title: Brain serotonin synthesis in MDMA (ecstasy) polydrug users: an alpha-[(11) C]methyl-l-tryptophan study.
abstract: 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) use may have long-term neurotoxic effects. In this study, positron emission tomography with the tracer alpha-[(11) C]methyl-l-tryptophan ((11) C-AMT) was used to compare human brain serotonin (5-HT) synthesis capacity in 17 currently drug-free MDMA polydrug users with that in 18 healthy matched controls. Gender differences and associations between regional (11) C-AMT trapping and characteristics of MDMA use were also examined. MDMA polydrug users exhibited lower normalized (11) C-AMT trapping in pre-frontal, orbitofrontal, and parietal regions, relative to controls. These differences were more widespread in males than in females. Increased normalized (11) C-AMT trapping in MDMA users was also observed, mainly in the brainstem and in frontal and temporal areas. Normalized (11) C-AMT trapping in the brainstem and pre-frontal regions correlated positively and negatively, respectively, with greater lifetime accumulated MDMA use, longer durations of MDMA use, and shorter time elapsed since the last MDMA use. Although the possibility of pre-existing 5-HT alterations pre-disposing people to use MDMA cannot be ruled out, regionally decreased 5-HT synthesis capacity in the forebrain could be interpreted as neurotoxicity of MDMA on distal (frontal) brain regions. On the other hand, increased 5-HT synthesis capacity in the raphe and adjacent areas could be due to compensatory mechanisms.
authors.affiliation: Department of Psychology, Queen's University, Kingston, Ontario, Canada; Department of Psychiatry, McGill University, Montreal, Quebec, Canada; Sainte-Justine Hospital Research Center, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Linda
authors.initials: L
authors.lastname: Booij
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Soucy
authors.forename: Simon N
authors.initials: SN
authors.lastname: Young
authors.forename: Martine
authors.initials: M
authors.lastname: Regoli
authors.forename: Paul
authors.initials: P
authors.lastname: Gravel
authors.forename: Mirko
authors.initials: M
authors.lastname: Diksic
authors.forename: Marco
authors.initials: M
authors.lastname: Leyton
authors.forename: Robert O
authors.initials: RO
authors.lastname: Pihl
authors.forename: Chawki
authors.initials: C
authors.lastname: Benkelfat
mesh_terms: D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000097:blood / Q000494:pharmacology; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D001931:Brain Mapping; D005260:Female; D006801:Humans; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects*; D049268:Positron-Emission Tomography; D057566:Self Report; D012701:Serotonin / Q000378:metabolism*; D012737:Sex Factors; D019966:Substance-Related Disorders / Q000000981:diagnostic imaging / Q000473:pathology*; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D055815:Young Adult
chemical_list: D018687:Antidepressive Agents, Second-Generation; C020774:alpha-methyltryptophan; D012701:Serotonin; D014364:Tryptophan; D018817:N-Methyl-3,4-methylenedioxyamphetamine
keywords: MDMA; drugs; ecstasy; positron emission tomography; serotonin; tryptophan