The Growing Evidence for Psilocybin-Facilitated Smoking Cessation

Comments from Matthew Johnson of Johns Hopkins provide an update on this research.

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Cigarette smoking is the leading cause of preventable death worldwide.1 Smoking cessation represents one of the most significant health choices an individual can make, and yet it remains a tragically difficult one. Current treatment options, including varenicline, bupropion, nicotine replacement therapy (NRT), and cognitive behavioral therapy (CBT), demonstrate limited effectiveness. When used optimally, only 25-35% of smokers who try to quit remain abstinent for six months or longer.2–5

Over the past decade, however, new evidence has emerged in favour of a treatment paradigm using psilocybin combined with CBT. Psilocybin is a compound found in so-called magic mushrooms. It is a prodrug of the active metabolite, psilocin. Research has demonstrated that psilocin binds to the serotonin 5-HT2A receptor and elicits psychedelic effects.6

Reviewing the Available Evidence

In 2014, Dr. Matthew Johnson and colleagues at Johns Hopkins University published the results of an open-label pilot study meant to assess the safety and potential efficacy of psilocybin in treating tobacco addiction, inspired in part by research on psychedelics from the 1950s-70s that demonstrated some efficacy in treating alcohol and opioid dependence.7–9

After thorough subject screening according to established psychedelic research safety guidelines, 15 psychiatrically healthy nicotine-dependent individuals – smoking an average of 19 cigarettes/day for 31 years, with a mean 6 previous lifetime quit attempts – were enrolled in the study.10 The participants received 15 weeks of CBT in combination with 2 or 3 psilocybin sessions. During the psilocybin sessions, subjects were given synthetic psilocybin in a capsule and were encouraged to focus on their intent to quit, while wearing eyeshades and headphones with music playing. Two research staff participated as facilitators, providing support and reassurance when necessary, without giving any smoking cessation-specific guidance.

The first psilocybin session was a moderate dose (20 mg/70kg) and coincided with the target quit date during week 5. Participants received a second psilocybin session at week seven and an optional third session during week 13, both of which were a high dose (30 mg/70 kg) unless a moderate dose was requested. Side effects associated with psilocybin included modest increases in heart rate and blood pressure, strong feelings of fear and anxiety, and post-session headaches of mild severity.

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At the 6-month follow-up, 12/15 participants (80%) were abstinent based on both self-reports and the presence of cotinine in urine and exhaled carbon monoxide, which are byproducts of nicotine metabolism and evidence of recent smoking. A longer-term follow-up study led by Albert Garcia-Romeu of Johns Hopkins showed 10/15 subjects (67%) remained abstinent after 12 months, and 9/12 after an average of 2.5 years following the target quit date.11 While the results are impressive compared to available treatment options, it is important to note the lack of randomization or control group prevents drawing direct conclusions about psilocybin’s efficacy.

Although the exact mechanism is unclear, those participants who had stronger psilocybin- occasioned mystical experiences were more likely to have reduced cravings and be successful in quitting.12 Studies of psilocybin’s efficacy in treating cancer-related anxiety and depression as well as alcohol dependence reveal a similar association between mystical-type experiences and positive therapeutic outcomes.13–15 This points to a potential common psychological mechanism precipitating changes in an individual’s sense of self and behavior. Qualitative research of participant accounts indicated that the psilocybin sessions gave vivid insights into their self-identity and reasons for smoking.16

The pilot trial results are supported by a survey study of 358 individuals who reported quitting or reducing their smoking after taking a classic psychedelic.17 Participants reported perceiving withdrawal symptoms such as depression or irritability to be less severe compared to previous quit attempts. Despite the limitations of the pilot study’s design and the low overall quality of evidence, abstinence rates of that magnitude after only 2-3 doses of a medication – otherwise unheard of in psychiatry – are hard to ignore and merit further inquiry.

Ongoing Research

The team at Johns Hopkins, again led by Dr. Johnson, is currently conducting a randomized controlled trial with 80 treatment-resistant, nicotine-dependent subjects. The trial is comparing a single high dose (30 mg/70 kg) psilocybin session to an 8 to 10-week standard course of NRT (via patch), both in adjunct to 13 weeks of CBT.18 Fifty of the participants will also undergo MRI brain scans before and after the target quit date to help determine which brain-based mechanisms may correlate with treatment success. The advantage of this design is in providing a direct comparison to a common form of treatment. It also avoids the challenges of blinding subjects and researchers, a common criticism of psychedelic research, since it is difficult to develop a credible placebo that blinds the psychedelic experience.19

Dr. Johnson informed Psychedelic Science Review that of the 44 subjects that have currently reached the 12-month follow-up point, 59% of the psilocybin group are biologically verified abstinent, compared to 23% in the NRT group.20 When asked about a possible decrease in efficacy related to the reduction of psilocybin sessions compared with the pilot study, Dr. Johnson was quick to put the results into context: “I think this misses the bigger picture because even the 59% number is higher than anything published in the scientific literature. Of course, this could change as the study continues.” The trial was originally estimated to be completed by December 2021, but due to the ongoing COVID-19 pandemic, new study participants are on hold while those who have already completed their sessions receive their biologically verified follow-up remotely.

