Melanotan II
Also known as: MT-II, MTII, Barbie drug, tanning jab, melanotan-II
Synthetic cyclic heptapeptide; non-selective melanocortin receptor agonist; alpha-melanocyte-stimulating hormone (α-MSH) analogue
What it is
Melanotan II (MTII) is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone (α-MSH) with the structure Ac-Nle4-Asp5-His6-D-Phe7-Arg8-Trp9-Lys10 α-MSH(4-10)-NH2. It acts as a potent, non-selective agonist at melanocortin receptors (MCRs), including MC1R, MC3R, and MC4R (PMID 13: 31953620, 52: 39296259). At MC1R on melanocytes, it stimulates eumelanin production, resulting in skin pigmentation independent of sun exposure. Via MC4R and MC3R in the central nervous system, it induces spontaneous penile erections and sexual stimulation, modulates energy homeostasis and food intake, promotes oxytocin release from the hypothalamic paraventricular nucleus, and can induce thermogenesis via sympathetic signalling to brown adipose tissue. MTII also activates the hypothalamic-pituitary-adrenal (HPA) axis and induces wakefulness via paraventricular hypothalamic vasopressin neurons projecting to lateral hypothalamic orexin neurons. In vitro and animal data suggest MC1R-mediated upregulation of PTEN and inhibition of COX-2/PGE2 signalling as a potential anti-melanoma mechanism.
Class: Synthetic cyclic heptapeptide; non-selective melanocortin receptor agonist; alpha-melanocyte-stimulating hormone (α-MSH) analogue
What it's studied for
- Skin tanning / melanogenesis Human observational
- Phase I pilot study in 3 normal male volunteers: subcutaneous MTII produced tanning activity (increased pigmentation in face, upper body, and buttock) after 5 low doses every other day. PMID 8637402 Dorr RT et al., Life Sciences (1996)
- Observational survey of online forum users: subcutaneous injection used illicitly to stimulate a tan; widespread unregulated use documented. PMID 30142729 Callaghan DJ, Dermatology Online Journal (2018)
- Qualitative analysis of 623 online discussion entries: motivations included pursuit of a tanned appearance; side effects and concerning practices documented. PMID 34464955 Gilhooley E et al., Dermatology (2021)
- Erectile dysfunction / sexual function enhancement Human RCT
- Double-blind, placebo-controlled crossover study in 10 men with psychogenic ED: 8/10 developed clinically apparent erections with MTII (0.025 mg/kg SC); mean tip rigidity >80% was 38 min vs 3 min placebo (p=0.0045). Side effects: nausea, stretching/yawning, decreased appetite. PMID 9679884 Wessells H et al., Journal of Urology (1998)
- Double-blind, placebo-controlled crossover RCT in 10 men with organic ED risk factors: MTII (0.025 mg/kg SC) initiated erections in 12/19 injections vs 1/21 placebo doses; mean tip rigidity >80% was 45.3 min vs 1.9 min (p=0.047). Increased sexual desire also reported. 4/19 injections associated with severe nausea. PMID 11018622 Wessells H et al., Urology (2000)
- Double-blind, placebo-controlled crossover study in 20 men with psychogenic and organic ED: penile erection in 17/20 men without sexual stimulation; 41 min mean tip rigidity >80%. Increased sexual desire in 68% vs 19% placebo. Nausea and yawning frequent; severe nausea in 12.9% at 0.025 mg/kg. PMID 11035391 Wessells H et al., International Journal of Impotence Research (2000)
- Review documenting that MTII enhanced erectile activity in human males and increased sexual desire and genital arousal in females; described as acting centrally at the level of the brain. PMID 15996790 Hadley ME, Peptides (2005)
- Obesity / energy homeostasis (MC4R pathway) Animal studies only
