Acute neuropsychological effects of MDMA and ethanol (co-)administration in healthy volunteers

Contains fulltext : 73592.pdf (publisher's version ) (Open Access)RATIONALE: In Western societies, a considerable percentage of young people expose themselves to 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"). Commonly, ecstasy is used in combination with other substances, in particular alcohol (ethanol). MDMA induces both arousing as well as hallucinogenic effects, whereas ethanol is a general central nervous system depressant. OBJECTIVE: The aim of the present study is to assess the acute effects of single and co-administration of MDMA and ethanol on executive, memory, psychomotor, visuomotor, visuospatial and attention function, as well as on subjective experience. MATERIALS AND METHODS: We performed a four-way, double-blind, randomised, crossover, placebo-controlled study in 16 healthy volunteers (nine male, seven female) between the ages of 18-29. MDMA was given orally (100 mg) and blood alcohol concentration was maintained at 0.6 per thousand by an ethanol infusion regime. RESULTS: Co-administration of MDMA and ethanol was well tolerated and did not show greater impairment of performance compared to the single-drug conditions. Impaired memory function was consistently observed after all drug conditions, whereas impairment of psychomotor function and attention was less consistent across drug conditions. CONCLUSIONS: Co-administration of MDMA and ethanol did not exacerbate the effects of either drug alone. Although the impairment of performance by all drug conditions was relatively moderate, all induced significant impairment of cognitive function

Inhibition of MDMA-induced increase in cortisol does not prevent acute impairment of verbal memory

BACKGROUND: Ecstasy use is commonly linked with memory deficits in abstinent ecstasy users. Similar impairments are being found during ecstasy intoxication after single doses of ± 3,4 metylenedioxymethamphetamine (MDMA). The concordance of memory impairments during intoxication and abstinence suggests a similar neuropharmacological mechanism underlying acute and chronic memory impairments. The mechanism underlying this impairment is to date not known. We hypothesized that cortisol might play an important role in this mechanism as cortisol, implicated in the regulation of memory performance, can be brought out of balance by stressors like MDMA. METHODS: In the present study, we aimed to block the MDMA-induced acute memory defect by giving participants a cortisol synthesis inhibitor (metyrapone) together with a single dose of MDMA. Seventeen polydrug MDMA users entered this placebo-controlled within subject study with four treatment conditions. The treatments consisted of MDMA (75 mg) and metyrapone (750 mg), alone and in combination, and double placebo. Pre-treatment with metyrapone or Placebo occurred 1 h prior to MDMA or Placebo administration. Memory performance was tested at peak drug concentrations by means of several memory tests. Cortisol levels were determined in blood and oral fluid; this served as a control measure to see whether manipulations were effective. RESULTS: Main findings indicated that whereas treatment with metyrapone blocked the expected MDMA-induced increase in cortisol levels in blood, it did not prevent the MDMA-induced memory deficit from happening. CONCLUSION: We therefore conclude that MDMA-induced increments in cortisol concentrations are not related to MDMA-induced memory impairments

Dissociable effects of a single dose of ecstasy (MDMA) on psychomotor skills and attentional performance

Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a psychoactive recreational drug widely used by young people visiting dance parties, and has been associated with poor cognitive function. The current study assessed the influence of a single dose of MDMA 75 mg and alcohol 0.5 g/kg on cognition, psychomotor performance and driving-related task performance. Twelve healthy recreational ecstasy users participated in an experimental study conducted according to a double-blind, double-dummy, placebo-controlled three-way cross-over design. MDMA improved psychomotor performance, such as movement speed and tracking performance in a single task, as well as in a divided attention task. MDMA impaired the ability to predict object movement under divided attention. However, the inability to accurately predict object movement after MDMA may indicate impairment of particular performance skills relevant to driving. There was no effect of MDMA on visual search, planning or retrieval from semantic memory

High-potency marijuana impairs executive function and inhibitory motor control

Human performance studies have usually relied on low-potency marijuana (4% THC) for determining THC-induced impairment. The present study was designed to assess the effects of high-potency marijuana (13% THC) on human performance. In all, 20 recreational users of marijuana participated in a double-blind, placebo controlled, three way cross-over study. The treatments consisted of single doses of 0, 250, and 500 mg/kg THC. Performance tests were conducted at regular intervals between 15 min and 6 h postsmoking and included measures of motor control (Critical tracking task), executive function (Tower of London) motor impulsivity (Stop signal task), and risk taking (Iowa gambling task). THC significantly impaired performance in the Critical tracking task and decreased the number of correct decisions in the Tower of London task. In addition, THC significantly increased stop reaction time and the proportions of commission and omission errors in the Stop signal task. THC-induced impairments lasted up to 6 h postsmoking as indicated by the absence of a THC Â Time after smoking interaction. Effect sizes for performance impairments produced by THC 250 mg/kg were relatively low but generally increased by a factor of two in case of THC 500 mg/kg. These data suggest that high potency marijuana consistently impairs executive function and motor control. Use of higher doses of THC in controlled studies may offer a reliable indication of THC induced impairment as compared to lower doses of THC that have traditionally been used in performance studies

Depressive and anxiety symptomatology in ecstasy users: the relative contribution of genes, trauma, life stress and drug use

Rationale: Previous research has identified elevated rates of depressive and anxiety symptoms amongst ecstasy users; however, few studies have examined which factors increase the likelihood of experiencing such symptoms. Objectives: The current study aimed to determine the relationship between ecstasy use and depressive/anxiety symptomatology after controlling for known environmental and genetic (polymorphism of the serotonin transporter gene) risk factors for depression and anxiety disorders. Methods: Participants consisted of a community sample of 184 18-35-year olds who had taken ecstasy at least once in the past 12 months. Participants completed an interview and questionnaires and provided a saliva sample. Mood symptoms were assessed using the Mood and Anxiety Symptom Questionnaire. Timeline methods were used to collect information on lifetime and recent ecstasy use, as well as recent other drug use and life stress. Trauma exposure was measured using the Composite International Diagnostic Interview-Trauma List. Genomic DNA was extracted from participant saliva samples. Results: Neither lifetime nor recent ecstasy use was associated with the severity of current mood symptoms, either alone or in combination with genetic risk factors. Rather, lifetime trauma, recent stressful life events, the frequency of tobacco use and recent polydrug use significantly predicted the severity of depressive and anxiety symptoms. Conclusions: These results highlight the need to consider the role of environmental factors when examining the relationship between ecstasy use and mood symptoms. Whether ecstasy exacerbates such symptoms in vulnerable individuals requires further investigation using prospective designs