Indications

As previously noted, psilocybin has been shown to be safe in a number of clinical trials, as well as effective in aiding with treatment for a range of mental health conditions (Halpern & Pope, 1999; Hasler et al., 2004; Studerus et al., 2011).

By 2005, for example, more than 2000 subjects had undergone psychedelic-assisted therapy in clinical trials with psilocybin (Metzner, 2005). Whether given alone or combined with therapy, psilocybin's ability to increase global integration in the brain leads to increased mental flexibility and interconnection, which is associated with antidepressant effects. This is also reflected in its demonstrated efficacy in reducing symptoms associated with the following conditions discussed on this page.

While the literature on psilocybin can be classified into either clinical research studies or observational research, this course focuses on clinical research studies.

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Demoralization of HIV/AIDS Survivors

HIV/AIDS pandemic survivors: In looking specifically at older age gay men who had survived AIDS in the long-term, group therapy combined with psilocybin displayed clinically significant reductions in demoralization at 3-month follow-up (Anderson et al., 2020).

Key Studies

Depression

In a study of 24 individuals examining depression treatment, 71% of the treatment group saw significant and rapid decrease of their depression ratings, an effect that continued at the 1-week and 4-week follow-up; 58% were in remission by the 1-week follow up, with this dropping to 54% by the 4-week follow-up (Davis et al., 2020). Indeed, in a study of 59 participants, psilocybin was shown to be superior to escitalopram for treating depression, with 57% achieving remission with psilocybin and only 28% with escitalopram; many other secondary outcomes also favoured psilocybin (Carhart-Harris et al., 2021).

Another trial displayed a rapid and significant effect after psilocybin-assisted therapy for depression, with effect sizes 2.5 times greater than therapy alone and 4 times greater than standard pharmacological treatments; not only were these effects sustained, but 54% achieved remission, while 71% had significant reductions in their illness at 4-week follow-up (Davis et al., 2021).

Key Studies

End-of-life Anxiety and Psychological Distress

One study for end-of-life anxiety among 51 patients with life-threatening cancer found that high psilocybin doses produced large decreases in measures of depressed mood and anxiety along with death anxiety, while combined with increases in quality of life, life meaning, and optimism; these changes were lasting, with 80% of participants displaying clinically significant improvement at 6-month follow-up (Griffiths et al., 2016).

Key Studies

Migraines

In a controlled study, adults who received 0.143 mg/kg of psilocybin maintained headache diaries over the span of two weeks. The study found a significant reduction in headaches in the psilocybin group compared to the control group. The weekly migraine days was reduced by 1.65 weekly compared to 0.15 in the control group (Schindler et al., 2021).

Key Studies

Obsessive Compulsive Disorder

In a study of 9 participants with obsessive-compulsive disorder, marked (though variable) improvement was seen in all participants, with these improvements generally lasting more than 24 hours after dosing; analysis of variance pointed towards time as a significant factor, though dose and dose/time interaction did not have an effect (Moreno et al., 2006).

Key Studies

Phantom Limb Pain

Ramachandran et al. (2018) describes how psilocybin was used in conjunction with mirror visual feedback exercises. It was observed that psilocybin temporarily relieved symptoms of phantom limb pain, however in combination with mirror visual feedback exercises, the client reported a 50% decrease in phantom limb pain long-term.

Key Studies

Substance Use Disorders

Smoking Cessation

An open-label pilot study using both moderate and high doses of psilocybin sought to treat 15 otherwise mentally healthy nicotine-dependent smokers; these individuals had an average of 6 previous quitting attempts, and smoked an average of 19 cigarettes per day, while averaging 31 years of smoking history (Johnson et al., 2014). 80% of participants were still abstinent at 6-month follow-up, a significant increase over existing behavioural and pharmacological treatments (Johnson et al., 2014). A follow-up study with this same population saw 60% abstinent after 12 months and 60% abstinent after 16 months, though only 80% of participants returned for these follow-up evaluations (Johnson, Garcia-Romeu, & Griffiths, 2017).

Alcohol Dependence

Another study examining 10 individuals with alcohol dependence combined psilocybin with Motivational Enhancement Therapy as well as preparation and integration; in this research, abstinence did not increase with the psychotherapy alone, but significantly increased once psilocybin was administered on the fourth week—an effect that largely persisted until follow-up at 36 weeks (Bogenschutz et al., 2015).

Qualitative research on the use of psilocybin-assisted therapy to treat alcohol use disorder demonstrated that psilocybin-assisted therapy helped participants to change their perceptions of themselves and their relationships to alcohol, while involving themes of self-compassion and forgiveness, love, catharsis, and mysticism (Bogenschutz et al., 2018).

Key Studies

Note

All this being said, not all published research supports psilocybin's efficacy over other treatments for mental health conditions, so continued research is needed (Carhart-Harris et al., 2021). As research progresses, it is possible that many other medical applications for psilocybin will emerge; for example, it has already been reported that psilocybin may be of use in treating cluster headaches and phantom limb pain (Ramachandran et al., 2018; Sewell et al., 2006).

Activity

Select one of the key studies above. Read through the study and summarize the main points in this document. The password for the document is psilocybin.

References

Agin-Liebes, G. I., Malone, T., Yalch, M. M., Mennenga, S. E., Ponté, K. L., Guss, J., . . . Ross, S. (2020). Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. Journal of Psychopharmacology, 34(2), 155-166.

