Psilocybin for depression

Psilocybin and other psychedelics are under investigation for use in several mental health conditions, including depression.1 Psilocybin, a prodrug that naturally occurs in “magic” mushrooms (genus Psilocybe), has been used for ritualistic purposes by indigenous populations of Central-North America for thousands of years.2 Its active metabolite, psilocin, targets 5-hydroxytryptamine type 2A receptors, whose potent activation of serotonergic pathways is largely responsible for producing psychedelic effects.3 Both rapidly induced changes in neuroplasticity4 and immediate “psychedelic” experiences5 are thought to contribute to the rapid antidepressant effects seen after just one or two doses of psilocybin. These attributes differ from those of established antidepressant strategies such as selective serotonin reuptake inhibitors (SSRIs) and psychotherapies.

The modest efficacy and tolerability of conventional treatments for depression have contributed to the emergence of a polarised debate about the efficacy and safety of psilocybin, fuelled by considerable interest among clinical researchers, the pharmaceutical industry, and the media.6789 Whether psychedelics should be widely used for the treatment of depression remains contentious, and polarised views between hard …