Applications of MDMA in Modern Medicine - A Literature Review
DOI:
https://doi.org/10.12775/JEHS.2025.77.56620Keywords
MDMA, psychiatry, psychotherapy, neurobiology, serotoninAbstract
MDMA or 3,4- methylenedioxymethamphetamine is a psychoactive substance, exhibiting mild hallucinogenic properties, that became widely known as a recreational party drug. However, its ability in helping individuals access deeply rooted emotions has prompted significant interest in its potential applications within clinical practice. MDMA’s mechanism of action involves increasing the release of serotonin, dopamine and oxytocin. This process enhances neuroplasticity, fosters empathy and aids in trauma processing and fear extinction. This study aims to explore the potential uses of MDMA in medicine, particularly in treating mental illnesses. The article was developed using data from the „PubMed” and „Google Scholar” databases, with particular emphasis on articles published after 2021. When combined with psychotherapy, MDMA offers significant therapeutic benefits, especially for patients resistant to conventional treatments. Existing research primarily highlights its effectiveness in managing post traumatic stress disorder (PTSD) and anxiety disorders, with emerging evidence suggesting potential benefits for conditions like depression and eating disorder. While recreational use of MDMA poses risks, its use in a controlled environment demonstrates a favourable safety profile. Despite the highly promising results of MDMA- assisted therapy so far, additional clinical research is crucial to enable this drug to revolutionise future treatment methods.
References
García-Montes JM, Pérez-Álvarez M, Sánchez-Moya MÁ, et al. Ecstasy (MDMA): A rebellion coherent with the system. Nordic Studies on Alcohol and Drugs. 2020;38(1):89-102. doi:https://doi.org/10.1177/1455072520954329
Cooper M, Kim A. MDMA in Psychiatry: Past, Present, and Future. American Journal of Psychiatry Residents’ Journal. 2018;13(2):10-10. doi:10.1176/appi.ajp-rj.2018.130204
Gregorio DD, Aguilar-Valles A, Preller KH, et al. Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine. Journal of Neuroscience. 2021;41(5):891-900. doi:https://doi.org/10.1523/JNEUROSCI.1659-20.2020
Sessa B, Nutt D. Making a medicine out of MDMA. Br J Psychiatry. 2015;206(1):4-6. doi:10.1192/bjp.bp.114.152751
Sáez-Briones P, Hernández A. MDMA (3,4-Methylenedioxymethamphetamine) Analogues as Tools to Characterize MDMA-Like Effects: An Approach to Understand Entactogen Pharmacology. Curr Neuropharmacol. 2013;11(5):521-534. doi:10.2174/1570159X11311050007
Hysek CM, Schmid Y, Simmler LD, et al. MDMA enhances emotional empathy and prosocial behavior. Soc Cogn Affect Neurosci. 2014;9(11):1645-1652. doi:10.1093/scan/nst161
Vamvakopoulou IA, Nutt DJ. Psychedelics: From Cave Art to 21st-Century Medicine for Addiction. Eur Addict Res. 2024;30(5):302-320. doi:10.1159/000540062
Meyer JS. 3,4-methylenedioxymethamphetamine (MDMA): current perspectives. Subst Abuse Rehabil. 2013;4:83-99. Published 2013 Nov 21. doi:10.2147/SAR.S37258
Drevin G, Pena-Martin M, Bauduin A, Baudriller A, Briet M, Abbara C. Pharmacogenomics of 3,4-Methylenedioxymethamphetamine (MDMA): A Narrative Review of the Literature. Pharmaceutics. 2024;16(8):1091. Published 2024 Aug 20. doi:10.3390/pharmaceutics16081091
