Psychiatric risks for worsened mental health after psychedelic use
In a pooled analysis of 807 naturalistic prospective studies, 16% of participants experienced a clinically meaningful decline in mental health four weeks after psychedelic use, with those reporting a prior personality disorder showing a disproportionate prevalence (31%) and a greater-than-fourfold elevated risk of adverse response. The authors conclude that personality disorder may be an important risk factor for psychedelic-related psychological harm, indicating a need for enhanced psychological support and therapeutic alliance for this group.
Authors
- Richard Zeifman
- Robin Carhart-Harris
- David Erritzoe
Published
Abstract
Background
Resurgent psychedelic research has largely supported the safety and efficacy of psychedelic therapy for the treatment of various psychiatric disorders. As psychedelic use and therapy increase in prevalence, so does the importance of understanding associated risks. Cases of prolonged negative psychological responses to psychedelic therapy seem to be rare; however, studies are limited by biases and small sample sizes. The current analytical approach was motivated by the question of whether rare but significant adverse effects have been under-sampled in psychedelic research studies.
Methods
A “bottom margin analysis” approach was taken to focus on negative responders to psychedelic use in a pool of naturalistic, observational prospective studies ( N = 807). We define “negative response” by a clinically meaningful decline in a generic index of mental health, that is, one standard error from the mean decrease in psychological well-being 4 weeks post-psychedelic use (vs pre-use baseline). We then assessed whether a history of diagnosed mental illness can predict negative responses.
Results
We find that 16% of the cohort falls into the “negative responder” subset. Parsing the sample by self-reported history of psychiatric diagnoses, results revealed a disproportionate prevalence of negative responses among those reporting a prior personality disorder diagnosis (31%). One multivariate regression model indicated a greater than four-fold elevated risk of adverse psychological responses to psychedelics in the personality disorder subsample ( b = 1.425, p < 0.05).
Conclusion
We infer that the presence of a personality disorder may represent an elevated risk for psychedelic use and hypothesize that the importance of psychological support and good therapeutic alliance may be increased in this population.
Research Summary of 'Psychiatric risks for worsened mental health after psychedelic use'
Introduction
Recent years have seen a renaissance in research into psychedelic-assisted interventions, with prior studies indicating potential safety and therapeutic benefit across conditions such as major depressive disorder, addiction, obsessive-compulsive disorder and end-of-life anxiety. However, the extracted text notes lingering uncertainties about rare but clinically meaningful adverse psychological responses, especially because modern clinical trials typically exclude people with histories of psychosis, bipolar disorder or personality disorders and apply careful screening and therapeutic support. The authors frame concerns that limited sample sizes, brief follow-ups, selective recruitment and measurement approaches in existing research may have under-sampled or missed low-prevalence but important negative outcomes following psychedelic use. Marrocu and colleagues set out to identify and characterise a ‘‘bottom margin’’ of individuals who experienced a clinically meaningful decline in psychological well‑being after an intentioned psychedelic experience in naturalistic contexts. Using pooled prospective survey data from three independent studies, they ask whether self‑reported prior psychiatric diagnoses predict membership in this negative‑response subset, operationalised as a decline on the Warwick‑Edinburgh Mental Well‑Being Scale (WEMWBS) at 4 weeks post‑use greater than the instrument’s standard error of measurement (SEM). The stated aim is to identify potentially vulnerable populations in order to inform risk‑mitigation for psychedelic use and therapy.
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Study Details
- Study Typeindividual
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- APA Citation
Marrocu, A., Kettner, H., Weiss, B., Zeifman, R. J., Erritzoe, D., & Carhart-Harris, R. L. (2024). Psychiatric risks for worsened mental health after psychedelic use. Journal of Psychopharmacology, 38(3), 225-235. https://doi.org/10.1177/02698811241232548
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