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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. ⋯ 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.