Research in plain language

Melanotan-2

What it is

Melanotan-2 (MT-2) is a synthetic cyclic analogue of the body's own alpha-melanocyte-stimulating hormone (alpha-MSH). It binds melanocortin receptors and was studied mainly for three things: darkening the skin (pigmentation), triggering penile erections, and reducing appetite/food intake in animals. It is not an approved medicine, and most human data come from very small early-phase studies plus case reports of harm.

How studies used it

Model: Human, 3 healthy adult men
Studied for: Skin pigmentation (tanning), Phase I safety/dose-finding
Dose: 0.01 mg/kg starting, escalated to 0.025-0.03 mg/kg. Already reported per kilogram by the authors, so no weight conversion is needed.
Dosing: Once daily on weekdays (Monday to Friday), alternating with saline placebo
Route: subcutaneous
Duration: 2 consecutive weeks of dosing

Effects measured: Two of the three subjects developed increased pigmentation in the face, upper body and buttock, measured by reflectance and visual assessment one week after treatment. The authors suggested 0.025 mg/kg/day for follow-up studies.

Side effects: Mild nausea at most dose levels (no antiemetics needed), grade II somnolence and fatigue in one subject at 0.03 mg/kg, plus a stretching-and-yawning complex with spontaneous penile erections lasting 1 to 5 hours after injection.

Sources: Dorr RT, et al. Life Sci. 1996 (Phase I pilot, MT-II pigmentation)

Model: Human, 10 men with organic erectile dysfunction
Studied for: Erectile dysfunction / penile erection and sexual desire
Dose: 0.025 mg/kg. Already reported per kilogram by the authors, so no weight conversion is needed.
Dosing: Two active injections and two placebo injections per man, in randomised order (crossover)
Route: subcutaneous
Duration: Single-dose sessions with 6 hours of RigiScan monitoring per injection

Effects measured: Subjectively reported erections occurred after 12 of 19 active injections versus 1 of 21 placebo doses. Mean rigidity score among responders was 6.9 out of 10. Mean duration of tip rigidity over 80 percent was 45.3 minutes with MT-2 versus 1.9 minutes with placebo (P = 0.047). Sexual desire was significantly higher after active drug.

Side effects: Nausea and a stretching/yawning response were more frequent with MT-2 than placebo; 4 of 19 active injections caused severe nausea.

Sources: Wessells H, et al. Urology. 2000 (MT-II, organic ED, crossover)

Model: Human, 20 men with erectile dysfunction (psychogenic and organic)
Studied for: Erectile dysfunction / penile erection and sexual motivation
Dose: 0.025 mg/kg. Already reported per kilogram by the authors, so no weight conversion is needed.
Dosing: Active and placebo doses per man in randomised order (crossover)
Route: subcutaneous (systemic)
Duration: Single-dose sessions with 6 hours of RigiScan penile-rigidity monitoring

Effects measured: Without any sexual stimulation, erection occurred in 17 of 20 men. Mean tip rigidity stayed above 80 percent for about 41 minutes. Increased sexual desire was reported after 13 of 19 (68 percent) MT-2 doses versus 4 of 21 (19 percent) placebo doses (P < 0.01).

Side effects: Nausea and yawning were frequently reported. Severe nausea occurred in about 12.9 percent of subjects at the 0.025 mg/kg dose.

Sources: Wessells H, et al. Int J Impot Res. 2000 (MT-II, ED, RigiScan)

Model: Rat (Sprague-Dawley)
Studied for: Appetite / feeding, plus drinking, body temperature and activity
Dose: 0.05 to 500 ng TOTAL per injection, delivered directly into the brain (third ventricle). This is a central nanogram dose, NOT a per-kilogram body-weight dose, and cannot be converted to mg/kg.
Dosing: Single intracerebroventricular injections per test, given before the nocturnal feeding period
Route: intracerebroventricular (third ventricle)
Duration: Acute, overnight observation per dose

Effects measured: A low central dose (0.05 ng) reduced overnight food intake without changing body temperature, drinking or activity. Higher central doses (50 ng and above) reduced feeding but also raised body temperature and altered drinking behaviour, which the authors flagged as possibly non-specific.

