Does psilocybin-assisted therapy work for depression?
Yes. Psilocybin-assisted therapy produces approximately 80-85% greater improvement in depression symptoms compared to waiting list control, with 71% of patients achieving treatment response and 54-58% achieving remission after just 2 sessions. A randomized clinical trial of 24 adults with major depressive disorder (16 women, 8 men, mean age 39.8 years) published in JAMA Psychiatry found that psilocybin combined with approximately 11 hours of supportive psychotherapy led to rapid and sustained antidepressant effects that persisted for at least 4 weeks.
Psilocybin works by activating serotonin receptors (particularly 5-HT2A receptors) and promoting neuroplasticity, potentially resetting brain circuits involved in depression. When combined with intensive psychological support, this creates a synergistic therapeutic effect that can produce rapid antidepressant benefits within hours to days.
What the data show:
- Treatment response: 71% of patients achieved clinically significant response (≥50% reduction in depression scores) at both week 1 and week 4
- Remission rates: 58% achieved remission at week 1 and 54% at week 4 (remission defined as depression score ≤7)
- Rapid effects: Depression scores decreased from 16.7 to 6.3 on day 1 after the first psilocybin session, representing approximately 80-85% greater improvement
- Sustained benefits: Improvements persisted through 4-week follow-up, with depression scores remaining approximately 65-70% lower than baseline
- Study scope: 24 of 27 participants (89%) completed the intervention, with 2 psilocybin sessions (20 mg/70 kg and 30 mg/70 kg) combined with approximately 11 hours of supportive psychotherapy
A randomized, waiting list-controlled clinical trial conducted at Johns Hopkins Center for Psychedelic and Consciousness Research demonstrates that psilocybin-assisted therapy produces large, rapid, and sustained antidepressant effects in patients with major depressive disorder, extending previous findings from cancer patients and those with treatment-resistant depression to the broader MDD population.
Dr. Kumar’s Take
This Johns Hopkins study is groundbreaking because it’s the first to test psilocybin-assisted therapy specifically in major depression rather than just treatment-resistant cases or cancer-related depression. The fact that they saw significant effects with just 1-2 treatment sessions challenges our entire approach to depression treatment. What’s particularly important is the “assisted therapy” component - this isn’t just giving someone psilocybin, it’s a comprehensive therapeutic intervention combining the medication with intensive psychological support. This represents a completely new treatment paradigm that could revolutionize how we approach depression.
Study Snapshot
This randomized clinical trial was conducted at Johns Hopkins Bayview Medical Center from August 2017 to April 2019, with 4-week primary outcome assessments completed in July 2019. Adults aged 21-75 years with MDD diagnosis who were not currently using antidepressant medications and had no histories of psychotic disorder, serious suicide attempts, or hospitalization were eligible. Twenty-seven participants were randomized to immediate treatment (n=15) or delayed treatment waiting list control (n=12).
Results in Real Numbers
This randomized clinical trial included 27 participants with major depressive disorder, of whom 24 (89%) completed the intervention and all follow-up assessments. The final sample consisted of 16 women (67%) and 8 men (33%), with a mean age of 39.8 years (range 21-75 years) and a mean baseline depression score of 22.8 points (indicating moderate to severe depression). Participants were randomized to immediate treatment (13 participants) or delayed treatment waiting list control (11 participants). The intervention involved 2 psilocybin sessions (20 mg/70 kg in session 1, 30 mg/70 kg in session 2) combined with approximately 11 hours of supportive psychotherapy over 8 weeks.
Participants in the immediate treatment group showed approximately 80-85% greater improvement in depression symptoms compared to the delayed treatment control group. Mean depression scores decreased from 22.9 at baseline to 8.0 at week 1 and 8.5 at week 4 in the immediate treatment group, while the delayed treatment group showed no improvement (scores of 22.5 at baseline, 23.8 at week 5, and 23.5 at week 8). Seventeen participants (71%) achieved clinically significant treatment response (≥50% reduction in depression scores) at both week 1 and week 4 follow-ups. Fourteen participants (58%) achieved remission at week 1, and 13 participants (54%) achieved remission at week 4. The self-reported depression measure (QIDS-SR) showed even more rapid effects, with scores decreasing from 16.7 at baseline to 6.3 on day 1 after the first psilocybin session, representing approximately 80-85% improvement that was sustained through the 4-week follow-up (score of 6.0). These effect sizes were approximately 2.5 times greater than those typically found in psychotherapy studies and more than 4 times greater than those found in psychopharmacological depression treatment studies, demonstrating the substantial therapeutic benefits of this intervention.
Who Benefits Most
Adults with major depressive disorder who are not currently on antidepressant medications may be ideal candidates for psilocybin-assisted therapy. The study specifically included patients without histories of psychotic disorders, serious suicide attempts, or psychiatric hospitalizations, suggesting these factors are important for treatment selection.
Patients open to intensive psychological work and willing to engage in the therapeutic process may derive maximum benefit, as the treatment requires active participation in both the psilocybin sessions and associated psychological support. Individuals seeking alternatives to daily medication regimens may find this approach particularly appealing.
Safety, Limits, and Caveats
Psilocybin-assisted therapy requires specialized clinical settings with trained personnel experienced in psychedelic therapy protocols. The treatment involves intensive psychological preparation, monitoring during sessions, and integration work afterward.
The study excluded patients with certain psychiatric histories, limiting generalizability to all depression populations. The sample size was relatively small (27 participants), and longer-term outcomes beyond 4 weeks require further investigation. Individual responses vary significantly, and the treatment is not appropriate for all patients with depression.
Practical Takeaways
- Understand that psilocybin-assisted therapy involves comprehensive psychological support, not just medication administration
- Recognize this as a potential option for major depression, particularly for those seeking alternatives to daily antidepressant medications
- Prepare for intensive therapeutic work including preparation sessions, the psilocybin experience itself, and integration sessions afterward
- Consider this approach if you’re not currently on antidepressants and don’t have contraindicated psychiatric histories
- Stay informed about clinical trial opportunities, as this treatment is not yet widely available outside research settings
What This Means for Depression Treatment
This Johns Hopkins trial validates psilocybin-assisted therapy as a promising treatment for major depression beyond just treatment-resistant cases. The integration of intensive psychological support as an essential component highlights the importance of comprehensive therapeutic approaches.
The findings support a shift toward considering psychedelic-assisted therapies as legitimate medical treatments requiring specialized training and clinical protocols rather than experimental interventions.
Related Studies and Research
Episode 31: Depression Explained — The Biology Behind the Darkness
Episode 32: Depression Recovery Roadmap: A Step-by-Step, Evidence-Based Plan
FAQs
How is psilocybin-assisted therapy different from just taking psilocybin?
Psilocybin-assisted therapy involves comprehensive psychological preparation, guided sessions with trained therapists, and integration work afterward, making it a complete therapeutic intervention rather than just medication.
Is psilocybin-assisted therapy safe for depression?
When conducted in specialized clinical settings with proper protocols and trained personnel, the Johns Hopkins study showed it can be safely administered to appropriate candidates.
How many psilocybin sessions are needed?
This study used 1 or 2 psilocybin sessions with psychological support, showing that relatively few sessions can produce meaningful antidepressant effects.
Bottom Line
Psilocybin-assisted therapy shows significant promise for major depressive disorder when conducted with proper psychological support in specialized clinical settings. This Johns Hopkins trial validates the approach beyond treatment-resistant cases, offering hope for a new paradigm in depression treatment that combines pharmacological and psychological interventions.
