrome; long-term safety data in off-label populations is limited.", "citations": [ { "title": "Treatment of growth hormone deficiency with long-acting growth hormones in children, adolescents and adults: Clinical evidence and practical considerations", "authors_year": "Linglart et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42727727/" } ], "reported_benefits": [ "increased lean muscle mass", "improved body composition", "enhanced recovery", "increased bone mineral density" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "FDA: 0.04-0.1 mg/kg/day (adult GHD). Off-label athletic use: typically 2-6 IU daily or 4-8 IU every other day." } ], "side_effects": [ "hyperglycemia", "insulin resistance", "carpal tunnel syndrome", "gynecomastia", "fluid retention", "joint pain" ], "safety_notes": "FDA-approved only for documented GHD. Off-label supraphysiological use carries undefined long-term risk. Contraindicated in active cancer. Requires monitoring of glucose, IGF-1, bone density.", "community_notes": "Widely sourced from underground labs and diverted pharmaceutical supply. Common protocols 2-10 IU daily, often stacked with secretagogues. Users report muscle/recovery gains alongside water retention and joint pain.", "related": [ "cjc-1295-dac", "ipamorelin", "sermorelin", "hexarelin" ], "mixing_notes": { "clinic_combos": [], "anecdotal_combos": [ "hcg" ], "reported_avoid": [ "aod-9604", "ara-290", "cjc-1295", "cjc-1295-dac", "mots-c", "nad" ] } }, "ghrp-2": { "name": "GHRP-2", "full_name": "Growth hormone releasing peptide-2 (pralmorelin)", "aliases": [ "pralmorelin", "GPA-748" ], "categories": [ "fitness-muscle", "recovery-healing" ], "tagline": "Potent synthetic growth hormone secretagogue with strong GH stimulation and emerging research support for tissue repair.", "status": "Research compound | Used experimentally in clinical settings", "origin": "Synthetic hexapeptide GH secretagogue mimicking ghrelin, INN pralmorelin. Originally developed for diagnostic testing of pituitary GH reserve.", "mechanism": "Potent agonist of GHSR1a on anterior pituitary somatotrophs, stimulating rapid GH release via Gq/11 signaling. Recent research suggests immune-modulation and tissue-repair effects independent of GH.", "research_summary": "Produces robust GH responses (peak >80 ng/mL) in diagnostic use. Animal studies show improved tendon-bone healing in rotator cuff models through macrophage modulation. Clinical applications remain limited to diagnostic testing; long-term data in non-clinical populations is sparse.", "citations": [ { "title": "Robust growth hormone responses to GH-releasing peptide 2 in adolescents", "authors_year": "Onuki et al. 2024", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/38958228/" } ], "reported_benefits": [ "growth hormone stimulation", "tendon/ligament healing", "reduced inflammation (animal models)", "muscle recovery" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "100-200 mcg once or twice daily; often stacked with other GHRPs or CJC-1295." } ], "side_effects": [ "appetite stimulation (mild)", "cortisol elevation with repeated doses", "prolactin elevation", "numbness/tingling" ], "safety_notes": "Not approved for human use outside clinical research. Repeated dosing may raise prolactin/cortisol. Limited long-term safety data.", "community_notes": "Used with CJC-1295 or ipamorelin as a peptide stack. Anecdotal reports of improved recovery and faster minor-injury healing.", "related": [ "ghrp-6", "hexarelin", "cjc-1295-dac", "ipamorelin" ], "mixing_notes": { "clinic_combos": [ "epithalon", "pt-141", "semax" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "ghrp-6": { "name": "GHRP-6", "full_name": "Growth hormone releasing hexapeptide", "aliases": [ "growth hormone releasing peptide-6" ], "categories": [ "fitness-muscle", "recovery-healing" ], "tagline": "Potent GH secretagogue with distinctive strong appetite stimulation via ghrelin receptor mimicry.", "status": "Research compound | Used experimentally", "origin": "Synthetic hexapeptide developed in the 1990s as a ghrelin receptor agonist, one of the earliest synthetic GH secretagogues. Used experimentally in GI motility research.", "mechanism": "Selective GHSR1a agonist that stimulates rapid GH secretion. Distinctively produces strong appetite stimulation via central ghrelin-like signaling in the arcuate nucleus and lateral hypothalamus.", "research_summary": "Stimulates GH release and robustly stimulates appetite in rodent and human studies. Accelerates GI transit in post-operative ileus models. Primary clinical research application has been GI motility disorders; evidence for muscle-building effects is limited to animal models and anecdote.", "citations": [ { "title": "The rat arcuate nucleus integrates peripheral signals provided by leptin, insulin, and a ghrelin mimetic", "authors_year": "Hewson et al. 2002", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/12453894/" } ], "reported_benefits": [ "growth hormone stimulation", "appetite stimulation", "gastrointestinal motility", "muscle recovery" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "100-200 mcg 1-3x daily; some use 50-100 mcg pre-meal to enhance appetite." } ], "side_effects": [ "strong appetite stimulation (pronounced)", "increased cortisol", "prolactin elevation", "water retention", "potential blood pressure elevation" ], "safety_notes": "Not approved outside research. Continuous ghrelin agonism can elevate cortisol and may cause salt-sensitive hypertension. Limited long-term human safety data.", "community_notes": "Popular for bulking phases due to the intense hunger effect. Often stacked with other GHRPs to smooth appetite effects.", "related": [ "ghrp-2", "hexarelin", "cjc-1295-dac", "ipamorelin" ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "hexarelin", "mgf", "semax", "thymalin" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "hexarelin": { "name": "Hexarelin", "full_name": "Growth hormone secretagogue hexarelin", "aliases": [ "Rix-002" ], "categories": [ "fitness-muscle", "anti-aging", "recovery-healing" ], "tagline": "Potent dual-receptor GH secretagogue with cardioprotective properties, limited by rapid receptor desensitization.", "status": "Research compound | Experimental cardiovascular use", "origin": "Synthetic hexapeptide GH secretagogue that also binds CD36 receptors on cardiac and endothelial cells, unlike GHRP-2/6 which target GHSR1a primarily. More chemically stable than natural ghrelin.", "mechanism": "GHSR1a agonism drives pituitary GH release; CD36 binding on cardiomyocytes triggers cardioprotective signaling via IL-1Ra upregulation and reduced myocardial oxidative stress during ischemia-reperfusion.", "research_summary": "Protects rat cardiomyocytes from ischemia-reperfusion injury via IL-1 signaling. Multiple rodent studies document cardioprotection. Major limitation: rapid tachyphylaxis, meaning GH response and possibly cardioprotection diminish sharply with repeated dosing. Clinical translation is limited.", "citations": [ { "title": "The Growth Hormone Secretagogue Hexarelin Protects Rat Cardiomyocytes From in vivo Ischemia/Reperfusion Injury Through Interleukin-1 Signaling Pathway", "authors_year": "Huang et al. 2017", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28321024/" } ], "reported_benefits": [ "growth hormone stimulation", "cardioprotection (animal evidence)", "anti-inflammatory effects (theoretical)" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "100-200 mcg 1-3x daily; cycling protocols (e.g. 5 days on/2 off) used to manage tachyphylaxis." } ], "side_effects": [ "appetite stimulation (mild-moderate)", "cortisol elevation", "prolactin elevation", "rapid tolerance development (tachyphylaxis)" ], "safety_notes": "Not FDA-approved. Primary concern is rapid receptor desensitization limiting utility. Cardioprotective effects are documented only in acute animal models; no human long-term outcome data.", "community_notes": "Adoption limited by tachyphylaxis. Some cycle or pulse-dose to maintain responsiveness; theoretical cardioprotective appeal in longevity circles.", "related": [ "ghrp-2", "ghrp-6", "cjc-1295-dac" ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "ghrp-6", "mgf", "semax" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "cjc-1295-dac": { "name": "CJC-1295 with DAC", "full_name": "CJC-1295 drug affinity complex (GHRH analog with albumin-binding modification)", "aliases": [ "CJC-1295 DAC", "CJC-1295/DAC" ], "categories": [ "fitness-muscle", "anti-aging", "recovery-healing" ], "tagline": "Long-acting GHRH analog with week-long half-life via albumin binding; distinct from daily-dosing CJC-1295.", "status": "Research compound | Used in compounding pharmacies", "origin": "A synthetic 30-amino-acid GHRH analog. The DAC (drug affinity complex) variant adds four lysine residues that bind serum albumin, stretching half-life from about 10 minutes to 7-10 days, unlike plain CJC-1295 (Mod GRF 1-29), which needs multiple daily doses.", "mechanism": "A selective GHRH receptor agonist on somatotrophs, stimulating pulsatile GH release via Gs/cAMP signaling. Albumin binding blocks rapid renal clearance, which is what makes it long-acting.", "research_summary": "GHRH analogs are potent GH stimulators used diagnostically and preclinically. CJC-1295 with DAC hasn't been extensively studied in published human trials; most evidence comes from compounding-pharmacy literature and community protocols. Its advantage over plain CJC-1295 is fewer injections, at the cost of less precise titration.", "citations": [], "reported_benefits": [ "growth hormone stimulation", "reduced injection frequency (weekly vs daily)", "improved muscle mass", "enhanced recovery" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "100-200 mcg to 2mg SC weekly; often stacked with GHRP-2 or GHRP-6." } ], "side_effects": [ "mild water retention", "joint aches (rare)", "carpal tunnel-like symptoms (rare)", "cortisol elevation at high doses" ], "safety_notes": "Not FDA-approved. The key distinction from plain CJC-1295: DAC produces steady-state albumin-bound hormone instead of pulsatile dosing. Long-term human safety data is limited.", "community_notes": "Widely used for convenient weekly dosing, frequently stacked with GHRP-2/6. It differs fundamentally from CJC-1295 without DAC (short half-life, about 30 minutes, requiring 2-3x daily dosing); the two get confused constantly despite being pharmacokinetically distinct compounds.", "related": [ "ghrp-2", "ghrp-6", "hexarelin", "ipamorelin", "sermorelin", "cjc-1295" ], "mixing_notes": { "clinic_combos": [ "bpc-157", "epithalon", "ghk-cu", "ghrp-6", "hexarelin", "ipamorelin", "mgf", "pe-22-28", "pinealon", "selank", "semax", "tb-500", "tesamorelin", "thymalin", "thymosin-alpha-1" ], "anecdotal_combos": [ "hcg" ], "reported_avoid": [ "aod-9604", "ara-290", "hgh-somatropin", "mots-c", "nad" ] } }, "mgf": { "name": "MGF", "full_name": "Mechano Growth Factor (IGF-1Ec splice variant)", "aliases": [ "mechano growth factor", "IGF-1Ec" ], "categories": [ "fitness-muscle", "recovery-healing" ], "tagline": "Muscle-specific IGF-1 isoform generated by mechanical stress; promotes local muscle repair and satellite cell activation.", "status": "Research compound | Experimental use", "origin": "IGF-1 splice variant produced locally in muscle after mechanical loading or injury, first described by Goldspink in the 1990s. Unlike systemic hepatic IGF-1, it acts autocrine/paracrine, right where it's made.", "mechanism": "Binds IGF-1 receptor on satellite cells, driving proliferation, differentiation, and fusion into myofibers via PI3K-Akt and MAPK-ERK signaling. First responder to muscle damage.", "research_summary": "Mechanistic work is mostly preclinical, animal and cell culture. Human trials of exogenous MGF are close to nonexistent. Compounding pharmacies sell it for experimental use, but human efficacy and safety are poorly characterized.", "citations": [], "reported_benefits": [ "local muscle hypertrophy", "muscle repair and recovery", "satellite cell activation" ], "dosing_protocols": [ { "route": "Local subcutaneous/intramuscular injection", "protocol": "100-200 mcg injected near target muscle post-workout, 2-3x weekly." } ], "side_effects": [ "local inflammation at injection site", "bruising", "potential systemic hypoglycemia if absorbed systemically" ], "safety_notes": "Not FDA-approved, minimal human trial data. Theoretical concern: exogenous IGF-1 pathway activity could feed occult malignancy growth, though this is speculative.", "community_notes": "Used post-workout for recovery. The local-MGF vs systemic PEG-MGF distinction matters for timing and use case.", "related": [ "ace-031", "hgh-somatropin", "ipamorelin" ], "variant_note": "PEG-MGF is a pegylated variant with extended half-life (minutes to hours) enabling more systemic distribution beyond the injection site, versus native MGF's local/periosteal action. Dosed similarly but with enhanced systemic bioavailability.", "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "ghrp-6", "hexarelin", "semax", "thymosin-alpha-1" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "ace-031": { "name": "ACE-031", "full_name": "ACVR2B-Fc fusion protein (soluble activin receptor type IIB fused to human IgG1)", "aliases": [ "ramatercept", "ACVR2B-Fc" ], "categories": [ "fitness-muscle" ], "tagline": "Myostatin decoy receptor that showed early promise in muscular dystrophy trials, then got shut down over vascular side effects.", "status": "Investigational (halted clinical trials) | Safety concerns unresolved", "origin": "Acceleron Pharma fused the ACVR2B ectodomain to IgG1 to build a high-affinity decoy receptor for myostatin and activins, aimed at muscle-wasting diseases like Duchenne muscular dystrophy.", "mechanism": "Binds myostatin and activins as a soluble decoy receptor, removing their brake on myogenesis and letting muscle protein synthesis run unopposed.", "research_summary": "A randomized placebo-controlled DMD trial was stopped early after vascular safety signals, epistaxis and telangiectasias, appeared. Before that, it showed non-significant trends toward maintained 6-minute walk distance and increased lean mass.", "citations": [ { "title": "Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial", "authors_year": "Campbell et al. 2016", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/27462804/" } ], "reported_benefits": [ "increased lean muscle mass (preclinical/animal)", "muscle strength preservation (animal models)" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Clinical trial dosing every 2-4 weeks, ascending; no community-standard dosing due to trial discontinuation." } ], "side_effects": [ "epistaxis (nosebleeds)", "telangiectasias (abnormal blood vessel proliferation)", "potential vascular complications" ], "safety_notes": "Trials were halted for vascular safety signals. Acceleron discontinued development entirely; no trials are ongoing. Using it outside a trial is experimental and not recommended.", "community_notes": "Some still chase it for myostatin inhibition, but manufacturing cost limits underground supply, and most informed users skip it given the safety signal.", "related": [ "hgh-somatropin", "mgf" ] }, "mt-2": { "name": "Melanotan II", "full_name": "alpha-Melanocyte-stimulating hormone (\u03b1-MSH) analog (synthetic)", "aliases": [ "melanotan-2", "MT-II" ], "categories": [ "sexual-health", "anti-aging" ], "tagline": "Unregulated synthetic melanocortin agonist used illicitly for tanning and erectile function, with significant cardiovascular and melanoma safety concerns.", "status": "Research chemical | Not approved for any medical indication | Significant safety signals", "origin": "Synthetic alpha-MSH analogue developed in the 1980s, unregulated globally, sold through uncontrolled internet suppliers and tanning networks. Known for UV-independent tanning and, coincidentally, libido-enhancing effects. It's the parent compound PT-141 was later developed from.", "mechanism": "Non-selective melanocortin agonist: activates MC1R on melanocytes for melanin production and tanning, and centrally MC3R/MC4R in the hypothalamus for pro-sexual behavior and erectile function via dopamine and nitric-oxide pathways. The non-selective binding also hits appetite and sympathetic tone.", "research_summary": "Human evidence is mostly anecdotal and case-report based. Dermatology literature documents