The effects of acute and repeated adolescent MDMA exposure on behavior, cognition, and the monoamine neurotransmitter systems: A review of human and pre-clinical research
Kristin A. Felsch, Jessica A. Siegel
Behavioural Brain Research February 10, 2026 DOI: 10.1016/j.bbr.2026.116098 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Population | Adolescent rodents and humans |
| Topics | MDMA Serotonin |
| Keywords | Stimulant Monoamine neurotransmitter Neurotransmitter systems Hallucinogen Psychomotor learning Amphetamine Pharmacology Dosing Drug Poison control |
| Key findings | Acute high-dose MDMA in adolescents increases locomotor activity and impairs the serotonin system, while repeated exposure effects are inconsistent and depend on dosing and testing conditions. |
Abstract
3,4-methylenedioxymethamphetamine (MDMA) is a psychomotor stimulant drug. While much research has examined the effects of MDMA in adults, relatively little research has examined the effects in adolescents. Adolescence is a unique period of brain development, and the effects of MDMA may differ in adolescents compared to adults. In this review, we summarize the literature on the effects of acute and repeated adolescent MDMA exposure on behavior, cognition, and the monoamine neurotransmitter systems in adolescent rodents and humans. PubMed was searched using predefined criteria, resulting in the evaluation of 1012 articles. Fifty-four articles met the search criteria, 48 of which examined the effects of adolescent MDMA exposure in adolescent rodents and 6 of which examined the effects in adolescent humans. Studies measuring the effects of acute MDMA exposure examine outcome measures following a single exposure to MDMA, and studies measuring the effects of repeated MDMA exposure examine outcome measures at some point following multiple exposures to MDMA. Exposure to acute higher doses of MDMA generally increases locomotor activity and causes impairments in the serotonin neurotransmitter system. The literature on the effects of repeated adolescent MDMA exposure shows conflicting results, and the findings are dependent on the dosing, testing environment, and timing of testing following MDMA exposure. There is a lack of literature examining the effects of MDMA in adolescent females. More research is needed with consistent exposure and dosing paradigms and in female subjects to better understand the effects of adolescent MDMA exposure.
Comparable studies
Other systematic reviews and meta-analyses on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A review of the acute subjective effects of MDMA/ecstasy | 2006 | Systematic review | |
| Adverse events in clinical treatments with serotonergic psychedelics and MDMA: A mixed-methods systematic review Patients in clinical trials with MDMA or serotonergic psychedelics | 2022 | Systematic review | n = 598 |
| Treating posttraumatic stress disorder with MDMA-assisted psychotherapy: A preliminary meta-analysis and comparison to prolonged exposure therapy Patients with PTSD | 2016 | Meta-analysis | |
| The neuropsychology of ecstasy (MDMA) use: a quantitative review MDMA users | 2007 | Meta-analysis | |
| Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review | 2022 | Systematic review |
Citations in the library
Cites 43
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine June 1, 2021
- MDMA enhances emotional empathy and prosocial behavior Social Cognitive and Affective Neuroscience October 4, 2013
- Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Journal of Neuroscience June 15, 1999
- Distinct acute effects of LSD, MDMA, and d-amphetamine in healthy subjects Neuropsychopharmacology November 16, 2019
- 3,4-Methylenedioxymethamphetamine-assisted psychotherapy for treatment of chronic posttraumatic stress disorder: A randomized phase 2 controlled trial. Journal of Psychopharmacology December 1, 2018
and 38 more in the library