The use of psilocybin for treatment-resistant depression

Psilocybin, a hallucinogen, shows promise as a treatment for treatment-resistant depression (TRD). A single 25 mg oral dose, accompanied by 5-8 hours of psychological support, produces antidepressant effects. Common side effects include headache, nausea, fatigue, and insomnia. A systematic review found significant antidepressant efficacy in certain groups, and a double-blind randomized study reported effects comparable to the SSRI escitalopram. In a phase 2 COMPASS Pathways study, about one third of participants experienced rapid response and remission within three weeks of psilocybin-COMP360 treatment. Recent studies indicate psilocybin significantly reduces depressive symptom severity and is generally well tolerated, though further research is needed before licensing for TRD.

Study at a glance

Abstract

The hallucinogen psilocybin is a potential novel treatment for treatment-resistant depression (TRD). Our goal is to review current knowledge on psilocybin and its efficacy in TRD. Literature searches were done on PubMed, Web of Science and Google Scholar, references reviewed in identified articles and other articles found on the website of COMPASS Pathways. Psilocybin treatment consists usually of a single oral administration of 25 mg of psilocybin along with psychological support for 5-8 hours during the ensuing hallucinogenic trip. Common side-effects include headache, nausea, fatigue and insomnia. A systematic review has demonstrated significant antidepressant efficacy in certain groups and a double-blind randomized study found antidepressant efficacy of psilocybin comparable to the SSRI escitalopram. In the phase 2 study of COMPASS Pathways, the psilocybin-COMP360 treatment led to a rapid response and remission as early as three weeks following the treatment for around one third of participants. Recent studies have shown that psilocybin significantly decreases the severity of depressive symptoms and is generally well tolerated. Further research will reveal whether it will be granted a license to treat treatment-resistant depression in the near future. There remains an urgent need for novel treatments for those who do not respond to current antidepressant therapies.