Anderson, B. T., Danforth, A., Daroff, P. R., Stauffer, C., Ekman, E., Agin-Liebes, G., . . . Woolley, J. (2020). Psilocybin-assisted group therapy for demoralized older long-term AIDS survivor men: An open-label safety and feasibility pilot study. EClinicalMedicine, 27, 100538.

Bogenschutz, M. P., Ross, S., Bhatt, S., Baron, T., Forcehimes, A. A., Laska, E., Mennenga, S. E., O'Donnell, K., Owens, L. T., Podrebarac, S., Rotrosen, J., Tonigan, J. S., & Worth, L. (2022). Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA psychiatry, 79(10), 953–962.

Bogenschutz, M., & Forehimes, A. (2016). Development of a psychotherapeutic model for psilocybin- assisted treatment of alcoholism. Journal of Humanistic Psychology, 57(4), 389-414.

Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A., Wilcox, C. E., Barbosa, P. C., & Strassman, R. J. (2015). Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. Journal of Psychopharmacology, 29(3), 289-299. https://doi.org/10.1177/0269881114565144

Bogenschutz, M. P., Podrebarac, S. K., Duane, J. H., Amegadzie, S. S., Malone, T. C., Owens, L. T., . . . Mennenga, S. E. (2018). Clinical Interpretations of Patient Experience in a Trial of Psilocybin- Assisted Psychotherapy for Alcohol Use Disorder. Front Pharmacol, 9, 100. https://doi.org/10.3389/fphar.2018.00100

Carhart-Harris, R., Giribaldi, B., Watts, R., Baker-Jones, M., Murphy-Beiner, A., Murphy, R., . . . Nutt, D. J. (2021). Trial of Psilocybin versus Escitalopram for Depression. N Engl J Med, 384(15), 1402- 1411. https://doi.org/10.1056/NEJMoa2032994

Carhart-Harris, R. L., Bolstridge, M., Day, C. M. J., Rucker, J., Watts, R., Erritzoe, D. E., . . . Nutt, D. J. (2018). Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology (Berl), 235(2), 399-408.

Carhart-Harris, R. L., Bolstridge, M., Rucker, J., Day, C. M. J., Erritzoe, D., Kaelen, M., . . . Nutt, D. J. (2016). Psilocybin with psychological support for treatment-resistant depression: An open-label feasibility study. The Lancet Psychiatry, 3(7), 619-627.

Carhart-Harris, R. L., Wall, M. B., Erritzoe, D., Kaelen, M., Ferguson, B., De Meer, I., . . . Nutt, D. J. (2014). The effect of acutely administered MDMA on subjective and BOLD-fMRI responses to favourite and worst autobiographical memories. Int J Neuropsychopharmacol, 17(4), 527-540.

Davis, A. K., Barrett, F. S., & Griffiths, R. R. (2019). Psychological flexibility mediates the relations between acute psychedelic effects and subjective decreases in depression and anxiety. Journal of Contextual Behavioural Science, 15, 39-45.

Davis, A. K., Barrett, F. S., May, D. G., . . ., & Griffiths, R. R. (2021). Effects of psilocybin-assisted therapy on major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 78, 481-9.

Goodwin, G. M., Aaronson, S. T., Alvarez, O., . . ., & Malievskaia, E. (2022). Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. The New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/NEJMoa2206443

Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., . . . Klinedinst, M. A. (2016). Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol, 30(12), 1181-1197. https://doi.org/10.1177/0269881116675513

Grob, C. S., Danforth, A. L., Chopra, G. S., Hagerty, M., McKay, C. R., Halberstadt, A. L., & Greer, G. R. (2011). Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry, 68(1), 71-78.

Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P., & Griffiths, R. R. (2014). Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. Journal of psychopharmacology (Oxford, England), 28(11), 983-992.

Johnson, M. W., Garcia-Romeu, A., & Griffiths, R. R. (2017). Long-term follow-up of psilocybin-facilitated smoking cessation. Am J Drug Alcohol Abuse, 43(1), 55-60.

Moreno, F. A., Wiegand, C. B., Taitano, E. K., & Delgado, P. L. (2006). Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. Journal of Clinical Psychiatry, 67(11), 1735-1740.

Ramachandran, V., Chunharas, C., Marcus, Z., Furnish, T., & Lin, A. (2018). Relief from intractable phantom pain by combining psilocybin and mirror visual-feedback (MVF) Neurocase, 249, 105–110.

Reiche, S., Hermle, L., Gutwinski, S., Jungaberle, H., Gasser, P., & Majic, T. (2018). Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. Prog Neuropsychopharmacol Biol Psychiatry, 81, 1-10.

Ross, C., Jain, R., Bonnett, C. J., & Wolfson, P. (2019). High-dose ketamine infusion for the treatment of posttraumatic stress disorder in combat veterans. Ann Clin Psychiatry, 31(4), 271-279.

Schindler, E. A. D., Sewell, R. A., Gottschalk, C. H., Luddy, C., Flynn, L. T., Lindsey, H., . . . D'Souza, D. C. (2021). Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin. Neurotherapeutics, 18(1), 534-543.

Sewell, R. A., Halpern, J. H., & Pope, H. G. (2006). Response of cluster headache to psilocybin and LSD. Neurology, 66(12), 1920-1922. https://doi.org/10.1212/01.wnl.0000219761.05466.43