Human trials and experiments involving Melanotan 2

Early Phase I healthy volunteer study

The first human exposure to Melanotan 2 came from a small Phase I pilot study involving three healthy male volunteers. MT-2 was administered via subcutaneous injection, with doses gradually increased from 0.01 mg per kg up to approximately 0.03 mg per kg over a two-week period.

Side effects were generally mild. Nausea was the most commonly reported issue, and one participant experienced fatigue or somnolence at higher doses. One notable observation was a recurring stretching and yawning response that appeared alongside spontaneous penile erections. These erections occurred without sexual stimulation and lasted intermittently from one to five hours depending on dose.

Although the study was extremely small, it clearly demonstrated that Melanotan 2 was biologically active in humans, producing systemic effects that extended well beyond skin pigmentation alone.

Dermatological and tanning effects observed in early trials

Alongside these neurological and sexual effects, researchers observed clear changes in skin pigmentation. Melanotan 2 activates melanocortin-1 receptors (MC1R) in melanocytes, stimulating melanin production in the skin.

Participants developed gradual, diffuse skin darkening over days to weeks, even in the absence of ultraviolet exposure. This pigmentation was not limited to sun-exposed areas and often appeared more uniform than a traditional UV-induced tan. Freckling and darkening of existing moles were also noted, reflecting increased melanocyte activity rather than UV damage.

Importantly, this tanning effect was considered the primary intended outcome of early MT-2 research. The compound was originally developed as a potential photoprotective agent, with the idea that increased melanin could reduce UV-induced skin damage and lower skin cancer risk. The sexual and neurological effects were unexpected findings that emerged during human testing.

Study in men with psychogenic erectile dysfunction

A later double-blind, placebo-controlled crossover study evaluated MT-2 in ten men with erectile dysfunction believed to be psychogenic rather than physical in origin.

Eight out of ten participants experienced clinically observable erections following Melanotan 2 injections, compared with very few during placebo sessions. Mean duration of strong tip rigidity exceeded 38 minutes with MT-2, compared with around 3 minutes under placebo.

Side effects were more common with MT-2 and included nausea, yawning or stretching, and decreased appetite. Skin pigmentation changes were not the focus of this study, but ongoing darkening was still noted in participants receiving repeated doses. Researchers concluded that MT-2 could initiate erections even in the absence of erotic stimulation.

Study in men with organic erectile dysfunction

Another double-blind, placebo-controlled crossover trial examined men with erectile dysfunction linked to physical causes.

Erections occurred in 12 of 19 MT-2 injections, compared with just 1 of 21 placebo injections. Among responders, average duration of strong tip rigidity was approximately 45 minutes with MT-2 versus under 2 minutes with placebo. Self-reported sexual desire was also significantly higher after MT-2 administration.

Side effects remained frequent, particularly nausea and yawning or stretching. In around 21 percent of injections, nausea was described as severe. As with earlier studies, progressive skin darkening was observed over time, reinforcing MT-2’s strong melanogenic activity.

Larger mixed erectile dysfunction analysis

A later review-style publication summarised data from a combined trial involving 20 men with either psychogenic or organic erectile dysfunction, using a double-blind, placebo-controlled crossover design.

Seventeen out of 20 participants developed erections following MT-2 injections without sexual stimulation. Mean duration of strong tip rigidity was approximately 41 minutes. Increased sexual desire was reported after 68 percent of MT-2 doses, compared with 19 percent of placebo doses.

Skin pigmentation changes were again reported as cumulative rather than immediate, developing gradually with repeated dosing. At the commonly used dose of 0.025 mg per kg, side effects remained a concern, with nausea and yawning common and severe nausea reported in about 12.9 percent of participants.

Understanding the tanning effect more fully

Melanotan 2 produces tanning by mimicking alpha-melanocyte-stimulating hormone (α-MSH), which signals melanocytes to increase melanin synthesis. Unlike UV-induced tanning, this process does not rely on DNA damage to trigger pigmentation, which initially made MT-2 attractive as a potential photoprotective agent.

However, the increased activity of melanocytes also raised concerns. Darkening of moles and the appearance of new pigmented lesions were observed, prompting questions about long-term melanoma risk. While no large trials were conducted to fully evaluate safety, these observations contributed to growing caution around clinical development.

What these studies show, and their limits

Across multiple small human studies, Melanotan 2 consistently demonstrated strong biological activity. It reliably induced skin pigmentation, often without UV exposure, and unexpectedly produced effects on sexual function and desire through central nervous system pathways.

At the same time, the evidence base remains limited. Sample sizes were small, dosing protocols were experimental, and side effects such as nausea, yawning, fatigue, and pigmentation changes were common.

The result is a compound with clearly demonstrated effects in humans, but one that never progressed far enough through formal clinical development to answer the most important questions.