Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction

This is the first study to use psilocybin and cognitive behavioural therapy (CBT) in concert for smoking cessation in an open-label format. Participants received a moderate (20 mg/70kg) and high (30 mg/70kg) of psilocybin with a 15-week smoking cessation protocol. At the six-month follow-up, 80% of participants were smoking-free.

Abstract of Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction

“Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, the rigorous follow-up has not been conducted. To determine the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment, we conducted an open-label pilot study administering moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin within a structured 15-week smoking cessation treatment protocol. Participants were 15 psychiatrically healthy nicotine-dependent smokers (10 males; mean age of 51 years), with a mean of six previous lifetime quit attempts and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake. Biomarkers assessing the smoking status and self-report measures of smoking behaviour demonstrated that 12 of 15 participants (80%) showed seven-day point prevalence abstinence at 6-month follow-up. The observed smoking cessation rate substantially exceeds rates commonly reported for other behavioural and/or pharmacological therapies (typically <35%). Although the open-label design does not allow for definitive conclusions regarding the efficacy of psilocybin, these findings suggest psilocybin may be a potentially efficacious adjunct to current smoking cessation treatment models. The present study illustrates a framework for future research on the efficacy and mechanisms of hallucinogen-facilitated treatment of addiction..”

Authors: Matthew W. Johnson, Albert Garcia-Romeu, Mary P. Cosimano & Roland R. Griffiths

Notes on Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction

• The first study on the use of psilocybin for tobacco addiction (smoking)
• 80% still weren’t smoking after six months (vs <35% for other interventions)
• A positive sign that psilocybin may be used for smoking cessation, but little follow-up studies in this area

This paper is followed up by qualitative and long-term follow-ups by Johnson, Garcia-Romeu & Griffiths (2016) and Noorani et al. (2018).

It also is followed up by an analysis of the music used by Strickland, Garcia-Romeu & Johnson (2020).

Another follow-up study by Garcia-Romeu and colleagues (2014) looked specifically at the mystical experience, which was higher in those who quit smoking.

A survey study of people who (fully/partially/temporarily) stopped smoking after psychedelic use was done by Johnson and colleagues (2017), which showed similar large and positive results.

As it was the first study with psilocybin for smoking cessation, the goal was to test safety and feasibility and give the first indication of efficacy. The study also highlights possible improvements and updates for future research.

“Based on the Timeline Follow-back and verified by CO and cotinine measures, 12 of 15 (80%) participants showed seven-day point prevalence abstinence at 6-month follow-up”.

Of those that did continue smoking, the daily total was significantly reduced (from 20 to 14 per day).

“Smoking-related mortalities in the USA are currently estimated at 480,000 annually (US Department of Health and Human Services, 2014), and 5 million annually worldwide (World Health Organization, 2011).”

Although there isn’t much follow-up (yet) to this study, and the protocols need to be refined, the problem that it’s tackling is far from insignificant. Also, the 80% stopping rate versus the typical 35% or less is quite significant.

“[L]ong-term abstinence may be enhanced by including multiple sessions, which may work by extending the “afterglow” period through the time of greatest relapse risk, or by increasing the probability of a transformative mystical experience.”

Multiple sessions may make it easier to get over the relapse period.

The participants had many moments of contact with the researchers/therapists:

• 90 min x4 preparatory meetings
• 8 hours session (x2 or x3)
• 60 min x1 after a session (x2 or x3)
• 45 min x10 support meetings
• 5 min x14 daily phone call

Cognitive-behavioural therapy (CBT) was part of the preparatory meetings. During the session, there was no active therapy; just like with other studies, the participants were directed inward and listened to music.

“Eleven (73%) rated at least one psilocybin session among the five most spiritually significant experiences of their lives, and 13 (87%) reported that their personal well-being or life satisfaction had increased very much as a result of at least one psilocybin session.”

In line with earlier research (e.g. Griffiths et al., 2008), this paper again shows how significant the sessions were to participants.

“However, the mechanistic role of psilocybin in smoking cessation remains unclear. Participant responses in the present study suggest that increased temporal horizon, increased self-efficacy, and altered life priorities may be involved.”

In the final discussion, the authors note that we don’t know exactly what it is in the psilocybin-assisted session that helps people stop smoking. This is, of course, something that will be readily studied in the coming years.

Summary of Pilot study of psilocybin in the treatment of tobacco addiction

Studies using 5-HT2AR agonist hallucinogens in treating drug dependence were promising from the 1950s through the 1970s. Still, they were abandoned due to controversy surrounding the recreational use of hallucinogens and regulatory restrictions impeding subsequent research.

Psilocybin was found to occasion mystical-type experiences in healthy volunteers and to decrease anxiety and depression in patients with advanced-stage cancer. These results suggest the feasibility of a psilocybin-facilitated intervention for addiction treatment.

Smoking-related mortalities in the USA are currently estimated at 480,000 annually and 5 million annually worldwide. A pilot study was conducted to determine the safety and feasibility of psilocybin-facilitated smoking cessation treatment.

The authors conducted an open-label pilot study with 15 psychiatrically healthy nicotine-dependent smokers and found that 80% of the participants showed seven-day point prevalence abstinence at a 6-month follow-up. This suggests that psilocybin may be a potentially efficacious adjunct to current smoking cessation treatment models