Looking Forward

Compass Pathways and Usona are two pharmaceutical companies that have received Breakthrough Therapy Status from the US Food and Drug Administration (FDA), using psilocybin-assisted therapy for treatment-resistant depression and major depressive disorder, respectively. Neither organization has stated the intention to expand to a smoking cessation indication. “It is too early to tell what organization might move psilocybin for smoking cessation into phase III trials for potential approval,” Johnson explains. 

Other companies are looking to alternate psychedelic compounds – such as DMT in the case of Entheon Biomedical – to have a similar effect in helping smokers quit. When discussing the translation of his research, Dr. Johnson is optimistic: “I have little doubt that any number of organizations would have that interest given the size of the smoking cessation market, and given the dozens of companies now in the psychedelic medication area.”

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    References
  1. WHO Report on the Global Tobacco Epidemic, 2019. World Health Organization; 2019. http://www.who.int/tobacco/global_report/en/
  2. Anthenelli RM, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. The Lancet. 2016;387(10037):2507-2520. doi:10.1016/S0140-6736(16)30272-0
  3. Hartmann‐Boyce J, Hong B, Livingstone‐Banks J, Wheat H, Fanshawe TR. Additional behavioural support as an adjunct to pharmacotherapy for smoking cessation. Cochrane Database of Systematic Reviews. 2019;(6). doi:10.1002/14651858.CD009670.pub4
  4. Cahill K, Stevens S, Lancaster T. Pharmacological Treatments for Smoking Cessation. JAMA. 2014;311(2):193-194. doi:10.1001/jama.2013.283787
  5. Mottillo S, Filion KB, Bélisle P, et al. Behavioural interventions for smoking cessation: a meta-analysis of randomized controlled trials. Eur Heart J. 2009;30(6):718-730. doi:10.1093/eurheartj/ehn552
  6. Madsen MK, Fisher PM, Burmester D, et al. Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. Neuropsychopharmacology. Published online January 26, 2019:1. doi:10.1038/s41386-019-0324-9
  7. Krebs TS, Johansen P. Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. Journal of psychopharmacology. 2012;26(7):994-1002. doi:10.1177/0269881112439253
  8. Savage C, McCabe OL. Residential Psychedelic (LSD) Therapy for the Narcotic Addict: A Controlled Study. Arch Gen Psychiatry. 1973;28(6):808-814. doi:10.1001/archpsyc.1973.01750360040005
  9. Johnson MW, Garcia-Romeu A, Cosimano MP, Griffiths RR. Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. J Psychopharmacol. 2014;28(11):983-992. doi:10.1177/0269881114548296
  10. Johnson M, Richards W, Griffiths R. Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology. 2008;22(6):603-620. doi:10.1177/0269881108093587
  11. Garcia-Romeu AP, Noorani T, Griffiths RR, Johnson MW. Long-term follow-up of psilocybin-facilitated smoking cessation: Abstinence outcomes and qualitative analysis of participant accounts. Drug & Alcohol Dependence. 2015;156:e78. doi:10.1016/j.drugalcdep.2015.07.1130
  12. Garcia-Romeu A, R. Griffiths R, W. Johnson M. Psilocybin-Occasioned Mystical Experiences in the Treatment of Tobacco Addiction. Current Drug Abuse Reviews. 2014;7(3):157-164. https://www.ingentaconnect.com/content/ben/cdar/2014/00000007/00000003/art00005
  13. Griffiths RR, Johnson MW, Carducci MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016;30(12):1181-1197. doi:10.1177/0269881116675513
  14. Ross S, Bossis A, Guss J, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 2016;30(12):1165-1180. doi:10.1177/0269881116675512
  15. Bogenschutz MP, Forcehimes AA, Pommy JA, Wilcox CE, Barbosa PCR, Strassman RJ. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. Journal of psychopharmacology. 2015;29(3):289-299. doi:10.1177/0269881114565144
  16. Noorani T, Garcia-Romeu A, Swift TC, Griffiths RR, Johnson MW. Psychedelic therapy for smoking cessation: Qualitative analysis of participant accounts. J Psychopharmacol. 2018;32(7):756-769. doi:10.1177/0269881118780612
  17. Johnson MW, Garcia-Romeu A, Johnson PS, Griffiths RR. An online survey of tobacco smoking cessation associated with naturalistic psychedelic use. J Psychopharmacol. 2017;31(7):841-850. doi:10.1177/0269881116684335
  18. Psilocybin-facilitated Smoking Cessation Treatment: A Pilot Study. ClinicalTrials.gov. Accessed July 9, 2020. https://clinicaltrials.gov/ct2/show/NCT01943994
  19. Sellers EdwardM, Romach MK, Leiderman DB. Studies with psychedelic drugs in human volunteers. Neuropharmacology. 2018;142:116-134. doi:10.1016/j.neuropharm.2017.11.029
  20. Matthew Johnson. Email communication. May 2020.