Psilocybin therapy

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 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]

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]

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.