Depression or Jail: Psilocybin as a Depression Treatment and Schedule 1 Hallucinogen

    The history of pharmaceutical research is filled with examples of unexpected benefits of existing substances. Whether it is a pill designed to treat hypertension that is found to induce erections (Viagra), or a cosmetic anti-wrinkle toxin that is found to relieve migraines (Botox), the interactions between drugs and our bodies are so complex that they often produce outcomes that are impossible to predict. A similar story is currently playing out with psilocybin, the hallucinogenic compound found in several species of fungi, collectively termed "magic mushrooms." While there is evidence of their recreational use up to 6,000 years ago (Akers et al., 2011), only recently have we begun to understand how psilocybin can alter neurological processes. The actual pharmacodynamics of psilocybin are complex and beyond the scope of this blog post, but suffice it to say it involves modulating levels of dopamine and serotonin. With this understanding came questions about whether psilocybin could be used to treat diseases like depression and PTSD. 

    In 2016, a study found that psilocybin induced rapid and enduring anti-anxiety and antidepressant effects in patients with cancer-related anxiety and depression, one of the first studies that examined psilocybin as a treatment (Ross et al., 2016). A subsequent open-label trial found that psilocybin was effective in reducing symptoms of treatment-resistant depression within five weeks, and were maintained at a six month follow up (Carhart-Harris et al., 2017). In initial comparisons against escitalopram (a commonly prescribed SSRI for depression) psilocybin appeared to produce similar levels of symptom reduction with slightly improved secondary outcomes, though the sample size was too small to draw any major conclusions (R. Carhart-Harris et al., 2021). The evidence prompted the FDA to authorize a "Breakthrough Therapy Designation" for psilocybin as a treatment for depression in 2018, allowing more research to be performed on psilocybin (Pathways, 2018). 

    So why is this important outside of psychiatry circles? Since the Controlled Substances Act of 1970, psilocybin has been classified as a Schedule 1 drug by the DEA, indicating a drug with "high potential for abuse, no currently accepted medical use in treatment in the United States, and a lack of accepted safety for use under medical supervision" (Psilocybin | Get Smart About Drugs, 2021). Despite recent findings, this designation has yet to be revised. The process for rescheduling a drug under the DEA can be complex and even contradictory, as the DEA will only accept rescheduling on the basis of large-scale studies, but obtaining the psilocybin to conduct these kinds of studies is incredibly difficult if a drug is Schedule 1. This can have detrimental effects on research into a drug, and it is the same hurdle faced by researchers wanting to explore marijuana, LSD, and other Schedule 1 drugs that have yet to be rescheduled (Nutt et al., 2013). Until the scheduling system is updated or revised, it is likely that psilocybin research will primarily occur abroad, and comprehensive reviews of its ability to help patients with depression will be significantly delayed. As Jay Campisi put it, "Anyone who tries to tells you politics and medicine are unrelated is not being realistic about the world we're living in."

Literature Cited

Akers, B. P., Ruiz, J. F., Piper, A., & Ruck, C. A. P. (2011). A Prehistoric Mural in Spain Depicting Neurotropic Psilocybe Mushrooms?1. Economic Botany, 65(2), 121–128. https://doi.org/10.1007/s12231-011-9152-5

Carhart-Harris, R., Giribaldi, B., Watts, R., Baker-Jones, M., Murphy-Beiner, A., Murphy, R., Martell, J., Blemings, A., Erritzoe, D., & Nutt, D. J. (2021). Trial of Psilocybin versus Escitalopram for Depression. New England Journal of Medicine, 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., Kaelen, M., Giribaldi, B., Bloomfield, M., Pilling, S., Rickard, J. A., Forbes, B., Feilding, A., Taylor, D., Curran, H. V., & Nutt, D. J. (2017). Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology, 235(2), 399–408. https://doi.org/10.1007/s00213-017-4771-x

Nutt, D. J., King, L. A., & Nichols, D. E. (2013). Effects of Schedule I drug laws on neuroscience research and treatment innovation. Nature Reviews Neuroscience, 14(8), 577–585. https://doi.org/10.1038/nrn3530

Pathways, C. (2018, October 23). COMPASS Pathways Receives FDA Breakthrough Therapy Designation for Psilocybin Therapy for Treatment-resistant Depression. COMPASS Pathways. https://www.prnewswire.com/news-releases/compass-pathways-receives-fda-breakthrough-therapy-designation-for-psilocybin-therapy-for-treatment-resistant-depression-834088100.html

Psilocybin | Get Smart About Drugs. (2021, September 2). Get Smart About Drugs. Retrieved November 24, 2021, from https://www.getsmartaboutdrugs.gov/drugs/psilocybin

Ross, S., Bossis, A., Guss, J., Agin-Liebes, G., Malone, T., Cohen, B., Mennenga, S. E., Belser, A., Kalliontzi, K., Babb, J., Su, Z., Corby, P., & Schmidt, B. L. (2016). Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of Psychopharmacology, 30(12), 1165–1180. https://doi.org/10.1177/0269881116675512