Psychiatric risks for worsened mental health after psychedelic use

This prospective observational pre-print study (n=807) analyzed negative psychological responses to psychedelics, defining it as a clinically meaningful decline in mental health four weeks post-use. They found that 16% of participants experienced negative responses, with a notably higher prevalence (31%) among those with a prior diagnosis of personality disorder. The study implies that individuals with a history of personality disorder might face elevated risks with psychedelic use, emphasizing the need for enhanced psychological support and therapeutic alliance in this population.

Abstract of Psychiatric risks for worsened mental health after psychedelic use

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 increases in prevalence, so does the importance of understanding associated risks. Cases of prolonged negative psychological responses to psychedelic therapy seem 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, i.e., a 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 fall 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 sub-sample (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.”

Authors: Alessia Marrocu, Hannes Kettner, Brandon Weiss, Richard J. Zeifman, David Erritzoe & Robin L. Carhart-Harris

Summary of Psychiatric risks for worsened mental health after psychedelic use


Psychedelic therapy has been shown to be safe and effective for a wide range of psychiatric disorders, including MDD, addiction, obsessive-compulsive disorder, and end-of-life anxiety. Additionally, evidence exists for post-psychedelic improvements in mental health outcomes in general populations. Psychedelic interventions are not risk-free, especially when their use is divorced from psychological support. Case reports have described the occurrence of symptoms resembling psychotic episodes and hallucinogen persisting perception disorder (HPPD), which emerged as a DSM-recognized condition in the 1980s. Few negative and mostly minor adverse effects have been documented in controlled research with psychedelics, and the prevalence of cases of iatrogenesis is less than 0.2% in vulnerable populations. This is likely due to careful screening and controlled experimental guidelines.

Psychedelics pose a risk of psychologically unpleasant acute experiences, and subjective responses remain unpredictable. A bottom-margin analysis is a method for analyzing a small subset of ‘worst-case’ responders in a large sample of individuals, tracked prospectively, who reported on real-world psychedelic use. In the present study, we assessed whether self-reported psychiatric history could predict adverse psychological responses to psychedelics. We hypothesized that clinical subgroups such as those commonly excluded from modern trials would be at particular risk of negative responses.

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Psychiatric risks for worsened mental health after psychedelic use

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Cite this paper (APA)

Marrocu, A., Kettner, H., Weiss, B., Zeifman, R., Erritzoe, D., & Carhart-Harris, R. (2023). Psychiatric risks for worsened mental health after psychedelic use.

Study details

807 Humans

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