Download Use of melanotan I and II in the general population

Use of melanotan I and II in the general population
Is unlicensed, unregulated, and potentially harmful
EDITORIALS Michael Evans-Brown researcher in performance enhancing drugs,
Centre for Public Health, Faculty of Health and Applied Social Sciences, Liverpool John
Moores University, Liverpool L3 [email protected] T Dawson responsible
medical officer, Drugs in Sport Clinic and Users’ Support, Rowlands Gill, Tyne and Wear
NE39 1DUMartin Chandler interagency drug misuse database manager, Centre for Public
Health, Faculty of Health and Applied Social Sciences, Liverpool John Moores University,
Liverpool L3 2AYJim McVeigh reader in substance use epidemiology, Centre for Public
Health, Faculty of Health and Applied Social Sciences, Liverpool John Moores University,
Liverpool L3 2AY
Competing interests: None declared.
Provenance and peer review: Not commissioned; externally peer reviewed.
Cite this as: BMJ 2009;338:b566
doi: 10.1136/bmj.b566
In 2002 the media reported that the demand for synthetic melanocortin
analogues melanotan I and melanotan II (melanotans) was likely to increase
in the general population.1 This was mainly because of their ability to tan the
skin, and—in the case of melanotan II—induce penile erections and increase
sexual desire.2 In 2008, several workers at needle and syringe programmes
in the United Kingdom contacted the substance use team at the Centre for
Public Health, Liverpool, for information on “melanotan” after their clients
reported injecting these drugs. Over the next year around 30 needle and
syringe programmes in England and Wales and several drug workers and
drug and alcohol action team commissioners have sought our advice in relation to the use of these drugs within the general population.
The prevalence of the use of these drugs is unknown. Even though the drugs
are unlicensed they are easily available through online shops (including, BMJ
| 21 february 2009 | Volume 338 425
until recently, eBay.co.uk) and are also sold and administered in tanning
salons, beauty parlours, and hairdressers (personal communication to MC,
2008). Warnings over their sale and use have been issued by drug regulatory
authorities in the United States and in Europe.3-6
A thriving online community of users exists—the most popular website
(Melanotan.org) has more than 5000 members. On this website, current users
discuss their experiences of using the drugs and prospective users seek
advice about where they can buy them and what regimen they should use.
Most people use the melanotans to obtain a cosmetic skin tan. Some people
use them for a range of conditions, including rosacea and fibromyalgia, after
becoming disillusioned with existing medical treatments (Melanotan.org).
The melanotans are potent non-selective melanocortin (MC) receptor
agonists with high affinity for MC1, MC3, MC4, and MC5 receptor subtypes.7
Their endogenous counterparts, the melanocortin peptides, help regulate a
range of physiological systems, including the pigmentation system, energy
homoeostasis, sexual functioning, the immune system, inflammation, and the
cardiovascular system.7 8 The melanotans are thought to induce skin tanning
by mimicking the actions of the melanocortin α-MSH (melanocyte stimulating
hormone) on the MC1 receptors of melanocytes,7 which results in increased
expression of eumelanin.9
Melanotan I (generic name afamelanotide) is currently undergoing phase III
clinical trials as a “photoprotective” drug for the skin disorders erythropoietic
protoporphyria and polymorphous light eruption.10 Melanotan II was being
developed as a treatment for sexual dysfunction but was abandoned in favour
of developing the metabolite bremelanotide (formerly known as PT-141).11
During clinical trials of bremelanotide, the drug was found to induce
hypertension in some people, which led to this work being discontinued. It is
now being developed as a treatment for haemorrhagic shock.11
Most users inject the melanotans subcutaneously after reconstitution with an
excipient such as bacteriostatic water. In common with other illicitly supplied
drugs, such as anabolic steroids,12 serious concerns exist about the quality of
the preparations that are currently available—not only the drug content and
dose, but also contaminants and sterility. Some users, especially those who
are injecting drugs for the first time, are reusing or sharing injecting
equipment, which places them and others at risk of infections, including
bloodborne viruses (personal communication to MC, 2008).
