Effects of acute MDMA intoxication on mood and impulsivity: role of the 5-HT2 and 5-HT1 receptors.

UNLABELLED: MDMA induces positive mood and increases impulse control during intoxication, but only a few studies on the neuropharmacological mechanisms underlying these processes have been conducted. It was hypothesized that pretreatment with 5-HT(1) and 5-HT(2) receptor blockers would prevent MDMA effects on mood and impulsivity. Subjects (N = 17) participated in a double-blind, placebo controlled, within-subject design involving 6 experimental conditions consisting of pretreatment (T1) and treatment (T2). T1 preceded T2 by 30 minutes. T1-T2 combinations were: placebo-placebo, 20 mg pindolol-placebo, 50 mg ketanserin-placebo, placebo-75 mg MDMA, 20 mg pindolol-75 mg MDMA and 50 mg ketanserin-75 g MDMA. Subjects completed a Profile of Mood States (POMS) questionnaire and several impulsivity tasks (Stop signal task, Matching familiar figures task, Cue dependent reversal learning task) at 1.5 hrs post-treatment. MDMA alone increased both positive (vigor, arousal, friendliness, elation, positive mood) and negative affect (anxiety, confusion) as assessed by the POMS questionnaire. MDMA also increased stop reaction time in the Stop signal task and reaction time in the Matching familiar figures task. Pretreatment with ketanserin blocked MDMA effects on positive affect, but not negative affect. Ketanserin did not influence the effects of MDMA on impulsivity. Pindolol did not interact with MDMA on any of the measures. In conclusion, 5-HT(2) receptors mediate positive moods induced by MDMA but not negative moods or impulsivity. 5-HT(1) receptors do not appear to be involved in MDMA effects on mood and impulse control. TRIAL REGISTRATION: Nederlands Trial Register NTR2352

Opposite effects of cannabis and cocaine on performance monitoring

Drug use is often associated with risky and unsafe behavior. However, the acute effects of cocaine and cannabis on performance monitoring processes have not been systematically investigated. The aim of the current study was to investigate how administration of these drugs alters performance monitoring processes, as reflected in the error-related negativity (ERN), the error positivity (Pe) and post-error slowing. A double-blind placebo-controlled randomized three-way crossover design was used. Sixty-one subjects completed a Flanker task while EEG measures were obtained. Subjects showed diminished ERN and Pe amplitudes after cannabis administration and increased ERN and Pe amplitudes after administration of cocaine. Neither drug affected post-error slowing. These results demonstrate diametrically opposing effects on the early and late phases of performance monitoring of the two most commonly used illicit drugs of abuse. Conversely, the behavioral adaptation phase of performance monitoring remained unaltered by the drugs

Opposite effects of cannabis and cocaine on performance monitoring

Drug use is often associated with risky and unsafe behavior. However, the acute effects of cocaine and cannabis on performance monitoring processes have not been systematically investigated. The aim of the current study was to investigate how administration of these drugs alters performance monitoring processes, as reflected in the error-related negativity (ERN), the error positivity (Pe) and post-error slowing. A double-blind placebo-controlled randomized three-way crossover design was used. Sixty-one subjects completed a Flanker task while EEG measures were obtained. Subjects showed diminished ERN and Pe amplitudes after cannabis administration and increased ERN and Pe amplitudes after administration of cocaine. Neither drug affected post-error slowing. These results demonstrate diametrically opposing effects on the early and late phases of performance monitoring of the two most commonly used illicit drugs of abuse. Conversely, the behavioral adaptation phase of performance monitoring remained unaltered by the drugs

Verbal memory impairment in polydrug ecstasy users:A clinical perspective

Ecstasy use has been associated with short-term and long-term memory deficits on a standard Word Learning Task (WLT). The clinical relevance of this has been debated and is currently unknown. The present study aimed at evaluating the clinical relevance of verbal memory impairment in Ecstasy users. To that end, clinical memory impairment was defined as decrement in memory performance that exceeded the cut-off value of 1.5 times the standard deviation of the average score in the healthy control sample. The primary question was whether being an Ecstasy user (E-user) was predictive of having clinically deficient memory performance compared to a healthy control group. Conclusion: The combination of the acute and long-term findings demonstrates that, while clinically relevant memory impairment is present during intoxication, it is absent during abstinence. This suggests that use of Ecstasy/MDMA does not lead to clinically deficient memory performance in the long term. Additionally, it has to be investigated whether the current findings apply to more complex cognitive measures in diverse ‘user categories’ using a combination of genetics, imaging techniques and neuropsychological assessments

Mean (SE) scores and Summary of main effects and interactions following 2 major GLM analyses for all dependent variables in the matching familiar figures task (MFF20), the stop signal task (SST) and the cue-dependent reversal learning task.

<p>Significance (p<.05) and non-significance (−) of main effects is shown.</p

Schematic representation of a testing day.

<p>Schematic representation of a testing day.</p

Mean (SE) ratings on the Profile of Mood States (POMS) questionnaire in every treatment condition (n = 17).

<p>ANX  =  anxiety, DEP  =  depression, ANG  =  anger, VIG  =  vigor, FTG  =  fatigue, CON  =  confusion, FRD  =  friendliness, ELT  =  elation, ASL  =  arousal, POS  =  positive mood.</p

The median (red line), 25th and 75th percentiles (box edges), range excluding outliers (whiskers), and outliers (red +) of the Total Immediate Recall (IR) Score (upper graph) and Delayed Recall (DR) Score (lower graph) of Controls, and Ecstasy users (E-Users) in the placebo condition and MDMA condition.

<p>The median (red line), 25th and 75th percentiles (box edges), range excluding outliers (whiskers), and outliers (red +) of the Total Immediate Recall (IR) Score (upper graph) and Delayed Recall (DR) Score (lower graph) of Controls, and Ecstasy users (E-Users) in the placebo condition and MDMA condition.</p

Mean and standard deviation of immediate recall (IR) and delayed recall (DR) in the word learning task for each study.

<p>Mean and standard deviation of immediate recall (IR) and delayed recall (DR) in the word learning task for each study.</p