- Systematic review: almost all MC4R agonist studies (including MTII) are in preclinical phase; no effective clinical treatments for MC4R-deficient obese patients yet established. PMID 23774329 Fani L et al., International Journal of Obesity (2014)
- Rat study: third-cerebroventricular MTII caused comparable anorexigenic effects and ACTH/corticosterone elevation to leptin; anorexigenic efficacy of MTII was not predictive of diet-induced obesity. PMID 16422967 van Dijk G et al., Endocrinology (2005)
- Rat study: chronic intra-CeA MTII injection reduced body mass and food intake over seven days with slight decrease in AMPKThr172. PMID 38815086 Castro G et al., Molecular and Cellular Endocrinology (2024)
- Mouse model: MTII (MC4R agonist) effectively suppressed feeding and weight gain in Htr2cF327L/Y mice on high-fat diet. PMID 38604549 Liu H et al., Endocrinology (2024)
- Autism spectrum disorder / social deficits Animal studies only
- Prairie vole study: MTII administered prior to social interactions selectively increased oxytocin-dependent nucleus accumbens activation during social context, and accelerated partner preference formation. Proposed mechanism for facilitating social learning. PMID 38253222 Ford CL et al., Neuropharmacology (2024)
- Zebrafish bioassay: MTII showed higher melanophore dispersion than human α-MSH; consistent with effectiveness in ASD mouse model for improving social deficits. PMID 34502223 Hong TI et al., International Journal of Molecular Sciences (2021)
- Depression / antidepressant-like effects Animal studies only
- Chronic unpredictable stress (CUS) rat model: daily intraperitoneal MTII (60 nmol/kg) reversed CUS-induced anhedonia, attenuated body weight suppression, adrenal hypertrophy, and decreased hippocampal BDNF levels. PMID 39442746 Inozemtseva LS et al., European Journal of Pharmacology (2024)
- Thermogenesis / brown adipose tissue activation Animal studies only
- Mouse study: daily peripheral MTII injections for 3 weeks during cold acclimation partially rescued impaired thermogenic capacity in PACAP-deficient mice and corrected lipid utilization deficit in response to adrenergic stimulation. PMID 33332767 McMillan TR et al., Experimental Physiology (2021)
- Review: fourth ventricular injections of MTII (MC3/4R agonist) triggered IBAT UCP-1 gene expression in chronic decerebration procedure, suggesting hindbrain circuitry sufficient for thermogenic responses. PMID 20935665 Bartness TJ et al., International Journal of Obesity (2010)
- Melanoma suppression (topical / experimental) In vitro only
- B16-F10 melanoma model in vitro and in vivo (mice): topical MTII inhibited migration, invasion, colony-forming capability, and tumor progression; induced apoptosis; upregulated PTEN and inhibited AKT/NFκB and COX-2/PGE2 via MC1R. PMID 31968661 Wu JC et al., International Journal of Molecular Sciences (2020)
- Drug delivery vehicle / ligand-drug conjugate for melanoma targeting In vitro only
- In vitro: camptothecin-MTII conjugate inhibited A375 melanoma cell growth (IC50 16 nM) via MC1R-mediated selective drug delivery; MTII moiety retained strong MC1R binding. PMID 33073191 Zhou Y et al., ACS Pharmacology & Translational Science (2020)
- Memory impairment reversal (high-fat diet model) Animal studies only
- Zebrafish study: MTII reversed HF diet-induced recognition memory impairment, elevated anxiety, and reduced exploratory behavior. PMID 37478579 Wekwejt P et al., Biomedicine & Pharmacotherapy (2023)
Community-reported dosing
| Route | Dose | Frequency / Duration | Population / context | Source tier |
|---|---|---|---|---|
