Adverse events in clinical treatments with serotonergic psychedelics and MDMA: A mixed-methods systematic review - PubMed (original) (raw)
Review
Adverse events in clinical treatments with serotonergic psychedelics and MDMA: A mixed-methods systematic review
Joost J Breeksema et al. J Psychopharmacol. 2022 Oct.
Abstract
Introduction: Small-scale clinical studies with psychedelic drugs have shown promising results for the treatment of several mental disorders. Before psychedelics become registered medicines, it is important to know the full range of adverse events (AEs) for making balanced treatment decisions.
Objective: To systematically review the presence of AEs during and after administration of serotonergic psychedelics and 3,4-methyenedioxymethamphetamine (MDMA) in clinical studies.
Methods: We systematically searched PubMed, PsycINFO, Embase, and ClinicalTrials.gov for clinical trials with psychedelics since 2000 describing the results of quantitative and qualitative studies.
Results: We included 44 articles (34 quantitative + 10 qualitative), describing treatments with MDMA and serotonergic psychedelics (psilocybin, lysergic acid diethylamide, and ayahuasca) in 598 unique patients. In many studies, AEs were not systematically assessed. Despite this limitation, treatments seemed to be overall well tolerated. Nausea, headaches, and anxiety were commonly reported acute AEs across diagnoses and compounds. Late AEs included headaches (psilocybin, MDMA), fatigue, low mood, and anxiety (MDMA). One serious AE occurred during MDMA administration (increase in premature ventricular contractions requiring brief hospitalization); no other AEs required medical intervention. Qualitative studies suggested that psychologically challenging experiences may also be therapeutically beneficial. Except for ayahuasca, a large proportion of patients had prior experience with psychedelic drugs before entering studies.
Conclusions: AEs are poorly defined in the context of psychedelic treatments and are probably underreported in the literature due to study design (lack of systematic assessment of AEs) and sample selection. Acute challenging experiences may be therapeutically meaningful, but a better understanding of AEs in the context of psychedelic treatments requires systematic and detailed reporting.
Keywords: LSD; MDMA; Psychedelics; adverse effects; adverse events; ayahuasca; psilocybin.
Conflict of interest statement
The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RS received a research grant from the Netherlands Organization Health Research and Development for a clinical study on oral esketamine, and is the co-investigator of a clinical study on psilocybin funded by Compass Pathways. He has also received an educational grant from Janssen, Pharmaceutical Companies of Johnson and Johnson, and honorarium from Clexio Biosciences. EV is the principal investigator of a clinical trial on MDMA funded by the Multidisciplinary Association for Psychedelic Studies. WvdB has been a consultant for Janssen Netherlands and is a member of the Scientific Advisory Board of Clearmind. JJB, BK and JK declare no conflicts of interest.
Figures
Figure 1.
Flowchart.
Similar articles
- Efficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and meta-analysis.
Yao Y, Guo D, Lu TS, Liu FL, Huang SH, Diao MQ, Li SX, Zhang XJ, Kosten TR, Shi J, Bao YP, Lu L, Han Y. Yao Y, et al. Psychiatry Res. 2024 May;335:115886. doi: 10.1016/j.psychres.2024.115886. Epub 2024 Mar 28. Psychiatry Res. 2024. PMID: 38574699 Review. - Psychedelics and Psychedelic-Assisted Psychotherapy.
Reiff CM, Richman EE, Nemeroff CB, Carpenter LL, Widge AS, Rodriguez CI, Kalin NH, McDonald WM; the Work Group on Biomarkers and Novel Treatments, a Division of the American Psychiatric Association Council of Research. Reiff CM, et al. Am J Psychiatry. 2020 May 1;177(5):391-410. doi: 10.1176/appi.ajp.2019.19010035. Epub 2020 Feb 26. Am J Psychiatry. 2020. PMID: 32098487 Review. - Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews.
Dos Santos RG, Bouso JC, Alcázar-Córcoles MÁ, Hallak JEC. Dos Santos RG, et al. Expert Rev Clin Pharmacol. 2018 Sep;11(9):889-902. doi: 10.1080/17512433.2018.1511424. Epub 2018 Aug 23. Expert Rev Clin Pharmacol. 2018. PMID: 30102078 Review. - Psychedelics: Alternative and Potential Therapeutic Options for Treating Mood and Anxiety Disorders.
Lowe H, Toyang N, Steele B, Grant J, Ali A, Gordon L, Ngwa W. Lowe H, et al. Molecules. 2022 Apr 14;27(8):2520. doi: 10.3390/molecules27082520. Molecules. 2022. PMID: 35458717 Free PMC article. Review. - [Efficacy of psychedelics in psychiatry, a systematic review of the literature].
Berkovitch L, Roméo B, Karila L, Gaillard R, Benyamina A. Berkovitch L, et al. Encephale. 2021 Aug;47(4):376-387. doi: 10.1016/j.encep.2020.12.002. Epub 2021 Apr 20. Encephale. 2021. PMID: 33888297 French.
Cited by
- Adverse Events in Studies of Classic Psychedelics: A Systematic Review and Meta-Analysis.
Hinkle JT, Graziosi M, Nayak SM, Yaden DB. Hinkle JT, et al. JAMA Psychiatry. 2024 Sep 4:e242546. doi: 10.1001/jamapsychiatry.2024.2546. Online ahead of print. JAMA Psychiatry. 2024. PMID: 39230883 - [Psychedelic and dissociative agents in psychiatry: challenges in the treatment].
Jungwirth J, Bavato F, Quednow BB. Jungwirth J, et al. Nervenarzt. 2024 Sep;95(9):803-810. doi: 10.1007/s00115-024-01727-0. Epub 2024 Aug 28. Nervenarzt. 2024. PMID: 39196383 Free PMC article. Review. German. - From chaos to kaleidoscope: Exploring factors in psychedelic self-treatment for mental health conditions.
Walker C, Piatkowski T, Ferris J, Davies E, Barratt M, Winstock A, Puljević C. Walker C, et al. J Psychopharmacol. 2024 Aug;38(8):749-760. doi: 10.1177/02698811241265762. Epub 2024 Jul 29. J Psychopharmacol. 2024. PMID: 39075756 Free PMC article. - Current Perspectives on the Clinical Research and Medicalization of Psychedelic Drugs for Addiction Treatments: Safety, Efficacy, Limitations and Challenges.
Gomez-Escolar A, Folch-Sanchez D, Stefaniuk J, Swithenbank Z, Nisa A, Braddick F, Idrees Chaudhary N, van der Meer PB, Batalla A. Gomez-Escolar A, et al. CNS Drugs. 2024 Oct;38(10):771-789. doi: 10.1007/s40263-024-01101-3. Epub 2024 Jul 20. CNS Drugs. 2024. PMID: 39033264 Review. - Personality traits explain the relationship between psychedelic use and less depression in a comparative study.
Sjöström DK, Claesdotter-Knutsson E, Kajonius PJ. Sjöström DK, et al. Sci Rep. 2024 May 3;14(1):10195. doi: 10.1038/s41598-024-60890-1. Sci Rep. 2024. PMID: 38702496 Free PMC article.
References
- Andersen KAA, Carhart-Harris R, Nutt DJ, et al.. (2020) Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern-era clinical studies. Acta Psychiatr Scand 2021 143: 101–118. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical