Balancing Therapeutic Efficacy and Safety of MDMA and Novel MDXX Analogues as Novel Treatments for Autism Spectrum Disorder.
Harpreet Kaur, Sedat Karabulut, James W Gauld, Stephen A Fagot, Kalee N Holloway, Hannah E. Shaw, William E Fantegrossi
Psychedelic Medicine September 1, 2023 DOI: 10.1089/psymed.2023.0023 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | MDMA |
| Keywords | Autism Psychopharmacology |
| Citations | 10 |
| Key findings | MDXX drugs, including MDMA and MBDB, may offer a promising chemical space for developing clinically effective and safer treatments for autism spectrum disorder. |
Abstract
Autism spectrum disorder (ASD) encompasses a range of neurodevelopmental syndromes diagnostically characterized by deficits in social communication and social interaction and repetitive, inflexible patterns of behaviors, interests, and thoughts. ASD affects people worldwide, irrespective of race, ethnicity, or socio-economic status, with debilitating effects on employment and interpersonal relationships. Though the atypical antipsychotics aripiprazole and risperidone are approved to treat irritability associated with ASD, these drugs may elicit treatment-limiting adverse effects, such as suicidal ideation, sedation, diarrhea, loss of appetite, dizziness, and weight gain. However, there are no approved pharmacotherapeutics for global symptoms of ASD, and better treatments are needed. Drugs with pro-social effects, such as 3,4-methylenedioxymethamphetamine (MDMA) and its analogues, may be beneficial here, as social anxiety and social avoidance are major complications of ASD that adversely impact the quality of life for sufferers and caregivers. This review describes the complex pharmacology of methylenedioxy amphetamine analogues (hereafter referred to as MDXX drugs), focusing on MDMA and 3,4-methylenedioxy-N-methyl-α-ethylphenylethylamine (MBDB) and how they may help treat ASD. Specifically, we address the roles of various drug-binding sites, metabolic enzymes, and chemical structure-activity relationships that mediate these substances' pharmacological and toxicological effects. Throughout the review, we emphasize the distinct profiles of individual stereoisomers of the MDXX drugs and how combining these enantiomers as racemic mixtures may explain the complexity of drug effects on behavior and physiology. We propose that the MDXX drugs represent a fruitful chemical space for developing clinically effective and relatively safer molecules and formulations for treating ASD.
Comparable studies
Other narrative reviews on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Human Pharmacology of MDMA | 2004 | Review | |
| Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research | 2001 | Review | |
| 3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans | 1994 | Review | |
| (±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Studies in Animals | 2000 | Review | |
| Amphetamine toxicities | 2010 | Review |
Citations in the library
Cited by 6
- MDMA enhances empathy-like behaviors in mice via 5-HT release in the nucleus accumbens. Science Advances April 26, 2024
- Investigating the impact of serotonergic psychedelic drugs, MDMA and ketamine on social cognition in psychiatric disorders: A scoping review. Psychopharmacology July 1, 2026
- Psychedelics and autism spectrum disorder: Mechanistic insights, translational evidence and ethical challenges Journal of Psychiatric Research June 23, 2026
- Hallucinogenic drug use and depression, psychological distress and suicidality among disabled adults in the US. Addictive Behaviors November 1, 2025
- MDMA in Psychiatry: From PTSD to emerging indications, safety, and future directions Psychedelics October 14, 2025
and 1 more in the library
Cites 68
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- The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Proceedings of the National Academy of Sciences March 1, 1992
and 63 more in the library