Psilocybin Research in 2021 – The Year in Review

Recent Updates in Therapeutic Uses of Psilocybin

A Brief History of Psilocybin

Psilocybin is the primary psychoactive compound found in “magic” mushrooms. Like most psychedelic drugs, psilocybin acts primarily on the serotonin neurotransmitter sites. Serotonin is primarily responsible for controlling perception and mood. Various cultures throughout the world have used psilocybin-containing mushrooms for thousands of years for religious and spiritual purposes.

Albert Hoffman first extracted psilocybin from magic mushrooms in a lab in 1957. Throughout the 1960s, psilocybin became widely recognized in the fields of psychology and psychiatry as holding potential for therapeutic benefits for wide range of maladies, including alcoholism and autism. As magic mushrooms gained popularity in the “hippie” counter-culture movement of the 60s, the Nixon Administration formed the Drug Enforcement Administration, which subsequently classified all psychedelics as Schedule I drugs. A Schedule I classification means that a drug has a high abuse potential and no therapeutic benefits. This classification had a chilling effect on research of psychedelics over the next several decades.

Modern Understanding of Psilocybin Effects on the Human Brain

Over the past few years, there has been a gradual yet steady resurgence in interest over potential therapeutic benefits of psilocybin and other psychedelic drugs. There are as many as 50 publicly-traded companies that are currently doing trials of various psychedelic drugs.

Some of the benefits of psilocybin include:

• Positive changes to personality and increased altruism
• Enhanced feelings of connectedness
• Decreased violent and criminal behavior
• Reduced suicidal ideation
• Increase in subjective sense of well-being

Recent Study Results in Psilocybin Research

• At the end of 2020, researchers at Johns Hopkins University found that two doses of psilocybin, combined with supportive psychotherapy, produced rapid and large reductions in depressive symptoms for people diagnosed with major depressive disorder. The study found that half of the participants achieved full remission four weeks after the treatment. What’s more, the trial found that psilocybin was approximately four times more effective than traditional anti-depressant drugs.
• In a study published in the New England Journal of Medicine in April 2021, researchers found psilocybin to be as effective as a traditional SSRIs at mediating the effects of major depressive disorder, and with fewer negative side effects.
• COMPASS Pathways published results of a study in November 2021 showing that a single 25mg dose of psilocybin produces a significant reduction in depression symptom severity.
• Researchers at the University of British Colombia, in a study published in November 2021, found that adults who microdose psychedelics are slightly less symptomatic of anxiety and depression than their peers who do not microdose.
• In July 2021, researchers at Yale University discovered that a single dose of psilocybin given to mice produced a sustained 10% increase in neuronal connections.
• In February 2022 researchers at Johns Hopkins concluded that two doses of psilocybin can have lasting anti-depressive effects for up to 12 months.
• In April 2022, researchers at the University of California – San Francisco found that psilocybin fosters greater connections between different regions of the brain in depressed people, freeing them up from long-held patters of excessive self-focus.
• Researchers also recently found in a double blind-study that administering a single dose of psilocybin to patients with treatment-resistant depression significantly reduced depression-related symptoms.

Conclusion

Researching psilocybin and other psychedelics remains a challenge due to their Schedule I status. Many therapists and academics have increasingly called on Congress to reschedule psychedelic drugs. In 2021, the Biden-Harris administration wrote a letter to Congress recommending the reduction of barriers to research on Schedule I drugs. Through continued research and understanding, the mental health field community will one day soon be able wield the full potential psilocybin has to offer.

I Nichols D.E. Psilocybin: From ancient magic to modern medicine. J. Antibiot. 2020;73:679–686. doi: 10.1038/s41429-020-0311-8

II https://psychedelicspotlight.com/2021-psychedelics-business-year-in-review/

III Elsey J.W. Psychedelic drug use in healthy individuals: A review of benefits, costs, and implications for drug policy. Drug Sci. Policy Law. 2017;3 doi: 10.1177/2050324517723232.

IV James E., Robertshaw T.L., Hoskins M., Sessa B. Psilocybin occasioned mystical-type experiences. Hum. Psychopharmacol. Clin. Exp. 2020;35 doi: 10.1002/hup.2742

V Hendricks P.S., Crawford M.S., Cropsey K.L., Copes H., Sweat N.W., Walsh Z., Pavela G. The relationships of classic psychedelic use with criminal behavior in the United States adult population. J. Psychopharmacol. 2018;32:37–48. doi: 10.1177/0269881117735685

VI Hendricks P.S., Johnson M.W., Griffiths R.R. Psilocybin, psychological distress, and suicidality. J. Psychopharmacol. 2015;29:1041–1043. doi: 10.1177/0269881115598338.

