Anxiety DisordersTobacco/Nicotine Use Disorder (TUD)Substance Use Disorders (SUD)Set & SettingLSDMescalinePsilocybin

The association between naturalistic use of psychedelics and co-occurring substance use disorders

Using 2017 NSDUH data (n=56,276), the authors found past naturalistic use of peyote/mescaline was associated with lower odds of past-year substance dependence or abuse (adjusted OR 0.68, p<0.001), whereas past LSD and psilocybin use were associated with increased odds; none of the classic psychedelics were linked to nicotine dependence. The paper notes it is unclear whether these differences reflect pharmacological properties or the cultural/ceremonial contexts of peyote/mescaline use.

Authors

  • Rabinowitz, J.
  • Lev-Ran, S.
  • Gross, R.

Published

Frontiers in Psychiatry
individual Study

Abstract

Objective

Classic psychedelics (LSD, psilocybin, and peyote/mescaline) have been used to support addiction treatment in a variety of contexts ranging from ceremonial use to clinical trials. The aim of this study was to test the hypothesis that past naturalistic use of classic psychedelics would be associated with decreased prevalence of substance use disorder, when controlling for known confounders.

Methods

This cross-sectional study used 2017 NSDUH survey data to evaluate the association between past use of the classic psychedelics LSD, psilocybin and peyote/mescaline and past year substance dependence or abuse. We calculated adjusted odds ratios by multivariate logistic regression, controlling for a range of sociodemographic variables, use of non-psychedelic illicit drugs and mental health related variables.

Results

A total of 56,276 participants were included in this study. Past use of LSD and psilocybin were associated with increased odds of substance dependence or abuse compared to those who had never used psychedelics before, and this was more likely for those who had used LSD more recently. However, prior use of peyote or mescaline was associated with lower odds of past year substance dependence or abuse compared to people who had never used psychedelics before (aOR = 0.68, p < 0.001). Past use of classic psychedelics was not associated with nicotine dependence.

Conclusion

Past use of peyote/mescaline was associated with decreased odds of substance use disorder compared to people who had never used psychedelics before, while past use of LSD or psilocybin was not. It remains unclear whether this difference is due to pharmacological differences between these compounds or simply due to the context in which peyote/mescaline are traditionally taken. Future research should investigate why naturalistic use of different psychedelics is associated with different substance use disorder effects.

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Research Summary of 'The association between naturalistic use of psychedelics and co-occurring substance use disorders'

Introduction

Alcohol and drug addiction impose a large and growing public‑health burden, and existing treatments for substance use disorders (SUD) have limited effectiveness for many patients. Earlier clinical and epidemiological research, including mid‑20th century LSD trials and more recent studies of psychedelic‑assisted psychotherapy, has suggested that classic psychedelics (principally LSD, psilocybin and mescaline) can produce enduring improvements in mood, anxiety and addictive behaviours. Proposed mechanisms include serotonin 5‑HT2A receptor agonism that increases glutamatergic transmission and neuroplasticity, psychological effects of mystical or peak experiences, and modulation of impulsivity; contemporary frameworks also emphasise the importance of context or "set and setting" in shaping outcomes, and point to longstanding ceremonial use of substances such as peyote in communal healing rituals. Amit and colleagues framed this work around a gap in population‑level evidence: while some large naturalistic studies report positive mental‑health associations for psychedelic use, there are few large, representative analyses that compare different classic psychedelics individually against a broad SUD outcome. The study therefore aimed to test whether lifetime naturalistic exposure to classic psychedelics (examined both as a class and separately as LSD, psilocybin and peyote/mescaline) was associated with lower prevalence of past‑year substance dependence or abuse after adjustment for sociodemographic, psychiatric and other drug‑use confounders, with nicotine dependence included as a secondary outcome.

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Study Details

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