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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 via OpenAlex

Summary

AI-generated from the abstract

MDMA is a psychomotor stimulant drug. Most research has focused on adults, but adolescence is a unique period of brain development where MDMA's effects may differ. This review summarizes 54 studies (48 in rodents, 6 in humans) on acute and repeated adolescent MDMA exposure. Acute high doses generally increase locomotor activity and impair the serotonin system. Repeated exposure shows conflicting results depending on dosing, testing environment, and timing. There is little research on adolescent females. More consistent dosing and female subjects are needed.

Study at a glance

Characteristics Systematic review Peer reviewed
Population Adolescent rodents and humans
Topics MDMA Serotonin
Keywords Stimulant Monoamine neurotransmitter Psychology
Key finding 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.

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