TY - JOUR
T1 - Adverse events in clinical treatments with serotonergic psychedelics and MDMA
T2 - A mixed-methods systematic review
AU - Breeksema, Joost J.
AU - Kuin, Bouwe W.
AU - Kamphuis, Jeanine
AU - van den Brink, Wim
AU - Vermetten, Eric
AU - Schoevers, Robert A.
N1 - Funding Information: 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. Publisher Copyright: © The Author(s) 2022.
PY - 2022/10
Y1 - 2022/10
N2 - 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.
AB - 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.
KW - LSD
KW - MDMA
KW - Psychedelics
KW - adverse effects
KW - adverse events
KW - ayahuasca
KW - psilocybin
UR - http://www.scopus.com/inward/record.url?scp=85136655260&partnerID=8YFLogxK
U2 - https://doi.org/10.1177/02698811221116926
DO - https://doi.org/10.1177/02698811221116926
M3 - Review article
C2 - 36017784
SN - 0269-8811
VL - 36
SP - 1100
EP - 1117
JO - Journal of psychopharmacology (Oxford, England)
JF - Journal of psychopharmacology (Oxford, England)
IS - 10
ER -