Melanotan Side Effects | What Researchers Must Know

Scientists interested in peptide research may wonder about the potential melanotan side effects to consider before including melanotan in their studies.

Melanotan is actually a collective term for the peptides melanotan 1 (MT-I) and melanotan 2 (MT-II), which are under active investigation for their potential to:

• Increase skin tone and UV-tolerance
• Improve sex drive and erections
• Facilitate weight loss

Both compounds have specific side effects and safety considerations of which researchers must be aware before incorporating either into their experiments.

In this comprehensive guide, we will break down the latest clinical data on adverse events observed in MT-I and MT-II trials and share details regarding each peptide's benefits, mechanisms, and dosage.

Ultimately, we will also share information about our most trusted vendors of MT-I and MT-II.

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What is Melanotan?

Melanotan 1 (MT-I) and melanotan II (MT-II) are modified versions of alpha-melanocyte-stimulating hormone (α-MSH or alpha-MSH). Alpha-MSH is a 13 amino acid peptide produced in the human body to regulate melanin (skin pigment) synthesis [1].

The hormone also plays a role in sexual desire, energy homeostasis, and appetite. These actions occur thanks to alpha-MSH’s affinity to melanocortin receptors (MCRs) in different tissues [1].

MT-I and MT-II have various modifications compared to α-MSH, affecting their affinity to the various MCRs and, thus, their potential effects. Further, the two compounds have been researched in different contexts and conditions [2].

Here is what researchers should know about melanotan 1:

• MT-I (aka afamelanotide) is a peptide made of 13 amino acids, similar to α-MSH. However, melanotan 1 has improved affinity to the melanocortin receptor in melanocytes due to its modifications [3].
• The peptide is also known as [Nle4, D-Phe7]-α-MSH due to its specific modifications, which include the replacement of methionine with norleucine at the fourth position and the substitution of L-phenylalanine with D-phenylalanine at the seventh position [3].

MT-II has additional modifications compared to MT-I, which broaden its receptor affinity and therapeutic spectrum. Here are the most notable facts about its structure:

• MT-II is a cyclic peptide made of seven amino acids, of which only four are retained from its precursor, MT-I. The peptide’s cyclic structure is due to the formation of a lactam bridge, made through a linkage between the side-chain carboxyl group of the aspartic acid situated at the second position and the side-chain amino group of the lysine residue at the seventh position [4].
• The structure of MT-II enhances its affinity to multiple MCRs, broadening its therapeutic potential [4].

MT-I is available under the brand name Scenesse for therapy in a rare skin condition called erythropoietic protoporphyria (EPP). To this end, the peptide is administered as a slow-release implant under the skin [5].

In addition, MT-I and MT-II are available as research peptides for subcutaneous administration. Although MT-II is not approved for human use, it is under active research for potential uses in skin tanning and sexual health [6, 7].

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What Does Melanotan Do?

MT-I and MT-II have several observed effects, including [4, 6, 7, 8]:

• Increasing melanin synthesis and tanning
• Increasing sex drive
• Reducing appetite
• Interacting with brain signaling

The above effects are exerted via the following five melanocortin receptors:

• Melanocortin 1 receptors (MC1Rs) are found in the skin, specifically in the melanin-producing cells called melanocytes. This receptor type is activated by both MT-I and MT-II; therefore, both peptides can lead to increased skin pigmentation and tanning [1, 9, 10].
• Melanocortin 2 receptors (MC2Rs) are found in the cortex of the adrenal glands and trigger the production of cortisol by these glands. Neither MT-I nor MT-II are believed to activate this receptor type [1, 10].
• Melanocortin 3 receptors (MC3Rs) are present in the brain and suggested to regulate appetite levels, metabolism, and energy homeostasis. Both MT-I and MT-II appear to activate this receptor type, with MT-II appearing to be a much more potent activator [1, 10, 11].
• Melanocortin 4 receptors (MC4Rs) are also found in the brain and play a role in appetite regulation. These receptors also upregulate sex drive in both males and females and help increase erections in men. MT-I may also have some affinity to this receptor, but MT-II is a potent activator that can significantly increase libido/erections [1, 10, 11].
• Melanocortin 5 receptors (MC5Rs) are known to exist but their exact function is unknown. MC5Rs are expressed in multiple tissues, and both MT-I and MT-II appear to have some affinity towards them [1, 10].

