Associations between classic psychedelics and opioid use disorder in a nationally-representative U.S. adult sample

This survey study used data from the U.S. National Survey on Drug Use and Health (2015–2019) (N = 214,505) to assess the association between psychedelic use and opioid use disorder (OUD). Lifetime psilocybin use was associated with lowered odds while no other substances, including other classic psychedelics, were associated with lowered odds of OUD.

Abstract

“Opioid use disorder (OUD) is a major source of morbidity and mortality in the U.S. and there is a pressing need to identify additional treatments for the disorder. Classic psychedelics (psilocybin, peyote, mescaline, LSD) have been linked to the alleviation of various substance use disorders and may hold promise as potential treatments for OUD. The aim of this study was to assess whether the aforementioned classic psychedelic substances conferred lowered odds of OUD. Furthermore, this study aimed to replicate and extend findings from Pisano et al. (2017) who found classic psychedelic use to be linked to lowered odds of OUD in a nationally representative sample. We used recent data from the National Survey on Drug Use and Health (2015–2019) (N = 214,505) and multivariable logistic regression to test whether lifetime use (yes/no) of classic psychedelics was associated with lowered odds of OUD. Lifetime psilocybin use was associated with lowered odds of OUD (aOR: 0.70; 95% CI [0.60, 0.83]). No other substances, including other classic psychedelics, were associated with lowered odds of OUD. Additionally, sensitivity analyses revealed psilocybin use to be associated with lowered odds of seven of the 11 DSM-IV criteria for OUD (aOR range: 0.66–0.83). Future clinical trials and longitudinal studies are needed to determine whether these associations are causal.”

Authors: Grant Jones, Jocelyn A. Ricard, Joshua Lipson & Matthew K. Nock

Summary

Opioid use disorder (OUD) is a major public health crisis in the United States, with methadone and buprenorphine being the gold-standard pharmacological treatments for opioid dependence. However, these treatments come with high risk of dependence, therefore often trading one addiction for another.

Classic psychedelics include LSD, psilocybin, ayahuasca, DMT, peyote, and mescaline, and have been shown to have promise as treatments for substance dependence and abuse. Additionally, 96% of patients who self-administered psychedelics before and after administration met criteria for a substance use disorder.

A few studies have hinted that the association between classic psychedelic use and OUD is worth exploring, however, and a landmark study has demonstrated that classic psychedelic use confers 27% reduced risk of past-year opioid dependence and 40% reduced risk of past-year opioid abuse.

This study uses the latest NSDUH data to replicate and extend the findings from Pisano et al. on the associations between naturalistic use of psychedelics and opioid dependence, as well as to examine the unique associations that individual classic psychedelics share with OUD.

Method

Data were collected from the National Survey on Drug Use and Health (NSDUH) in 2015 and 2019. All adults aged 18 years were included in this study.

We used survey-weighted multivariable logistic regression models to analyze the NSDUH data and found that classic psychedelics were associated with lowered odds of opioid use disorder (OUD).

We included lifetime use of the four most frequently used classic psychedelics in the NSDUH as well as demographic factors and substances as covariates within our analyses.

Dependent variables included past year diagnosis of OUD and each of the 11 DSM-IV diagnostic criteria for opioid dependence or abuse.

Opioid use caused serious problems for the user, including problems with emotions, nerves, mental health, or physical health, and reduced or given up participation in important activities due to opioid use.

Psilocybin was the only substance associated with lowered odds of OUD, while all other substances examined were either no association with OUD or were associated with increased odds of OUD.

Results

Psilocybin use was associated with lowered odds of seven out of 11 DSM-IV criteria for opioid dependence and abuse.

Psilocybin users who have versus have not misused opioids differed from one another on all of the demographic traits assessed, suggesting that third-variable demographic variables partially mediate the associations between psilocybin and lowered odds of OUD.

Discussion

Psilocybin was the sole classic psychedelic substance associated with lowered odds of past year opioid use disorder in a large, nationally-representative sample of the U.S. population.

This study replicates Pisano et al. ‘s original finding that lifetime use of psychedelics conferred lowered odds of opioid dependence and abuse. It suggests that psilocybin-based treatments for opioid addiction may be effective.

Limitations include the fact that the results are based on cross-sectional data and that under-reporting might be a confound in the analyses and conclusions. Additionally, the NSDUH does not assess homelessness status or collect information on individuals who are currently incarcerated or serving as active-duty military members.

Potential mediators include the effects of psilocybin on the serotonin system, which are linked to the protective association of psilocybin with OUD.

There is suggestive evidence that serotonin agonists may support the treatment of opioid addiction by indirectly inhibiting the release of dopamine, a key neurotransmitter implicated in the maladaptive reward system changes associated with opioid addiction.

Psilocybin induces mystical-type experiences, which may explain the protective associations between psilocybin and OUD. Further inquiry into the role of mystical-type experiences in promoting recovery from addiction is needed.

Additionally, demographic differences associated with psilocybin use and OUD may contribute to our observed associations. Further research should investigate how demographic differences impact the associations between psilocybin use and lowered odds of OUD.

Psilocybin was associated with a lowered odds of opioid dependence and abuse in the DSM-IV, but no other classic psychedelic substance was.

Conclusion

This study replicates Pisano et al.’s finding that classic psychedelics may lower odds of opioid use disorder, but only for psilocybin. Future clinical trials should test whether this association is causal, and identify which mediators may underlie this association.

Additional information

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