rapid mole darkening, dysplastic nevi, and melanoma emergence during or after use, though causality isn't firmly established. Priapism, hypertension, and thrombotic concerns are reported. No large prospective trials exist; regulatory bodies have issued safety warnings.", "citations": [ { "title": "Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review.", "authors_year": "Habbema et al. 2017", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28266027/" }, { "title": "Melanotropic peptides: more than just 'Barbie drugs' and 'sun-tan jabs'?", "authors_year": "Langan et al. 2010", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/20545686/" } ], "reported_benefits": [ "skin darkening/tanning", "increased libido and sexual arousal (anecdotal)", "improved erectile function (anecdotal)" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Typical self-dosing: loading 0.25-1 mg every 1-2 days until desired tan, then 0.5-1 mg/week maintenance. Uncontrolled, forum-derived protocols." } ], "side_effects": [ "nausea", "facial flushing", "rapid darkening/proliferation of moles", "dysplastic nevi", "priapism", "hypertension", "possible increased melanoma risk (case reports)" ], "safety_notes": "Multiple case reports document melanomas emerging from existing or new moles during or after use. Causality is unproven but has prompted formal health-authority warnings. Priapism can require emergency intervention. Strongly contraindicated with a personal or family melanoma history.", "community_notes": "Popular for rapid tanning (5-14 days) and reported spontaneous erections and increased libido, though tolerance to the sexual effects often develops over weeks to months. Communities warn of priapism risk.", "related": [ "pt-141", "mt-1" ], "mixing_notes": { "clinic_combos": [ "tb-500" ], "anecdotal_combos": [ "hcg" ], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "mt-1": { "name": "Melanotan I", "full_name": "Afamelanotide (NDP-\u03b1-MSH)", "aliases": [ "afamelanotide", "Scenesse" ], "categories": [ "anti-aging", "recovery-healing" ], "tagline": "FDA- and EU-approved MC1R agonist for erythropoietic protoporphyria; regulated pharmaceutical with photoprotection benefits, distinct from unregulated MT-2.", "status": "FDA approved (2019, USA) | EMA approved (2014, EU) | Indication: Erythropoietic Protoporphyria (EPP)", "origin": "Chemically modified, MC1R-selective \u03b1-MSH analogue developed by Clinuvel Pharmaceuticals for photosensitivity disorders, notably erythropoietic protoporphyria. The structural modifications give it receptor selectivity and better stability than the non-selective MT-2.", "mechanism": "Selectively activates MC1R on melanocytes, increasing eumelanin synthesis via cAMP signaling for UV-absorbing photoprotection. The MC1R selectivity minimizes the CNS and systemic off-target effects seen with MT-2.", "research_summary": "Phase III trials in EPP patients showed significant reduction in phototoxic reaction frequency and severity, combined with photoprotection measures. Safety is well-characterized: adverse events are mostly mild nausea and injection-site effects. The cardiovascular, melanoma, and priapism signals seen with MT-2 haven't shown up in controlled afamelanotide trials.", "citations": [ { "title": "Hormones and skin pigmentation: fundamentals and clinical relevance.", "authors_year": "B\u00f6hm et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41489668/" } ], "reported_benefits": [ "significant reduction in phototoxic reactions in EPP", "increased skin pigmentation/UV photoprotection", "improved quality of life in photosensitive patients" ], "dosing_protocols": [ { "route": "Subcutaneous implant", "protocol": "FDA-approved (EPP): 16 mg subcutaneous implant every 2 months, combined with strict photoprotection." } ], "side_effects": [ "injection-site erythema/induration", "nausea (5-10%, usually transient)", "headache (mild)", "hyperpigmentation" ], "safety_notes": "Strong safety profile in controlled trials, with none of MT-2's cardiovascular, melanoma, or priapism signals. Use is restricted to documented photoprotection deficiency, with specialist dermatological surveillance recommended.", "community_notes": "Off-label tanning or anti-aging use is uncommon due to regulatory restriction and cost. No solid evidence supports cosmetic tanning or general anti-aging use outside the approved EPP indication.", "related": [ "mt-2" ], "mixing_notes": { "clinic_combos": [ "tb-500" ], "anecdotal_combos": [ "hcg" ], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "gonadorelin": { "name": "Gonadorelin acetate", "full_name": "Gonadotropin-releasing hormone (GnRH) decapeptide acetate", "aliases": [ "GnRH", "LHRH", "luliberin" ], "categories": [ "sexual-health" ], "tagline": "GnRH agonist peptide that stimulates endogenous LH and FSH to preserve testicular function and fertility during testosterone replacement therapy.", "status": "FDA approved | Off-label: HPG-axis preservation during TRT", "origin": "A synthetic decapeptide copy of endogenous GnRH, FDA-approved since 1981 for evaluating gonadotropin reserve and treating hypogonadotropic hypogonadism. Increasingly used off-label to prevent testicular suppression from exogenous testosterone.", "mechanism": "Agonizes GnRH receptors on pituitary gonadotrophs, stimulating LH and FSH release. Pulsatile dosing maintains HPG-axis output; continuous exposure paradoxically suppresses it, the basis of medical castration. In TRT-suppressed men, pulsatile/low-dose gonadorelin restimulates endogenous testosterone and spermatogenesis.", "research_summary": "A 2026 narrative review identified GnRH-based strategies as promising for TRT-induced reproductive suppression, though evidence for full spermatogenesis/fertility restoration remains limited. Small studies show combination therapy (TRT + low-dose gonadorelin + hCG) partially restores FSH/LH and reduces testicular atrophy, with variable success.", "citations": [ { "title": "Emerging peptide and neuroendocrine strategies for TRT-induced reproductive suppression and functional male hypogonadism: a narrative review.", "authors_year": "Cretu et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42666625/" } ], "reported_benefits": [ "preservation/restoration of endogenous testosterone in TRT users", "maintenance of spermatogenesis during TRT", "reduced testicular atrophy" ], "dosing_protocols": [ { "route": "Subcutaneous or intravenous injection", "protocol": "Off-label TRT protocol: ~150 mcg subcutaneous twice weekly, or pulsatile pump dosing; not well standardized." } ], "side_effects": [ "local injection-site reactions", "transient nausea and headache", "gynecomastia", "mood changes" ], "safety_notes": "Generally well-tolerated at low/pulsatile dosing. Continuous high-dose agonism causes prolonged suppression. Pulsatile administration is critical to avoid paradoxical effects. Caution with pituitary pathology.", "community_notes": "TRT users report using low-dose gonadorelin alongside testosterone to maintain the HPG axis and fertility, often combined with hCG and clomiphene. Reported outcomes are variable.", "related": [ "hcg", "pt-141" ] }, "hcg": { "name": "Human Chorionic Gonadotropin", "full_name": "Human chorionic gonadotropin (hCG), placental hormone", "aliases": [ "hCG", "Pregnyl", "Novarel" ], "categories": [ "sexual-health", "fitness-muscle" ], "tagline": "Placental hormone that mimics LH to stimulate testicular testosterone production and sperm output. Used clinically for hypogonadism/fertility, off-label in TRT, and in doping.", "status": "FDA approved | Off-label/illicit use: TRT adjunct, anabolic steroid doping", "origin": "A glycoprotein hormone produced by the placenta during pregnancy, purified from urine or produced recombinantly. Approved since the mid-20th century for male hypogonadotropic hypogonadism and female ovulation induction, and a ubiquitous TRT/AAS adjunct in the fitness community.", "mechanism": "Binds LH receptors on testicular Leydig cells, stimulating testosterone synthesis. Unlike exogenous testosterone, hCG stimulates endogenous production and helps maintain spermatogenesis and testicular size during TRT.", "research_summary": "hCG monotherapy restores testosterone and can induce spermatogenesis in ~70% of men with hypogonadotropic hypogonadism. Small studies support combined hCG + testosterone protocols for fertility preservation on TRT, with variable response; dosing strategies are empirically derived rather than from large RCTs.", "citations": [ { "title": "Human Chorionic Gonadotropin monotherapy for the treatment of hypogonadal symptoms in men with total testosterone > 300 ng/dL.", "authors_year": "Madhusoodanan et al. 2019", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/31408289/" }, { "title": "Systematic review of hormone replacement therapy in the infertile man.", "authors_year": "El Meliegy et al. 2017", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/29713545/" } ], "reported_benefits": [ "stimulation of endogenous testosterone production", "maintenance/recovery of spermatogenesis", "reduced testicular atrophy during TRT", "fertility preservation" ], "dosing_protocols": [ { "route": "Intramuscular or subcutaneous injection", "protocol": "Hypogonadotropic hypogonadism: 1,000-2,000 IU IM 2-3x weekly. TRT adjunct (off-label): 250-500 IU 3x weekly." } ], "side_effects": [ "gynecomastia", "acne", "testicular discomfort", "mood swings", "elevated hematocrit", "potential thrombotic complications at doping doses" ], "safety_notes": "Well-tolerated at therapeutic TRT-adjunct doses. High doping doses risk excessive testosterone, severe gynecomastia, and polycythemia. Requires periodic monitoring of testosterone, estradiol, hematocrit.", "community_notes": "Extremely common in TRT/PED communities; typical protocol 250-500 IU 2-3x weekly alongside testosterone. Higher doses (1,000-5,000 IU) used in AAS cycles to maintain testicular size.", "related": [ "gonadorelin" ], "variant_note": "HMG (human menopausal gonadotropin / menotropins) is a related fertility drug providing both FSH and LH (unlike hCG's LH-only activity), making it more effective for complete spermatogenesis recovery. Used clinically, often combined with hCG, but has a thinner off-label TRT following due to cost and complexity; not covered as a separate leaf page.", "mixing_notes": { "clinic_combos": [], "anecdotal_combos": [ "bpc-157", "cjc-1295-dac", "hgh-somatropin", "mt-1", "mt-2" ], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "ss-31": { "name": "SS-31", "full_name": "Elamipretide; Szeto-Schiller peptide 31", "aliases": [ "elamipretide", "Bendavia", "MTP-131" ], "categories": [ "longevity", "fitness-muscle", "recovery-healing" ], "tagline": "Mitochondria-targeted tetrapeptide that stabilizes cardiolipin and restores oxidative phosphorylation. FDA-approved for rare Barth syndrome, investigational in heart failure and aging-related conditions.", "status": "FDA Accelerated Approval (2025) for Barth Syndrome | Investigational in heart failure/HFpEF | Not approved for longevity use", "origin": "Designed by Hazel Szeto and Peter Schiller to cross the mitochondrial membrane and stabilize cardiolipin. Developed by Stealth BioTherapeutics/Reata, it received FDA Accelerated Approval in 2025 for Barth syndrome, a rare cardiolipin-remodeling genetic disorder, the first FDA-approved mitochondrial medicine.", "mechanism": "Accumulates in the inner mitochondrial membrane, binding and stabilizing cardiolipin, essential for respiratory chain complex assembly. Restoring cardiolipin integrity improves electron transport efficiency, raises ATP production, and cuts mitochondrial ROS.", "research_summary": "Preclinical/animal models show reduced oxidative stress and prevention of cardiomyocyte/skeletal muscle senescence. Phase 2 heart failure trials (HFrEF/HFpEF) show modest-to-moderate functional improvements. Barth syndrome trial data led to accelerated approval, but clinical benefit size is still being characterized. Human longevity/aging evidence is extremely limited.", "citations": [ { "title": "Targeting Mitochondrial Dysfunction With Elamipretide (SS-31) Improves Skeletal Muscle Performance in a HFpEF Rat Model.", "authors_year": "Vahle et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42290373/" } ], "reported_benefits": [ "improved mitochondrial respiratory capacity", "reduced oxidative stress (preclinical)", "prevention of cellular senescence (cell/animal models)", "FDA-approved benefit in Barth syndrome" ], "dosing_protocols": [ { "route": "Intravenous infusion", "protocol": "Investigational off-label protocols: ~0.05-0.1 mg/kg IV once daily or 2-3x weekly; no consensus dosing outside approved indication." } ], "side_effects": [ "generally well tolerated in Phase 2 trials", "headache/dizziness", "infusion-site reactions", "rare hypotension/syncope" ], "safety_notes": "Excellent tolerability in Phase 2 trials to date, no major organ toxicity reported. Long-term safety outside rare-disease populations isn't established.", "community_notes": "High interest in longevity forums based on the mitochondrial mechanism, but human access is limited to clinical trials or high-cost research sourcing. Enthusiasm exceeds current human evidence.", "related": [ "foxo4-dri", "mots-c" ] }, "foxo4-dri": { "name": "FOXO4-DRI", "full_name": "FOXO4 D-Retro-Inverso peptide (senolytic)", "aliases": [ "FOXO4-DRI" ], "categories": [ "longevity", "anti-aging" ], "tagline": "Senolytic peptide that disrupts the FOXO4-p53 interaction to induce selective apoptosis of senescent cells. Highly promising in mouse models, with minimal human evidence.", "status": "Research compound | Preclinical-stage (mostly mouse models) | Not FDA approved for any indication", "origin": "Developed at Utrecht University from the discovery that senescent cells depend on the FOXO4-p53 interaction for survival. A D-retro-inverso peptide (mirror-image, reversed-sequence variant) emerged around 2017 as senolytic therapy gained attention. Most published evidence is mouse-based.", "mechanism": "Binds FOXO4, disrupting the FOXO4-p53 complex that normally shields senescent cells from apoptosis. Restoring p53 pro-apoptotic signaling in cells with high FOXO4-p53 complexes triggers selective apoptosis in senescent cells while sparing normal ones.", "research_summary": "In aged mice, FOXO4-DRI reduces senescent cell burden across tissues and improves function/healthspan in some models, including Alzheimer's disease-model mice. A 2022 study found senolytic depletion (including FOXO4-DRI) paradoxically worsened pulmonary hypertension in mice, showing the effect is context-dependent. No published human trials exist as of 2026.", "citations": [ { "title": "The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI.", "authors_year": "Bourgeois et al. 2025", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/40593617/" }, { "title": "Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression.", "authors_year": "Born et al. 2022", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/36515093/" } ], "reported_benefits": [ "selective apoptosis of senescent cells (mouse models)", "reduced senescent cell burden across tissues (mouse studies)", "improved organ function in aged mice (specific models)" ], "dosing_protocols": [ { "route": "Intravenous or intraperitoneal injection", "protocol": "Mouse studies: 5-10 mg/kg IV/IP 2-3x weekly. No established human protocol; community dosing entirely speculative." } ], "side_effects": [ "minimal direct toxicity reported in mouse studies", "potential harmful effects in specific disease contexts (e.g. worsened pulmonary hypertension)", "human safety essentially unknown" ], "safety_notes": "Senolytic depletion is not universally beneficial: context-dependent harm has been shown in at least one disease model. No Phase 2/3 human trials exist. Access outside research is via unregulated suppliers with unverified purity.", "community_notes": "High enthusiasm in longevity communities based on mouse lifespan data, but real human experience is essentially nonexistent. The gap between mouse promise and human evidence is large.", "related": [ "ss-31" ] }, "ahk-cu": { "name": "AHK-Cu", "full_name": "Alanyl-Histidyl-Lysine Copper(II) Complex", "aliases": [ "copper tripeptide-3" ], "categories": [ "anti-aging", "recovery-healing" ], "tagline": "Topical copper tripeptide marketed for hair follicle