Thanks to its increased affinity to MC1Rs, MT-I can increase melanin levels and reduce the damaging effects of ultraviolet (UV) light and sunlight in conditions related to photosensitivity. The peptide is approved for reducing pain and photosensitivity in EPP by the United States Food and Drug Administration (FDA) [12].

Patients with EPP have increased sensitivity to ultraviolet (UV) light due to the buildup of a compound called protoporphyrin IX in the skin and blood. Protoporphyrin IX is photosensitive and damages the tissues when exposed to UV light. By increasing melanin levels in the skin, MT-I creates a natural shield that absorbs UV light before it reaches protoporphyrin IX [13].

On the other hand, MT-II has gained attention primarily for its ability to activate MC4Rs and increase sexual desire. The peptide has been shown to significantly increase the frequency and duration of erection in men [11].

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Melanotan Side Effects and Safety

MT-I and MT-II appear to have favorable safety profiles with a low risk of adverse reactions. Yet, there are certain differences between the two peptides' safety profiles; hence, we will discuss each separately below.

Melanotan 1 Side Effect

Based on the results of phase-3 clinical trials, MT-I is well tolerated with a low risk of side effects. Here are the most commonly reported adverse events from melanotan 1 trials:

• Implant site reaction – 21%
• Nausea – 19%
• Oropharyngeal pain – 7%
• Cough – 6%
• Fatigue – 6%
• Skin hyperpigmentation – 4%
• Dizziness – 4%
• Moles (Melanocytic nevus) – 4%
• Respiratory tract infection – 4%
• Somnolence – 2%
• Non-acute porphyria – 2%
• Skin irritation – 2%

New moles were also twice as common in the treatment group compared to controls [5].

Melanotan 2 Side Effects

Studies on melanotan 2 are considerably smaller, with a notable review by Wessells et al. reporting on two studies with 80 male subjects. Based on this publication, the most commonly reported side effects of melanotan 2 were nausea and stretching/yawning [7].

A total of 41% of the study volunteers had nausea, which varied in severity:

• Mild: 21%
• Moderate: 3%
• Severe: 15%

Further, about 56% of the study volunteers complained of stretching and yawning, which also varied in severity:

• Mild: 36%
• Moderate: 13%
• Severe: 8%

Other recorded side effects included in this review were flushing, increased or decreased appetite, and drowsiness. None occurred significantly more often with MT-II compared to placebo [7, 14].

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Is Melanotan Safe?

Data on melanotan safety vary significantly, depending on whether they relate to MT-I or MT-II.

For instance, the clinical data on MT-I include 8+ month long trials (one implant every two months, with a total of five implants received), reporting a favorable safety profile and no significant side effects, even after 180-270 days of follow-up [5].

On the other hand, the safety of melanotan 2 has been studied only in the short term. Based on the available data, the peptide is well tolerated in short-term studies. Yet, some case studies report an incidence of prolonged, painful erections (priapism) [15].

Other case studies also suggest the occurrence of rapidly changing moles and even skin cancer [16, 17]. Yet, these case reports involve prolonged use of MT-II (over a month of daily use) alongside other tanning procedures, such as sunbed tanning—a major melanoma risk factor [17].

Melanotan 1 and melanotan 2 have not been studied for their safety in children, or pregnant and breastfeeding women. Other contraindications include allergies to the compounds, severe renal and hepatic diseases, and a history of skin cancer.

Numerous national health organizations have issued safety warnings regarding both melanotan 1 and 2, since their mechanism of action centers on the stimulation of melanocytes, the type of skin cell that can develop into cutaneous malignant melanoma (CMM).

