Classic Psychedelics in Addiction Treatment: The Case for Psilocybin in Tobacco Smoking Cessation

This book chapter (2022) reviews the use of psilocybin in the treatment of addiction with a specific focus on smoking (tobacco use disorder, TUD). After exploring the historical use of psychedelics to treat addiction, modern research on the topic is reviewed. The anti-addiction properties of psychedelics differ but are consistent with the notion that the persisting positive behaviour change prompted by psychedelic therapy is due to the amplification of psychotherapeutic processes.

Abstract

“This manuscript reviews research suggesting that classic psychedelics (5-HT2A receptor agonists) are effective in treating addictions including tobacco use disorder. I review historical research from the 1950s to 1970s suggesting that classic psychedelics are associated with addiction recovery across pharmacologically distinct drugs of addiction. I then review anthropological reports about the ceremonial use of classic psychedelics and epidemiological studies that are consistent with anti-addiction efficacy. I review modern research using psilocybin in the treatment of alcohol use disorder and tobacco use disorder. Both lines of research show high success rates in preliminary studies. General anti-addiction efficacy across a variety of classes of addictive drugs is consistent with the notion that the persisting positive behaviour change prompted by psychedelic therapy is due to the amplification of psychotherapeutic processes. Future research should examine the classic psychedelic treatment of additional substance use disorders including for opioids, cocaine, methamphetamine, and cannabis, and other disorders broadly characterized as addictions (e.g., obesity, problem gambling, hypersexual disorder). Future research should also explore addiction treatments with other classic psychedelics including LSD, mescaline, DMT, 5-MeO-DMT, and yet-to-be-discovered compounds. Experimental research is also needed to test different protocols for the delivery of classic psychedelic therapy for addictions. Given the staggering societal costs of substance use disorders, including the mortality caused by tobacco smoking, it is critical that public funding be made available for scientists to follow up on promising early findings of classic psychedelics in addiction treatment. The costs and risks of not conducting such research are too great.”

Author: Matthew W. Johnson

Summary

This manuscript reviews research suggesting that classic psychedelics are effective in treating addictions including tobacco use disorder. It also reviews anthropological reports about ceremonial use of classic psychedelics and epidemiological studies that are consistent with anti-addiction efficacy.

Annual smoking-related mortalities are estimated at 480,000 in the USA and nine million annually worldwide. Most behavioral interventions and pharmacotherapies for smoking cessation have only modest long-term success rates.

This manuscript reviews evidence suggesting that classic psychedelics may be effective in treating substance use disorders, including tobacco use disorder. A special focus will be placed on work examining psilocybin as a smoking cessation medication for tobacco use disorder.

1 Historical Research

5-HT2AR agonists were used by indigenous peoples as sacraments and healing agents before recorded history, and were later used in the treatment of addiction and cancer-related existential distress.

Early research hinted that psychedelics might have broad applicability in treating substance use disorders beyond alcoholism. A study of 78 heroin-using individuals under judicial correctional supervision found that individuals who received LSD showed significantly greater biologically confirmed drug abstinence.

Despite initial excitement, research on 5-HT2AR agonists became marginalized due to their use outside of clinical research settings, and their association with the counter-culture movement. In the 1990s, a small number of investigators re-initiated human studies with 5-HT2AR agonists. Researchers have used 5-HT2AR agonists for depression and anxiety related to cancer and other life-threatening illness, major depressive disorder, tobacco use disorder, and alcohol use disorder. These studies have reported rapid efficacy persisting for at least 6 months after one or a few 5-HT2AR agonist administrations.

3 Anthropological Evidence

Various anthropological reports suggest that 5-HT2A agonist use in the context of ritualized sacramental practices of indigenous cultures is associated with high rates of recovery from addiction, achievement of long-term abstinence, and lower rates of addictive substance use.

4 Epidemiological Research

A lifetime history of 5-HT2AR agonist use was associated with a 27% reduced risk of opioid dependence in the past year. In an online survey, individuals with prior AUD reported cessation or reduction in alcohol use and cannabis, opioid, or stimulant use following 5-HT2AR agonist use in nonclinical settings. Greater 5-HT2AR agonist dose, insight, and personal meaning were associated with greater reductions in substance use.

6 Psychedelics in Tobacco Smoking Cessation

Given the older studies and anthropological studies suggesting anti-addiction efficacy of 5-HT2AR agonists across distinct classes of addictive drugs, my laboratory conducted an open-label pilot study in 15 nicotine-dependent, treatment-resistant cigarette smokers. The intervention involved a 15-week program of manualized cognitive behavioral therapy for smoking cessation, including four preparation sessions for a collective total of approximately 8 h. The dose delivered in the first session was 20 mg/70 kg, and two additional sessions at 2 and 8 weeks after the target quit date.

At 6 months post-target quit date, 80% of participants showed biologically verified 7-day point-prevalence abstinence. At 12 month follow-up and at 2.5 year follow-up, 67% and 60% of participants showed biologically verified continuous abstinence, respectively. Nine out of 15 participants had a “complete” mystical-type experience in at least one of their multiple sessions. Those who were smoking abstinent at 6 months had significantly higher mystical-type experience scores on their session days.

We conducted structured qualitative interviews with 12 of the 15 participants 2.5 years after the target quit date, and found that the psilocybin sessions had led to insights into self-identity and reasons for smoking, as well as increased prosocial behavior.

The Hopkins laboratory conducted a survey study on individuals claiming to have quit or reduced smoking due to 5-HT2AR agonists (largely psilocybin and LSD) use in nonclinical settings. The results suggest that affective processing is a commonality in psychedelic therapy.

7 Future Directions

The reviewed data suggests that classic psychedelics hold promise as treatments for substance use disorders. Additional rigorous research should explore the use of psilocybin in the treatment of tobacco use disorder and alcohol use disorder.

Psychedelic therapies may work against a wide variety of substance use disorders, regardless of the class of addictive drug being treated, and may be due to the amplification of psychotherapeutic processes such as the construction of meaning, corrective emotional experiences, and a change in self-narrative.

Given these potential general mechanisms, additional substance use disorders and other disorders that can be broadly characterized as addictions should be explored as treatment targets for classic psychedelics. These include opioid use disorder, chronic pain, problem gambling, and hypersexual disorder.

Research should be conducted with other classic psychedelics compounds, including DMT and 5-MeO-DMT, in the treatment of substance use disorders. If the longer duration of action is not always necessary for therapeutic effect, a shorter-duration treatment model would entail less cost.

Research should examine how classic psychedelic therapy is delivered, including the use of eyeshades and encouragement toward introspection. A recent study manipulated the music played during sessions, but more research should be done.

Given the staggering society costs of substance use disorders, it is critical that scientists conduct rigorous clinical trials to investigate the use of classic psychedelics in the treatment of substance use disorders and other addictions.