Meyer JS. 3,4-methylenedioxymethamphetamine (MDMA): current perspectives. Subst Abuse Rehabil. 2013;4:83-99. Published 2013 Nov 21. doi:10.2147/SAR.S37258
Gołembiowska K, Jurczak A, Kamińska K, Noworyta-Sokołowska K, Górska A. Effect of Some Psychoactive Drugs Used as 'Legal Highs' on Brain Neurotransmitters. Neurotox Res. 2016;29(3):394-407. doi:10.1007/s12640-015-9569-1
Zhen Z, Sun X, Yuan S, Zhang J. Psychoactive substances for the treatment of neuropsychiatric disorders. Asian Journal of Psychiatry. 2024;101:104193-104193. doi:https://doi.org/10.1016/j.ajp.2024.104193
Sottile RJ, Vida T. A proposed mechanism for the MDMA-mediated extinction of traumatic memories in PTSD patients treated with MDMA-assisted therapy. Front Psychiatry. 2022;13:991753. Published 2022 Oct 12. doi:10.3389/fpsyt.2022.991753
Marchetta E, Mancini GF, Morena M, Campolongo P. Enhancing Psychological Interventions for Post-Traumatic Stress Disorder (PTSD) Treatment with Memory Influencing Drugs. Curr Neuropharmacol. 2023;21(3):687-707. doi:10.2174/1570159X21666221207162750
Mitchell JM, Ot'alora G M, van der Kolk B, et al. MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial [published correction appears in Nat Med. 2024 Nov;30(11):3382. doi: 10.1038/s41591-024-03331-w]. Nat Med. 2023;29(10):2473-2480. doi:10.1038/s41591-023-02565-4
Tedesco S, Gajaram G, Chida S, et al. The Efficacy of MDMA (3,4-Methylenedioxymethamphetamine) for Post-traumatic Stress Disorder in Humans: A Systematic Review and Meta-Analysis. Cureus. 2021;13(5):e15070. Published 2021 May 17. doi:10.7759/cureus.15070
Zagorski N. Australia Legalizes Psychedelics for Use in Depression, PTSD Therapy. Psychiatric News. 2023;58(09). doi:10.1176/appi.pn.2023.09.9.20
Rijkers C, Schoorl M, van Hoeken D, Hoek HW. Eating disorders and posttraumatic stress disorder. Curr Opin Psychiatry. 2019;32(6):510-517. doi:10.1097/YCO.0000000000000545
Convertino AD, Mendoza RR. Posttraumatic stress disorder, traumatic events, and longitudinal eating disorder treatment outcomes: A systematic review. Int J Eat Disord. 2023;56(6):1055-1074. doi:10.1002/eat.23933
Brewerton TD, Lafrance A, Mithoefer MC. The potential use of N-methyl-3,4-methylenedioxyamphetamine (MDMA) assisted psychotherapy in the treatment of eating disorders comorbid with PTSD. Med Hypotheses. 2021;146:110367. doi:10.1016/j.mehy.2020.110367
Brewerton TD, Wang JB, Lafrance A, et al. MDMA-assisted therapy significantly reduces eating disorder symptoms in a randomized placebo-controlled trial of adults with severe PTSD. J Psychiatr Res. 2022;149:128-135. doi:10.1016/j.jpsychires.2022.03.008
Calder A, Mock S, Friedli N, Pasi P, Hasler G. Psychedelics in the treatment of eating disorders: Rationale and potential mechanisms. Eur Neuropsychopharmacol. 2023;75:1-14. doi:10.1016/j.euroneuro.2023.05.008
Nechita D, Nechita F, Motorga R. A review of the influence the anxiety exerts on human life. Rom J Morphol Embryol. 2018;59(4):1045-1051
Lear MK, Smith SM, Pilecki B, Stauffer CS, Luoma JB. Social anxiety and MDMA-assisted therapy investigation: a novel clinical trial protocol. Front Psychiatry. 2023;14:1083354. Published 2023 Jul 14. doi:10.3389/fpsyt.2023.1083354
Sartori SB, Singewald N. Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders. Pharmacol Ther. 2019;204:107402. doi:10.1016/j.pharmthera.2019.107402
