Psilocybin therapy

Psilocybin therapy is the use of psilocybin (the psychoactive ingredient in psilocybin mushrooms) in treating a range of mental health conditions, such as depression, anxiety, addictions,[1] obsessive compulsive disorder, and psychosis.[2] It is one of several forms of psychedelic therapy under study. Psilocybin was popularized as a psychedelic recreational drug in the 1970s and was classified as a Scheudle I drug. Research on psilocybin as a medical treatment was restricted until the 1990s because of the sociocultural fear of dependence on this drug. As of 2022, psilocybin is the most commonly researched psychedelic due to its safety and low potential for abuse and dependence.[2]

Psilocybin-containing mushrooms

History

The first historical record of psilocybin use dates back to Mesoamerica. A Codex known as the "Yuta Tnoho" that belonged to the Mixtec culture in the 1500s BCE depicted religious ritual ingestion of psilocybin-containing mushrooms.[1]

Ritualistic consumption of psilocybe mushrooms continues into modern spiritual and medicinal practice. The hallucinations produced by the psilocybin induces a trance-like state that is believed to allow the soul to disconnect from the body, resulting in healing and spiritual enlightenment.[1]

In 1959, Albert Hofmann, a Swiss chemist, was the first person to extract pure psilocybin from the mushroom Psilocybe mexicana. Sandoz, the company that employed Hofmann, then began to sell the active compound to clinicians as an aid in psychedelic psychotherapy.[3]

In August 1960, Timothy Leary conducted a self-experiment using psilocybin mushrooms. After trying pure, extracted psilocybin, he and Dr. Richard Alpert tested whether it could help reduce recidivism rate and constitute an effective psychotherapy aid. In 1963, Leary and Alpert were suspended from their jobs at Harvard University, due to irresponsible and dangerous experimentation with psilocybin mushrooms.[4] Psilocybin research in the United States ended in 1970 when the use and possession of psilocybin mushrooms became illegal.[5][3]

In 2018–19, the United States Food and Drug Administration (FDA) granted breakthrough therapy designation to facilitate further research for psilocybin in the possible treatment of depressive disorders.[6]

Research

Research has shown the importance of preparing individuals before undergoing psilocybin therapy and controlling the setting in order to maximize the therapeutic effect and minimize risk.[1]

As of 2022, there are over 60 clinical trials researching the therapeutic effects of psilocybin by the United States National Institute of Health (NIH). While short-term effects have been acknolwedged, the long-term efficacy and safety of psilocybin therapy is yet to be determine due to most trials being ongoing. However, preliminary results indicate that psilocybin therapy is efficacious in treating depression, smoking cessation, alcohol use disorder, and obsessive-compulsive disorder.[1]

Studies investigating the effectiveness in psilocybin therapy in treating major depressive disorder (MDD) have found that psilocybin had comparable efficacy to selective serotonin repute inhibitors (SSRIs). Further, meaningful clinical change was observed in the treatment of obsessive-compulsive disorder.[1]

Research has also been conducted on psilocybin therapy for the treatment of migraines[7][8] and cluster headaches.[9]

Neuroscience and Pharmacology

Given that most studies on psilocybin therapy are in early phases, little is understood about the highly complicated mechanisms that support the efficacy of psilocybin therapy. Psilocybin is a prodrug for psilocin, meaning that psilocybin is dephosphorylated to psilocin in the body so it can cross the blood-brain barrier. Psilocin primarily bonds to the 5-HT1A and 5-HT1B serotonin receptors. Although to a lesser extent, psilocin also bonds to dopamine-3 receptors, which may aid in treating substance use disorders.[2]

Chemical compound of psilocybin

Further, psilocin has some effect on the amygdala and hypothalamus that aids in circadian rhythm regulation.[2]

