Psilocybin For Depression: What the Research Shows

Bottom line: Psilocybin with psychotherapy was associated with lasting improvements in treatment-resistant depression, but results are nuanced and not guaranteed.

A year after receiving psilocybin and psychotherapy, people with treatment-resistant depression still showed significant improvements — but the results are nuanced and not a guaranteed solution. This is the largest follow-up study on the topic, tracking 144 participants over 12 months and revealing both the promise and the gaps in our understanding.

The study was a follow-up to a phase 2b trial, where participants were randomly assigned to different psilocybin dosing regimens — 25 mg, 5 mg, or a combination — all paired with seven psychotherapy sessions. The main measure of depression was the Hamilton Rating Scale for Depression (HAMD17), which the researchers tracked at six and twelve months.

At both time points, the average depression scores dropped by about 7.7 to 7.9 points — a clinically meaningful reduction that lasted even when participants were taking other antidepressants or using other psychedelics during the follow-up. This suggests that psilocybin with psychotherapy may have lasting benefits, even in the presence of other treatments.

But there’s a twist. Those who restarted antidepressant medication during the follow-up had worse depression scores. It’s not clear whether the medication caused the worsening or if people who needed more help were more likely to go back on it. Either way, the data hint that combining psilocybin therapy with antidepressants may not be straightforward.

The results are promising, but they don’t prove that psilocybin is a cure or that it works for everyone. The study’s findings apply to a specific dosing schedule and therapy setup. Other regimens — different doses, fewer or more therapy sessions — haven’t been tested in the same way. Also, the study doesn’t explain how psilocybin actually works, or whether its effects can be made more durable.

Frequently Asked Questions

1. What is the significance of using psilocybin with adjunct psychotherapy?
   – The therapy sessions help patients process their experiences and integrate them into their lives, which seems to amplify the effects of psilocybin.

2. How does the study account for the placebo effect?
   – An active placebo group was used to separate the effects of psilocybin from the effects of the setting or expectations.

3. What are the implications of the study’s findings for clinical practice?
   – Psilocybin with psychotherapy may offer a long-lasting option for people who haven’t responded to other treatments.

4. Are there any known risks or side effects associated with psilocybin therapy?
   – Psychedelic sessions can cause temporary psychological discomfort, and some people may feel worse.

5. What future research is needed to further understand the effects of psilocybin therapy?
   – Researchers need to explore how psilocybin works, what the best dosing is, and how it affects different people long term.

Sources

• ¶Long-Term Efficacy of Psilocybin with Adjunct Psychotherapy in Treatment-Resistant Major Depression (EPIsoDE): 6- and 12-Month Naturalistic Follow-Up of a Phase 2b Trial
• ¶Supplementary Material for: Long-Term Efficacy of Psilocybin with Adjunct Psychotherapy in Treatment-Resistant Major Depression (EPIsoDE): 6- and 12-Month Naturalistic Follow-Up of a Phase 2b Trial
• ¶Supplementary Material for: Long-Term Efficacy of Psilocybin with Adjunct Psychotherapy in Treatment-Resistant Major Depression (EPIsoDE): 6- and 12-Month Naturalistic Follow-Up of a Phase 2b Trial

Educational Disclaimer

This article is for informational and educational purposes only. It is not medical advice, mental health advice, diagnosis, treatment guidance, or a recommendation to use any substance, supplement, therapy, or protocol.

We review publicly available research and explain what the evidence may suggest. Some studies may be early-stage, observational, animal-based, lab-based, theoretical, or incomplete. Always consult a qualified professional before making health-related decisions.

Researched and drafted by Spore, ShroomWire’s AI research assistant, and reviewed by the ShroomWire editorial team before publishing.