stimulation, distinct from (and less studied than) GHK-Cu.", "status": "Cosmetic ingredient (topical, unregulated as drug)", "origin": "A synthetic copper-peptide complex built as a hair-focused variant of the better-studied GHK-Cu, leaning on copper's role in collagen synthesis and wound healing, aimed at androgenetic alopecia and scalp health.", "mechanism": "Delivers bioavailable copper to dermal papilla cells, where it acts as an enzymatic cofactor. In-vitro data suggests it upregulates VEGF for follicle blood flow and extends the anagen (growth) phase, but this hasn't been validated on intact human scalp.", "research_summary": "Evidence is in-vitro and cosmetic-industry sourced. The foundational study showed tripeptide-copper complexes stimulate isolated human hair follicles in culture, but no human RCTs exist. Most efficacy claims lean on the GHK-Cu literature rather than AHK-Cu-specific data.", "citations": [ { "title": "The effect of tripeptide-copper complex on human hair growth in vitro", "authors_year": "2007", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/17703734/" } ], "reported_benefits": [ "stimulation of hair follicle anagen phase", "increased follicle blood flow (theoretical)", "improved hair density claims" ], "dosing_protocols": [ { "route": "Topical serum/solution", "protocol": "Applied to scalp 1-2x daily, sometimes with microneedling; concentrations 2-5% in cosmetic formulations, no standardized dose." } ], "side_effects": [ "local scalp irritation (rare)", "contact dermatitis in sensitive individuals" ], "safety_notes": "Systemic absorption through intact skin is low, but long-term human safety data doesn't exist. Avoid if you have copper sensitivity or Wilson disease.", "community_notes": "Used in scalp serums, often stacked with minoxidil or finasteride. Users report subjective improvement after 3-6 months, though expectations are probably inflated by confusing it with GHK-Cu's stronger evidence.", "related": [ "ghk-cu", "matrixyl", "ptd-dbm" ] }, "snap-8": { "name": "Snap-8", "full_name": "Acetyl Octapeptide-3", "aliases": [ "acetyl octapeptide-3" ], "categories": [ "anti-aging" ], "tagline": "Topical cosmetic peptide marketed as a non-invasive alternative to Botox for expression lines.", "status": "Cosmetic ingredient (topical, unregulated as drug)", "origin": "A derivative of Argireline (hexapeptide-3), synthesized in the 2000s as an anti-wrinkle cosmetic ingredient. Entirely topical; no injectable formulations or clinical trials exist.", "mechanism": "Theorized to interfere with the SNARE protein complex/SNAP-25 involved in acetylcholine release at the neuromuscular junction, potentially dampening repetitive facial-muscle contraction. Unproven in human skin; peptide skin penetration at cosmetic concentrations is poor.", "research_summary": "Minimal independent clinical evidence specific to Snap-8; most claims derive from older Argireline research. Cosmetic studies report modest, mixed results, mostly industry-sponsored and non-blinded. Skin hydration/smoothness improvements are more consistently documented than muscle-relaxation effects.", "citations": [], "reported_benefits": [ "reduced appearance of expression lines/crow's feet", "improved skin smoothness and hydration" ], "dosing_protocols": [ { "route": "Topical cosmetic serum/cream", "protocol": "Applied 1-2x daily; commercial concentrations 3-10%; results if any require 4-12 weeks of use." } ], "side_effects": [ "minimal; rare contact dermatitis/irritation" ], "safety_notes": "Strong safety record in cosmetic use given low systemic absorption. The real concern is overstated marketing claims, not safety.", "community_notes": "Mixed user reports of subtle softening of fine lines after 8-12 weeks. Community acknowledges the evidence gap versus Botox/retinoids.", "related": [ "matrixyl", "ghk-cu" ] }, "matrixyl": { "name": "Matrixyl", "full_name": "Palmitoyl Pentapeptide-4", "aliases": [ "palmitoyl pentapeptide-4", "KTTKS" ], "categories": [ "anti-aging" ], "tagline": "Lipidated collagen-mimetic peptide (palmitoyl-KTTKS) that pushes fibroblasts to make more collagen and glycosaminoglycans.", "status": "Cosmetic ingredient (topical, unregulated as drug)", "origin": "Developed in the early 2000s. KTTKS mimics a bioactive fragment of type I procollagen that fibroblasts recognize; a palmitoyl fatty-acid tail was added for skin penetration. Classic 'matrikine' cosmetic strategy.", "mechanism": "Triggers fibroblast matrikine signaling, activating TGF-\u03b2 and boosting synthesis of collagen I/III, fibronectin, and glycosaminoglycans. Restores dermal support and reduces wrinkle depth.", "research_summary": "Better cosmetic data than Snap-8, still thin next to pharmaceutical standards. Trials show significant wrinkle-depth improvement over 12 weeks in photoaged skin, but cohorts are small (20-60 participants) and industry-funded. Effect size: 10-20% wrinkle-depth reduction, roughly matching mild retinoids.", "citations": [ { "title": "Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin", "authors_year": "Robinson et al. 2008", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/18492182/" } ], "reported_benefits": [ "reduced wrinkle depth and fine lines", "improved skin elasticity/firmness", "increased dermal hydration" ], "dosing_protocols": [ { "route": "Topical serum/cream/moisturizer", "protocol": "2-5% palmitoyl pentapeptide-4 applied 1-2x daily; measurable improvement may take 8-12 weeks." } ], "side_effects": [ "minimal; rare local irritation/sensitization" ], "safety_notes": "Strong topical safety record. Peptide size and lipid modification keep systemic absorption negligible.", "community_notes": "Common in anti-aging serums, often paired with vitamin C and retinoids. Seen as better-evidenced than Snap-8 but weaker than prescription retinoids.", "related": [ "snap-8", "ghk-cu" ] }, "ptd-dbm": { "name": "PTD-DBM", "full_name": "Protein Transduction Domain\u2013Dishevelled Binding Motif", "aliases": [ "CXXC5 inhibitor", "DBM peptide" ], "categories": [ "anti-aging", "recovery-healing" ], "tagline": "Preclinical peptide that blocks a Wnt-pathway inhibitor (CXXC5) in hair follicles, designed to restore hair regrowth through molecular disinhibition.", "status": "Research chemical | Preclinical stage (no human trials)", "origin": "Developed after researchers found that DHT upregulates CXXC5 in balding-scalp dermal papilla cells, where CXXC5 normally suppresses the Wnt/beta-catenin signaling hair growth needs. PTD-DBM was designed to displace CXXC5 and restore that signaling, often paired experimentally with valproic acid.", "mechanism": "The PTD domain enables cell penetration; the DBM domain competes with CXXC5 for Dishevelled (Dvl) binding, displacing CXXC5 and freeing up Wnt/beta-catenin signaling, which upregulates downstream hair-growth genes.", "research_summary": "All evidence is preclinical. Mouse studies show stimulated hair regrowth and follicle neogenesis. As of 2026, no completed human clinical trials, Phase I safety data, or dosing studies exist.", "citations": [], "reported_benefits": [ "stimulation of hair follicle anagen phase (mouse models)", "follicle neogenesis in rodents", "reversal of DHT-mediated Wnt suppression (theoretical)" ], "dosing_protocols": [ { "route": "Topical application (preclinical only)", "protocol": "No human dosing protocols exist; unregulated vendors offer unvalidated topical formulations." } ], "side_effects": [ "unknown in humans; animal studies report no acute toxicity" ], "safety_notes": "No human safety data. Theoretical oncology concern: disinhibiting Wnt/beta-catenin, which is upregulated in several cancers, in genetically predisposed individuals. Contraindicated in pregnancy given the absence of reproductive toxicology data.", "community_notes": "Used by underground hair-loss self-experimenters, often stacked with minoxidil, finasteride, and valproic acid. Anecdotal, uncontrolled reports of regrowth over 3-6 months.", "related": [ "ahk-cu", "bpc-157" ] }, "ll-37": { "name": "LL-37", "full_name": "Human Cathelicidin Antimicrobial Peptide 37", "aliases": [ "cathelicidin LL-37", "hCAP18" ], "categories": [ "recovery-healing", "anti-aging" ], "tagline": "Endogenous antimicrobial and immunomodulatory peptide with evidence for topical wound healing and emerging systemic applications.", "status": "FDA Category 1 bulk drug (compounding-pharmacy use only) | Investigational for systemic use", "origin": "The sole cathelicidin antimicrobial peptide encoded by the human genome, produced by neutrophils and epithelial cells, cleaved from the hCAP18 precursor. Studied for three decades as a bridge between innate and adaptive immunity, now explored for wound healing and infection.", "mechanism": "Direct antimicrobial activity via amphipathic alpha-helical membrane disruption of bacteria, fungi, and enveloped viruses. Also signals through FPRL1 to recruit immune cells, and promotes keratinocyte migration/angiogenesis for tissue repair.", "research_summary": "The strongest human clinical evidence of this batch. A Phase IIb trial in venous ulcer patients found complete wound closure in 28.1% on LL-37 vs 8.1% placebo in large-wound subgroups. A diabetic foot ulcer trial showed greater granulation and faster closure. However, LL-37 complexes with self-DNA in psoriasis pathogenesis and drives rosacea inflammation, and pro-tumorigenic activity has been documented in several cancers; exogenous use may exacerbate both.", "citations": [ { "title": "Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial", "authors_year": "2013", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/25041740/" }, { "title": "Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial", "authors_year": "2023", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/37480520/" } ], "reported_benefits": [ "enhanced venous/diabetic ulcer closure", "antimicrobial activity against bacteria/fungi/viruses", "promotion of angiogenesis and keratinocyte migration" ], "dosing_protocols": [ { "route": "Topical cream/gel (wound application)", "protocol": "Clinical trials used 0.5-1.6 mg/mL applied topically 2-3x weekly for 8-13 weeks." } ], "side_effects": [ "topical: local skin reactions (erythema, irritation)" ], "safety_notes": "Good topical safety in wound trials, but LL-37 is an established autoantigen in psoriasis and a driver of rosacea; systemic or high topical exposure may worsen these conditions. Pro-tumorigenic effects documented in cancer cell lines suggest caution in cancer patients.", "community_notes": "Used primarily in clinical/compounding-pharmacy wound-care contexts. Some functional-medicine practitioners theorize intranasal benefits, but this is speculative. Because LL-37 is itself part of the innate immune system's own antimicrobial-peptide arsenal, some caution that introducing it exogenously can trigger an inflammatory response \u2014 another reason people who do try it tend to start at low doses.", "related": [ "vip", "bpc-157" ], "mixing_notes": { "clinic_combos": [ "selank", "semax", "tb-500", "thymosin-alpha-1" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "vip": { "name": "VIP", "full_name": "Vasoactive Intestinal Peptide", "aliases": [ "vasoactive intestinal polypeptide" ], "categories": [ "recovery-healing", "nootropics-cognitive" ], "tagline": "Endogenous neuropeptide and vasodilator with immunomodulatory properties, used investigationally for mold-illness immune dysregulation and pulmonary hypertension.", "status": "FDA investigational (synthetic aviptadil had Fast Track status for COVID-19, not approved) | Compounding-pharmacy use only", "origin": "A naturally occurring 28-amino-acid neuropeptide produced in the central/peripheral nervous system and gut. Its vasodilatory and anti-inflammatory properties drove cardiovascular/inflammatory-disorder research. The CIRS (chronic inflammatory response syndrome/mold illness) community adopted intranasal VIP off-label based on proposed immune mechanisms.", "mechanism": "Binds VPAC1/VPAC2/PAC1 GPCRs, elevating cAMP and suppressing NF-\u03baB inflammatory signaling, reducing pro-inflammatory cytokines and expanding regulatory T cells. Also drives direct vasodilation via smooth-muscle relaxation.", "research_summary": "Strong mechanistic foundation. The synthetic analog aviptadil showed selective pulmonary vasodilation, reducing vascular resistance ~50% in trials. Human RCT evidence for compounded intranasal VIP specifically for CIRS is limited; small case series suggest symptom improvement but lack blinding/placebo control. FDA Fast Track for aviptadil in COVID-19 was granted but never led to approval.", "citations": [], "reported_benefits": [ "reduction in systemic inflammation markers", "pulmonary vasodilation and improved cardiac output (early data)", "immune dysregulation correction (CIRS community anecdote)" ], "dosing_protocols": [ { "route": "Intranasal spray (compounded)", "protocol": "Compounding-pharmacy formulations: 0.5-2 mg per dose, 1-3x daily; not FDA-standardized." } ], "side_effects": [ "transient nasal irritation/rhinitis", "flushing/mild headache", "symptomatic hypotension", "gastrointestinal effects" ], "safety_notes": "Low reported adverse-event frequency in small case series, but systemic hypotension is a real concern, particularly with baseline low blood pressure. Compounding-pharmacy quality/sterility varies.", "community_notes": "Enthusiastically adopted in the CIRS/mold-illness community based on theoretical mechanisms. Patient reports describe improved fatigue and cognition over weeks to months, but no blinded human data support CIRS-specific efficacy.", "related": [ "ll-37", "bpc-157" ] }, "teriparatide": { "name": "Teriparatide", "full_name": "Parathyroid Hormone 1-34 (PTH 1-34)", "aliases": [ "Forteo" ], "categories": [ "recovery-healing", "anti-aging", "fitness-muscle" ], "tagline": "FDA-approved PTH analog that stimulates bone formation. Used clinically for osteoporosis and investigationally for stress fractures and fracture healing.", "status": "FDA-approved for osteoporosis in post-menopausal women and men", "origin": "Recombinant human PTH 1-34, the N-terminal active fragment of parathyroid hormone. FDA-approved in 2002 as an anabolic bone agent, unlike antiresorptive bisphosphonates, with 20+ years of post-market surveillance.", "mechanism": "Binds PTH1 receptors on osteoblasts, activating Wnt/beta-catenin signaling and increasing osteoid production. Intermittent (daily) dosing favors bone anabolism over resorption, building cortical and trabecular bone mass.", "research_summary": "Large RCTs demonstrated a 65% reduction in vertebral fracture risk and a 53% reduction in non-vertebral fracture risk. Post-market surveillance of over 75,000 patients found zero attributable osteosarcoma cases despite a rat-toxicology signal at very high doses; the FDA removed the black-box osteosarcoma warning in 2023. Off-label use for stress fractures/delayed union is growing but less evidenced. PTH resistance caps therapy at 2 years maximum.", "citations": [ { "title": "The US postmarketing surveillance study of adult osteosarcoma and teriparatide: study design and findings from the first 7 years", "authors_year": "2012", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/22991313/" }, { "title": "Teriparatide and Osteosarcoma Risk: History, Science, Elimination of Boxed Warning, and Other Label Updates", "authors_year": "2023", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/36111201/" } ], "reported_benefits": [ "significant increase in bone mineral density", "65% reduction in vertebral fracture risk", "53% reduction in non-vertebral fracture risk", "off-label: potential acceleration of stress-fracture healing" ], "dosing_protocols": [ { "route": "Subcutaneous self-injection", "protocol": "FDA-approved: 20 mcg once daily via pen injector; maximum duration 2 years." } ], "side_effects": [ "dizziness (transient, first 4 hours post-dose)", "injection-site reactions", "mild hypercalcemia", "nausea", "leg cramps" ], "safety_notes": "Black-box osteosarcoma warning removed in 2023 following a large surveillance study. Contraindicated in active/history of bone metastases, skeletal malignancies, prior skeletal radiation, and Paget's disease. Requires periodic calcium/phosphate monitoring.", "community_notes": "Clinical osteoporosis use is well-established. Off-label athletic/orthopedic interest for stress-fracture