Brain serotonin synthesis in MDMA (ecstasy) polydrug users: an alpha-[(11) C]methyl-l-tryptophan study.
Linda Booij, Jean‐Paul Soucy, Simon N. Young, Martine Regoli, Paul Gravel, Mirko Diksic, Marco Leyton, Robert O. Pihl, Chawki Benkelfat
Journal of Neurochemistry December 2014 DOI: 10.1111/jnc.12826 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case-control study Peer reviewed |
|---|---|
| Sample size | 35 |
| Population | 17 currently drug-free MDMA polydrug users and 18 healthy matched controls |
| Measures | alpha-[11C]methyl-l-tryptophan (11C-AMT) positron emission tomography |
| Topics | MDMA Serotonin |
| Keywords | Drugs Positron emission tomography Tryptophan |
| Key findings | MDMA polydrug users showed lower normalized 11C-AMT trapping in prefrontal, orbitofrontal, and parietal regions and higher trapping in brainstem and frontal and temporal areas compared with controls, with differences more widespread in males. The authors interpret decreased forebrain serotonin synthesis capacity as possible MDMA neurotoxicity and increased raphe-area capacity as possible compensation, while noting pre-existing serotonin alterations cannot be ruled out. |
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.
Comparable studies
Other observational and cohort studies on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subjective Reports of the Effects of MDMA in a Clinical Setting Individuals who took MDMA in a clinical setting | 1986 | Observational study | |
| Memory impairment in abstinent MDMA ("Ecstasy") users Abstinent MDMA users | 1998 | Observational cohort | |
| Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Otherwise healthy young people | 2000 | Observational | |
| The Psychological and Physiological Effects of MDMA on Normal Volunteers Older, more educated, drug-experienced individuals | 1986 | Observational cohort | |
| Cognitive performance in recreational users of MDMA or 'ecstasy': evidence for memory deficits Young people who were regular or novice MDMA users, or non-users | 1998 | Observational cohort | n = 30 |
Citations in the library
Cited by 2
- Longitudinal Examination of Learning and Memory in Rats Following Adolescent Exposure to 3,4-Methylenedioxymethamphetamine or 5-Methoxy-N,N-Diisopropyltryptamine Journal of Behavioral and Brain Science 2017
- Measuring effects of MDMA (ecstasy) abuse on the rate of cerebral serotonin synthesis Journal of Neurochemistry December 1, 2014
Cites 10
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- The Nature of 3, 4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonergic Dysfunction: Evidence for and Against the Neurodegeneration Hypothesis Current Neuropharmacology March 1, 2011
- Single oral doses of (±) 3,4-methylenedioxymethamphetamine (‘Ecstasy’) produce lasting serotonergic deficits in non-human primates: relationship to plasma drug and metabolite concentrations The International Journal of Neuropsychopharmacology May 1, 2013
and 5 more in the library