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Toxic effect of MDMA on brain serotonin neurons

1999; Elsevier BV; Volume: 353; Issue: 9160 Linguagem: Inglês

10.1016/s0140-6736(05)66942-5

1474-547X

Anthony Klugman, Susan Hardy, Torsten Baldeweg, John Gruzelier,

Neurotransmitter Receptor Influence on Behavior

The finding of U D McCann and colleagues1McCann U Szabo Z Scheffel U Dannals RF Ricaute GA Positron emission tomographic evidence of toxic effect of MDMA (“Ecstasy”) on brain serotonin neurons in human beings.Lancet. 1998; 352: 1433-1437Summary Full Text Full Text PDF PubMed Scopus (563) Google Scholar of reduced serotonin transporter binding in heavy users of MDMA lends support to evidence of the harmful effect of this drug on the serotonin system, which was previously reported in animals.2Ricaurte G Forno L Wilson M et al.3,4-Methylenedioxymethamphetamine selectively damages central serotonergic neurons in nonhuman primates.JAMA. 1988; 260: 51-55Crossref PubMed Scopus (281) Google Scholar However, as the investigators acknowledge, little is known of the functional effects of MDMA-induced brain serotonin neurotoxic lesions. We report the effect of long-term consumption of MDMA on cognitive function. We recruited participants who had a history of substantial and predominant MDMA use (mean estimated number of tablets consumed 235 [range 12–2600]) through popular magazines and the internet. The MDMA group (n=36; age 24·1 [SD 4·9] years; duration of MDMA use 4·3 [2·6] years) was compared with a control group (n=19; age 22·7 [2·3] years) who had never used illicit or prescribed psychoactive substances. The MDMA users had not taken the drug or any other psychoactive drug for some days before testing (79 days [2–400 days]). We took a detailed history of each participant's drug use together with current and past psychiatric state (Present State Examination). Four drug users met criteria for a diagnosis of neurotic depression, but there were no group differences between groups on the Beck depression inventory (p=0·304), and congnitive impairment was unrelated to diagnosis and depression scores. A multivariate analysis of variance of cognitive scores showed significant impairment of MDMA users on tests of learning, recognition, and recall.* Compared with controls, users of MDMA had worse immediate recall of words from a list, showed impairment in recognition memory for faces and in learning a repeatedly administered word list and a sequence of digits. Associative learning tasks revealed impairment in learning spatial information. By contrast, executive (frontal lobe) functions (measured by verbal fluency tests, and verbal and non-verbal working memory) were not impaired. Compared with normative data for the learning and memory tests, three MDMA users scored below the 2 SD limit on two tests, as did an additional eight users on one test, whereas only one control scored lower than the 1 SD limit on one test (p=0·021). Most users of MDMA have also taken other illicit psychoactive drugs that may contribute to cognitive impairment and to serotinergic depletion. We selected individuals whose use of MDMA was more frequent and regular than of any other drug; we also recorded the frequency and use of other drugs. Other drugs did not correlate significantly with the deficits found with MDMA, although other deficits were implicated, such as frontal impairment with cannabis use. Our results do not represent a global impairment of cognitive function, instead we found discrete deficits in verbal and non-verbal memory and learning while other cognitive functions were intact. Accordingly, the deficits could not be explained as the result of impaired attention or poor motivation, which substantiates evidence of patterned cognitive impairment.3Krystal J Price L Chronic 3,4-methylenedioxymethamphetamine (MDMA) use: effects on mood and neuropsychological function?.Am J Drug Alcohol Abuse. 1992; 18: 331-334Crossref PubMed Scopus (148) Google Scholar, 4Parrott A Lees A Garnham N Jones M Wesnes K Cognitive performance in recreational users of MDMA or ‘ecstasy’: evidence for memory deficits.J Psychopharmacol. 1998; 12: 79-83Crossref PubMed Scopus (195) Google Scholar Chronic disruption of serotonergic transmission by MDMA is a possible explanation for the memory and learning deficits we found. *Full details available from the authors, on request. Toxic effect of MDMA on brain serotonin neuronsAuthors' reply Full-Text PDF