healing is growing on mechanistic appeal, though RCT evidence for that use remains limited; competitive-sport use raises doping/ethical concerns.", "related": [ "ll-37", "bpc-157" ] }, "cerebrolysin": { "name": "Cerebrolysin", "full_name": "Porcine brain-derived neuropeptide complex", "aliases": [ "cerebrolysine" ], "categories": [ "nootropics-cognitive", "longevity", "recovery-healing" ], "tagline": "Porcine neuropeptide preparation with clinical use for stroke and dementia in non-US countries.", "status": "Approved in 40+ countries (Austria, Russia, Eastern Europe, Asia); not FDA-approved in US", "origin": "A standardized complex of neuropeptides and free amino acids derived from porcine brain tissue, developed in Austria and used clinically in Europe and Asia since the 1970s-80s for stroke, dementia, and Alzheimer's disease.", "mechanism": "Modulates inflammatory cytokines, reducing IL-1\u03b2 and IL-6 while boosting IL-10, enhances neurotrophic signaling, promotes neuroplasticity (dendritic spine density in hippocampus and cortex), and stabilizes the blood-brain barrier.", "research_summary": "Neuroprotective effects are documented in in-vitro stroke and TBI models, with improved memory and increased hippocampal spine density in animal models. Clinical trials in dementia and vascular cognitive impairment show modest cognitive benefits, particularly post-stroke, mostly from European and Eastern European institutions. No large US FDA-track trials have been completed.", "citations": [ { "title": "Cerebrolysin treatment improved short-term memory deficits while simultaneously increasing hippocampal spine density in hypertensive female rats", "authors_year": "Espinoza et al. 2025", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/39826813/" } ], "reported_benefits": [ "cognitive support in dementia", "stroke recovery", "post-TBI neuroprotection", "neuroinflammation reduction" ], "dosing_protocols": [ { "route": "Intravenous or intramuscular injection", "protocol": "Typically 30 mL (1000-1500 mg) daily for 10-20 days in clinical trials; varies by indication." } ], "side_effects": [ "generally well tolerated", "rare local injection-site reactions", "rare mild allergic responses" ], "safety_notes": "Derived from animal tissue, carrying a theoretical prion-disease risk that hasn't shown up clinically. Decades of European clinical use report good tolerability. Not recommended in pregnancy.", "community_notes": "Nootropic users report modest subjective cognitive benefit. Legal and available by prescription or import in many non-US jurisdictions.", "related": [ "epithalon", "thymalin", "semax" ] }, "pe-22-28": { "name": "PE 22-28", "full_name": "PE 22-28; shortened spadin analog", "aliases": [ "mini-spadin" ], "categories": [ "nootropics-cognitive" ], "tagline": "Engineered spadin analog with improved TREK-1 channel inhibition and fast-acting antidepressant properties.", "status": "Research chemical; investigational, not approved for human use", "origin": "A shortened 7-amino-acid analog of spadin, itself derived from sortilin/NTSR3 receptor maturation, engineered by French researchers (CNRS) to improve metabolic stability and TREK-1 potency over the parent molecule. First described in 2017.", "mechanism": "Blocks TREK-1, a two-pore-domain potassium channel implicated in depression. This increases serotonergic neuron firing in the dorsal raphe nucleus, producing rapid antidepressant effects, and stimulates hippocampal neurogenesis and synaptogenesis.", "research_summary": "Shows better TREK-1 binding affinity and longer in-vivo action (23 hours vs spadin's 7 hours). Demonstrates antidepressant efficacy in mouse behavioral tests and neuroprotection in stroke and post-stroke-depression models. All evidence is preclinical; no human trials published.", "citations": [ { "title": "Shortened Spadin Analogs Display Better TREK-1 Inhibition, Stability and Antidepressant Activity", "authors_year": "Djillani et al. 2017", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28955242/" } ], "reported_benefits": [ "antidepressant effect (rapid onset in animal models)", "neuroprotection in stroke models", "neurogenesis stimulation" ], "dosing_protocols": [ { "route": "Intraperitoneal injection (research only)", "protocol": "Mouse models: 0.03-3 \u03bcg/kg; no human dosing established." } ], "side_effects": [ "no human data", "good tolerability at therapeutic doses in animal studies" ], "safety_notes": "Zero human safety data. Crosses the blood-brain barrier. Not recommended for self-administration outside research settings.", "community_notes": "Virtually no self-experimenter reports. Too obscure and research-only at present.", "related": [ "semax", "cerebrolysin" ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "ipamorelin" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "p21": { "name": "P21", "full_name": "P21 neurogenic peptide (CNTF-derived)", "aliases": [ "P-21" ], "categories": [ "nootropics-cognitive", "longevity" ], "tagline": "CNTF-derived peptide with claimed neurogenic potential; adamantane-conjugated variant designed for blood-brain barrier penetration.", "status": "Investigational research compound; adamantane variant not approved for human use", "origin": "Proposed to derive from or mimic the activity domain of ciliary neurotrophic factor (CNTF). The adamantane-conjugated variant was engineered for better blood-brain-barrier penetration via the adamantane cage structure.", "mechanism": "Proposed as a CNTF mimetic, activating CNTF receptor signaling (gp130/STAT3, PI3K/Akt) to support neuronal survival, differentiation, and neurogenesis. The adamantane conjugate adds lipophilicity to improve CNS delivery.", "research_summary": "Primary literature on P21 as a therapeutic peptide is very thin; most PubMed hits are for the unrelated cyclin-dependent kinase inhibitor p21 protein. No peer-reviewed clinical trials or systematic preclinical reports exist. Evidence quality is very low.", "citations": [ { "title": "The effect of exogenous ciliary neurotrophic factor on cell cycle and neural differentiation markers of in vitro model cells", "authors_year": "Ghasemi et al. 2021", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/33890305/" } ], "reported_benefits": [ "neurogenesis stimulation (theoretical)", "neuroprotection (theoretical)", "appetite stimulation (anecdotal)" ], "dosing_protocols": [ { "route": "Subcutaneous injection (research; no human standard)", "protocol": "No validated human dose exists for either form." } ], "side_effects": [ "insufficient human data" ], "safety_notes": "Essentially unevaluated in humans. CNTF itself has mixed effects, neuroprotective at some doses, neurotoxic at high ones, and P21 may carry similar risks. Not recommended outside formal research.", "community_notes": "Occasionally mentioned in nootropic forums with anecdotal cognitive and appetite claims. Use is rare, evidence speculative.", "related": [ "cerebrolysin", "semax" ], "variant_note": "The adamantane-conjugated form (sometimes marketed as 'Adamax') is a blood-brain-barrier-penetration modification of the same peptide, with essentially no published pharmacology or safety data beyond community discussion.", "mixing_notes": { "clinic_combos": [], "anecdotal_combos": [ "selank", "semax" ], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "pnc27": { "name": "PNC27", "full_name": "PNC-27; p53-derived HDM-2-targeting membrane-disrupting peptide", "aliases": [ "PNC-27" ], "categories": [ "longevity" ], "tagline": "CANCER RESEARCH ONLY: p53-derived peptide inducing tumor cell necrosis through HDM-2 interaction; no human clinical trials, and no longevity or anti-aging protocol exists.", "status": "Preclinical oncology research only; no human trials", "origin": "A 32-residue chimeric peptide fusing a p53-derived HDM-2 (MDM2) binding domain to a cell-penetrating penetratin leader sequence, built to target the p53-MDM2 interaction specifically in cancer cells that overexpress membrane-associated HDM-2.", "mechanism": "Binds membrane-associated HDM-2 with high affinity, forming complexes that dimerize and create transmembrane pores. This causes rapid necrosis selectively in cells expressing surface HDM-2, a feature of transformed, not normal, cells.", "research_summary": "Shows selective tumor cell killing in multiple cancer xenograft mouse models (pancreatic, leukemia, colon, ovarian) and ex vivo patient-derived samples. NO human clinical trials exist or are registered. All data are preclinical mouse xenograft or ex vivo findings, not evidence of human safety or efficacy.", "citations": [ { "title": "Anti-Cancer Peptide PNC-27 Kills Cancer Cells by Unique Interactions with Plasma Membrane-Bound hdm-2 and with Mitochondrial Membranes Causing Mitochondrial Disruption", "authors_year": "Krzesaj et al. 2024", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/38802154/" }, { "title": "PNC-27, a Chimeric p53-Penetratin Peptide Binds to HDM-2 in a p53 Peptide-like Structure, Induces Selective Membrane-Pore Formation and Leads to Cancer Cell Lysis", "authors_year": "Sarafraz-Yazdi et al. 2022", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/35625682/" } ], "reported_benefits": [ "tumor cell necrosis in vitro and in xenograft models", "efficacy against chemotherapy-resistant cancers (preclinical)" ], "dosing_protocols": [ { "route": "Intravenous or intraperitoneal (mouse studies only)", "protocol": "Mouse models: ~50-100 \u03bcg/kg; NO human dosing exists or should be attempted." } ], "side_effects": [ "NO HUMAN DATA", "membrane-pore-forming mechanism could plausibly cause severe tissue damage if misapplied in vivo" ], "safety_notes": "CRITICAL: this is a cancer-research tool, not an approved or investigational human therapeutic. Zero human trials, zero healthy-volunteer data. Self-administration would be extremely dangerous and no evidence supports it.", "community_notes": "Some longevity forums mistakenly categorize PNC27 as a life-extension peptide. It isn't \u2014 it's pure oncology research. Legitimate anecdotal human use essentially doesn't exist.", "related": [] }, "thymalin": { "name": "Thymalin", "full_name": "Thymic peptide bioregulator", "aliases": [ "thymus peptide" ], "categories": [ "bioregulators", "longevity", "recovery-healing" ], "tagline": "Thymic bioregulator from the Khavinson family with long-term human mortality follow-up and immune-modulating effects.", "status": "Approved in Russia and Eastern Europe; used in clinical practice", "origin": "Isolated from thymic tissue extracts, developed by Vladimir Khavinson's laboratory at the St. Petersburg Institute of Bioregulation and Gerontology, part of the Russian bioregulation-therapy tradition emerging in the late 1980s-90s.", "mechanism": "Stimulates differentiation of T lymphocyte precursors into mature CD4+/CD8+ T cells, reduces apoptosis of aging thymocytes, and modulates cytokine balance (lower IL-6/IL-1\u03b2, higher IL-10), normalizing immune homeostasis in aging.", "research_summary": "A long-running Russian/Ukrainian cohort study (~266 elderly participants over 6-8 years) reported a 2.0-2.1-fold reduction in all-cause mortality in the Thymalin group versus controls, and 2.5-fold when combined with Epithalamin. Secondary outcomes included fewer acute respiratory infections and cardiovascular events. These are large effect sizes from small, Russian-led trials with limited Western replication, a caveat that applies to the whole bioregulator family.", "citations": [ { "title": "Peptides of pineal gland and thymus prolong human life", "authors_year": "Khavinson & Morozov 2003", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/14523363/" }, { "title": "Results and Prospects of Using Activator of Hematopoietic Stem Cell Differentiation in Complex Therapy for Patients with COVID-19", "authors_year": "Khavinson et al. 2021", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/33575961/" } ], "reported_benefits": [ "immune function restoration", "reduced infection rates in elderly", "reduced cardiovascular disease incidence", "improved wound healing" ], "dosing_protocols": [ { "route": "Intramuscular or subcutaneous injection", "protocol": "Typical Russian protocol: 10-20 mg IM daily or every other day for 10-20 days, repeated every 6-12 months." } ], "side_effects": [ "rare mild local inflammation", "rare transient fever", "rare allergic reaction" ], "safety_notes": "Derived from animal thymic tissue, carrying a theoretical (undocumented) prion-disease risk. 15+ years of Russian clinical use report no serious adverse events. Not tested in pregnancy.", "community_notes": "Available in Russia/Eastern Europe; some Western users order through offshore channels. Anecdotal reports of reduced illness frequency; no Western regulatory pathway exists.", "related": [ "vilon", "epithalon", "pinealon", "thymosin-alpha-1" ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "ghk-cu", "ghrp-6", "ipamorelin", "pinealon", "selank", "semax", "tb-500", "thymosin-alpha-1" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "vilon": { "name": "Vilon", "full_name": "Thymic dipeptide (Lysyl-Glutamic acid, Lys-Glu)", "aliases": [ "lysyl-glutamic acid" ], "categories": [ "bioregulators", "longevity" ], "tagline": "Short-form thymic dipeptide bioregulator with immunomodulatory and T-cell differentiation effects.", "status": "Available in Russia and some Eastern European countries", "origin": "A short dipeptide (Lys-Glu) isolated from thymic tissue extracts as part of Khavinson's bioregulation program, a 'short-form' analog of longer preparations like Thymalin.", "mechanism": "Stimulates differentiation of CD5+ lymphocyte precursors into mature CD4+/CD8+ T cells and promotes thymocyte proliferation (Ki-67 expression) in organotypic thymic culture; also modulates pineal lymphoid tissue differentiation.", "research_summary": "Multiple small in-vitro studies from Khavinson's laboratory show Vilon stimulates T-cell/B-cell differentiation from precursors in thymic and pineal cultures. No human clinical trials with mortality or large-cohort endpoints exist for Vilon specifically; evidence comes exclusively from Russian research institutions and remains unreplicated in the West.", "citations": [ { "title": "Immunomodulating effects of Vilon and its analogue in the culture of human and animal thymus cells", "authors_year": "Sevostianova et al. 2013", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/23486604/" } ], "reported_benefits": [ "T-cell differentiation/maturation", "immune cell proliferation", "potential thymic rejuvenation" ], "dosing_protocols": [ { "route": "Intramuscular or subcutaneous injection", "protocol": "Typical Russian dosing: 5-10 mg IM daily or alternate-day for 10 days, repeated seasonally." } ], "side_effects": [ "minimal documented; rare local injection-site reaction" ], "safety_notes": "Simple dipeptide with likely low intrinsic toxicity, but no Western toxicology or safety monitoring data are published.", "community_notes": "Less well-known than Thymalin in Western communities; most references are Russian or translated. Availability outside Russia is limited.", "related": [ "thymalin", "epithalon", "pinealon" ] }, "pinealon": { "name": "Pinealon", "full_name": "Pineal-gland peptide bioregulator (distinct short peptide, not to be confused with epithalon)", "aliases": [ "pineal peptide" ], "categories": [ "bioregulators", "nootropics-cognitive" ], "tagline": "Pineal-derived peptide bioregulator with cognitive and neuroprotective positioning.", "status": "Available in Russia and some international peptide suppliers", "origin": "A peptide bioregulator from pineal-gland-tissue isolation work by Khavinson's group, positioned for cognitive and CNS support. A distinct product from Epitalon/epithalon, though closely related in research tradition and often confused with it in marketing.", "mechanism": "Proposed to act as a tissue-specific bioregulator supporting pineal and CNS cell function, with claimed effects on neuronal signaling molecule expression and antioxidant activity in brain tissue.", "research_summary": "Evidence is limited to small Khavinson-group studies, largely unreplicated in Western literature. Human data are essentially anecdotal reports of improved sleep and mood in older adults. Overall evidence quality is very low.", "citations": [ { "title": "Effect of short peptides on expression of signaling molecules