VII Griffiths R.R., Richards W.A., Johnson M.W., McCann U.D., Jesse R. Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. J. Psychopharmacol. 2008;22:621–632. doi: 10.1177/0269881108094300

VIII Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial, November 4, 2020, JAMA Psychiatry. 2021;78(5):481-489. doi:10.1001/jamapsychiatry.2020.3285

IX Trial of Psilocybin versus Escitalopram for Depression, April 15, 2021, N Engl J Med 2021; 384:1402-1411
DOI: 10.1056/NEJMoa2032994

X COMPASS Pathways Shares Positive Topline Results from Phase 2b COMP360 Study,Press Release, November 9, 2021.

XI Psychedelic spurs growth of neural connections lost in depression, Bill Hathaway, Yale News, July 5, 2021
https://news.yale.edu/2021/07/05/psychedelic-spurs-growth-neural-connections-lost-depression

XII Gukasyan N, Davis AK, Barrett FS, et al. Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. Journal of Psychopharmacology. 2022;36(2):151-158. doi:10.1177/02698811211073759

XIII Richard E. Daws, Christopher Timmermann, Bruna Giribaldi, James D. Sexton, Matthew B. Wall, David Erritzoe, Leor Roseman, David Nutt, Robin Carhart-Harris. Increased global integration in the brain after psilocybin therapy for depression. Nature Medicine, April 11, 2022; DOI: 10.1038/s41591-022-01744-z

XIV Guy M. Goodwin, Scott T. Aaronson. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. November 3, 20221. N Engl J Med 2022; 387:1637-1648. DOI: 10.1056/NEJMoa2206443

XV https://www.whitehouse.gov/ondcp/briefing-room/2021/09/02/biden-harris-administration-provides-recommendations-to-congress-on-reducing-illicit-fentanyl-related-substances/

Nichols D.E. Psilocybin: From ancient magic to modern medicine. J. Antibiot. 2020;73:679–686. doi: 10.1038/s41429-020-0311-8

https://psychedelicspotlight.com/2021-psychedelics-business-year-in-review/

Elsey J.W. Psychedelic drug use in healthy individuals: A review of benefits, costs, and implications for drug policy. Drug Sci. Policy Law. 2017;3 doi: 10.1177/2050324517723232.

James E., Robertshaw T.L., Hoskins M., Sessa B. Psilocybin occasioned mystical-type experiences. Hum. Psychopharmacol. Clin. Exp. 2020;35 doi: 10.1002/hup.2742

Hendricks P.S., Crawford M.S., Cropsey K.L., Copes H., Sweat N.W., Walsh Z., Pavela G. The relationships of classic psychedelic use with criminal behavior in the United States adult population. J. Psychopharmacol. 2018;32:37–48. doi: 10.1177/0269881117735685

Hendricks P.S., Johnson M.W., Griffiths R.R. Psilocybin, psychological distress, and suicidality. J. Psychopharmacol. 2015;29:1041–1043. doi: 10.1177/0269881115598338.

Griffiths R.R., Richards W.A., Johnson M.W., McCann U.D., Jesse R. Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. J. Psychopharmacol. 2008;22:621–632. doi: 10.1177/0269881108094300

Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial, November 4, 2020, JAMA Psychiatry. 2021;78(5):481-489. doi:10.1001/jamapsychiatry.2020.3285

Trial of Psilocybin versus Escitalopram for Depression, April 15, 2021, N Engl J Med 2021; 384:1402-1411
DOI: 10.1056/NEJMoa2032994

COMPASS Pathways Shares Positive Topline Results from Phase 2b COMP360 Study,

Psychedelic spurs growth of neural connections lost in depression, Bill Hathaway, Yale News, July 5, 2021

https://news.yale.edu/2021/07/05/psychedelic-spurs-growth-neural-connections-lost-depression

Gukasyan N, Davis AK, Barrett FS, et al. Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. Journal of Psychopharmacology. 2022;36(2):151-158. doi:10.1177/02698811211073759

Richard E. Daws, Christopher Timmermann, Bruna Giribaldi, James D. Sexton, Matthew B. Wall, David Erritzoe, Leor Roseman, David Nutt, Robin Carhart-Harris. Increased global integration in the brain after psilocybin therapy for depression. Nature Medicine, April 11, 2022; DOI: 10.1038/s41591-022-01744-z

Guy M. Goodwin, Scott T. Aaronson. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. November 3, 20221. N Engl J Med 2022; 387:1637-1648. DOI: 10.1056/NEJMoa2206443

https://www.whitehouse.gov/ondcp/briefing-room/2021/09/02/biden-harris-administration-provides-recommendations-to-congress-on-reducing-illicit-fentanyl-related-substances/