Side effects: Hyperthermia and disrupted drinking patterns at the higher central doses. No human-style adverse-event monitoring applies in this animal model.

Sources: Murphy B, et al. J Appl Physiol. 2000 (central MTII, feeding/temperature in rats)

Model: Human, single case (39-year-old man)
Studied for: Cosmetic tanning use leading to acute systemic toxicity (safety/harm report)
Dose: 6 mg injected as a single dose, described as six times the recommended starting dose. Weight was not reported; at a typical 70 to 90 kg adult man this is roughly 0.07 to 0.09 mg/kg, but the actual body weight was not given, so treat this conversion as an estimate only.
Dosing: Single self-administered injection
Route: subcutaneous
Duration: Acute presentation within about 2 hours, then roughly 3 days in intensive care

Effects measured: Sympathomimetic picture: diffuse body aches, sweating, anxiety, elevated blood pressure (151/85 mmHg) and tachycardia (heart rate 130 to 146 bpm), with mydriasis and tremor.

Side effects: Rhabdomyolysis (creatine kinase peaked at 17,773 IU/L), acute kidney injury (creatinine 2.25 mg/dL), elevated troponin (0.23 ng/mL). Managed with benzodiazepines, IV fluids and sodium bicarbonate; recovered over about 3 ICU days.

Sources: Nelson ME, et al. Clin Toxicol (Phila). 2012 (MT-II, rhabdomyolysis and AKI case)

Model: Human, single case report
Studied for: Skin/mole changes after melanotan II use (safety/harm report)
Dose: A single mono-dose injection of melanotan II; the exact milligram amount and body weight were not given in the abstract, so no mg/kg figure can be calculated.
Dosing: Single injection
Route: injection (route not specified beyond injectable use)
Duration: Effects observed within 24 hours

Effects measured: Eruptive (newly appearing) naevi and darkening of pre-existing naevi were seen 24 hours after one injection.

Side effects: The naevi changes themselves are the adverse event. Sudden eruption and darkening of moles is concerning because it complicates monitoring for skin cancer.

Sources: Schulze F, et al. Eur J Dermatol. 2014 (eruptive/darkening naevi after single MT-II dose)

How solid the evidence is

Honest picture: the evidence base for Melanotan-2 is thin and old. The only human efficacy data come from tiny early-phase studies run largely by the same Arizona group that helped develop the peptide (a clear sponsorship/conflict consideration): a 3-man Phase I pigmentation pilot (PMID 8637402) and two small erectile-dysfunction crossover studies of 10 and 20 men (PMIDs 11018622, 11035391). These reported per-kilogram doses around 0.01 to 0.03 mg/kg and showed measurable pigmentation and erection signals, but the numbers are small, short-term, and not designed to establish safety. The appetite/feeding data (PMID 10904062) are from rats and used central brain (intracerebroventricular) nanogram doses that are NOT comparable to a per-kilogram injected human dose, so they say nothing about human dosing. There is NO established, validated human dosing protocol for Melanotan-2; it is an unlicensed compound. The safety side is dominated by case reports of real harm: systemic sympathomimetic toxicity with rhabdomyolysis and acute kidney injury after a 6 mg dose (PMID 23121206), sudden eruption and darkening of moles within 24 hours (PMID 24334249), and several reports of melanoma and melanoma in situ associated with use (PMIDs 21564053, 22724573). Common adverse effects even at study doses include nausea (sometimes severe), yawning/stretching, spontaneous erections, and blood-pressure/heart-rate changes. Bottom line: weak, dated, small-sample human efficacy evidence, animal-only appetite data, no proven safe protocol, and documented serious harms. This is research-only information, not medical guidance.

Sources

Study data, research use only. No established human dosing protocol.