Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction

From the 1950s to the early 1970s, research into 5-HT2A receptor agonist psychedelics (classic hallucinogens) explored their potential as treatments for addiction, with mixed results attributed in part to methodological variability. Earlier clinical work with LSD suggested possible therapeutic effects for alcoholism and opioid dependence, and pioneering investigators emphasised the subjective, often spiritual or mystical, character of psychedelic experiences as potentially important to outcomes. After decades of limited human research, renewed studies with psilocybin have shown it can elicit highly meaningful and spiritually significant experiences in healthy volunteers and, when administered in controlled clinical settings, may have therapeutic potential for conditions such as end-of-life anxiety and substance use disorders including tobacco dependence. Garcia-Romeu and colleagues present a secondary analysis of data from their open-label pilot study of psilocybin-facilitated smoking cessation. The paper aims to characterise the mystical-type experiences occasioned by psilocybin in this clinical sample and to examine whether those subjective experiences—measured acutely and retrospectively—are associated with smoking cessation outcomes at 6-month follow-up. The analysis probes potential psychological mechanisms that might mediate treatment effects in psychedelic-assisted addiction therapy.

This report is a secondary analysis of an open-label, single-arm pilot study of psilocybin as an adjunct to smoking cessation treatment. Fifteen physically and psychiatrically healthy adult smokers (10 male) from the Baltimore area enrolled and completed the 15-week intervention. Inclusion features reported in the extracted text included smoking ≥10 cigarettes/day, multiple prior unsuccessful quit attempts, no regular psychotropic medication, and a desire to quit. The sample had a mean (SD) age of 51 (10.5) years, smoked a mean (SD) of 19 (2.9) cigarettes/day for an average of 31 (9.9) years, and had a mean (SD) of 6 (3.6) prior quit attempts; 14 participants were White and one was Asian. The study was approved by the institutional review board and participants gave informed consent. The manualised behavioural intervention comprised weekly meetings for 15 weeks based largely on cognitive-behavioural therapy (CBT) drawn from the Quit for Life programme, with added mindfulness training and guided imagery. Psilocybin sessions were scheduled alongside behavioural treatment: a moderate dose (20 mg/70 kg) at week 5 (the Target Quit Date), a high dose (30 mg/70 kg) at week 7, and an optional third high-dose session at week 13. Facilitators met weekly after sessions to process experiences and support abstinence. Biological verification of smoking status was obtained weekly via breath carbon monoxide (CO) and urine cotinine; cutoff values were ≤6 ppm for CO and <200 ng/mL for cotinine. Subjective and smoking-related measures included the Timeline Follow-Back (TLFB) for daily cigarette use, the 32-item Questionnaire on Smoking Urges (QSU), the Smoking Abstinence Self-Efficacy Scale (SASE), and several measures of acute drug-related experience. Psilocybin-session subjective measures were the Hallucinogen Rating Scale (HRS; intensity subscale reported), an adapted 32-item Mysticism Scale, and the 100-item States of Consciousness Questionnaire (SOCQ) with 43-item mystical subscales. The SOCQ-based criteria for a “complete” mystical experience were pre-specified as ≥60% on each of six subscales (unity, transcendence of time/space, ineffability, sacredness, noetic quality, positive mood). One week after each session participants rated personal meaning, spiritual significance, and impact on well-being; retrospective ratings were also collected at end of treatment. Analyses compared participants who were biologically verified as 7-day point-prevalence abstinent at 6 months (n=12) with those still smoking at 6 months (n=3). Two-tailed unpaired t-tests evaluated baseline group differences and differences on session experience measures; Welch’s correction was applied when variances were unequal. Change scores from intake to 6 months were computed for smoking-related outcomes (CO, cotinine, TLFB, QSU, SASE), and Pearson correlations examined relationships among change scores, mean SOCQ/Mysticism/HRS scores, and mean ratings of personal meaning, spiritual significance, and well-being. The extracted text does not report whether analyses followed an intention-to-treat principle, nor does it provide details beyond the tests described.