in organotypic pineal cell culture", "authors_year": "Khavinson et al. 2011", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/22803060/" } ], "reported_benefits": [ "sleep quality support", "circadian rhythm support (theoretical)", "cognitive support claims", "antioxidant effects (theoretical)" ], "dosing_protocols": [ { "route": "Subcutaneous or intramuscular injection, or oral capsule", "protocol": "Reported Russian protocols: 10 mg IM daily for 10 days, or oral capsule courses; poorly standardized." } ], "side_effects": [ "insufficient human data; animal studies show good tolerability" ], "safety_notes": "Extremely limited safety data. No formal toxicology or long-term human studies published.", "community_notes": "Appears in Western longevity and biohacker circles, sometimes marketed under names overlapping with Epitalon, which causes confusion between the two. Claims often exceed evidence.", "related": [ "epithalon", "thymalin", "cerebrolysin" ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "ipamorelin", "kisspeptin", "pt-141", "selank", "tb-500", "thymalin", "thymosin-alpha-1" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "testagen": { "name": "Testagen", "full_name": "Testicular/vascular bioregulator peptide", "aliases": [ "testis peptide" ], "categories": [ "bioregulators", "sexual-health" ], "tagline": "Testis-targeted bioregulator peptide from the Khavinson family, proposed for testicular and vascular function.", "status": "Experimental research compound; minimal published data", "origin": "A peptide bioregulator derived from testicular-tissue peptide extraction, developed within Khavinson's bioregulation research framework alongside thymic and pineal preparations. Specific isolation methodology isn't well documented in English-language literature.", "mechanism": "Proposed to support testicular function and testosterone production through tissue-specific bioregulatory effects (theoretical Leydig-cell stimulation and vascular support), analogous to Thymalin's action on thymic tissue.", "research_summary": "Zero peer-reviewed research articles specifically on Testagen are indexed in PubMed. Vendor/community sources reference it as a 'testis bioregulator' with claims about testosterone and fertility, entirely anecdotal and unsupported by published studies, the lowest evidence tier of the bioregulator family.", "citations": [], "reported_benefits": [ "testosterone support (community claim, unproven)", "erectile function support (community claim, unproven)", "fertility support (community claim, unproven)" ], "dosing_protocols": [ { "route": "Subcutaneous or intramuscular injection", "protocol": "No standardized dosing; online reports suggest 5-10 mg IM weekly, entirely unvalidated." } ], "side_effects": [ "unknown; no published data" ], "safety_notes": "No pharmacokinetics, toxicology, or human safety data published anywhere. Any hormonal claims are unproven; self-administration carries unknown risk.", "community_notes": "Appears in men's health forums with anecdotal libido/fertility claims; availability limited to a few international suppliers.", "related": [ "thymalin", "vilon" ] }, "bronchogen": { "name": "Bronchogen", "full_name": "Bronchogen (Ala-Glu-Asp-Leu)", "aliases": [ "AEDL peptide" ], "categories": [ "bioregulators", "recovery-healing" ], "tagline": "Organ-targeted bioregulator from the Khavinson lineage, aimed at bronchial and respiratory tissue.", "status": "Approved in Russia", "origin": "Developed by Vladimir Khavinson's group at the St. Petersburg Institute of Bioregulation and Gerontology from amino-acid analysis of bronchial and respiratory tissue extracts; part of the Russian tissue-specific bioregulator program dating to the 1980s.", "mechanism": "Proposed to stimulate differentiation factors like CXCL12 and Hoxa3 in bronchial epithelial cells, especially in aging cultures, supporting lung tissue homeostasis.", "research_summary": "Research is limited and comes almost entirely from Khavinson's group. A 2012 study showed tissue-specific stimulation of differentiation markers in human bronchial epithelial cells in vitro; older work showed stimulatory effects in organotypic lung culture. No human trials or large-cohort data exist in English-language literature. Evidence is small-sample, Russian-led, and unreplicated in the West.", "citations": [ { "title": "Peptides tissue-specifically stimulate cell differentiation during their aging", "authors_year": "Khavinson et al. 2012", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/22808515/" } ], "reported_benefits": [ "support for respiratory tissue structure", "enhancement of bronchial epithelial cell renewal (preclinical)", "potential immunoprotective effects on lung tissue" ], "dosing_protocols": [ { "route": "Intramuscular injection or oral tablet", "protocol": "Russian clinical use reports vary; community sourcing reports 10-20 mg subcutaneously, unstandardized in Western literature." } ], "side_effects": [ "minimal reported; low toxicity profile typical of short peptide preparations" ], "safety_notes": "No serious adverse effects reported in Russian studies. Sterility and purity of imported or self-compounded preparations can't be guaranteed, and long-term human safety is undocumented.", "community_notes": "Sourced by Western biohackers from Russian compounding services as part of the broader Khavinson suite; use is anecdotal with no systematic monitoring.", "related": [ "cardiogen", "cortagen", "livagen", "pancragen", "prostamax", "epithalon", "thymosin-alpha-1" ] }, "cardiogen": { "name": "Cardiogen", "full_name": "Cardiogen (cardiac tissue peptide bioregulator)", "aliases": [ "cardiac bioregulator" ], "categories": [ "bioregulators", "longevity" ], "tagline": "Organ-targeted bioregulator from the Khavinson lineage aimed at cardiac tissue repair.", "status": "Approved in Russia", "origin": "Developed by Khavinson's group from amino-acid analysis of bovine cardiac tissue extracts, registered in Russia as both an injectable (cytamin) and oral tablet (cytomax), dating to the 1980s-90s bioregulator program.", "mechanism": "Proposed to regulate cardiac cell proliferation and block apoptosis. In-vitro work shows stimulated myocardial explant growth and reduced p53 expression, pointing to a pro-survival, regenerative effect on heart tissue.", "research_summary": "Research is limited to small Russian studies. A 2009 organotypic-culture study showed stimulated myocardial proliferation and reduced apoptosis markers in both young and aged rat tissue; a related gene-expression study found an altered cardiac transcriptome after treatment. All evidence is in-vitro or animal; no human trials exist, and none of it is replicated in Western labs.", "citations": [ { "title": "[The effect of the amino acids and cardiogen on the development of myocard tissue culture from young and old rats]", "authors_year": "Chalisova et al. 2009", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/20210190/" } ], "reported_benefits": [ "support for cardiac tissue repair/regeneration (preclinical)", "potential inhibition of myocardial apoptosis", "claimed anti-aging effects on heart tissue" ], "dosing_protocols": [ { "route": "Intramuscular injection or oral tablet", "protocol": "Community dosing reports: 10-20 mg subcutaneously; no standardized human protocol validated in literature." } ], "side_effects": [ "minimal reported; cardiac safety monitoring data unavailable" ], "safety_notes": "No serious adverse events reported, but the critical nature of cardiac tissue warrants caution, and no long-term human safety data exists. Anyone with pre-existing cardiac disease should get medical oversight before use.", "community_notes": "One of the more-discussed Khavinson peptides in Western longevity circles for cardiovascular aging; all anecdotal and uncontrolled.", "related": [ "bronchogen", "cortagen", "livagen", "pancragen", "prostamax", "epithalon", "thymosin-alpha-1" ] }, "cortagen": { "name": "Cortagen", "full_name": "Cortagen (Ala-Glu-Asp-Pro, brain cortex peptide)", "aliases": [ "AEDP" ], "categories": [ "bioregulators", "nootropics-cognitive" ], "tagline": "Organ-targeted Khavinson peptide aimed at cerebral cortex structure and cognitive function.", "status": "Approved in Russia", "origin": "Synthesized from the amino-acid composition of a natural cerebral-cortex peptide extract related to Cortexin, derived from bovine brain-cortex tissue preparations, approved in Russia as injectable and oral formulations.", "mechanism": "Proposed to regulate cerebral cortex cell differentiation and reduce brain oxidative stress, with suggested effects on neurotrophic factor expression and circadian melatonin regulation in aging models.", "research_summary": "A 2007 study documented antioxidant effects and reduced oxidative-stress markers in rat cerebral cortex; earlier organotypic culture work established tissue-specific effects. Research comes almost entirely from Khavinson's group, and no human trials appear in English-language literature.", "citations": [ { "title": "Effects of bioactive tetrapeptides on free-radical processes", "authors_year": "Kozina et al. 2007", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/18239817/" } ], "reported_benefits": [ "support for cortical cell renewal (preclinical)", "potential reduction in brain oxidative stress", "claimed cognitive/neuroprotective support" ], "dosing_protocols": [ { "route": "Subcutaneous/intramuscular injection or oral tablet", "protocol": "Community dosing: 10-20 mg subcutaneously or intramuscularly; oral forms 10-30 mg; no validated human protocol." } ], "side_effects": [ "minimal reported; neurological monitoring data unavailable" ], "safety_notes": "No serious adverse events reported in Russian studies, but CNS effects are poorly characterized in humans, and long-term safety is undocumented.", "community_notes": "Discussed in Western nootropics and longevity communities for mental clarity and cognitive aging support. The evidence base is minimal and largely inaccessible to Western practitioners.", "related": [ "bronchogen", "cardiogen", "livagen", "pancragen", "prostamax", "epithalon", "thymosin-alpha-1" ] }, "livagen": { "name": "Livagen", "full_name": "Livagen (Lys-Glu-Asp-Ala, hepatic bioregulator)", "aliases": [ "KEDA" ], "categories": [ "bioregulators", "recovery-healing" ], "tagline": "Organ-targeted peptide bioregulator designed to support liver tissue repair and hepatic function.", "status": "Approved in Russia", "origin": "Synthesized from bovine liver tissue extract amino-acid analysis by Khavinson's group. Registered in Russia as injectable (cytamin/hepatamin) and oral tablet formulations, also known as tetrapeptide KEDA.", "mechanism": "Proposed to regulate hepatic cell regeneration, normalize immune/antioxidant status in liver tissue, and support structural homeostasis during metabolic dysfunction and aging.", "research_summary": "A 2020 review documented hepatoprotective and anti-aging properties in animal/in-vitro liver fibrosis models; older organotypic culture studies established tissue-specific effects in liver cultures from young vs aged rats. No human clinical trials identified in English-language literature; evidence is small-sample and unreplicated outside Russia.", "citations": [ { "title": "[The influence of polypeptide liver complex and tetrapeptide KEDA on organism physiological function in norm and age-related pathology]", "authors_year": "Kuznik et al. 2020", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/32362099/" } ], "reported_benefits": [ "support for hepatic tissue repair/regeneration (preclinical)", "potential hepatoprotective effects", "claimed anti-aging effects on liver" ], "dosing_protocols": [ { "route": "Subcutaneous/intramuscular injection or oral tablet", "protocol": "Community dosing: 10-20 mg subcutaneously or intramuscularly; oral forms 10-30 mg daily; unvalidated in humans." } ], "side_effects": [ "minimal reported; hepatotoxicity monitoring data unavailable" ], "safety_notes": "No serious adverse events reported in available studies. Anyone with pre-existing hepatic disease should avoid use without medical supervision.", "community_notes": "Discussed in Western biohacker circles for liver/metabolic health support; anecdotal only, with unassured purity when sourced outside Russia.", "related": [ "bronchogen", "cardiogen", "cortagen", "pancragen", "prostamax", "epithalon", "thymosin-alpha-1" ] }, "pancragen": { "name": "Pancragen", "full_name": "Pancragen (Lys-Glu-Asp-Trp, pancreatic bioregulator)", "aliases": [ "KEDT" ], "categories": [ "bioregulators", "fat-loss" ], "tagline": "Organ-targeted peptide bioregulator designed to support pancreatic function and glucose metabolism.", "status": "Approved in Russia", "origin": "Synthesized from bovine pancreatic tissue extract by Khavinson's group. Registered in Russia as injectable and oral formulations, and in Russian clinical practice for pancreatic and metabolic health since the 1990s.", "mechanism": "Proposed to regulate pancreatic islet and acinar cell differentiation, possibly via developmental transcription factors (Pdx1, Pax6, Pax4, Foxa2), normalizing insulin secretion and glucose tolerance.", "research_summary": "A 2013 study showed pancragen stimulated differentiation markers in pancreatic cell cultures, more so in aged cultures. Two primate studies (2014-2015) showed normalized glucose tolerance and insulin dynamics in aged rhesus monkeys, but with small samples (4-9 animals). No randomized human trials exist; evidence is limited to animal and cellular models.", "citations": [ { "title": "Effects of pancragen on the differentiation of pancreatic cells during their ageing", "authors_year": "Khavinson et al. 2013", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/23486591/" }, { "title": "[Correction of impaired glucose tolerance using tetrapeptide (Pancragen) in old female rhesus monkeys]", "authors_year": "Goncharova et al. 2015", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28509500/" } ], "reported_benefits": [ "support for pancreatic cell regeneration (preclinical)", "potential normalization of glucose metabolism (primate data)", "claimed anti-diabetic effects" ], "dosing_protocols": [ { "route": "Subcutaneous/intramuscular injection or oral tablet", "protocol": "Primate studies used 50-500 \u00b5g/animal/day for 10 days IM; community dosing 10-20 mg subcutaneously, unvalidated in humans." } ], "side_effects": [ "minimal reported; glucose/metabolic monitoring data limited" ], "safety_notes": "No serious adverse events reported in animal or in-vitro studies. People with diabetes should only use it under medical supervision given its potential glucose effects.", "community_notes": "Popular in metabolic-health biohacker circles for glucose control claims. Human evidence is entirely absent, and imported peptide quality is unassured.", "related": [ "bronchogen", "cardiogen", "cortagen", "livagen", "prostamax", "epithalon", "thymosin-alpha-1" ] }, "prostamax": { "name": "Prostamax", "full_name": "Prostamax (also known as Prostatilen; prostate-derived peptide bioregulator)", "aliases": [ "Prostatilen" ], "categories": [ "bioregulators", "sexual-health" ], "tagline": "Organ-targeted peptide bioregulator designed to support prostate tissue structure and urogenital function.", "status": "Approved in Russia", "origin": "Derived from bovine prostate tissue extracts by Khavinson's group and collaborators. Registered in Russia as injectable (cytamin/prostatamin) and oral formulations, in Russian urology and gerontology practice since the 1980s-90s under the clinical name Prostatilen.", "mechanism": "Proposed to regulate prostate cell differentiation and regeneration and support structural integrity of prostate tissue, with theorized immunoprotective effects.", "research_summary": "Formal human clinical trials for Prostamax are absent from PubMed. A related study on vesugen showed tissue-specific stimulation in human prostate fibroblasts, suggesting a shared mechanism; a 1997 study of a related prostate peptide preparation showed protective effects in a rat decompression model. Evidence is largely Russian-language and unreplicated in the West.", "citations": [ { "title": "Peptides tissue-specifically stimulate cell differentiation during their aging", "authors_year": "Khavinson et al. 2012", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/22808515/" } ], "reported_benefits": [ "support for prostate tissue structure (preclinical)", "claimed enhancement of prostate function", "possible support for urinary/sexual health" ], "dosing_protocols": [ { "route": "Subcutaneous/intramuscular injection or oral tablet", "protocol": "Community dosing: 10-20 mg subcutaneously or intramuscularly; oral forms 10-30 mg daily; unvalidated in humans." } ], "side_effects": [ "minimal reported; long-term monitoring data absent" ], "safety_notes": "No serious adverse events documented. Effects on hormone-sensitive prostate tissue aren't well characterized. Anyone with prostate cancer or significant prostate disease should avoid use without medical evaluation.", "community_notes": "Discussed in men's health and biohacker communities for prostate support and urinary flow. Anecdotal only; human research validation is absent.", "related": [ "bronchogen", "cardiogen", "cortagen", "livagen", "pancragen", "epithalon", "thymosin-alpha-1" ] }, "cartalax": { "name": "Cartalax", "full_name": "Cartalax (cartilage-targeted peptide bioregulator)", "aliases": [], "categories": [ "bioregulators", "recovery-healing" ], "tagline": "Organ-targeted Khavinson peptide aimed at cartilage and joint tissue regeneration.", "status": "Approved in Russia; research compound", "origin": "Synthesized by the St. Petersburg Institute of Bioregulation and Gerontology in the Khavinson organ-targeted bioregulator tradition, on the premise that short synthetic peptides can selectively influence specific tissues through epigenetic mechanisms.", "mechanism": "Proposed to activate cartilage cell proliferation and differentiation by interacting with DNA promoter regions in cartilage-specific genes, regulating chondrogenic markers and extracellular matrix proteins.", "research_summary": "No English-language peer-reviewed studies indexed in PubMed exist for Cartalax specifically. It's referenced only in Russian-language literature and commercial or community sources, unreplicated in Western academic literature. Evidence quality here is the lowest tier in the family.", "citations": [], "reported_benefits": [ "claimed joint cartilage regeneration", "claimed improved cartilage cell proliferation", "claimed reduced joint degeneration" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Community reports: 10-20 mg daily or every other day for 10-20 days, repeated after 3-6 months." } ], "side_effects": [ "localized injection-site reactions when injected" ], "safety_notes": "Published safety data is limited. Russian regulatory approval suggests a history of use, but Western trials are absent, and compounded or imported preparation quality may vary.", "community_notes": "Community reports suggest positive effects on joint pain and mobility, entirely anecdotal. Typically sourced through import from Russia.", "related": [ "chonluten", "vesugen", "pancragen", "epithalon", "thymosin-alpha-1" ] }, "chonluten": { "name": "Chonluten", "full_name": "Chonluten (bronchial/pulmonary peptide bioregulator)", "aliases": [], "categories": [ "bioregulators", "recovery-healing" ], "tagline": "Organ-targeted peptide for bronchial and pulmonary tissue support.", "status": "Approved in Russia; research compound", "origin": "Developed by the St. Petersburg Institute of Bioregulation and Gerontology as an organ-targeted bioregulator for lung and bronchial tissue, following the Khavinson model.", "mechanism": "Proposed to enhance proliferation and differentiation of bronchial and alveolar epithelial cells through epigenetic gene regulation, supporting airway repair and immune defense.", "research_summary": "No English-language peer-reviewed studies indexed in PubMed exist for Chonluten specifically. It's documented only in Russian-language literature and community sources; evidence quality is the family's lowest tier.", "citations": [], "reported_benefits": [ "claimed bronchial tissue repair", "claimed improved respiratory function", "claimed reduced respiratory tract inflammation" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Community reports: 10-20 mg daily or every other day for 10-20 days, repeated seasonally." } ], "side_effects": [ "minimal systemic effects reported", "localized injection-site reactions possible" ], "safety_notes": "Published safety data outside Russian sources is limited. Not recommended in pregnancy, and compounded preparation quality varies.", "community_notes": "Some self-experimenters use it for chronic respiratory conditions; evidence is testimonial only.", "related": [ "bronchogen", "vesugen", "crystagen", "epithalon", "thymosin-alpha-1" ] }, "crystagen": { "name": "Crystagen", "full_name": "Crystagen (immune-system-targeted peptide bioregulator)", "aliases": [], "categories": [ "bioregulators", "longevity" ], "tagline": "Organ-targeted Khavinson peptide aimed at immune activation and B-cell function.", "status": "Approved in Russia; limited Western literature", "origin": "Synthesized by the St. Petersburg Institute of Bioregulation and Gerontology as an immune-targeted bioregulator, part of the Khavinson family aimed at modulating tissue-specific immune function.", "mechanism": "Proposed to activate B-cell populations in the spleen by affecting proliferation and apoptosis regulation.", "research_summary": "A 2014 paper found Crystagen activates immune B-cells by modulating apoptosis, with a narrower overall cell-renewal effect than other family members like Vilon. The research base is small and mostly confined to Russian-language literature from the St. Petersburg Institute, with little independent Western replication.", "citations": [ { "title": "Molecular aspects of immunoprotective activity of peptides in spleen during the ageing process", "authors_year": "Khavinson et al. 2014", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28976144/" } ], "reported_benefits": [ "claimed B-cell immune activation", "claimed enhanced immune response in aging", "claimed reduced immune senescence" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Community reports: 10-20 mg daily for 10-20 days, repeated every 3-6 months." } ], "side_effects": [ "generally well tolerated", "localized injection-site reactions possible" ], "safety_notes": "Safety data is limited to Russian studies. Not recommended for pregnant women or anyone with autoimmune conditions, where B-cell activation could be problematic.", "community_notes": "Community reports suggest immune-support benefits, often stacked with Vilon or Thymalin, entirely anecdotal.", "related": [ "thymalin", "vilon", "pinealon", "epithalon", "thymosin-alpha-1" ] }, "ovagen": { "name": "Ovagen", "full_name": "Ovagen (ovarian-tissue-targeted peptide bioregulator)", "aliases": [], "categories": [ "bioregulators", "sexual-health" ], "tagline": "Organ-targeted peptide supporting ovarian tissue function and reproductive health.", "status": "Approved in Russia; veterinary research applications documented", "origin": "Developed by the St. Petersburg Institute of Bioregulation and Gerontology as an ovarian-targeted bioregulator. Unlike most peptides in its family, it's been extensively used in veterinary reproduction research as an FSH alternative.", "mechanism": "Proposed to act as an FSH analog or potentiator, enhancing follicular development and oocyte maturation.", "research_summary": "Documented in peer-reviewed veterinary literature (dairy cattle, sheep, goats, 2003-2010) for improved follicle emergence and oocyte recovery in assisted reproduction. No human clinical trials for reproductive use turn up in PubMed. Evidence is moderate for veterinary use, essentially absent for human use.", "citations": [ { "title": "Effects of low-dose follicle-stimulating hormone administration on follicular dynamics and preovulatory follicle characteristics in dairy cows during the summer", "authors_year": "Friedman et al. 2010", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/20399062/" } ], "reported_benefits": [ "ovarian follicle stimulation (veterinary evidence)", "claimed improved fertility support in humans (unproven)" ], "dosing_protocols": [ { "route": "Subcutaneous or intramuscular injection", "protocol": "Veterinary applications: 2.2-4.4 mg on specific estrous-cycle days; human protocols not documented in Western literature." } ], "side_effects": [ "minimal reported in animal studies", "potential ovarian hyperstimulation (dose-dependent, theoretical in humans)" ], "safety_notes": "Safety data comes mainly from veterinary and Russian sources. Human reproductive use lacks Western clinical trials and needs medical supervision if attempted.", "community_notes": "Little community discussion. Most literature is veterinary and agricultural, not human self-experimentation.", "related": [ "testagen", "pancragen", "prostamax", "epithalon", "thymosin-alpha-1" ] }, "vesugen": { "name": "Vesugen", "full_name": "Vesugen (vascular-tissue-targeted peptide bioregulator, Lys-Glu-Asp / KED)", "aliases": [ "KED peptide" ], "categories": [ "bioregulators", "longevity" ], "tagline": "Organ-targeted peptide supporting vascular endothelial cell function and tissue regeneration.", "status": "Approved in Russia; PubMed-indexed research available", "origin": "Developed by the St. Petersburg Institute of Bioregulation and Gerontology as a vascular-targeted bioregulator. The tripeptide Lys-Glu-Asp (KED) was synthesized within the organ-targeted peptide tradition.", "mechanism": "Activates proliferation and renewal in vascular endothelial cells (increasing Ki-67, reducing p53), normalizes endothelin-1 expression in atherosclerotic endothelium, and increases SIRT1 expression involved in DNA repair.", "research_summary": "A 2016 paper described molecular mechanisms of vasoprotection including endothelin-1 normalization; a 2014 paper showed the KED tripeptide reduces adhesion molecules involved in atherosclerotic plaque formation. Other studies document effects on endothelial proliferation and erectile function in elderly men with atherosclerosis. Research base is small, a handful of PubMed-indexed studies, primarily from Russian institutions, with limited independent Western replication.", "citations": [ { "title": "Molecular aspects of vasoprotective peptide KED activity during atherosclerosis and restenosis", "authors_year": "Khavinson et al. 2016", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28539025/" }, { "title": "Molecular aspects of anti-atherosclerotic effects of short peptides", "authors_year": "Khavinson et al. 2014", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/25408528/" } ], "reported_benefits": [ "vascular endothelial cell regeneration (preclinical)", "claimed improved blood flow/circulation", "claimed reduced atherosclerotic plaque formation", "claimed improved erectile function in atherosclerosis-related ED" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Community reports: 10-20 mg daily or every other day for 10-20 days, repeated every 3-6 months." } ], "side_effects": [ "generally well tolerated", "localized injection-site reactions possible", "one study noted prooxidant activity in a chemiluminescence assay" ], "safety_notes": "Safety data comes primarily from Russian studies. Not recommended in pregnancy; patients on anticoagulants should consult a physician given the cardiovascular mechanism claims.", "community_notes": "Discussed in longevity communities for cardiovascular support, sometimes combined with other vascular-support peptides; entirely anecdotal.", "related": [ "epithalon", "pinealon", "pancragen", "cardiogen", "thymosin-alpha-1" ] }, "peg-mgf": { "name": "PEG-MGF", "full_name": "PEGylated Mechano Growth Factor", "aliases": [ "Pegylated MGF", "PEG MGF" ], "categories": [ "fitness-muscle" ], "tagline": "Native MGF with a polyethylene glycol tag bolted on to stretch its otherwise minutes-long half-life into something injectable a few times a week; the underlying human data is essentially borrowed from other pegylated IGF-1 work, not PEG-MGF itself.", "status": "Unapproved research compound, no regulatory approval for any human indication. Sold through the same research-chemical channels as unmodified MGF.", "origin": "MGF (mechano growth factor, the IGF-1Ec splice variant) is produced locally in muscle tissue after mechanical loading or damage and is cleared within minutes. PEG-MGF is a synthetic version with polyethylene glycol chains attached to the peptide backbone, a modification used across biologics (PEGylated interferons, PEGylated growth hormone, etc.) specifically to slow renal clearance and proteolysis.", "mechanism": "Proposed to act the same way as native MGF, binding IGF-1 receptors on satellite cells to trigger proliferation and fusion into myofibers, but with PEGylation increasing hydrodynamic size and shielding the peptide from clearance so it persists in circulation rather than acting only locally and briefly.", "research_summary": "No PubMed-indexed studies test PEG-MGF itself in animals or humans. What exists is indirect: a first-in-human trial of a differently PEGylated IGF-1 molecule (not MGF) showed PEGylation extended IGF-1 half-life from a matter of hours to roughly 140-200 hours and blunted the hypoglycemia and GH-suppression seen with unmodified IGF-1, demonstrating PEGylation's general effect on this protein family's pharmacokinetics. Separately, human muscle-biopsy studies confirm native MGF mRNA is induced transiently by resistance exercise and that this response is blunted in older adults. A 2026 narrative review of unregulated performance-enhancing peptides lists PEG-MGF among compounds being self-administered off-label and explicitly flags the absence of human pharmacokinetic or efficacy data for it specifically, contrasting it with better-studied compounds in the same drug class.", "reported_benefits": [ "claimed longer-lasting, more systemic muscle-building effect than native MGF (theoretical, extrapolated from PEGylation's known effect on IGF-1 half-life)", "reduced injection frequency compared to native MGF due to slower clearance", "same satellite-cell activation/hypertrophy claims made for native MGF, unverified for the pegylated form" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Commonly reported at 200-500 mcg per injection, roughly 2x weekly, sometimes framed as once-weekly given the claimed extended half-life. No clinical dosing standard exists; these figures come from self-experimentation reporting, not trials." } ], "side_effects": [ "injection site irritation", "theoretical hypoglycemia risk from IGF-1 receptor activation", "unknown long-term effects of chronic PEG accumulation (a general PEGylation concern seen with other pegylated biologics, not established for PEG-MGF specifically)" ], "safety_notes": "There is no published human safety data for PEG-MGF as a distinct molecule. Safety claims lean entirely on data for native MGF and on unrelated PEGylated IGF-1/growth-hormone products, which is a real evidentiary gap, not a formality. Theoretical concerns carried over from the IGF-1 pathway generally (mitogenic signaling, malignancy risk in susceptible tissue) apply here too and are, if anything, amplified by the longer systemic exposure PEGylation is designed to produce.", "community_notes": "Discussed in bodybuilding and peptide self-experimentation circles as the 'systemic' counterpart to local MGF injections, used post-training with claims of prolonged muscle-building signaling. Reports are anecdotal; users generally acknowledge there's no controlled human trial behind the protocols being passed around.", "related": [ "mgf" ], "citations": [ { "title": "The emerging landscape of performance-enhancing peptides modulating GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration", "authors_year": "Dominikowski et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42395176/" }, { "title": "First-in-man study with a novel PEGylated recombinant human insulin-like growth factor-I", "authors_year": "Kletzl et al. 2017", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28110155/" }, { "title": "Expression of IGF-1 isoforms after exercise-induced muscle damage in humans: characterization of the MGF E peptide actions in vitro", "authors_year": "Philippou et al. 2009", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/19567392/" }, { "title": "Expression of IGF-I splice variants in young and old human skeletal muscle after high resistance exercise", "authors_year": "Hameed