Translational psychiatryJun 4, 2026

Short-term effects of MDMA with and without an extra booster dose in healthy people

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 28, 2026

Abstract

Essence

A 60 mg MDMA booster given 2 hours after 120 mg MDMA prolonged acute subjective effects in healthy volunteers without increasing peak subjective or autonomic effects.

Evidence

This double-blind, randomized, placebo-controlled crossover study in 25 healthy volunteers, with 23 completers, found longer overall subjective drug-effect duration with MDMA plus booster than with a single MDMA dose (5.6 +/- 1.8 h vs 4.6 +/- 1.2 h, p = 0.001), while adverse effects were more common after both MDMA conditions than placebo.

Caveat

The study tested acute effects in healthy participants rather than therapeutic outcomes, so whether the longer drug effect improves MDMA-assisted psychotherapy remains unknown.

Simplified

3,4-Methylenedioxymethamphetamine (MDMA)-assisted psychotherapy (MDMA-AT) is being investigated as a treatment for several psychiatric disorders, particularly posttraumatic stress disorder. Phase 2 and 3 trials typically administered a first dose of MDMA followed by a second "booster" dose 1.5-2.5 h later, to extend the acute effect duration. However, the risks and benefits of the booster dose have not been systematically investigated. In this double-blind, randomized, placebo-controlled, cross-over study, we compared 120 mg MDMA followed by a 60 mg booster dose or placebo after 2 h, and placebo followed by placebo. The primary outcome was the overall duration of any subjective drug effects, measured by a Visual Analog Scale. Secondary outcomes included additional subjective effects, adverse effects, vital signs, and plasma concentrations of MDMA, oxytocin, and neurophysin I. Twenty-five healthy volunteers were included, and twenty-three (12 male, 11 female) completed all dosing sessions. The booster dose of MDMA prolonged the acute subjective effects of MDMA compared with the single dose (mean ± SD, 5.6 ± 1.8 h vs. 4.6 ± 1.2 h, p = 0.001), while no differences in subjective or autonomic peak effects were observed. Acute (0-9 h) and subacute (up to 3 days) adverse effects were more common after both MDMA conditions than placebo. These results indicate that acute MDMA effects can be prolonged by using a booster dose, as intended in clinical trials of MDMA-AT. Whether this translates into clinical benefit remains to be investigated.