Cognitive Effects of MDMA in Laboratory Animals: A Systematic Review Focusing on Dose.
Madeline M. Pantoni, Stephan G Anagnostaras
Pharmacological Reviews July 1, 2019 DOI: 10.1124/pr.118.017087 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Population | Animals |
| Intervention | MDMA |
| Dose | less than 3 mg/kg; 3 mg/kg or greater, frequently 5 to 20 times greater than an average dose |
| Topics | MDMA |
| Keywords | Animals, laboratory N-methyl-3,4-methylenedioxyamphetamine Cognition Dose-response relationship, drug |
| Key findings | The authors report no evidence that MDMA doses below 3 mg/kg produce cognitive deficits in animals, and doses of 3 mg/kg or greater also failed to produce deficits in a slight majority of experiments. They conclude that preclinical evidence of MDMA-induced cognitive deficits is weak and may reflect unrealistically high dosing, arguing that short-term, infrequent, ultra-low-dose therapeutic MDMA is unlikely to pose significant cognitive risks. |
Abstract
±3,4-Methylenedioxymethamphetamine (MDMA) is a synthetic, psychoactive drug that is primarily used recreationally but also may have some therapeutic value. At low doses, MDMA produces feelings of relaxation, empathy, emotional closeness, and euphoria. Higher doses can produce unpleasant psychostimulant- and hallucinogen-like adverse effects and therefore are usually not taken intentionally. There is considerable evidence that MDMA produces neurotoxicity and cognitive deficits at high doses; however, these findings may not generalize to typical recreational or therapeutic use of low-dose MDMA. Here, we systematically review 25 years of research on the cognitive effects of MDMA in animals, with a critical focus on dose. We found no evidence that doses of less than 3 mg/kg MDMA-the dose range that users typically take-produce cognitive deficits in animals. Doses of 3 mg/kg or greater, which were administered most often and frequently ranged from 5 to 20 times greater than an average dose, also did not produce cognitive deficits in a slight majority of experiments. Overall, the preclinical evidence of MDMA-induced cognitive deficits is weak and, if anything, may be the result of unrealistically high dosing. While factors associated with recreational use such as polydrug use, adulterants, hyperthermia, and hyponatremia can increase the potential for neurotoxicity, the short-term, infrequent, therapeutic use of ultra low-dose MDMA is unlikely to pose significant cognitive risks. Future studies must examine any adverse cognitive effects of MDMA using clinically relevant doses to reliably assess its potential as a psychotherapeutic.
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
Cited by 16
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- Neurotoxicity of MDMA: Main effects and mechanisms. Experimental Neurology October 1, 2021
- Lifetime use of MDMA/ecstasy and psilocybin is associated with reduced odds of major depressive episodes Journal of Psychopharmacology 2022
- MDMA-assisted psychotherapy for PTSD in adolescents: rationale, potential, risks, and considerations. European Child & Adolescent Psychiatry November 1, 2024
- MDMA-assisted psychotherapy for PTSD: Growing evidence for memory effects mediating treatment efficacy. Progress in Neuro-Psychopharmacology and Biological Psychiatry January 10, 2024
and 11 more in the library
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