Data corroborating these concerns thus far come mostly from case studies, whereas statistical power is needed to disprove or prove causality. The mechanism-based rationale for concerns is strong, however, especially if applied to settings in which these peptides are used on a long-term basis [2, 24].

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Is Melanotan Legal?

MT-I is legally available for EPP patients with a prescription from a licensed medical professional.

In addition, both MT-I and MT-II are legally available as reference materials for research. Qualified researchers and laboratory professionals can purchase them online for experimental and educational purposes.

Both qualified researchers and consumers must note that melanotan cannot be purchased over the counter or used as a dietary supplement. It is illegal and potentially dangerous to mislabel melanotan 1 or melanotan 2 as a supplement.

It may be against the law for individuals who are not qualified researchers or laboratory professionals, or who do not possess a valid prescription for MT-I, to purchase or possess these peptides.

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Is Melanotan a Steroid?

Both MT-I and MT-II have peptide structures made of amino acids, although the former has a linear structure while the latter has a cyclical structure [3, 4].

Therefore, melanotan peptides cannot be classified as steroids, which by definition are made of four carbon rings that form a specific steroidal backbone.

Further, MT-I and MT-II do not possess any anabolic properties or affinity to the same receptors as steroids and are not controlled substances. Nevertheless, they are legally available for research only for qualified professionals.

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Melanotan Benefits

Several trials underscore the notable potential of MT-I and MT-II in various therapeutic applications. Below, we have outlined key melanotan benefits observed in such studies.

Melanotan 1 Benefits

MT-I has been primarily studied for its compelling impacts on skin health, demonstrating noteworthy benefits in enhancing tanning and addressing specific skin conditions. Some of the most pivotal studies have uncovered the following:

• Reduced Sunburn: Researchers observed a 47% reduction in sunburn cells in melanotan 1 test subjects after UV/sunlight exposure [4].
• Potential Acne Treatment: A small study in 2012 hinted at MT-I's ability to diminish inflammation in acne lesions, albeit through unidentified mechanisms [18].
• Erythropoietic Protoporphyria (EPP) Treatment: MT-I is FDA-approved as a treatment for EPP, demonstrating the ability to mitigate symptoms by increasing melanin in the skin, absorbing UV, and reducing skin damage and pain [5].
• Polymorphic Light Eruption (PLE) Mitigation: MT-I has been reported to minimize the severity of rashes in PLE patients when administered as 16mg implants over a 4-month duration, per a 2010 phase-3 trial [19].

Melanotan 2 Benefits

The exploration of MT-II has revolved considerably around its influences on sexual function and potential weight management implications. Various studies have provided insightful findings, elucidated below:

• Male Sexual Function: MT-II has been clinically shown to enhance erections in 85% of males with erectile dysfunction (ED) and heighten sexual desire in 68% of volunteers. It has even been posited as a prospective alternative to existing ED drugs like PDE5 inhibitors [7].
• Female Sexual Desire: Preliminary research on rats indicates that MT-II, particularly when used with specific hormones, might enhance proactive sexual behaviors, possibly hinting at a future application in elevating female sexual desire [20].
• Appetite Suppression: Through potential interactions with MC3R and MC4R, MT-II has exhibited a capability for appetite suppression in preclinical studies, showing a dose-dependent reduction in appetite and consequential weight loss [6, 21].

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Melanotan 1 vs. Melanotan 2

Below, researchers will find a direct comparison between the most important aspects of MT-I and MT-II, namely their structures, mechanisms, research objectives, dosage, and side effects:

