Prediction of MDMA response in healthy humans: a pooled analysis of placebo-controlled studies
Pooling data from 10 placebo-controlled cross-over studies in 194 healthy volunteers, the authors found that MDMA plasma concentration—shaped by dose per body weight and CYP2D6 activity—was the strongest predictor of acute physiological and psychological effects. Personality and mood also contributed independently: higher openness predicted greater feelings of closeness and oceanic boundlessness, whereas high neuroticism or trait anxiety increased the likelihood of unpleasant or anxious reactions, with implications for therapeutic MDMA use.
Authors
- Patrick Vizeli
- Matthias Liechti
- Lukas Ley
Published
Abstract
Background
3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) is used both recreationally and therapeutically. Little is known about the factors influencing inter- and intra-individual differences in the acute response to MDMA. Effects of other psychoactive substances have been shown to be critically influenced by personality traits and mood state before intake.
Methods
We pooled data from 10 randomized, double-blind, placebo-controlled, cross-over studies performed in the same laboratory in 194 healthy subjects receiving doses of 75 or 125mg of MDMA. We investigated the influence of drug dose, body weight, sex, age, drug pre-experience, genetics, personality and mental state before drug intake on the acute physiological and psychological response to MDMA.
Results
In univariable analyses, the MDMA plasma concentration was the strongest predictor for most outcome variables. When adjusting for dose per body weight, we found that (a) a higher activity of the enzyme CYP2D6 predicted lower MDMA plasma concentration, (b) a higher score in the personality trait “openness to experience” predicted more perceived “closeness”, a stronger decrease in “general inactivation”, and higher scores in the 5D-ASC (5 Dimensions of Altered States of Consciousness Questionnaire) scales “oceanic boundlessness” and “visionary restructuralization”, and (c) subjects with high “neuroticism” or trait anxiety were more likely to have unpleasant and/or anxious reactions.
Conclusions
Although MDMA plasma concentration was the strongest predictor, several personality traits and mood state variables additionally explained variance in the response to MDMA. The results confirm that both pharmacological and non-pharmacological variables influence the response to MDMA. These findings may be relevant for the therapeutic use of MDMA.
Research Summary of 'Prediction of MDMA response in healthy humans: a pooled analysis of placebo-controlled studies'
Introduction
MDMA (3,4-methylenedioxymethamphetamine) is both a recreational drug and an investigational adjunct to psychotherapy, producing acute effects such as enhanced mood, openness, trust and empathy. Prior work has shown that responses to psychoactive substances are influenced not only by pharmacology (dose, pharmacokinetics, genetics) but also by non‑pharmacological factors often grouped as set (personality, mood, expectations) and setting (physical and social environment). Although several small studies have examined isolated predictors of MDMA response, few have jointly evaluated a broad range of pharmacological and non‑pharmacological factors while adjusting for confounders. Studerus and colleagues set out to quantify the relative contributions of multiple predictor domains to the acute physiological and psychological response to MDMA. Using pooled individual‑level data from 10 randomized, double‑blind, placebo‑controlled, cross‑over experiments performed in the same laboratory, the study aimed to test whether drug dose and exposure, demographic variables, prior drug experience, CYP2D6 genotype, personality traits and pre‑intake mood states predict acute MDMA effects. This is presented as the first comprehensive evaluation of such predictors in a single controlled dataset of healthy volunteers.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Studerus, E., Vizeli, P., Harder, S., Ley, L., & Liechti, M. E. (2021). Prediction of MDMA response in healthy humans: a pooled analysis of placebo-controlled studies. Journal of Psychopharmacology, 35(5), 556-565. https://doi.org/10.1177/0269881121998322
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