Psilocybin-Assisted Therapy Significantly and Enduringly Decreases Major Depressive Disorder

psilocybe cubensis, Psilocybin
With current treatments having limited effectiveness and adherence, researchers looked at psilocybin with psychological support to produce an antidepressant effect.

Psilocybin combined with supportive psychotherapy is efficacious in treating major depressive disorder (MDD), according to the results of a study published in JAMA Psychiatry.

Studies have shown 1 or 2 administrations of psilocybin in combination with psychological support to produce antidepressant effects in patients with cancer and treatment-resistant depression, but the effect of psilocybin therapy in patients with MDD has not yet been evaluated.

To determine if psilocybin is an effective treatment for MDD, data from 24 participants (67% women) with moderate to severe MDD episodes were analyzed. The average age of participants was 39.8±12.2 years of age. Individuals who were taking pharmacotherapy for depression at the trial screening or who had alcohol or drug use disorders were excluded. Participants were randomly assigned to immediate or delayed treatment groups.

All participants underwent two administrations of psilocybin 3 weeks apart. The psilocybin dosage was 20 mg/70 kg for the first session and 30 mg/70 kg for the second. Approximately 11 hours of supportive psychotherapy supplemented the administration of psilocybin. Depression severity was measured with the GRID-Hamilton Depression Rating Scale (GRID-HAMD.) Individuals with a GRID-HAMD score of ≥17 at baseline were included.

In week 1 and 4 after the second administration of psilocybin, significantly lower depression scores were found compared with the control group (P <.001), significantly lower depression scores were observed from baseline (P <.001), and the majority of participants experienced a ≥50% reduction in their GRID-HAMD score while more than half met the criteria for remission of depression (≤7 GRID-HAMD score).

The results of this study indicated that psilocybin-assisted therapy had substantial rapid and enduring antidepressant effects for individuals with MDD. Unlike ketamine, psilocybin administration persisted for at least 4 weeks and therefore may be a more effective therapy. This study observed effect sizes significantly greater than what has been observed in studies of psychotherapy and psychopharmacology in isolation and did not observe any serious adverse effects.

Limitations to this study include the small population size, the high proportion of White non-Hispanic participants, and the lack of participants with suicidal ideation or at risk for suicide. Additional limitations include the short-term follow-up and lack of placebo group.

Further research studies with larger, more diverse populations, longer follow-up, and a placebo control are warranted.


Davis AK, Barrett FS, May DG, et al. Effects of psilocybin-assisted therapy on major depressive disorder [published online November 4, 2020]. JAMA Psychiatry. doi: 10.1001/jamapsychiatry.2020.3285