In a Phase 2 double-blind trial, Psilocybin at a single dose of 25 mg, but not 10 mg, considerably decreased depression scores when compared to a 1-mg dose in adults with treatment-resistant depression. Researchers aimed to explore the safety and efficacy of Psilocybin for depression management.

Participants were randomly allocated to get a proprietary synthetic formulation of Psilocybin at doses of 25 mg, 10 mg, or 1 mg (control), in combination with psychological assistance. Alteration from baseline to the third week in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS) was the major end point. Secondary outcomes were: (1)  Remission at third week (MADRS total score ≤10), (2) Response at third week (≥50% reduction from baseline in MADRS total score), and (3) Maintained response at twelve weeks (fulfilling response criteria at third week and all the subsequent visits).

The 25 mg group had 79 participants, the 10 mg group had 75, and the 1 mg group had 79 participants. In each arm, the mean MADRS total score at the baseline was reported to be 32 or 33. The least-squares mean alterations in the score from baseline to week 3 were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg. The difference between 25 mg and 1 mg groups was -6.6, and the difference between 10 mg and 1 mg groups was -2.5.

In the 25-mg arm, the occurrence of response and remission at three weeks, but not sustained response at twelve weeks, were usually supportive of the primary findings. Notably, 179 out of 233 volunteers (77%) had adverse effects, which included dizziness, headache, and nausea. There were instances of suicidal thoughts, actions, or self-harm in every dosing group.

Using 25 mg Psilocybin (but not 10 mg) substantially reduced depression scores over the course of three weeks when compared to a 1 mg dose, although it was also linked with side effects. To ascertain the effectiveness and safety of  Psilocybin for this disorder, larger and longer trials are necessary, including comparisons with currently available therapies.