| Subcutaneous injection | 0.01 mg/kg starting dose, escalated by 0.005 mg/kg increments to 0.025–0.03 mg/kg; recommended Phase I dose 0.025 mg/kg/day | 5 doses over 2 weeks (Monday–Friday, alternating saline/MT-II) | human | Research PMID 8637402 |
| Subcutaneous injection | 0.025 mg/kg | Single dose (crossover; each arm administered twice) | human | Research PMID 9679884 |
| Subcutaneous injection | 0.025 mg/kg | Single dose (crossover; each condition administered twice) | human | Research PMID 11018622 |
| Subcutaneous injection | 0.025 mg/kg | Single dose (crossover design) | human | Research PMID 11035391 |
| Subcutaneous injection | 6 mg (self-reported; described as six times the recommended starting dose per the patient) | Single self-administration | human | Research PMID 23121206 |
| Intraperitoneal injection | 60 nmol/kg of body weight daily | Duration of chronic unpredictable stress protocol (not specified exactly beyond chronic treatment) | animal | Research PMID 39442746 |
| Peripheral injection (route not further specified) | Not specified numerically (described as daily peripheral injections) | 3 weeks | animal | Research PMID 33332767 |
| Intra-nucleus accumbens microinjection | 0.1, 0.3, and 1 nmol (bilateral microinjection, 100 nl/side) | Single injection per experiment | animal | Research PMID 56: 36155088 |
| Third-cerebroventricular | Equi-anorexigenic doses (exact amount not specified in abstract) | Single injection | animal | Research PMID 16422967 |
| Intra-CeA (central nucleus of the amygdala) injection | Not specified numerically | Not specified numerically beyond chronic administration | animal | Research PMID 38815086 |
| subcutaneous injection | 0.25 mg | daily | first-time users, fair-skinned individuals (Fitzpatrick I-II) seeking tanning | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 0.5 mg | daily | general biohacker/tanning community, Fitzpatrick I-III skin types | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 1 mg | daily | experienced MT-II users, Fitzpatrick III-IV skin types, or those with blunted response at lower doses | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 0.5-1 mg | 2-3x per week (maintenance) | users who have completed a loading phase and achieved desired tan | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 0.025 mg | daily, titrated up by 0.025 mg every few days | highly nausea-sensitive users, Fitzpatrick type I ('Barbie drug' community on Reddit) | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| intranasal (nasal spray) | 0.5 mg | daily or as needed | users seeking needle-free administration; common in UK/European tanning communities | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 0.5-1 mg | 1x per week | fully saturated, well-tanned users seeking minimal-dose preservation | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 0.1 mg | daily | cautious first-time users; often recommended by veteran community members to newcomers | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 0.5 mg | 30-60 minutes before sexual activity (on-demand dosing) | men using MT-II for erectile dysfunction or libido enhancement | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 0.25 mg | on-demand, 30-60 minutes before sexual activity | men using MT-II for erectile dysfunction who are sensitive to side effects | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
| subcutaneous injection | 0.5 mg | daily | bodybuilders and fitness community users combining tanning with physique goals pre-competition | [S] Claude Sonnet 4.6 — synthesized from aggregate training data |
Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.