Kuypers KPC, Dolder PC, Ramaekers JG, Liechti ME. Multifaceted empathy of healthy volunteers after single doses of MDMA: A pooled sample of placebo-controlled studies. J Psychopharmacol. 2017;31(5):589-598. doi:10.1177/0269881117699617
Danforth AL, Grob CS, Struble C, et al. Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study. Psychopharmacology (Berl). 2018;235(11):3137-3148. doi:10.1007/s00213-018-5010-9
Marx W, Penninx BWJH, Solmi M, et al. Major depressive disorder. Nat Rev Dis Primers. 2023;9(1):44. Published 2023 Aug 24. doi:10.1038/s41572-023-00454-1
Majumder I, White JM, Irvine RJ. Antidepressant-like effects of 3,4-methylenedioxymethamphetamine in an animal model of depression. Behav Pharmacol. 2011;22(8):758-765. doi:10.1097/FBP.0b013e32834d0f05
Mithoefer MC, Mithoefer AT, Feduccia AA, et al. 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. Lancet Psychiatry. 2018;5(6):486-497. doi:10.1016/S2215-0366(18)30135-4
Pantoni MM, Kim JL, Van Alstyne KR, Anagnostaras SG. MDMA and memory, addiction, and depression: dose-effect analysis [published correction appears in Psychopharmacology (Berl). 2022 Jul;239(7):2369. doi: 10.1007/s00213-022-06126-4]. Psychopharmacology (Berl). 2022;239(3):935-949. doi:10.1007/s00213-022-06086-9
Wunderli MD, Vonmoos M, Fürst M, et al. Discrete memory impairments in largely pure chronic users of MDMA. Eur Neuropsychopharmacol. 2017;27(10):987-999. doi:10.1016/j.euroneuro.2017.08.425
Costa G, Gołembiowska K. Neurotoxicity of MDMA: Main effects and mechanisms. Exp Neurol. 2022;347:113894. doi:10.1016/j.expneurol.2021.113894
Mustafa NS, Bakar NHA, Mohamad N, et al. MDMA and the Brain: A Short Review on the Role of Neurotransmitters in Neurotoxicity. Basic Clin Neurosci. 2020;11(4):381-388. doi:10.32598/bcn.9.10.485
Kermanian F, Seghatoleslam M, Mahakizadeh S. MDMA related neuro-inflammation and adenosine receptors. Neurochem Int. 2022;153:105275. doi:10.1016/j.neuint.2021.105275
van Amsterdam J, Pennings E, van den Brink W. Fatal and non-fatal health incidents related to recreational ecstasy use. J Psychopharmacol. 2020;34(6):591-599. doi:10.1177/0269881119897559
van Amsterdam J, Brunt TM, Pierce M, van den Brink W. Hard Boiled: Alcohol Use as a Risk Factor for MDMA-Induced Hyperthermia: a Systematic Review. Neurotox Res. 2021;39(6):2120-2133. doi:10.1007/s12640-021-00416-z
Bonsignore A, Barranco R, Morando A, Fraternali Orcioni G, Ventura F. MDMA Induced Cardio-toxicity and Pathological Myocardial Effects: A Systematic Review of Experimental Data and Autopsy Findings. Cardiovasc Toxicol. 2019;19(6):493-499. doi:10.1007/s12012-019-09526-9
Wang E, Mathai DS, Gukasyan N, Nayak S, Garcia-Romeu A. Knowledge, attitudes, and concerns about psilocybin and MDMA as novel therapies among U.S. healthcare professionals. Sci Rep. 2024;14(1):28022. Published 2024 Nov 14. doi:10.1038/s41598-024-78736-1
Zeifman RJ, Kettner H, Pagni BA, et al. Co-use of MDMA with psilocybin/LSD may buffer against challenging experiences and enhance positive experiences. Sci Rep. 2023;13(1):13645. Published 2023 Aug 22. doi:10.1038/s41598-023-40856-5
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Wiktoria Podlasiewicz, Paweł Siudziński, Mateusz Łyko, Alicja Skoczylas, Jakub Kurasz, Wojciech Maj, Wiktoria Tomaszewska, Katarzyna Pala, Piotr Dudziak, Anna Nowak, Maria Golińska
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 12
Number of citations: 0