Single-dose psilocybin shows therapeutic potential in treatment-resistant depression

Administering a single dose of psilocybin results in a significant reduction in depression scores over a period of 3 weeks but at the expense of increased adverse effects, according to the results of a phase II trial.

The trial randomized adult patients with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 (n=79), 10 (n=75), or 1 mg (control; n=79), along with psychological support.

The primary endpoint was the change in the total score on the Montgomery–Åsberg Depression Rating Scale (MADRS 0–60, with higher scores indicating more severe depression) at week 3. Secondary endpoints were response at week 3 (≥50-percent decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits).

At baseline, the mean MADRS total score ranged between 32 and 33 across the treatment groups. The mean least-squares mean changes at week 3 in the MADRS total score were −12.0 with the 25-mg, −7.9 with the 10-mg, and −5.4 with the 1-mg dose. Only the difference between the 25- and 1-mg dose groups achieved statistical significance (−6.6, 95 percent confidence interval [CI], −10.2 to −2.9; p<0.001; 10 mg vs 1 mg: −2.5, 95 percent CI, −6.2 to 1.2; p=0.18).

The incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, in the 25-mg dose group validated the primary results.

However, treatment led to increased frequency of adverse events, which occurred in 179 of 233 participants (77 percent). The most common events were headache, nausea, and dizziness. All patients in all dose groups had suicidal ideation or behaviour or self-injury.