Psychedelic use is associated with reduced daily opioid use among people who use illicit drugs in a Canadian setting

This longitudinal study (2021) assessed data from three ongoing open prospective cohorts of people who use drugs (PWUD) in Vancouver, Canada to investigate the relationship between psychedelic use and daily opioid use. This is the first study to find that recent psychedelic use was associated with 55% reduced odds of daily opioid use.

Abstract

“Background: Research into the therapeutic and naturalistic uses of psychedelics for improving outcomes related to mental health disorders has generated increasing interest in recent years. While controlled clinical trials of psychedelics have signaled benefits for treating substance use disorders, this area has not been well studied in the context of naturalistic psychedelic use. This study sought to investigate the possible relationship between recent naturalistic psychedelic use and subsequent daily illicit opioid use among people who use drugs (PWUD).

Methods: Data (2006–2018) were drawn from three harmonized prospective cohorts of community-recruited PWUD in Vancouver, Canada. We used multivariable generalized linear mixed-effects modeling (GLMM) to estimate the independent association between psychedelic use and subsequent daily illicit opioid use.

Results: Among 3813 PWUD at baseline, 1093 (29%) reported daily use of illicit opioids and 229 (6%) reported psychedelic use in the past six months. Over study follow-up after adjusting for a range of potential confounders, psychedelic use remained independently associated with a significantly reduced odds of subsequent daily opioid use (Adjusted Odds Ratio: 0.45; 95% Confidence Interval: 0.29 to 0.70).

Conclusion: While confirmation in other settings is required, these findings align with growing evidence that psychedelic use may be associated with detectable reductions in subsequent substance use including illicit opioid use.”

Authors: Elena Argento, M. Eugenia Socias, Kanna Hayashi, JinCheol Choi, Lindsay Mackay, Devon Christie, M-J. Milloy & Kora DeBeck

Authors Highlights

• Recent psychedelic use was associated with 55% reduced odds of daily opioid use.

• This is the first longitudinal study to link psychedelic use with lower daily opioid use.

• More studies are needed to elucidate the therapeutic potential of psychedelics.

Summary

Introduction

Opioid use disorder is a major public health issue, with more Americans dying from drug overdoses than in the entire Vietnam War. In Canada and internationally, opioid-related deaths continue to rise due to the contamination of the illicit drug supply with fentanyl and related analogues. The COVID-19 pandemic has also contributed to the increase in overdose deaths. While some interventions are proven effective at improving outcomes from opioid use disorder, they are not without limitations. Therefore, innovative strategies are urgently needed to augment existing public health and treatment approaches.

Recent scientific research has re-emphasized the potential of naturalistic psychedelic use for addressing substance use disorders. The activation of serotoninergic/5-HT2A receptors is believed to increase neural plasticity and have anti-addictive, anti-depressive, and anxiolytic effects. Classic psychedelics have been used as adjuncts to psychotherapy for treating alcohol and opioid use disorders, and have shown promising results for treating a range of mental health issues. They are also known to elicit powerful mystical experiences and emotional responses, which appear to mediate therapeutic impacts.

Observational research has pointed to possible long-term beneficial impacts of naturalistic psychedelic use for individuals with substance use disorders, including reduced suicidality, psychological distress, recidivism and intimate partner violence.

Evidence from observational and prospective cohort-based studies that collect detailed information on substance use patterns and psychedelic use remain lacking.

Methods

This study drew on longitudinal data from three ongoing cohorts of PWUD in Vancouver, Canada, which were recruited via community outreach and self-referral.

The VIDUS, ACCESS, and ARYS studies include HIV-negative adults, HIV-positive adults, and street-involved youth who provide information relating to sociodemographic characteristics, substance-use patterns, engagement with healthcare services and law enforcement, and other social, behavioural and environmental factors.

The primary outcome of interest was time-updated use of any classic psychedelics in the last six months, and the primary explanatory variable was daily use of any illicit opioids in the last six months.

Data were self-reported and time-updated at each follow-up using the last six months as the reference, with the exception of time-fixed demographic variables considered at baseline: age, gender, ethnicity, and childhood trauma. Other factors included and treated as time-updated covariates and considered as potential confounders: HIV seropositivity, homelessness, incarceration, sex work, experiences of physical or sexual violence.

