Cognitive performance in recreational ecstasy polydrug users: A two-year follow-up study

Behavioral Neurology and Dementia Research Group, Neuropsychopharmacology Program, IMIM-Hospital del Mar, Barcelona, Spain.
Journal of Psychopharmacology (Impact Factor: 3.59). 02/2008; 22(5):498-510. DOI: 10.1177/0269881107081545
Source: PubMed


There is important preclinical evidence of long lasting neurotoxic and selective effects of ecstasy MDMA on serotonin systems in non-human primates. In humans long-term recreational use of ecstasy has been mainly associated with learning and memory impairments. The aim of the present study was to investigate the neuropsychological profile associated with ecstasy use within recreational polydrug users, and describe the cognitive changes related to maintained or variable ecstasy use along a two years period. We administered cognitive measures of attention, executive functions, memory and learning to three groups of participants: 37 current polydrug users with regular consumption of ecstasy and cannabis, 23 current cannabis users and 34 non-users free of illicit drugs. Four cognitive assessments were conducted during two years. At baseline, ecstasy polydrug users showed significantly poorer performance than cannabis users and non-drug using controls in a measure of semantic word fluency. When ecstasy users were classified according to lifetime use of ecstasy, the more severe users (more than 100 tablets) showed additional deficits on episodic memory. After two years ecstasy users showed persistent deficits on verbal fluency, working memory and processing speed. These findings should be interpreted with caution, since the possibility of premorbid group differences cannot be entirely excluded. Our findings support that ecstasy use, or ecstasy/cannabis synergic effects, are responsible for the sub-clinical deficits observed in ecstasy polydrug users, and provides additional evidence for long-term cognitive impairment owing to ecstasy consumption in the context of polydrug use.

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    • "Thus, it is difficult to determine whether the differences between controls and ecstasy users are actually based on MDMA use. Indeed, when groups of ecstasy users are compared with groups of participants who do not use ecstasy, but are matched with respect to use of marijuana or other drugs, several studies have found comparable cognitive deficits (e.g., Croft, Mackay, Mills, & Gruzelier, 2001; Dafters, Hoski, & Talbot, 2004; de Sola et al., 2008), although others have found more severe deficits in ecstasy users (Daumann et al., 2005; Nulsen et al., 2010). "
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    ABSTRACT: The effects of acute and sub-chronic MDMA were assessed using a procedure designed to test rodent working memory capacity: the odor span task (OST). Rats were trained to select an odor that they had not previously encountered within the current session, and the number of odors to remember was incremented up to 24 during the course of each session. In order to separate drug effects on the OST from more general performance impairment, a simple olfactory discrimination was also assessed in each session. In Experiment 1, acute doses of MDMA were administered prior to select sessions. MDMA impaired memory span in a dose-dependent fashion, but impairment was seen only at doses (1.8 and 3.0 mg/kg) that also increased response omissions on both the simple discrimination and the OST. In Experiment 2, a sub-chronic regimen of MDMA (10.0 mg/kg, twice daily over four days) was administered after OST training. There was no evidence of reduced memory span following sub-chronic MDMA, but a temporary increase in omission errors on the OST was observed. In addition, rats exposed to sub-chronic MDMA showed delayed learning when the simple discrimination was reversed. Overall, the disruptive effects of both acute and sub-chronic MDMA appeared to be due to non-mnemonic processes, rather than effects on specific memory functions.
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    • "Longitudinal studies of up to 2 years in length have also asked whether cognitive function keeps declining with continued ecstasy use, and whether cessation of use leads to a recovery of cognitive function. In general, such studies have found neither further deterioration in users nor recovery of function in subjects who discontinued ecstasy use76–78 (see Zakzanis and Campbell79 for an exception to these findings). Because in these studies the ecstasy users already differed from controls at the time of initial testing, the results are difficult to interpret. "
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    ABSTRACT: Ecstasy is a widely used recreational drug that usually consists primarily of 3,4-methylenedioxymethamphetamine (MDMA). Most ecstasy users consume other substances as well, which complicates the interpretation of research in this field. The positively rated effects of MDMA consumption include euphoria, arousal, enhanced mood, increased sociability, and heightened perceptions; some common adverse reactions are nausea, headache, tachycardia, bruxism, and trismus. Lowering of mood is an aftereffect that is sometimes reported from 2 to 5 days after a session of ecstasy use. The acute effects of MDMA in ecstasy users have been attributed primarily to increased release and inhibited reuptake of serotonin (5-HT) and norepinephrine, along with possible release of the neuropeptide oxytocin. Repeated or high-dose MDMA/ecstasy use has been associated with tolerance, depressive symptomatology, and persisting cognitive deficits, particularly in memory tests. Animal studies have demonstrated that high doses of MDMA can lead to long-term decreases in forebrain 5-HT concentrations, tryptophan hydroxylase activity, serotonin transporter (SERT) expression, and visualization of axons immunoreactive for 5-HT or SERT. These neurotoxic effects may reflect either a drug-induced degeneration of serotonergic fibers or a long-lasting downregulation in 5-HT and SERT biosynthesis. Possible neurotoxicity in heavy ecstasy users has been revealed by neuroimaging studies showing reduced SERT binding and increased 5-HT2A receptor binding in several cortical and/or subcortical areas. MDMA overdose or use with certain other drugs can also cause severe morbidity and even death. Repeated use of MDMA may lead to dose escalation and the development of dependence, although such dependence is usually not as profound as is seen with many other drugs of abuse. MDMA/ecstasy-dependent patients are treated with standard addiction programs, since there are no specific programs for this substance and no proven medications. Finally, even though MDMA is listed as a Schedule I compound by the Drug Enforcement Agency, MDMA-assisted psychotherapy for patients with chronic, treatment-resistant posttraumatic stress disorder is currently under investigation. Initial results show efficacy for this treatment approach, although considerably more research must be performed to confirm such efficacy and to ensure that the benefits of MDMA-assisted therapy outweigh the risks to the patients.
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    • "Favorable reports about cognitive function, memory, and concentration on the LTFU Questionnaire were consistent with findings from formal measures of cognitive function that were taken before and after psychotherapy with MDMA versus placebo, in the original study. Though reports from actual testing are more reliable than reports of perceived cognitive function, this long-term selfreported evidence is still important, because of the controversy surrounding theories that there are potential risks of neurocognitive decline resulting from MDMA administration, as has been suggested by animal studies and some retrospective studies in recreational drug users (Thomasius et al., 2006; Kalechstein et al., 2007; Laws and Kokkalis, 2007; Zakzanis et al., 2007; De Sola Llopis et al., 2008; Jager et al., 2008; Schilt et al., 2008; Brown et al., 2010; Kish et al., 2010; Verbaten, 2010) and one prospective "
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