• Structure: MT-I is a tridecapeptide with a linear structure, while MT-II is a heptapeptide with a cyclic structure [3, 4].
• Mechanisms: MT-I primarily activates the MC1R, while MT-II has increased affinity towards the MC3R and MC4R [6, 9].
• Research objectives: MT-I is primarily researched for its ability to increase tanning and tolerance to UV/sunlight. MT-II can also stimulate melanogenesis but is mostly researched for its potent libido-boosting effects [4, 7].
• Dosage: When researched for their tanning potential, MT-I has been administered for up to 10 days in doses of 1-2mg/daily, while MT-II administration has been limited to 0.5mg/daily for up to 14 days [4, 18]. In addition, researchers investigating MT-II's libido-boosting effects may administer 1-2mg/day up to four times a month, with at least 48 hours in between administrations [22, 19].
• Side effects: Both MT-I and MT-II can lead to nausea, fatigue, somnolence (drowsiness), darkening of the skin, and formation of moles [5, 7, 14]. In addition, MT-II has been linked to stretching/yawning, priapism, and risk of melanoma [7, 16, 17].

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Where to Buy Melanotan Online? | 2024 Edition

To ensure success and safety in research, we recommend carefully selecting suppliers of reference materials such as MT-I and MT-II.

Factors to consider when selecting a vendor of research-grade melanotan 1 and/or 2 include quality control, cost-effectiveness, shipping policies, and client testimonials.

Based on our experience buying from major online peptide vendors, we recommend the following two prime sources of high-purity melanotan.

Xcel Peptides

Xcel Peptides is our go-to source of melanotan 1 and melanotan 2, plus a host of other compounds.

They top our vendor list here due to several merits:

• Quality Assurance: Xcel Peptides assures the purity of its MT-I peptide by subjecting each batch to rigorous third-party laboratory testing, ensuring adherence to strict quality control.
• Efficient Shipping: Based in the United States, Xcel Peptides delivers domestic shipments to researchers within 2-3 days. Fees for orders over $200 are waived.
• Customer Excellence: Xcel Peptides’ service and support team thoroughly responds to email inquiries within 24 hours.

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Limitless Life

Limitless Life is an excellent source of pure, high-quality research peptides. They are committed to quality and a streamlined experience.

Here are some of the main reasons Limitless Life is unique in the peptide community:

• Third-Party Testing for Quality and Purity: By partnering with third-party labs, Limitless Life is able to ensure product quality, potency, and purity.
• Highly Rated: Limitless Life is dedicated to conducting good business. They are the only peptide company accredited by the Better Business Bureau, and they’ve also earned excellent reviews from customers on third-party sites like Trustpilot.
• Overnight Shipping Available: Limitless Life offers two-day shipping via FedEx for all domestic orders, with overnight options available for an extra fee for researchers who need their research materials faster.
• Hassle-free Order Returns: Limitless Life proves their commitment to customer satisfaction by offering a straightforward returns process, as well as inexpensive shipping insurance that covers lost or damaged shipments.

Don’t forget, researchers can order MT-1 from the Limitless Life VIP Club by clicking below and signing up:

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Melanotan and Bacteriostatic Water

When utilized in research settings, melanotan peptides are typically available in the form of lyophilized powder that requires reconstitution before application.

To reconstitute melanotan peptides, researchers must use a solvent with a non-toxic preservative like bacteriostatic water — which includes 0.9% benzyl alcohol, ensuring a shelf-life extension of up to four weeks under refrigeration 36 to 46°F (2 to 8°C) [23].

Additional materials for the reconstitution process include:

• Sterile syringes & needles
• Alcohol swabs
• Sharps container

After securing the necessary materials, researchers should follow best practices for the reconstitution of melanotan.

Researchers are encouraged to consult any product labeling to maintain integrity and reliability in experimental results.

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Side Effects of Melanotan | Verdict

Melanotan 1 and melanotan 2 are α-MSH analogs that fall under the melanotan umbrella term and carry substantial prospective research value in skin health, sexual wellness, and weight management.

Based on available studies, the side effects of MT-I and MT-II appear relatively mild, especially when contrasted with the well-documented side effects of traditional sun-tanning methods.

Despite this, it's crucial to note that there are gaps in the existing data, highlighting numerous areas requiring further research.

Researchers eager to delve deeper into melanotan 1 and melanotan 2 are advised to select a reputable peptide source that emphasizes product quality and purity.

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