User:Coyotesniper6547/Psilocybin therapy in major depressive disorders

molecular structure of psilocybin

Psilocybe Cubensis

Article Draft

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). 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. 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. 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. There is some new evidence that prolonged activation of the 5HT2B receptor could contribute to valvular heart disease.

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.

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.

In 1959, Albert Hofmann, a Swiss chemist, was the first person to isolate the compound from the mushroom Psilocybe Mexicana and then synthesize pure psilocybin so that a consistent dose could be administered. Sandoz, the company that employed Hofmann, then began to sell the active compound to clinicians as an aid in psychedelic psychotherapy.

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. Psilocybin research in the United States ended in 1970 when the use and possession of psilocybin mushrooms became illegal.

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.

Research

Psilocybin is the main psychoactive compound in the mushroom genus Psilocybe. Psilocybin (O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine) and its active metabolite psilocin (4-hydroxy-N,N-dimethyltryptamine) are part of a group of tryptamine/indolamine hallucinogens that are related to serotonin. In the GI tract psilocybin is converted to psilocin. Psilocyn is a selective agonist of the 5HT receptors, specifically 5-HT1A, 5-HT2A, 5-HT2B, and 5-HT2C. As of 2020, results from preliminary research conducted on psilocybin therapy included effects on anxiety and depression in people with cancer diagnoses, and alcohol use disorder. In a randomized clinical study conducted by Johns Hopkins University in 2017-2019 of 27 adults age 21-75 who scored at least a 17 on the GRID-HAMD depression score, used no drugs, agreed to use no anti depressants for at least 5 half lives before and after the study, were not pregnant or lactating, used birth control and no history of bipolar disorder or psychosis were given two separate doses during a full day session. The first was 20mg/kg and the second was 30mg/kg along with 18 in person visits for each participant. The sessions were 1.6 weeks apart and the participant's relined in a chair with eye shades and headphones and focused on inward reflection. In the place of a placebo 12 participants were delayed eight weeks and then received the same psilocybin treatment. GRID-HAMD score were taken again at five weeks, eight weeks and at one and four weeks after session two. A significant reduction was defined as a 50% reduction from baseline. Other metrics that were monitored were suicidal ideation, standard depression, anxiety and blood pressure. After five and eight weeks the non delayed group had significantly better GRID-HAMD scores than the delayed treatment group. After the psilocybin treatment 67% and at week four 71% had clinically significant GRID-HAMD scores and 58% at week 1 and 54% at week four were in remission.

Research has also been conducted on psilocybin therapy for the treatment of migraines0, and cluster headaches.

Legal status

See also: Legality of psilocybin mushrooms

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

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. Colorado in November of 2022 also decriminalized psychedelic mushrooms for use in state regulated "healing centers".