The promising effects of magic mushrooms for depression

This is Article 2 in a series on psychiatric disorders and the brain. Previous article: Inside out: the chemistry of depression. Next article coming soon.

What is psilocybin?

Psilocybin is a naturally occurring psychedelic tryptamine alkaloid found in over 200 species of mushrooms (Psilocybin mushrooms), commonly known as magic mushrooms or shrooms. Upon ingestion, the body converts psilocybin into its active metabolite, psilocin, which acts as a serotonin receptor agonist, primarily impacting 5-HT2A receptors.

What is psilocybin useful for?

In recent years, clinical research has shown that psilocybin-assisted therapy, can quickly and meaningfully reduce symptoms of depression, often within days rather than weeks, when given in a safe, controlled medical setting with psychological support.

Importantly, these studies don’t just look at mood while someone is under the influence. They measure long-term changes weeks or months after treatment. Studies, such as Gukasyan et al., 2022 and Goodwin et al., 2022, have shown that 1-2 doses of psilocybin plus therapy have led to sustained reductions in depressive symptoms that last at least 8-12 weeks, and in some cases 12 months later.

Research has also demonstrated potential benefits for individuals whose depression has not responded to conventional antidepressant treatments. A large phase II double-blinded trial, by  Griffiths et al., 2016, involving people with treatment-resistant depression found that those given a therapeutic dose (25 mg) of psilocybin had noticeably greater improvement in their depression scores compared with a very low dose (10 mg).

Scientists, for example Daws et al., 2022, believe psilocybin works differently from standard antidepressants. It appears to temporarily increase connections between different parts of the brain and may help break rigid patterns of negative thinking that are typical in depression.

If psilocybin is effective, why is it not currently used in treatment for depression?

Psilocybin remains classified as a Schedule I controlled substance under the United Nations 1971 Convention on Psychotropic Substances, meaning it is considered to have a high potential for abuse and no accepted medical use. For psilocybin to become an approved clinical treatment for depression, it must be rescheduled through formal regulatory review, a process that involves extensive clinical testing and bureaucratic steps.

In many countries, including the United States, rescheduling controlled substances can be slow and complex. For example, in 2022-2023, the U.S. government reviewed the scheduling of marijuana (cannabis) after presidential direction to federal agencies, but a final rescheduling decision was still pending as of late 2025. According to the U.S. Drug Enforcement Administration, Schedule III drugs are defined as substances with moderate to low potential for physical and psychological dependence, whereas Schedule I substances are defined as having no currently accepted medical use and a high potential for abuse.

Because psilocybin is still Schedule I in most jurisdictions, it cannot yet be prescribed as a mainstream treatment for depression, despite promising clinical trial results.

Written by Chloe Kam

Related article: What does depression do to your brain?