At study intake the only smoking-related difference between eventual abstainers and non-abstainers was urine cotinine: participants who were still smoking at 6 months (n=3) had significantly higher baseline cotinine (mean [SD] 2329 [771] ng/mL) than those abstinent at 6 months (n=12; mean [SD] 1513 [443] ng/mL; t(13)=2.49, p=0.027). No baseline differences were observed for breath CO, TLFB, QSU, or SASE. Measures of psilocybin-session experience differed between outcome groups. Mean SOCQ scores (the session-day measure of mystical-type experience) were significantly higher among participants who were abstinent at 6 months compared with those who continued smoking. By contrast, the adapted Mysticism Scale and the HRS intensity subscale did not show significant between-group differences. Ratings made one week after sessions for personal meaning, spiritual significance, and impact on well-being were all significantly higher in the abstinent group than in the non-abstinent group. Across the 15 participants there were 42 psilocybin sessions. Thirteen sessions (31%) met the a priori SOCQ criteria for a “complete” mystical experience. Ten of these 13 complete experiences (77%) occurred during high-dose (30 mg/70 kg) sessions and three (23%) during moderate-dose (20 mg/70 kg) sessions. Nine participants (60%) experienced at least one complete mystical session. Distribution of complete experiences among outcome groups was mixed: of the three participants still smoking at 6 months, one had no complete mystical experience, one had one, and one had two; among the 12 abstainers, five had none, four had one, and three had two complete experiences. Acute challenging experiences (e.g. fear) occurred at least once in six participants (40%), were managed by staff, resolved within sessions, and no clinically significant adverse events were reported in the extracted text. Correlation analyses showed that mean SOCQ scores correlated significantly with mean Mysticism scale and HRS intensity scores, and with mean ratings of spiritual significance and impact on well-being; SOCQ scores were not significantly correlated with average ratings of personal meaning. Importantly, mean SOCQ scores were significantly correlated with change scores for cigarette craving (QSU) and urine cotinine, implying an association between mystical-type session features and reductions in craving and biochemical smoking markers. Mean ratings of personal meaning correlated significantly with change scores for breath CO, urine cotinine, TLFB daily smoking, and both SASE confidence and temptation subscales. Mean spiritual significance ratings correlated with change scores for urine cotinine and SASE scales, while impact-on-well-being ratings correlated with urine cotinine, TLFB daily smoking, and SASE measures. The extracted text notes that three correlations between session-experience measures and smoking-cessation outcomes reached significance at p<.01, but specific correlation coefficients and confidence intervals are not reported in the available extraction.

Garcia-Romeu and colleagues interpret these secondary analyses as supporting a relationship between psilocybin-occasioned mystical-type experiences and smoking cessation outcomes in this small, open-label sample. They note that psilocybin administered in an addiction-treatment context produced “complete” mystical experiences at rates comparable to those seen in healthy volunteer studies, and participant written reports were consistent with features of mystical experience such as unity and sacredness. The pattern of associations—stronger mystical-type scores and higher retrospective ratings of personal meaning, spiritual significance, and impact on well-being among 6-month abstainers—led the investigators to propose that mystical qualities of the sessions may be specifically related to long-term abstinence, whereas overall intensity of drug effects (HRS intensity) was not. The authors suggest plausible psychological mechanisms consistent with their findings: that highly meaningful, mystical-type sessions may reduce temptation and craving and increase self-efficacy to abstain, which in turn could support sustained behaviour change. They situate these results alongside prior clinical and anecdotal findings and a small ketamine study showing similar mediation of craving by mystical-type effects. Garcia-Romeu and colleagues also acknowledge the possibility of reverse causation or confounding: retrospective ratings collected one week after sessions may have been influenced by subsequent smoking outcomes. Key limitations are emphasised. The study’s open-label design, lack of a control group, small and racially homogeneous sample, and the post-hoc nature of some analyses limit causal inference and generalisability. The authors note that not all long-term abstainers had “complete” mystical experiences and not all participants with complete experiences quit smoking, indicating that other unexamined aspects of the experience or treatment may have contributed to outcomes. Multiple comparisons and the exploratory framing of these secondary analyses are also cited as reasons for caution. Finally, the investigators propose a conceptual framing in which a single salient psychedelic-occasioned peak experience might produce enduring beneficial behavioural changes—an “inverse PTSD-like” effect—while stressing that underlying biological mechanisms remain poorly understood. They recommend further research with larger, more diverse samples and additional attention to non-mystical experiential factors that could mediate therapeutic effects.