Safety pharmacology of acute MDMA administration in healthy subjects
This analysis of data from nine double-blind, placebo-controlled studies (n=166) investigated the short-term psychological and physiological safety profile of MDMA (75-125mg) and found that effects were overall positive and risks were low, although adverse effects were more frequent in women than in men.
Authors
- Patrick Vizeli
- Matthias Liechti
Published
Abstract
3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is being investigated in MDMA-assisted psychotherapy. The present study characterized the safety pharmacology of single-dose administrations of MDMA (75 or 125 mg) using data from nine double-blind, placebo-controlled, crossover studies performed in the same laboratory in a total of 166 healthy subjects. The duration of the subjective effects was 4.2 ± 1.3 h (range: 1.4-8.2 h). The 125 mg dose of MDMA produced greater ‘good drug effect’ ratings than 75 mg. MDMA produced moderate and transient ‘bad drug effect’ ratings, which were greater in women than in men. MDMA increased systolic blood pressure to >160 mmHg, heart rate >100 beats/min, and body temperature >38°C in 33%, 29% and 19% of the subjects, respectively. These proportions of subjects with hypertension (>160 mmHg), tachycardia, and body temperature >38°C were all significantly greater after 125 mg MDMA compared with the 75 mg dose. Acute and subacute adverse effects of MDMA as assessed by the List of Complaints were dose-dependent and more frequent in females. MDMA did not affect liver or kidney function at EOS 29 ± 22 days after use. No serious adverse events occurred. In conclusion, MDMA produced predominantly acute positive subjective drug effects. Bad subjective drug effects and other adverse effects were significantly more common in women. MDMA administration was overall safe in physically and psychiatrically healthy subjects and in a medical setting. However, the risks of MDMA are likely higher in patients with cardiovascular disease and remain to be investigated in patients with psychiatric disorders.
Research Summary of 'Safety pharmacology of acute MDMA administration in healthy subjects'
Introduction
MDMA (3,4-methylenedioxymethamphetamine; ecstasy) is investigated clinically as an adjunct to psychotherapy, notably for post‑traumatic stress disorder, but broader clinical adoption depends on robust evidence of safety as well as efficacy. Earlier experimental studies have described MDMA’s subjective and physiological effects, but most were small (n = 6–30) and not expressly designed to quantify adverse events that occur at low frequency. The authors note a need for larger, standardised data sets to characterise acute and subacute safety in healthy volunteers prior to wider patient trials. Using pooled data from nine Phase I double‑blind, placebo‑controlled, crossover studies conducted at a single centre, the investigators aimed to describe the safety pharmacology of single oral doses of MDMA (75 mg and 125 mg). Primary objectives were to characterise the time course and magnitude of subjective effects, cardiovascular and thermogenic responses during the acute MDMA response (0–6 h), subacute adverse effects up to 24 h, and laboratory indices of liver and kidney function at end‑of‑study follow‑up. The analysis also tested dose and sex as moderators of these responses and reported plasma MDMA concentrations alongside clinical measures.
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Vizeli, P., & Liechti, M. E. (2017). Safety pharmacology of acute MDMA administration in healthy subjects. Journal of Psychopharmacology, 31(5), 576-588. https://doi.org/10.1177/0269881117691569
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