title: 4-Methyl-amphetamine: a health threat for recreational amphetamine users.
abstract: 4-Methylamphetamine (4-MA) was originally developed as an appetite suppressant, but development was halted due to side effects. It has recently resurfaced as a new psychoactive substance in Europe, and is mostly found together with amphetamine. Around 11.5% of tested Dutch speed samples were positive for 4-MA. In Belgium, 4-MA was also found in speed samples. In 2011 and 2012, several fatal incidents after amphetamine use were observed in Belgium, the United Kingdom and The Netherlands. In all victims, toxicological analysis confirmed the presence of 4-MA, in addition to amphetamine. The observed blood amphetamine levels were too low to be fatal. Contrary to amphetamine, which displays noradrenergic and dopaminergic activity, 4-MA also shows serotonergic activity, which may contribute to the observed toxicity. Other mechanisms of toxicity are put forward in this paper as well. To conclude, the observed toxicity is most likely the result of the combined dopaminergic activity of amphetamine and the serotonergic activity of 4-MA. In addition, the presence of 4-MA may have dampened the psychoactive effects of amphetamine by attenuation of the amphetamine-induced dopamine release, potentially inclining users to ingest higher doses of contaminated speed. Also, slower metabolism of 4-MA and its MAO-inhibiting properties can also contribute to the unusual high toxicity of 4-MA.
authors.affiliation: Belgian Early Warning System on Drugs, Scientific Institute of Public Health, Brussels, Belgium. peter.blanckaert@hotmail.com
authors.forename: P
authors.initials: P
authors.lastname: Blanckaert
authors.forename: Jgc
authors.initials: J
authors.lastname: van Amsterdam
authors.forename: Tm
authors.initials: T
authors.lastname: Brunt
authors.forename: Jdj
authors.initials: J
authors.lastname: van den Berg
authors.forename: F
authors.initials: F
authors.lastname: Van Durme
authors.forename: K
authors.initials: K
authors.lastname: Maudens
authors.forename: Jch
authors.initials: J
authors.lastname: van Bussel
mesh_terms: D000661:Amphetamine / Q000009:adverse effects* / Q000097:blood; D019969:Amphetamine-Related Disorders / Q000097:blood / Q000453:epidemiology / Q000209:etiology / Q000523:psychology*; D000662:Amphetamines / Q000008:administration & dosage* / Q000097:blood; D015259:Dopamine Agents / Q000009:adverse effects / Q000097:blood; D055030:Drug Users / Q000523:psychology*; D006801:Humans; D008694:Methamphetamine / Q000009:adverse effects* / Q000097:blood; D009426:Netherlands / Q000453:epidemiology; D018490:Serotonin Agents / Q000009:adverse effects / Q000097:blood; D015813:Substance Abuse Detection / Q000379:methods / Q000523:psychology
chemical_list: D000662:Amphetamines; D015259:Dopamine Agents; D018490:Serotonin Agents; D008694:Methamphetamine; C000592889:1-(4-methylphenyl)propane-2-amine; D000661:Amphetamine
keywords: 4-methylamphetamine; amphetamines; neuropharmacology; new psychoactive substances; toxicology