A single 25 mg dose of psilocybin, but not 10 mg, reduced depression scores more than a 1 mg control dose over three weeks in adults with treatment-resistant depression. In this phase 2 trial, 233 participants were randomly assigned to 25 mg, 10 mg, or 1 mg of synthetic psilocybin with psychological support. The 25 mg group showed an average 12-point drop on the MADRS depression scale versus a 5.4-point drop in the 1 mg group, a significant difference. The 10 mg group did not differ significantly from control. Response and remission rates at three weeks supported the primary result, but sustained response at 12 weeks was not significantly different.
A growing body of preliminary clinical research indicates that psilocybin, a compound found in hallucinogenic fungi, combined with psychological support can improve mood, reduce anxiety, and enhance quality of life. An open-label study showed marked reductions in depression symptoms among participants with treatment-resistant depression. The underlying neurobiological changes include altered brain connectivity and activity in the amygdala and default mode network, as well as increased synaptogenesis and neural plasticity. A randomized, double-blind trial has recently launched across Europe and North America, including a center in Ireland, to further test psilocybin's efficacy for treatment-resistant depression.