Short answer
The strongest evidence is for treatment-resistant depression, where two Phase 3 trials succeeded and an FDA application is underway. Randomized trials also support psilocybin for major depression, depression and anxiety in people with cancer, and alcohol use disorder. PTSD and smoking cessation have promising early results. Anorexia, OCD, migraine, and cluster headaches have only small pilot studies so far.
Key takeaways
- Phase 3 proof: treatment-resistant depression.
- Randomized trials: major depression, cancer-related distress, alcohol use disorder.
- Promising early data: PTSD, smoking cessation.
- Small pilots only: anorexia, OCD, migraine, cluster headaches. Interesting, not proven.
The list, ranked by evidence
| Condition | Best evidence so far | Strength |
|---|---|---|
| Treatment-resistant depression | Two positive Phase 3 trials; FDA filing underway1 | Strong |
| Major depressive disorder | Randomized trials in JAMA and JAMA Psychiatry23 | Strong |
| Depression and anxiety with cancer | Two randomized trials, lasting benefit at 6 months4 | Promising |
| Alcohol use disorder | Randomized trial, 93 participants5 | Promising |
| PTSD | Open-label Phase 2; late-stage trial cleared in 20266 | Promising |
| Smoking cessation | Pilot study, 15 participants7 | Early |
| Anorexia nervosa | Feasibility study, 10 participants8 | Early |
| OCD | Pilot study, 9 participants9 | Early |
| Cluster headache and migraine | Small controlled trials10 | Early |
Depression: the strongest case
This is where psilocybin has moved from interesting to serious. Compass Pathways' second Phase 3 trial in treatment-resistant depression found 39% of patients who received two doses responded, and most kept that benefit through six months.1 Earlier randomized trials in major depression found fast, large effects, including one where 71% of participants responded within four weeks.2 The details, including the less flattering results, are in psilocybin for depression.
Distress in serious illness
In 2016, two randomized trials at Johns Hopkins and NYU gave psilocybin to people with life-threatening cancer who were struggling with depression or anxiety. A single session produced large decreases in both, and roughly 80% of the Johns Hopkins participants still showed meaningful improvement six months later.4 See psilocybin for anxiety.
Addiction
A 2022 randomized trial in people with alcohol use disorder found the psilocybin group had heavy drinking days on 9.7% of days over eight months, versus 23.6% for placebo.5 A small smoking-cessation pilot reported that 80% of participants were abstinent six months later, an eye-catching number from a study with no control group.7 Larger trials are underway. Read psilocybin for addiction.
PTSD
In a 22-person open-label study, a single dose of psilocybin cut PTSD symptom scores by about 30 points on the standard CAPS-5 scale, with no serious adverse events. In January 2026, the FDA cleared Compass to start a late-stage trial.6 More in psilocybin for PTSD.
Early-stage research
Anorexia, OCD, migraine, and cluster headaches each have small studies with encouraging signals.8910 They also have tiny sample sizes and, in some cases, no placebo group. They're reasons for bigger trials, not reasons to self-treat. We cover these, along with the stronger anecdotal claims, in psilocybin's unproven uses.
What happens outside clinical trials
Oregon's legal program is the first large real-world test. In a 2026 study of 346 clients across 24 licensed service centers, the risk of depression at three months was 60% lower than at baseline, and anxiety dropped even more, with 92% saying they benefited.11 There was no control group, so it isn't a clinical trial, but it's encouraging evidence that benefits show up outside the lab too.
Common questions
Is psilocybin FDA approved for anything?
Not yet. Compass Pathways expects to finish its FDA application for treatment-resistant depression in Q4 2026, with a possible launch in the first half of 2027 if approved and rescheduled.
Why does one drug seem to help so many different conditions?
Researchers think psilocybin works less like a targeted fix and more like a reset for rigid patterns of thinking and behavior, which show up in depression, addiction, and obsessive conditions alike. That theory is still being tested.
Can I use psilocybin to treat myself?
We'd strongly advise against self-treating a serious condition. The trial results above come from screened patients, measured doses, and trained professionals. Legal options include state programs in Oregon and Colorado and clinical trials.
Sources
- Compass Pathways. Six month data from second Phase 3 trial confirming rapid and durable profile. July 7, 2026. businesswire.com
- Davis AK, et al. Effects of psilocybin-assisted therapy on major depressive disorder. JAMA Psychiatry. 2021. doi.org/10.1001/jamapsychiatry.2020.3285
- Raison CL, et al. Single-dose psilocybin treatment for major depressive disorder. JAMA. 2023. doi.org/10.1001/jama.2023.14530
- Griffiths RR, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer. Journal of Psychopharmacology. 2016. doi.org/10.1177/0269881116675513
- Bogenschutz MP, et al. Percentage of heavy drinking days following psilocybin-assisted psychotherapy vs placebo in the treatment of adult patients with alcohol use disorder. JAMA Psychiatry. 2022. doi.org/10.1001/jamapsychiatry.2022.2096
- HealingMaps. FDA clears Compass Pathways to begin late-stage psilocybin trial for PTSD. January 13, 2026. healingmaps.com
- Johnson MW, et al. Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. Journal of Psychopharmacology. 2014. doi.org/10.1177/0269881114548296
- Peck SK, et al. Psilocybin therapy for females with anorexia nervosa: a phase 1, open-label feasibility study. Nature Medicine. 2023. doi.org/10.1038/s41591-023-02455-9
- Moreno FA, et al. Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. Journal of Clinical Psychiatry. 2006. doi.org/10.4088/JCP.v67n1110
- Schindler EAD, et al. Psilocybin pulse regimen reduces cluster headache attack frequency in the blinded extension phase of a randomized controlled trial. Journal of the Neurological Sciences. 2024. doi.org/10.1016/j.jns.2024.122993
- Korthuis PT, et al. Safety and mental health outcomes of Oregon state-regulated psilocybin services. JAMA Network Open. 2026. doi.org/10.1001/jamanetworkopen.2026.30608
This article is for education only and is not medical or legal advice. Psilocybin is a Schedule I substance under U.S. federal law. Talk with a licensed clinician before making decisions about your health. In a crisis, call or text 988.