et al. 2003", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/12562960/" } ] }, "glutathione": { "name": "Glutathione", "full_name": "Glutathione (gamma-L-glutamyl-L-cysteinyl-glycine, GSH)", "aliases": [ "GSH", "reduced glutathione", "L-glutathione" ], "categories": [ "anti-aging" ], "tagline": "The body's main intracellular antioxidant tripeptide; oral supplementation genuinely raises body stores in trials, but the skin-lightening and detox claims built on top of that are much thinner.", "status": "Sold over-the-counter as an oral supplement, and used off-label as an IV or injectable product in wellness/aesthetic clinics; not FDA-approved for any indication marketed to consumers.", "origin": "A tripeptide (glutamate-cysteine-glycine) synthesized in nearly every cell, not obtained from diet as an intact peptide. It's the most abundant low-molecular-weight thiol in the body and central to redox buffering and detoxification.", "mechanism": "The cysteine thiol group lets glutathione cycle between reduced (GSH) and oxidized (GSSG) states, neutralizing reactive oxygen species and peroxides via glutathione peroxidase, and conjugating with xenobiotics via glutathione S-transferases for excretion. Proposed skin-lightening effects come from direct and indirect inhibition of tyrosinase and a shift in melanin synthesis from darker eumelanin toward lighter pheomelanin.", "research_summary": "Oral bioavailability was long assumed to be near zero because gut peptidases break glutathione down, but a 6-month randomized placebo-controlled trial in healthy adults showed daily oral GSH (250 or 1000 mg) did raise blood, erythrocyte, and buccal-cell glutathione levels in a dose- and time-dependent way, with levels falling back to baseline after a washout month. For the skin-lightening use case specifically, multiple human RCTs exist and reviews of them are mixed: some show modest melanin reduction with oral or topical glutathione, effects are inconsistent across body sites and populations, not long-lasting after stopping, and IV/parenteral glutathione carries real safety concerns (anaphylaxis, hepatotoxicity reports) that oral and topical forms don't. General antioxidant/longevity/detox benefit claims beyond raising measured GSH levels are not well supported by controlled human trials.", "reported_benefits": [ "reliably raises measured glutathione levels in blood and tissue with sustained oral dosing (best-supported claim)", "modest, inconsistent skin-lightening/depigmentation effect reported in some RCTs, not durable after discontinuation", "marketed general antioxidant/detox and anti-aging support, largely unproven beyond the biomarker changes above" ], "dosing_protocols": [ { "route": "Oral capsule", "protocol": "Trial doses of 250-1000 mg/day for up to 6 months raised body glutathione stores in a dose-dependent way; community use commonly mirrors this range." }, { "route": "IV infusion (clinic setting)", "protocol": "Widely used off-label for skin lightening at clinic-set doses with no standardized protocol; reviews note this route has the least standardization and the worst safety signal of the three." }, { "route": "Topical", "protocol": "Used in cosmetic formulations for localized skin-lightening effect; reported better tolerated than IV but with variable, non-durable results." } ], "side_effects": [ "oral: generally well tolerated, mild GI upset reported occasionally", "IV/parenteral: flushing, and rarer but serious reports of anaphylaxis and hepatotoxicity", "topical: mostly local irritation" ], "safety_notes": "Oral glutathione has the best safety and mechanistic evidence of the three routes and is where the strongest trial (Richie et al. 2014) sits. IV glutathione, despite being popular in aesthetic clinics for skin lightening, has weaker efficacy evidence and a real, documented risk of serious adverse events including anaphylaxis and liver injury; regulators in some countries have issued warnings against off-label IV use for this purpose. Long-term safety of sustained high-dose supplementation of any form isn't well characterized.", "community_notes": "Frequently paired with NAD+ in longevity and detox-focused wellness stacks, marketed as antioxidant/anti-aging support alongside NAD+'s energy-metabolism pitch. In cosmetic-focused communities it's discussed mainly for skin lightening, where users generally note effects fade if supplementation stops.", "related": [ "nad" ], "citations": [ { "title": "Randomized controlled trial of oral glutathione supplementation on body stores of glutathione", "authors_year": "Richie et al. 2015", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/24791752/" }, { "title": "Exploring the Safety and Efficacy of Glutathione Supplementation for Skin Lightening: A Narrative Review", "authors_year": "Alzahrani et al. 2025", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/40013212/" }, { "title": "Systemic Glutathione as a Skin-Whitening Agent in Adult", "authors_year": "Sitohang & Ninditya 2020", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/32373172/" }, { "title": "Glutathione as a skin whitening agent: Facts, myths, evidence and controversies", "authors_year": "Sonthalia et al. 2016", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/27088927/" } ] }, "fgl-l": { "name": "FGL(L)", "full_name": "FGL Peptide (NCAM-derived FG-Loop Peptide)", "aliases": [ "FGL", "FG-Loop peptide", "FGLL", "NCAM mimetic peptide FGL" ], "categories": [ "nootropics-cognitive" ], "tagline": "A 15-amino-acid fragment of the neural cell adhesion molecule that activates FGFR1 in rodent brains \u2014 real synaptic-plasticity data, zero human trials.", "status": "Unapproved research compound. No FDA/EMA approval, no clinical trials registered in humans as of 2026; all published work is in vitro or in rodent models.", "origin": "FGL is a synthetic 15-amino-acid peptide (sequence EVYVVAENQQGKSKA) corresponding to the second fibronectin type III (F3) module of the neural cell adhesion molecule (NCAM), first described by Cambon et al. (2004). It is not naturally circulating \u2014 it's a lab-designed mimetic of a binding loop within a much larger cell-surface protein.", "mechanism": "FGL binds and activates fibroblast growth factor receptor 1 (FGFR1), the same receptor NCAM engages via heterophilic interaction, without requiring the full NCAM protein. Downstream, this triggers PKC and CaMKII signaling that facilitates synaptic AMPA receptor delivery and NMDA-receptor-dependent long-term potentiation (LTP) in hippocampal neurons, and separately drives neurotrophic and anti-inflammatory effects (suppressing microglial activation via neuronal CD200 upregulation).", "research_summary": "All evidence is preclinical \u2014 cell culture and rodent studies, no human data. In rats, systemic or intracerebroventricular FGL improved spatial and fear-conditioning memory consolidation, facilitated hippocampal LTP in the dentate gyrus, and reduced amyloid-beta-induced CA1 pyramidal cell loss with partial rescue of social recognition memory in an Alzheimer's-relevant lesion model. In vitro, FGL promoted synaptogenesis, enhanced presynaptic function, mobilized neural stem cells, and suppressed neuroinflammatory microglial activation in aged rats. One study also found FGL alone (without amyloid-beta) reduced CA1 pyramidal cell counts by 40%, a caution against assuming benign effects outside disease models.", "reported_benefits": [ "Enhanced spatial learning and memory consolidation (rodent studies)", "Facilitated hippocampal long-term potentiation (LTP)", "Partial protection against amyloid-beta-induced neuronal loss and memory deficits (rodent AD model)", "Anti-inflammatory / anti-microglial activation effects in aged rat brain", "Promoted synaptogenesis and neural stem cell mobilization in vitro" ], "dosing_protocols": [ { "route": "Subcutaneous (rodent research dose)", "protocol": "Published rat studies typically used single or repeated doses in the range of ~1-3 mg/kg systemically; no human dosing data exists. Self-experimentation reports describing human doses are anecdotal extrapolations, not validated protocols." }, { "route": "Intracerebroventricular (research only)", "protocol": "Used exclusively in animal studies (microgram-range local infusion) to demonstrate direct CNS mechanism \u2014 not a route relevant to human self-use." } ], "side_effects": [ "Unknown in humans \u2014 no human safety data exists", "In rats, FGL alone (without pathology present) was associated with a reduction in CA1 pyramidal neuron counts in one study, suggesting effects may not be uniformly beneficial in a healthy brain", "Theoretical concern: FGFR1 agonism is not tissue-restricted to brain \u2014 systemic off-target growth-factor signaling effects are unstudied" ], "safety_notes": "FGL has never been tested in a human clinical trial; everything known comes from rodent behavioral studies and cell culture. The finding that FGL alone reduced CA1 neuron counts in non-lesioned tissue is a real red flag in the literature that self-experimentation communities often omit. Long-term safety, pharmacokinetics, immunogenicity (as a foreign peptide fragment), and optimal dosing are all unknown.", "community_notes": "FGL circulates in nootropic/longevity peptide forums as a theoretical 'NCAM mimetic' for memory enhancement, usually referenced alongside other FGFR-pathway peptides. Discussion tends to lean heavily on the Cambon 2004 and Knafo 2012 papers while glossing over the mixed CA1-neuron finding; actual self-reported use logs are sparse compared to better-established nootropic peptides.", "related": [ "semax", "selank", "cerebrolysin" ], "citations": [ { "title": "A synthetic neural cell adhesion molecule mimetic peptide promotes synaptogenesis, enhances presynaptic function, and facilitates memory consolidation", "authors_year": "Cambon K, Hansen SM, Venero C, et al. (2004)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/15115815/" }, { "title": "A novel anti-inflammatory role of NCAM-derived mimetic peptide, FGL", "authors_year": "Downer EJ, Cowley TR, Lyons A, et al. (2008)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/18468731/" }, { "title": "Amyloid-beta induced CA1 pyramidal cell loss in young adult rats is alleviated by systemic treatment with FGL, a neural cell adhesion molecule-derived mimetic peptide", "authors_year": "Corbett NJ, Gabbott PL, Klementiev B, et al. (2013)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/23951173/" }, { "title": "Facilitation of AMPA receptor synaptic delivery as a molecular mechanism for cognitive enhancement", "authors_year": "Knafo S, Venero C, S\u00e1nchez-Puelles C, et al. (2012)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/22363206/" }, { "title": "The neural cell adhesion molecule-derived peptide FGL facilitates long-term plasticity in the dentate gyrus in vivo", "authors_year": "Dall\u00e9rac G, Zerwas M, Novikova T, et al. (2011)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/21508096/" }, { "title": "The synthetic NCAM mimetic peptide FGL mobilizes neural stem cells in vitro and in vivo", "authors_year": "Klein R, Blaschke S, Neumaier B, et al. (2014)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/24817672/" } ] }, "met-enkephalin": { "name": "Met-Enkephalin", "full_name": "Methionine-Enkephalin (Opioid Growth Factor, OGF)", "aliases": [ "OGF", "[Met5]-enkephalin", "Methionine enkephalin", "Opioid Growth Factor" ], "categories": [ "bioregulators" ], "tagline": "An endogenous five-amino-acid opioid that quietly puts a brake on cell division \u2014 well-studied in oncology and immunology labs, but that's not the same as a validated self-use protocol.", "status": "Endogenous human peptide (naturally produced). Not FDA-approved as a drug in its own right; investigated in early-phase oncology trials as 'OGF' biotherapy and mechanistically tied to low-dose naltrexone (LDN) research, which itself is used off-label.", "origin": "Met-enkephalin (Tyr-Gly-Gly-Phe-Met) is one of the body's native opioid peptides, derived from proteolytic processing of proenkephalin. Beyond its classical role as a weak opioid-receptor ligand, a specific pool of it functions as the 'opioid growth factor' (OGF) \u2014 an autocrine/paracrine signal that acts through a distinct, non-classical receptor (OGFr) to regulate cell replication.", "mechanism": "OGF (Met-enkephalin) binds OGFr and traffics into the cell nucleus, where it upregulates cyclin-dependent kinase inhibitors (p16, p21), delaying the G1/S transition of the cell cycle and slowing proliferation. This is the same axis proposed to underlie low-dose naltrexone's effects: brief opioid receptor blockade triggers compensatory upregulation of OGF and OGFr, amplifying the inhibitory signal once blockade wears off \u2014 a rebound mechanism distinct from naltrexone's classical opioid antagonism.", "research_summary": "Human data is limited mostly to small early-phase oncology trials using OGF as an adjunct biotherapy, plus indirect clinical experience via low-dose naltrexone (which is not the same compound but is mechanistically linked). The bulk of solid evidence is in vitro and in xenograft/animal models: the OGF-OGFr axis has been shown to inhibit proliferation across multiple human cancer cell lines (triple-negative breast, thyroid follicular, pancreatic, ovarian, colorectal, squamous cell), consistently via p16/p21-mediated cell-cycle arrest, and mutations in OGFr found in human tumors can blunt this response. Immune-modulating and wound-healing/homeostatic roles are also documented, chiefly in rodent models. No robust randomized controlled trial has established Met-enkephalin itself as a clinical therapy.", "reported_benefits": [ "Cell-cycle arrest / growth inhibition of cancer cell lines in vitro and in animal xenograft models", "Proposed synergy with chemotherapy agents (e.g., paclitaxel) in preclinical models", "Immune-modulatory and homeostatic signaling implicated in wound healing and autoimmune disease models", "Mechanistic basis cited for low-dose naltrexone's reported effects in autoimmune and oncology self-experimentation contexts" ], "dosing_protocols": [ { "route": "Intravenous (clinical trial context, historical)", "protocol": "Early oncology trials investigated OGF infusions in defined clinical protocols under medical supervision; these are not replicable or safe outside a trial/clinical setting and specific dosing is not something to extrapolate for self-use." }, { "route": "Subcutaneous (self-experimentation reports)", "protocol": "Community-reported use (loosely modeled on published rodent dosing, roughly 0.1-1 mg/kg equivalents scaled down) is speculative and not validated in controlled human studies \u2014 genuine dosing standards do not exist outside supervised trials." } ], "side_effects": [ "Because it interacts with opioid-receptor-adjacent pathways, theoretical risk of interaction with opioid medications or endogenous opioid tone", "Injection-site reactions reported anecdotally", "Unknown long-term effects of exogenous administration outside short clinical trial windows", "Tumor cells with OGFr mutations may not respond as expected, complicating any assumption of predictable growth-inhibitory effect" ], "safety_notes": "Met-enkephalin/OGF has real oncology-research pedigree, but that pedigree is early-phase and mechanistic, not a settled clinical protocol. It should not be conflated with low-dose naltrexone, which is a different molecule with a much larger (though still mostly off-label) human-use footprint. Self-administering a peptide whose only rigorous human data comes from monitored trials is a meaningfully different risk profile than trials themselves.", "community_notes": "In self-experimentation and biohacking circles, Met-enkephalin/OGF is discussed mostly as the 'mechanistic explanation' for why low-dose naltrexone might work in autoimmune and oncology-adjacent contexts, rather than as a peptide people commonly inject directly \u2014 actual first-hand use reports are far rarer than LDN reports themselves.", "related": [ "ll-37", "thymosin-alpha-1", "bpc-157" ], "citations": [ { "title": "The opioid growth factor-opioid growth factor receptor axis: homeostatic regulator of cell proliferation and its implications for health and disease", "authors_year": "McLaughlin PJ, Zagon IS (2012)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/22687282/" }, { "title": "Opioid