The health risks associated with the pharmacological effects of the
melanotans are not clear. Adverse effects from short term administration in
small clinical trials seem to be limited to transient facial flushing, nausea, and
vomiting.2 One of the greatest concerns, however, is that these drugs are
non-specific melanocortin receptor agonists that could interact with several
physiological systems.7 This is particularly important because of the need for
long term administration to maintain a tan.
We are now seeing a trend whereby some drugs undergoing preclinical and
clinical development are being illicitly manufactured and supplied because of
direct demand from the general population, thus short circuiting the safety
mechanisms that are part of the normal drug life cycle. The use of the
melanotans is part of a broader phenomenon of using a range of drugs not
only for lifestyle reasons,12 but also as self prescribed medical treatments.
The challenge to healthcare professionals is not only to recognise this new
phenomenon and understand the complex forces that drive it, but also to
develop strategies to engage with patients, and, more broadly, the general
population to reduce associated harm and promote health. Such a response
should include giving patients information and counselling about the dangers
of using illicitly supplied drugs, along with reporting suspected adverse drug
reactions (through the Yellow Card Scheme in the UK). Sterile injecting equipment and safer injecting advice must be provided for people who are injecting
drugs. Finally, in the case of drugs that induce erections or increase sexual
desire, or both (such as melanotan II), advice on safer sex should be
provided.
Although action to reduce the illicit supply of such drugs should be an
important part of any response, its effect will be limited unless the demand for
these products is reduced. This, however, will require substantial changes in
society’s attitudes, particularly towards drugs taken for lifestyle reasons—the
demand for which seems to be insatiable.
1 McCarthy W. Thin! Tan! Hotter than hell! Wired 2002 June 10.
www.wired.com/wired/archive/10.06/melanotan.html.
Hadley ME, Dorr RT. Melanocortin peptide therapeutics: historical 2
milestones, clinical studies and commercialization. Peptides 2006;27:92130.
US Food and Drug Administration. 3 FDA warns about unapproved
product, Melanotan II. 2007.
www.fda.gov/consumer/updates/melanotan090507.html.
Danish Medicines Authority. 4 Warning against the product Melanotan.
2008. www.dkma.dk/1024/visUKLSArtikel.asp?artikelID=13865.
Medicines and Healthcare Products Regulatory Agency. 5 “Tan jab” is an
unlicensed medicine and may not be safe—warns medicines regulator.
2008. www.mhra.gov.uk/NewsCentre/Pressreleases/CON031009.
Norwegian Medicines Agency. 6 Legemiddelverket advarer mot bruk av
Melanotan. 2008.
www.legemiddelverket.no/templates/InterPage____65110.aspx.
Wikberg JE, Muceniece R, Mandrika I, Prusis P, Lindblom J, Post C, et 7
al. New aspects on the melanocortins and their receptors. Pharmacol Res
2000;42:393-420.
Wikberg JE, Mutulis F. Targeting melanocortin receptors: an approach 8 to
treat weight disorders and sexual dysfunction. Nat Rev Drug Discov
2008;7:307-23.
Dorr RT, Dvorakova K, Brooks C, Lines R, Levine N, Schram K, et 9 al.
Increased eumelanin expression and tanning is induced by a superpotent
melanotropin [Nle4-D-Phe7]-alpha-MSH in humans. Photochem Photobiol
2000;72:526-32.
Clinuvel Pharmaceuticals Limited. 10 Annual report 2008. 2008.
www.clinuvel.com/resources/pdf/annual_reports/2008/annual_report_2008.
pdf.
Palatin Technologies Incorporated. 11 Bremelanotide for organ protection
and related indications.www.palatin.com/pdfs/bremelanotide.pdf.
Evans-Brown MJ, McVeigh J. An introduction