Psilocybin for depression: what the research shows

What the research shows

1. Clinical trialNew England Journal of Medicine, 2022

   Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression

   In 233 adults with treatment-resistant depression, one 25 mg dose cut depression scores more than a 1 mg dose at 3 weeks; the advantage was less clear at 12 weeks, and suicidal thoughts or self-harm were reported in every group.

2. Clinical trialJAMA, 2023

   Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial

   In 104 adults with major depression, one 25 mg dose cut depression scores about 12 points more than an active placebo at 6 weeks, with no serious adverse events but more side effects overall.

3. Clinical trialNew England Journal of Medicine, 2021

   Trial of Psilocybin versus Escitalopram for Depression

   In 59 adults, psilocybin was compared with six weeks of escitalopram; the primary depression measure did not differ significantly (P = 0.17). Response and remission rates leaned towards psilocybin, but those secondary measures were not corrected for multiple comparisons.

4. Clinical trialJAMA Psychiatry, 2021

   Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial

   In 27 adults with major depression, two psilocybin sessions with therapy cut depression scores more than a waiting-list delay.

5. Observational studyJournal of Psychedelic Studies, 2025

   Five-year outcomes of psilocybin-assisted therapy for Major Depressive Disorder

   Five years later, 67% of the 18 participants followed up were in remission; a small sample with no control group.

6. Clinical trialThe Lancet Psychiatry, 2016

   Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study

   An open-label study of 12 patients with treatment-resistant depression: two doses were tolerated and depression scores fell through 3 months, with no control group.

7. Clinical trialJournal of Psychopharmacology, 2016

   Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial

   In a crossover trial of 51 adults with life-threatening cancer, a high dose produced large drops in depression and anxiety, and about 80% were still improved at 6 months.

8. Clinical trialJAMA Network Open, 2024

   Psilocybin Therapy for Clinicians With Symptoms of Depression From Frontline Care During the COVID-19 Pandemic: A Randomized Clinical Trial

   In 30 US clinicians with depression after frontline COVID-19 work, depression scores fell 21.3 points with psilocybin and 9.3 with an active placebo at 28 days.

Each study links to its own page with the design, size, results and limits, checked against PubMed.

Risks to know

• Adverse events in the COMP360 phase 2b trial

  In the NEJM phase 2 trial of a single dose of COMPASS's synthetic psilocybin for treatment-resistant depression (233 participants), adverse events occurred in 179 participants (77%), including headache, nausea and dizziness, and suicidal ideation or behaviour or self-injury occurred in all dose groups. (New England Journal of Medicine, 2022)

• Psychosis and severe psychiatric history

  Published research safety guidelines recommend excluding volunteers with a personal or family history of psychotic disorders or other severe psychiatric disorders, and note prolonged psychoses triggered by hallucinogens are less common than acute distress. Oregon's Client Information Form bars anyone who has ever been diagnosed with or treated for active psychosis. (Journal of Psychopharmacology, 2008; Oregon Health Authority, Public Health Division, 2026)

• Bipolar disorder

  In an international survey of 541 people with self-reported bipolar disorder who had used psilocybin, 32.2% described new or increasing symptoms after trips, prominently manic symptoms, sleep problems and anxiety; 3.3% used emergency medical services. The authors say bipolar symptoms may emerge or intensify after psilocybin use. (Journal of Psychopharmacology, 2023)

• Seizures were reported in almost half of lithium plus psychedelic reports.

  An analysis of online reports found that 47% of 62 reports of lithium taken with a classic psychedelic (such as psilocybin or LSD) involved seizures and 39% involved medical attention. Oregon's licensed programme bars anyone who has taken lithium in the last 30 days from an administration session. (Pharmacopsychiatry, 2021; Oregon Health Authority, Public Health Division, 2026)

• Effects are often weaker; serotonin syndrome risk is described as low.

  In a survey of 611 reports of taking mushrooms with an antidepressant, the probability of weaker than expected effects was 0.47 for SSRIs, and reduced effects may persist up to 3 months after stopping. A review of serotonin toxicity concluded that serotonergic drugs without MAOIs are low risk with psychedelics that also lack MAOIs, such as psilocybin. (Journal of Psychopharmacology, 2023; Neuropsychopharmacology, 1996; Psychopharmacology (Berl), 2022)

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Lawful ways to get it

What it costs

These are retreat prices, not the cost of medical treatment.

• Oregon does not require service centres to report what sessions cost, so there is no official price data. (Oregon Health Authority, 2026)
• Ask any trial team whether taking part costs anything, which expenses such as travel or lodging are reimbursed, and whether your insurance covers what the research does not. (National Institute on Aging (NIH), current page)

Recruiting trials for depression

86 trials were recruiting on ClinicalTrials.gov on 26 Oct 2026, 49 with US sites, testing any psychedelic or ketamine; 33 of them test Psilocybin. The first 3 are below; the full list, by state, is on its own page.

• Phase 3Psilocybin·NCT07226232

  Psilocybin Intervention for Veterans Overcoming Treatment-Resistant Depression (PIVOT)

  Conditions:

  Major Depression

  Sponsor:

  VA Office of Research and Development

  Who:

  ages 18 Years to 75 Years, 240 participants planned

  • Birmingham VA Medical Center, Birmingham, AL, Birmingham, Alabama
  • Tuscaloosa VA Medical Center, Tuscaloosa, AL, Tuscaloosa, Alabama
  • VA Portland Health Care System, Portland, OR, Portland, Oregon
  • Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, Philadelphia, Pennsylvania
  • VA Puget Sound Health Care System Seattle Division, Seattle, WA, Seattle, Washington

• Early phase 1Psilocybin·NCT04123314

  Psilocybin for Depression in People With Mild Cognitive Impairment or Early Alzheimer's Disease

  Conditions:

  Depressive Symptoms; Depression; Alzheimer Disease; Mild Cognitive Impairment

  Sponsor:

  Johns Hopkins University

  Who:

  ages 18 Years to 85 Years, 20 participants planned

  • Johns Hopkins Center for Psychedelic and Consciousness Research, Baltimore, Maryland

• Phase 2Psilocybin·NCT06132178

  Psilocybin rTMS for Treatment Resistant Depression (PSILOBSD)

  Conditions:

  Treatment Resistant Depression; MDD; Major Depressive Disorder; Recurrent Depression; Depression

  Sponsor:

  University of Texas at Austin

  Who:

  ages 22 Years to 65 Years, 100 participants planned

  • Health Discovery Building (HDB), 1601 Trinity St., Bldg B., Z0600, Austin, Texas

All 86 recruiting trials for depression