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Effects of Acute MDMA Intoxication on Mood and Impulsivity: Role of the 5-HT2 and 5-HT1 Receptors

Janelle H. P. van Wel, Kim P. C. Kuypers, Eef L. Theunissen, Wendy M. Bosker, Katja Bakker, Johannes G. Ramaekers

PLoS ONE July 10, 2012 DOI: 10.1371/journal.pone.0040187 via OpenAlex

Summary

AI-generated from the abstract

MDMA increases both positive moods (vigor, arousal, friendliness, elation) and negative moods (anxiety, confusion) while also slowing reaction times on impulsivity tasks, indicating greater impulse control. Blocking 5-HT(2) receptors with ketanserin prevented the positive mood effects but not the negative mood or impulsivity changes. Blocking 5-HT(1) receptors with pindolol had no effect on any MDMA-related mood or impulse measures. Thus, 5-HT(2) receptors are specifically involved in MDMA's positive mood enhancement, while 5-HT(1) receptors do not appear to play a role in these effects.

Study at a glance

Characteristics Randomized controlled trial Placebo-controlled Double-blind Peer reviewed
Sample size 17
Population Human subjects
Interventions MDMA pindolol ketanserin
Dose 75 mg MDMA, 20 mg pindolol, 50 mg ketanserin
Duration 30-minute pretreatment interval, assessments at 1.5 hours post-treatment
Topics MDMA
Keywords Impulsivity Ketanserin Placebo Mood
Citations 121
Key finding 5-HT(2) receptor blockade with ketanserin prevents MDMA-induced positive mood but not negative mood or impulsivity changes, while 5-HT(1) receptor blockade with pindolol has no effect on any MDMA-related mood or impulse control measures.

Abstract

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.

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