Psilocybin-containing mushrooms have been consumed by various cultures in many different parts of the world for thousands of years. Psilocybin, a classic psychedelic, contains unique psychoactive properties and has been incorporated into religious ceremonies and investigated for its medicinal value. In the mid-20th century, psilocybin, along with most other classic psychedelics (5HT-2A agonists), was classified as a Schedule I substance, bringing a halt to research on its medicinal utility. The resurgence of clinical trials involving psilocybin in the 21st century has produced promising results concerning the treatment of addiction, depression, and end-of-life mood disorders. Results from these trials have shown significant reductions in depression and anxiety when compared with a placebo, and one trial found no significant difference when compared to a routinely prescribed selective serotonin reuptake inhibitor (SSRI). Studies conducted with patients with advanced-stage cancer have demonstrated that psilocybin may also be beneficial at reducing depression and anxiety associated with psychological crises due to a terminal diagnosis. Psilocybin therapy in the treatment of addiction, which is notoriously difficult to treat, has shown encouraging results. Due to its low toxicity and low risk of overuse, psilocybin has the potential to have a significant influence in the field of addiction medicine. Psilocybin addiction research has been primarily focused on nicotine and alcohol and, in a few small, open-label trials, has shown superiority over traditional therapies.

Psilocybin has a relatively unique and incompletely understood mechanism of action, which allows it to be given at several isolated periods. This infrequent dosing regimen has been shown to produce durable effects with minimal toxicity. This review analyzes the potential of psilocybin in the treatment of addiction, depression, and end-of-life mood disorders. In addition, it will discuss the difficulties involved with conducting scientific research on psychedelic compounds, adverse effects, and the therapeutic measures that are necessary to accompany the safe and effective administration of these psychoactive chemicals.