growth factor - opioid growth factor receptor axis inhibits proliferation of triple negative breast cancer", "authors_year": "Zagon IS, Porterfield NK, McLaughlin PJ (2013)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/23918871/" }, { "title": "Low-dose naltrexone targets the opioid growth factor-opioid growth factor receptor pathway to inhibit cell proliferation: mechanistic evidence from a tissue culture model", "authors_year": "Donahue RN, McLaughlin PJ, Zagon IS (2011)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/21807817/" }, { "title": "Growth inhibition of thyroid follicular cell-derived cancers by the opioid growth factor (OGF) - opioid growth factor receptor (OGFr) axis", "authors_year": "McLaughlin PJ, Zagon IS, Park SS, et al. (2009)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/19835629/" }, { "title": "Mutations in the opioid growth factor receptor in human cancers alter receptor function", "authors_year": "Kren NP, Zagon IS, McLaughlin PJ (2015)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/26005722/" } ] }, "leuphasyl": { "name": "Leuphasyl", "full_name": "Pentapeptide-18", "aliases": [ "Pentapeptide-18", "Leu-DAP", "SNAP-8 alternative", "Enkephalin-analog pentapeptide" ], "categories": [ "anti-aging" ], "tagline": "A stabilized enkephalin fragment marketed as a topical, needle-free alternative to neuromuscular-blocking wrinkle treatments \u2014 the mechanism is plausible, the human wrinkle-reduction evidence is thin.", "status": "Unregulated cosmetic ingredient (not a drug); sold in serums/creams, not injectables. No FDA or EMA drug approval process applies because it isn't marketed as a therapeutic.", "origin": "Leuphasyl is a synthetic pentapeptide (Tyr-D-Ala-Gly-Phe-Leu) derived from the endogenous opioid peptide Leu-enkephalin, with a D-amino acid substitution at position 2 to resist enzymatic degradation and extend stability in topical formulations. It is a cosmetic-industry ingredient, not a pharmaceutical.", "mechanism": "Proposed to act at the neuromuscular junction interface in skin by binding opioid-receptor-like sites and dampening catecholamine and acetylcholine release, theoretically reducing the frequency and force of the micro-contractions in facial muscles that contribute to expression-line formation. This is distinct from Botox's mechanism (SNARE-protein cleavage) and from Argireline's (SNARE-complex assembly inhibition); Leuphasyl is generally pitched as complementary to both.", "research_summary": "Published data are almost entirely in vitro and in silico: molecular docking/dynamics and spectroscopic studies show Leuphasyl binding to inflammation- and matrix-remodeling targets (MMP-13, TGF-\u03b2, TNF-\u03b1 pathways) and formulation studies confirm it is stable and non-cytotoxic to skin cell lines when delivered in lipid nanocarriers. No randomized, placebo-controlled human trial of Leuphasyl alone measuring wrinkle depth has been located on PubMed; manufacturer-reported efficacy claims are not independently peer-reviewed. By contrast, its usual co-formulant Argireline (acetyl hexapeptide-3) does have a small published RCT showing modest anti-wrinkle effects.", "reported_benefits": [ "Reported softening of expression lines (crow's feet, forehead lines) with regular topical use, per manufacturer and formulation literature", "Marketed as a synergistic partner to Argireline for combined 'triple mechanism' wrinkle serums", "Non-injectable, no downtime, compatible with routine skincare layering" ], "dosing_protocols": [ { "route": "topical", "protocol": "Typically formulated at 5-10% of a peptide-complex solution, itself included in a finished serum/cream at low single-digit percentages; applied once or twice daily to clean, dry skin, often in combination products with Argireline and/or Matrixyl-type peptides" } ], "side_effects": [ "Mild irritation or contact sensitivity in a minority of users, as with most concentrated peptide serums", "No systemic side effects reported given negligible dermal penetration at typical topical concentrations" ], "safety_notes": "Cosmetic peptides at these concentrations have a good short-term dermal safety record, but there is no dedicated long-term human safety dataset for Leuphasyl specifically, and efficacy claims rest almost entirely on industry-funded formulation studies rather than independent clinical trials.", "community_notes": "Discussed mainly in skincare/DIY-formulation circles as a budget, non-invasive component of 'peptide facial serums,' almost always stacked with Argireline; users report subtle, gradual softening rather than Botox-like results, and skepticism about marketing claims is common even among enthusiasts.", "related": [ "zinc-thymulin" ], "citations": [ { "title": "Pentapeptide-18 as an anti-aging candidate: Spectroscopic characterization and molecular interaction analysis", "authors_year": "Akhan et al., 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41722287/" }, { "title": "Integrative In Silico and In Vitro Evaluation of Vialox and Leuphasyl Pentapeptides for Antiaging Applications", "authors_year": "Akhan et al., 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42116636/" }, { "title": "Solid Lipid Nanoparticles Incorporated with Retinol and Pentapeptide-18\u2014Optimization, Characterization, and Cosmetic Application", "authors_year": "Paw\u0142owska et al., 2024", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/39337562/" }, { "title": "D-tyrosine adds an anti-melanogenic effect to cosmetic peptides", "authors_year": "Park et al., 2020", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/31937863/" }, { "title": "The anti-wrinkle efficacy of argireline, a synthetic hexapeptide, in Chinese subjects: a randomized, placebo-controlled study", "authors_year": "Wang et al., 2013", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/23417317/" } ] }, "zinc-thymulin": { "name": "Zinc-thymulin", "full_name": "Zinc-bound Thymulin (Zn-FTS, zinc-dependent thymic nonapeptide)", "aliases": [ "Zn-thymulin", "FTS (Facteur Thymique S\u00e9rique)", "Zinc-thymulin nonapeptide" ], "categories": [ "anti-aging" ], "tagline": "A zinc-dependent thymic hormone with real, decades-old immunology behind it, repackaged for topical hair-loss use on evidence that is mostly adjacent, not direct.", "status": "Not an approved drug for hair loss anywhere; sold as a cosmetic/topical ingredient in hair serums. Thymulin itself has a long research history in immunology, unrelated to any hair-specific approval.", "origin": "Thymulin is an endogenous nonapeptide hormone (Glu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn) produced by thymic epithelial cells; it is biologically inactive unless bound to a zinc ion, which is required for receptor binding and immune activity \u2014 hence 'zinc-thymulin.' In topical cosmetics, a synthesized or recombinant zinc-thymulin complex is applied to the scalp on the premise that local immune modulation in hair follicles can influence hair cycling and pigmentation.", "mechanism": "Physiologically, zinc-thymulin regulates T-lymphocyte differentiation and maturation and modulates cytokine expression. The hair-loss rationale extends this to the hair follicle's mini-immune environment: androgenetic alopecia and alopecia areata both involve local immune/inflammatory dysregulation around the follicle bulb, and zinc itself is an established cofactor for hair follicle keratinocyte turnover, so the proposed mechanism is restoring local immune balance and zinc-dependent follicular signaling rather than a direct androgen pathway effect.", "research_summary": "The zinc-thymulin biology (zinc-dependence, T-cell modulation, age-related decline) is well established in PubMed-indexed immunology and aging literature going back to the 1990s-2000s, mostly in the context of thymic involution and autoimmune disease, not hair. Separately, zinc deficiency is independently associated with alopecia areata and implicated as a modifiable factor in non-scarring hair loss in dermatology reviews. No PubMed-indexed clinical trial directly testing a topical zinc-thymulin formulation for androgenetic alopecia or hair pigmentation was found; the hair-specific application appears to be a cosmetic-industry extrapolation from these two separate literatures rather than a studied combination.", "reported_benefits": [ "Claimed reduction in hair shedding and support for hair density in androgenetic alopecia (manufacturer/industry claims, not independently trialed)", "Claimed support for maintaining hair pigmentation, based on zinc's and immune modulation's roles in follicle melanocyte function", "General scalp health support attributed to zinc's role in keratinocyte turnover" ], "dosing_protocols": [ { "route": "topical (scalp serum/solution)", "protocol": "Applied directly to scalp, typically once daily, as part of a hair-serum formulation; concentrations are not standardized across products and no clinical dosing protocol exists in the literature" } ], "side_effects": [ "Local scalp irritation possible with any concentrated topical actives", "No systemic toxicity expected at topical doses; injectable/systemic thymulin (studied in unrelated immunology contexts) is not the same use case as topical scalp application" ], "safety_notes": "The underlying zinc-thymulin biology is legitimate and well-studied, but that evidence base is about systemic immune function and thymic aging, not scalp application \u2014 safety and efficacy for topical hair use has essentially no direct human trial data, so claims should be treated as unproven extrapolation rather than established fact.", "community_notes": "Appears in peptide/hair-loss self-experimentation forums as a niche, 'immune-modulation angle' alternative or add-on to minoxidil/finasteride regimens, usually discussed with acknowledgment that evidence is indirect and results anecdotal; framed more as a plausible mechanism worth trying than a proven treatment.", "related": [ "leuphasyl" ], "citations": [ { "title": "Plasticity of neuroendocrine-thymus interactions during ontogeny and ageing: role of zinc and arginine", "authors_year": "Mocchegiani et al., 2006", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/16904953/" }, { "title": "The Role of Vitamins and Minerals in Hair Loss: A Review", "authors_year": "Almohanna et al., 2018", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/30547302/" }, { "title": "The Role of Micronutrients in Alopecia Areata: A Review", "authors_year": "Thompson et al., 2017", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28508256/" }, { "title": "Altered thymic endocrine activity along with impairments of peripheral zinc metabolism and T-lymphocyte populations are associated with myasthenia gravis: a follow-up study", "authors_year": "Licastro et al., 1997", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/9258245/" } ] }, "slu-pp-332": { "name": "SLU-PP-332", "full_name": "SLU-PP-332 (synthetic pan-ERR agonist)", "aliases": [ "SLU-PP-332", "ERR pan-agonist SLU-PP-332" ], "categories": [ "longevity" ], "tagline": "A rodent-only 'exercise in a pill' compound that genuinely turns on exercise-like gene programs \u2014 but it is a small molecule, not a peptide, and has never been dosed in a human trial.", "status": "Preclinical research chemical only. No human trials registered or published; not approved or reviewed by any regulatory agency for any use. Sold in the gray-market research-chemical space alongside peptides, but it is chemically unrelated to peptides.", "origin": "IMPORTANT: SLU-PP-332 is NOT a peptide, despite being commonly sold and discussed alongside peptide research compounds. It is a synthetic small-molecule drug \u2014 a designed pan-agonist of the three estrogen-related receptor subtypes (ERR\u03b1, ERR\u03b2, ERR\u03b3), orphan nuclear receptors unrelated to estrogen signaling itself. It was developed and first reported by academic pharmacology labs (Washington University in St. Louis / Saint Louis University / University of Florida groups) as a chemical tool to probe ERR biology.", "mechanism": "ERRs are master transcriptional regulators of mitochondrial biogenesis, oxidative phosphorylation, and fatty acid oxidation, and are activated physiologically during aerobic exercise. SLU-PP-332 binds and activates all three ERR subtypes (with highest potency at ERR\u03b1), driving an ERR\u03b1-dependent gene program that mimics acute aerobic exercise \u2014 including induction of Ddit4 and Slc25a25, increased type IIa oxidative muscle fiber content, and enhanced cellular respiration \u2014 without the animal actually exercising.", "research_summary": "All published evidence is preclinical: cell-based assays and mouse studies show SLU-PP-332 increases mitochondrial function and exercise endurance, reduces fat mass, and improves insulin sensitivity in diet-induced-obesity and metabolic syndrome mouse models. A 2026 structure-activity-relationship paper further characterizes its binding and identifies analogues (including the orally bioavailable follow-up compound SLU-PP-915) with improved pharmacokinetics. No human pharmacokinetic, safety, or efficacy data exist; a 2026 doping-control analytical paper characterizes its metabolites specifically because anti-doping labs are watching for illicit human use, which underscores that it is being taken by people despite zero human trials.", "reported_benefits": [ "In mice only: increased treadmill endurance, increased oxidative (type IIa) muscle fiber proportion, and improved aerobic capacity", "In mouse obesity/metabolic syndrome models: reduced fat mass, increased energy expenditure, improved insulin sensitivity", "Proposed (unproven in humans) as a mitochondrial-biogenesis and 'exercise mimetic' strategy for sarcopenia, metabolic disease, and aging-related muscle decline" ], "dosing_protocols": [ { "route": "not established for humans", "protocol": "All published dosing is intraperitoneal or oral administration in mice at research doses (mg/kg); no human dosing protocol exists, and self-administration in humans is unstudied off-label use of a research chemical with unknown human pharmacokinetics" } ], "side_effects": [ "No human safety data exists at all \u2014 side effect profile in humans is unknown", "Mouse studies report no evident toxicity at studied doses, but this does not establish human safety", "Flagged by anti-doping researchers as a potential performance-enhancing substance of concern, implying real-world human use is already occurring ahead of any safety data" ], "safety_notes": "This is the single largest gap in the whole profile: a compound with zero published human trials is being self-administered based on mouse data alone. Long-term effects of chronic ERR pan-activation in humans \u2014 including any off-target effects, since it hits all three ERR subtypes rather than a single isoform \u2014 are completely uncharacterized.", "community_notes": "Discussed in fitness/longevity research-chemical circles as a next-generation 'exercise mimetic,' often mentioned in the same breath as peptide compounds even though it is chemically distinct; self-experimenters extrapolate mouse dosing to humans by body-weight scaling, a practice with no validated basis and no reported pharmacokinetic grounding.", "related": [], "citations": [ { "title": "Synthetic ERR\u03b1/\u03b2/\u03b3 Agonist Induces an ERR\u03b1-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity", "authors_year": "Billon et al., 2023", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/36988910/" }, { "title": "A Synthetic ERR Agonist Alleviates Metabolic Syndrome", "authors_year": "Billon et al., 2024", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/37739806/" }, { "title": "An orally active estrogen receptor-related receptor agonist, SLU-PP-915, enhances aerobic exercise capacity", "authors_year": "Billon et al., 2025", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41421047/" }, { "title": "Chemical optimization of the exercise mimetic SLU-PP-332 enables insight into estrogen-related receptor signaling", "authors_year": "Okda et al., 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41850449/" }, { "title": "[Pharmacological Activation of ERR\u03b1/\u03b2/\u03b3 as an Exercise Mimetic: Potential Therapeutic Applications]", "authors_year": "de Souza-Lima et al., 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42024694/" } ] } }