Statistical analyses

The present study used data from participants who completed at least one study visit between January 2006 and December 2018. It examined the relationship between explanatory variables and daily opioid use.

Random intercepts were applied to account for unmeasured individual-specific confounding over time, and the primary explanatory variable of interest (recent psychedelic use) was recoded to reflect the value at the preceding visit. In a multivariable GLMM confounding model, variables significantly associated with the outcome in bivariate analysis were subsequently fitted into a reduced model in a stepwise manner, removing covariates that resulted in the smallest relative coefficient change for the main explanatory variable.

Results

3818 PWUD completed at least one study visit; 5 participants were removed due to missing data. The remaining 3813 participants contributed to a total of 34,831 observations over the study period. Baseline characteristics of participants stratified by psychedelic use are presented in Table 1. Those who reported recent psychedelic use were significantly more likely to be younger, identify as white, have experienced recent homelessness and violence, report daily cannabis use and heavy alcohol use, and report daily opioid or crack use.

At baseline, 29% of participants reported daily use of illicit opioids, and 22% reported daily use at follow-up. 92% injected opioids, 54% used pharmaceutical opioids non-medically, and 54% ever had a prior non-fatal overdose.

In the GLMM analysis, factors associated with daily opioid use included younger age, identifying as a woman, recent homelessness, incarceration, sex work and violence, and experiencing barriers to accessing treatment. Living with HIV, daily cannabis use, heavy alcohol use, and being enrolled in drug treatment reduced odds of daily opioid use.

Discussion

This study provided data on community-recruited PWUD to elucidate the possible relationship between naturalistic psychedelic use and daily opioid use as a marker for OUD. Psychedelic use remained independently associated with significantly reduced odds of subsequent daily illicit opioid use.

These findings are consistent with previous research and growing literature that shows psychedelics have a therapeutic potential for addressing mental health and substance use disorders. Furthermore, historical use of psychedelics is associated with a reduced risk of suicide and a protective moderating effect on the association between pharmaceutical opioid use and suicide.

Preliminary clinical trials have shown that psychedelics may have lasting benefits in the context of psychotherapy, with the strongest evidence thus far being in the treatment of alcohol use disorder.

Ketamine-assisted therapy has also demonstrated benefit for alcohol, opioid, and cocaine use disorders in recent RCTs, and psilocybin-assisted therapy has shown to have an outsize impact on tobacco smoking cessation.

The spiritual components of the psychedelic experience are thought to play a primary role in mediating therapeutic impacts, and are significantly correlated with positive treatment outcomes. Psychedelic and mystical experiences appear to have long-lasting impacts on mood, behaviours and overall wellbeing, and are not known to lead to addiction or dependence. They may also facilitate pro-social behaviors and reduced harm from addictions and other mental health disorders.

This study of community-recruited PWUD has several strengths, including the large sample size and prospective design with detailed individual-level participant data. However, there are several notable limitations, including the observational nature of the study and reliance on self-report potentially leading to recall and response biases. We lagged the primary explanatory variable to address the issue of temporality, which may have biased the results towards the null.

This study found that people who use psychedelics are more likely to use opioids than people who do not, but a sensitivity analysis was conducted to address potential bias. The results suggest that psychedelic-assisted psychotherapy should be considered alongside interventions that address upstream and root causes of substance use disorders.

Conclusion

Psychedelic use was independently associated with a significantly reduced odds of subsequent daily illicit opioid use among a community-based sample of PWUD. Additional qualitative studies are required to elucidate the possible psycho-social mechanisms underpinning psychedelic experiences.

Contributions

All authors contributed to the conception and design of the study, and to the analysis and interpretation of the data.

Declarations of Interest

Drs. Argento, Mackay and Christie are consultants to Numinus Wellness, a Canadian mental health company interested in the use of psychedelics for medical purposes. M-J Milloy is the Canopy Growth professor of cannabis science.

Acknowledgments

This study was supported by the US National Institutes of Health and the Canadian Institutes of Health Research. Elena Argento, M. Eugenia Socias, Kanna Hayashi, M-J Milloy, and Kora DeBeck contributed to the study design, data collection, analysis, interpretation, writing of the report, and decision to submit for publication.