Comparison of acute effects of 3,4-methylenedioxymethamphetamine (MDMA) with and without a supplemental booster dose in healthy participants: a double-blind, randomized, placebo-controlled, crossover study
Mélusine Humbert‐droz, Anna M Becker, Jan Valenta, Deborah Rudin, Dino Luethi, Ina Vukalović, Anne Eckert, Matthias E. Liechti, Lorenz Mueller
Translational Psychiatry June 4, 2026 DOI: 10.1038/s41398-026-04148-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, randomized, placebo-controlled, cross-over study Peer reviewed |
|---|---|
| Sample size | 23 |
| Population | Healthy volunteers |
| Intervention | MDMA |
| Dose | 120 mg MDMA followed by a 60 mg booster dose or placebo after 2 h |
| Duration | Up to 3 days subacute follow-up |
| Topics | MDMA |
| Keywords | Placebo Adverse effect Crossover study Dosing Clinical trial Anesthesia Booster rocketry Drug |
| Key points | A 60 mg booster dose of MDMA given 2 hours after an initial 120 mg dose prolongs the duration of acute subjective drug effects compared with a single dose alone. |
Abstract
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.
Comparable studies
Other randomized controlled trials on MDMA, most cited first.