Safety signals
- Sympathomimetic toxicity (tachycardia up to 146 bpm, hypertension, diaphoresis, mydriasis, anxiety, diffuse muscle tremors) after subcutaneous self-injection PMID 23121206
- Rhabdomyolysis (peak CPK 17,773 IU/L) and acute renal dysfunction (creatinine 2.25 mg/dL) after subcutaneous self-injection of 6 mg PMID 23121206
- Acute ischemic priapism requiring cavernosal aspiration, intracavernous phenylephrine, and operative (penoscrotal) decompression PMID 33460908
- Acute low-flow priapism managed with cavernosal aspiration and intracavernosal phenylephrine; incomplete erectile function recovery at 4-week follow-up PMID 30796078
- Eruptive new melanocytic nevi (including atypical/dysplastic features) and darkening of pre-existing nevi reported within days to weeks of use PMID 19380666
- Atypical melanocytic naevi appearing within one week of two Melanotan injections PMID 23914578
- Eruptive nevi and darkening of pre-existing naevi 24 hours after a single subcutaneous injection PMID 24334249
- Dermoscopic changes in melanocytic nevi during use making differentiation from melanoma difficult PMID 23052015
- Melanoma (cutaneous) reported in a 20-year-old female after 3–4 week course of self-injections combined with sunbed use PMID 24355990
- Melanoma in situ associated with injectable melanotropic peptide use PMID 22724573
- Melanotan-associated melanoma (case report) PMID 21564053
- Mucosal malignant melanoma of the anterior maxilla in a 22-year-old female who used Melanotan II nasal spray for tanning PMID 40210573
- Oral/gingival mucosal brown pigmentation after self-injection; gingival pigmentation persisted at 3-month follow-up PMID 41752902
- Renal infarction possibly attributed to Melanotan II; thrombotic and direct toxic renal effects considered PMID 31953620
- Sympathomimetic symptoms (treated with lorazepam, supplemental potassium, and IV fluid resuscitation) after subcutaneous self-administration PMID 35736369
- Nausea (including severe nausea in 12.9% at 0.025 mg/kg dose) and stretching/yawning complex in clinical trials PMID 11035391
- Grade II somnolence and fatigue at 0.03 mg/kg dose in Phase I study PMID 8637402
- Risk of product contamination, manufacturing impurities, wrong active ingredient, or incorrect dosage in illicitly sourced preparations; purity as low as 30% documented in forensic analysis PMID 39302005
- Risk of infectious disease transmission due to unregulated injection practices; polypharmacy and sunbed co-exposure noted in forum-based qualitative study PMID 34464955
- Supports development of new pigmented and dysplastic naevi per previous research cited in case report PMID 35736369
Contraindications
- History of melanoma or multiple dysplastic nevi: synthetic α-MSH peptides can drive proliferation of neoplastic melanocytic cells in predisposed patients, presenting increased risk of melanoma development PMID 19380666
- General contraindication for use in any individual given unregulated, unlicensed status; lack of established human safety profile and association with severe adverse events including rhabdomyolysis, renal infarction, and malignant melanoma PMID 42757290
References
- [1] PMID 8637402 — Phase I pilot study in 3 normal male volunteers: subcutaneous MTII produced tanning activity (increased pigmentation in face, upper body, and buttock) after 5 l
- [2] PMID 30142729 — Observational survey of online forum users: subcutaneous injection used illicitly to stimulate a tan; widespread unregulated use documented.
- [3] PMID 34464955 — Qualitative analysis of 623 online discussion entries: motivations included pursuit of a tanned appearance; side effects and concerning practices documented.
- [4] PMID 9679884 — Double-blind, placebo-controlled crossover study in 10 men with psychogenic ED: 8/10 developed clinically apparent erections with MTII (0.025 mg/kg SC); mean ti
- [5] PMID 11018622 — Double-blind, placebo-controlled crossover RCT in 10 men with organic ED risk factors: MTII (0.025 mg/kg SC) initiated erections in 12/19 injections vs 1/21 pla
- [6] PMID 11035391 — Double-blind, placebo-controlled crossover study in 20 men with psychogenic and organic ED: penile erection in 17/20 men without sexual stimulation; 41 min mean
- [7] PMID 15996790 — Review documenting that MTII enhanced erectile activity in human males and increased sexual desire and genital arousal in females; described as acting centrally
- [8] PMID 23774329 — Systematic review: almost all MC4R agonist studies (including MTII) are in preclinical phase; no effective clinical treatments for MC4R-deficient obese patients
- [9] PMID 16422967 — Rat study: third-cerebroventricular MTII caused comparable anorexigenic effects and ACTH/corticosterone elevation to leptin; anorexigenic efficacy of MTII was n
- [10] PMID 38815086 — Rat study: chronic intra-CeA MTII injection reduced body mass and food intake over seven days with slight decrease in AMPKThr172.
- [11] PMID 38604549 — Mouse model: MTII (MC4R agonist) effectively suppressed feeding and weight gain in Htr2cF327L/Y mice on high-fat diet.
