Bipolar DisorderSchizophreniaDepressive DisordersAdolescentsSubstance Use Disorders (SUD)

Adolescent Psychedelic Use and Psychotic or Manic Symptoms

In a large Swedish twin cohort, after adjusting for other substance use, lifetime naturalistic psychedelic use was associated with lower self‑reported psychotic symptoms in adolescents. However, psychedelic use interacted with genetic liability for schizophrenia or bipolar I disorder to predict higher self‑reported manic symptoms, so the observational findings warrant cautious interpretation.

Authors

  • Otto Simonsson
  • Wojciech Osika

Published

JAMA Psychiatry
individual Study

Abstract

Importance

While psychedelic-assisted therapy has shown promise in the treatment of certain psychiatric disorders, little is known about the potential risk of psychotic or manic symptoms following naturalistic psychedelic use, especially among adolescents.

Objective

To investigate associations between naturalistic psychedelic use and self-reported psychotic or manic symptoms in adolescents using a genetically informative design.

Design, Setting, and Participants

This study included a large sample of adolescent twins (assessed at age 15, 18, and 24 years) born between July 1992 and December 2005 from the Swedish Twin Registry and cross-sectionally evaluated the associations between past psychedelic use and psychotic or manic symptoms at age 15 years. Individuals were included if they answered questions related to past use of psychedelics. Data were analyzed from October 2022 to November 2023.

Main Outcomes and Measures

Primary outcome measures were self-reported psychotic and manic symptoms at age 15 years. Lifetime use of psychedelics and other drugs was also assessed at the same time point.

Results

Among the 16 255 participants included in the analyses, 8889 were female and 7366 were male. Among them, 541 participants reported past use of psychedelics, most of whom (535 of 541 [99%]) also reported past use of other drugs (ie, cannabis, stimulants, sedatives, opioids, inhalants, or performance enhancers). When adjusting for substance-specific and substance-aggregated drug use, psychedelic use was associated with reduced psychotic symptoms in both linear regression analyses (β, −0.79; 95% CI, −1.18 to −0.41 and β, −0.39; 95% CI, −0.50 to −0.27, respectively) and co-twin control analyses (β, −0.89; 95% CI, −1.61 to −0.16 and β, −0.24; 95% CI, −0.48 to −0.01, respectively). In relation to manic symptoms, likewise adjusting for substance-specific and substance-aggregated drug use, statistically significant interactions were found between psychedelic use and genetic vulnerability to schizophrenia (β, 0.17; 95% CI, 0.01 to 0.32 and β, 0.17; 95% CI, 0.02 to 0.32, respectively) or bipolar I disorder (β, 0.20; 95% CI, 0.04 to 0.36 and β, 0.17; 95% CI, 0.01 to 0.33, respectively).

Conclusions and Relevance

The findings in this study suggest that, after adjusting for other drug use, naturalistic use of psychedelic may be associated with lower rates of psychotic symptoms among adolescents. At the same time, the association between psychedelic use and manic symptoms seems to be associated with genetic vulnerability to schizophrenia or bipolar I disorder. These findings should be considered in light of the study’s limitations and should therefore be interpreted with caution.

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Research Summary of 'Adolescent Psychedelic Use and Psychotic or Manic Symptoms'

Introduction

Recent increases in LSD use among adolescents and rising interest in 5-HT2A agonist psychedelics such as psilocybin have prompted concern about psychiatric risks associated with naturalistic psychedelic use, particularly psychotic or manic symptoms. While controlled clinical settings have provided some safety data, prior observational evidence is vulnerable to familial confounding and other biases, and contemporary trial guidelines exclude individuals with personal or family histories of psychotic or bipolar disorders, limiting empirical characterisation of risk in those groups. The introduction therefore frames a gap in understanding how adolescent psychedelic use relates to psychotic and manic symptoms and whether familial or genetic vulnerability explains any observed associations. Simonsson and colleagues set out to address this gap by analysing data from a large, genetically informative sample of Swedish twins. Their aims were to (1) estimate associations between lifetime naturalistic use of LSD or psilocybin and self-reported psychotic and manic symptoms at age 15, (2) use co-twin control models to assess whether associations persist after accounting for familial confounding, and (3) test gene–environment interactions by examining whether associations vary with polygenic liability for schizophrenia or bipolar I disorder.

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Study Details

References (5)

Papers cited by this study that are also in Blossom

Human hallucinogen research: guidelines for safety

Johnson, M. W., Richards, W. A., Griffiths, R. R. · Journal of Psychopharmacology (2008)

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Rucker, J., Iliff, J., Nutt, D. J. · Neuropharmacology (2017)

Psychedelics and mental health: a population study

Krebs, T. S., Johansen, P. ˚. Ø. · PLOS ONE (2013)

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