Exploring protective associations between the use of classic psychedelics and cocaine use disorder: a population-based survey study

This survey study (n=214,505) assessed the associations between lifetime use of classic psychedelics may share with cocaine use disorder (CUD) within a nationally representative sample of the U.S. Peyote (but not mescaline (the active ingredient in peyote), psilocybin, and LSD) use conferred lower odds of CUD.

Abstract

“Cocaine Use Disorder (CUD) is a significant public health problem associated with elevated morbidity and mortality within the United States. Current behavioural treatments have limited efficacy and there are currently no FDA approved pharmacological treatments for CUD. Classic psychedelics might be associated with lowered odds of substance misuse and may effectively treat various forms of addiction. Thus, the goal of this study is to assess protective associations that lifetime use of classic psychedelics may share with CUD within a nationally representative sample of the U.S. We used data from The National Survey on Drug Use and Health (NSDUH) (2015–2019) and conducted survey-weighted multivariable logistic regression to test whether each of four classic psychedelics (peyote, mescaline, psilocybin, LSD) conferred lowered odds of CUD and its related 11 sub-criteria. Participants were 214,505 adults in the NSDUH (2015–2019) aged 18 and older. Peyote conferred lowered odds of CUD, reducing the odds of CUD by over 50% (aOR: 0.47). All other substances (including other classic psychedelics) either shared no association to CUD or conferred increased odds of CUD. Furthermore, sensitivity analyses revealed peyote to confer sharply lowered odds of the majority (seven of 11) of CUD criteria as well (aOR range: 0.26–0.47). Peyote use is associated with lowered odds of CUD. Future inquiries into third variable factors (i.e., demographic/personality profiles of individuals who use peyote, motivational/contextual factors surrounding peyote use) that may underlie our observed associations may reveal protective factors that can inform treatment development for CUD. Additionally, future longitudinal studies can shed further light on whether there is a temporal link between peyote use and lowered odds of CUD.”

Authors: Grant M. Jones & Matthew K. Nock

Summary

Cocaine use disorder (CUD) is a major public health problem afflicting approximately one million people within the United States. There are currently no FDA-approved pharmacological interventions for CUD, and researchers are working to develop novel treatment approaches.

Classic psychedelics are hallucinogens that give rise to perceptual shifts, such as time dilation, visual and auditory hallucinations, and profound spiritual experiences. They are used by indigenous cultures for thousands of years as sacrament within ceremony and ritual.

Research suggests that classic psychedelics may alleviate substance use disorders. Several studies have linked classic psychedelics to reductions in substance use disorder, including a proof-of-concept trial with psilocybin that promoted lasting abstinence in 10 individuals with alcohol use disorder.

Although the research linking classic psychedelics to the alleviation of CUD is limited, existing research indicates that the non-psychedelic hallucinogen ketamine may alleviate CUD. Additionally, mediators of the link between ketamine and the alleviation of CUD suggest pathways through which classic psychedelics may plausibly protect against CUD.

Inspired by Pisano et al., we sought to examine the association between lifetime use of classic psychedelics and lowered odds of CUD within the past year in a nationally representative population-based survey data.

Method

Data for this project were collected from The National Survey on Drug Use and Health (NSDUH), a computer-assisted self-interviewing format that involves NSDUH representatives administering the survey in participants’ homes.

We included lifetime use of peyote, mescaline, psilocybin, LSD as an independent variable and the following demographic factors and lifetime substance use variables as covariates for our analyses: sex, age, race/ethnicity, educational attainment, self-reported engagement in risky behavior, annual household income, marital status, and comorbid diagnosis of hallucinogen use disorder.

We used multivariable logistic regression and the Survey package in R to test the associations between lifetime use of various classic psychedelics and CUD and its related DSM-IV criteria.

We tested whether use of four classic psychedelics was associated with lowered odds of CUD. If so, we conducted sensitivity analyses to determine whether use of the substance conferred lowered odds of the DSM-IV criteria for CUD.

Results

In the preliminary analyses, individuals with past year cocaine use disorder were more likely to be single, less formally educated, younger, male, Black, lower-income, and more prone to risky behavior. Additionally, individuals with past year cocaine use disorder were more likely to have tried a classic psychedelic substance.

We examined the relationships between peyote use and the 11 DSM-IV criteria for CUD and found that peyote use reduced the odds of each of the 11 criteria by more than 50%.

We conducted posthoc analyses to explore any demographic differences between lifetime peyote users who have versus have not used cocaine. The results revealed significant differences on the following demographic factors: marital status, education level, age, sex, race.

Discussion

This paper assessed whether lifetime use of four commonly used classic psychedelics was associated with past year CUD. Peyote was the sole substance associated with lowered odds of CUD.

This study has many limitations, and cannot be used to infer causality. Further longitudinal studies are needed to determine whether peyote can effectively prevent CUD.

Multivariable logistic regression model predicting past year cocaine use disorder (CUD) + frequency of lifetime use of various substances (unweighted N).

Peyote use was assessed over a lifetime, and CUD was assessed over the past year. We cannot establish clear temporal precedent between peyote use and CUD.

The NSDUH does not collect data from key populations, including homelessness, currently incarcerated individuals, or active-duty military members, which may be important to understanding the link between psychedelic use and CUD.

LSD and classic psychedelic use may be associated with increased odds of CUD, and the potential pathways by which classic psychedelics may lead to adverse outcomes are discussed.

Acute classic psychedelic use can cause experiences of paranoia, anxiety, and extreme distress, which may explain why some people experience CUD.

Hallucinogen use disorder can be caused by psychedelics, and this disorder may drive or exacerbate the misuse of cocaine. There is also a link between psychotic disorders and substance use issues.

Peyote and LSD use have differing relationships with mental health outcomes, and future research can elucidate whether the morbidity associated with hallucinogen persisting perception disorder might lead to increased risk of substance use disorders and CUD.

Peyote use was associated with a lowered odds of cocaine use disorder in eleven multivariable logistic regression models.

This study establishes a preliminary link between peyote use and decreased odds of developing CUD. Furthermore, it is one of the first studies to link peyote use to salutary mental health and behavioral outcomes.

Future research should examine the pharmacological dynamics of peyote, as well as the chemical composition of peyote, to better understand why peyote and mescaline share differing associations to CUD.

Research indicates that pre-existing personality factors may contribute to the association between peyote use and lowered odds of CUD. For instance, higher levels of openness and spirituality may be associated with higher rates of classic psychedelic use and lowered odds of deleterious mental health outcomes.

Demographic differences likely underlie our observed findings as well. There are likely many additional demographic factors not included in the NSDUH dataset that could shed further light on our observed associations between peyote and CUD.

Studies into the motivations and contexts for peyote use can produce invaluable information on the link between peyote and CUD. Additionally, these studies can shed light on the differences in findings between peyote and mescaline.

Conclusion

This study demonstrates that lifetime peyote use is associated with lowered odds of CUD and a majority of CUD criteria, and that future studies should investigate the genetic and behavioral profiles of individuals who use peyote.

Funding

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