- [12] PMID 38253222 — Prairie vole study: MTII administered prior to social interactions selectively increased oxytocin-dependent nucleus accumbens activation during social context,
- [13] PMID 34502223 — Zebrafish bioassay: MTII showed higher melanophore dispersion than human α-MSH; consistent with effectiveness in ASD mouse model for improving social deficits.
- [14] PMID 39442746 — Chronic unpredictable stress (CUS) rat model: daily intraperitoneal MTII (60 nmol/kg) reversed CUS-induced anhedonia, attenuated body weight suppression, adrena
- [15] PMID 33332767 — Mouse study: daily peripheral MTII injections for 3 weeks during cold acclimation partially rescued impaired thermogenic capacity in PACAP-deficient mice and co
- [16] PMID 20935665 — Review: fourth ventricular injections of MTII (MC3/4R agonist) triggered IBAT UCP-1 gene expression in chronic decerebration procedure, suggesting hindbrain cir
- [17] PMID 31968661 — B16-F10 melanoma model in vitro and in vivo (mice): topical MTII inhibited migration, invasion, colony-forming capability, and tumor progression; induced apopto
- [18] PMID 33073191 — In vitro: camptothecin-MTII conjugate inhibited A375 melanoma cell growth (IC50 16 nM) via MC1R-mediated selective drug delivery; MTII moiety retained strong MC
- [19] PMID 37478579 — Zebrafish study: MTII reversed HF diet-induced recognition memory impairment, elevated anxiety, and reduced exploratory behavior.
- [20] PMID 23121206 — 6 mg (self-reported; described as six times the recommended starting dose per the patient) Subcutaneous injection (human)
- [21] PMID 33460908 — Acute ischemic priapism requiring cavernosal aspiration, intracavernous phenylephrine, and operative (penoscrotal) decompression
- [22] PMID 30796078 — Acute low-flow priapism managed with cavernosal aspiration and intracavernosal phenylephrine; incomplete erectile function recovery at 4-week follow-up
- [23] PMID 19380666 — Eruptive new melanocytic nevi (including atypical/dysplastic features) and darkening of pre-existing nevi reported within days to weeks of use
- [24] PMID 23914578 — Atypical melanocytic naevi appearing within one week of two Melanotan injections
- [25] PMID 24334249 — Eruptive nevi and darkening of pre-existing naevi 24 hours after a single subcutaneous injection
- [26] PMID 23052015 — Dermoscopic changes in melanocytic nevi during use making differentiation from melanoma difficult
- [27] PMID 24355990 — Melanoma (cutaneous) reported in a 20-year-old female after 3–4 week course of self-injections combined with sunbed use
- [28] PMID 22724573 — Melanoma in situ associated with injectable melanotropic peptide use
- [29] PMID 21564053 — Melanotan-associated melanoma (case report)
- [30] PMID 40210573 — Mucosal malignant melanoma of the anterior maxilla in a 22-year-old female who used Melanotan II nasal spray for tanning
- [31] PMID 41752902 — Oral/gingival mucosal brown pigmentation after self-injection; gingival pigmentation persisted at 3-month follow-up
- [32] PMID 31953620 — Renal infarction possibly attributed to Melanotan II; thrombotic and direct toxic renal effects considered
- [33] PMID 35736369 — Sympathomimetic symptoms (treated with lorazepam, supplemental potassium, and IV fluid resuscitation) after subcutaneous self-administration
- [34] PMID 39302005 — Risk of product contamination, manufacturing impurities, wrong active ingredient, or incorrect dosage in illicitly sourced preparations; purity as low as 30% do
- [35] PMID 42757290 — General contraindication for use in any individual given unregulated, unlicensed status; lack of established human safety profile and association with severe ad
- [36] PMID 13 — in-prose reference
- [37] PMID 36155088 — in-prose reference
- [38] PMID 35907397 — in-prose reference
- [39] PMID 21 — in-prose reference