Safety

In the United States, psilocybin and other psychedelic drugs have been heavily criminalized since the 1960s, classified as a Schedule I substance under the federal Controlled Substances Act (Schedule I is defined as a substance having substantial potential for abuse, absence of adequate safety evidence, and no currently accepted clinical uses for therapy).[10] Prior to the 1960s, psychedelics were not considered "hard drugs," and were studied extensively for their immense medicinal potential for treating psychiatric disorders; the criminalization of psychedelics via their classification as Schedule I substances is inconsistent with over 70 years of scientific and medical research and was contrary to all available evidence at the time.[11] According to the largest controlled clinical study of psilocybin to date at Kings College London, volunteers who received doses of psilocybin experienced no serious adverse side effects, experiencing some changes in mood and perception but no negative effects on cognitive or emotional functioning.[12] Recent studies have shown that psilocybin frequently falls at the end of the scales with the least harm to users and society. Psilocybin also is lowest in the potential for lethal overdose as there is no known overdose level. Research indicates that psilocybin is one of the least harmful psychedelics.[13]

As of 2020, psilocybin has no federally-accepted medical use in the United States.[5] In Germany, psilocybin mushrooms and spores are considered as controlled substances illegal to possess or transport.[14]

In November 2020, the U.S. state of Oregon legalized psilocybin for people age 21 and older, and decriminalized possession or use of psilocybin mushrooms for medical conditions, such as depression, anxiety, or PTSD.

References

  1. Van Court, R.C.; Wiseman, M.S.; Meyer, K.W.; Ballhorn, D.J.; Amses, K.R.; Slot, J.C.; Dentinger, B.T.M.; Garibay-Orijel, R.; Uehling, J.K. (April 2022). "Diversity, biology, and history of psilocybin-containing fungi: Suggestions for research and technological development". Fungal Biology. 126 (4): 308–319. doi:10.1016/j.funbio.2022.01.003.
  2. Geiger, Haden A.; Wurst, Madeline G.; Daniels, R. Nathan (2018-10-17). "DARK Classics in Chemical Neuroscience: Psilocybin". ACS Chemical Neuroscience. 9 (10): 2438–2447. doi:10.1021/acschemneuro.8b00186. ISSN 1948-7193.
  3. Daniel, Jeremy; Haberman, Margaret (2018-03-23). "Clinical potential of psilocybin as a treatment for mental health conditions". The Mental Health Clinician. 7 (1): 24–28. doi:10.9740/mhc.2017.01.024. ISSN 2168-9709. PMC 6007659. PMID 29955494.
  4. "When Did Psilocybin Mushrooms First Appear In Human Culture?". The Third Wave. 2016-07-27. Retrieved 2018-05-15.
  5. "Psilocybin" (PDF). Drug Enforcement Agency, US Department of Justice. 1 April 2020. Retrieved 24 March 2021.
  6. "FDA grants Breakthrough Therapy Designation to Usona Institute's psilocybin program for major depressive disorder". www.businesswire.com. 2019-11-22. Retrieved 2019-11-25.
  7. Schindler, EAD; Sewell, RA; Gottschalk, CH; Luddy, C; Flynn, LT; Lindsey, H; Pittman, BP; Cozzi, NV; D'Souza, DC (12 November 2020). "Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin". Neurotherapeutics. 18 (1): 534–543. doi:10.1007/s13311-020-00962-y. PMC 8116458. PMID 33184743.
  8. Dolan, Eric W. (2021-05-18). "A single dose of psilocybin has a lasting therapeutic effect on migraine headache, according to a new placebo-controlled study". PsyPost. Retrieved 2022-09-30.
  9. Sewell, RA; Halpern, JH; Pope HG, Jr (27 June 2006). "Response of cluster headache to psilocybin and LSD". Neurology. 66 (12): 1920–2. doi:10.1212/01.wnl.0000219761.05466.43. PMID 16801660. S2CID 31220680.
  10. "Psilocybin (magic mushrooms)". Drugs.com. 2021. Retrieved 24 March 2021.
  11. Sproul, Conrad (2021). ""Don't Kill My Buzz, Man!" - Explaining the Criminalization of Psychedelic Drugs". Oregon Undergraduate Research Journal. 19 (1).
  12. "Magic mushroom compound psilocybin found safe for consumption in largest ever controlled study". The Independent. 2019-12-18. Retrieved 2022-08-24.
  13. "Reclassification Recommendations for Drug in 'Magic Mushrooms'". Johns Hopkins Medicine Newsroom. 2018-09-26. Retrieved 2022-04-07.
  14. "Anlage I BtMG - Einzelnorm". www.gesetze-im-internet.de. Retrieved 2021-03-24.
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