Psilocybin, the main psychoactive compound in “magic mushrooms,” is the leading candidate to become the first classic psychedelic medicine approved in the United States. This article walks through the evidence, from small academic studies to large Phase 3 programs.

Early academic studies

Researchers at Johns Hopkins and Imperial College London ran small trials in the 2010s and early 2020s. A Johns Hopkins trial of 24 adults with major depression, published in JAMA Psychiatry in 2021, reported that about 71% had a clinically significant response and about 54% were in remission at four weeks after treatment with psilocybin and psychotherapy. The study had no placebo group, since it compared immediate with delayed treatment, so it could not rule out expectation effects. These studies were small but sparked broader research.

The Phase 2b trial

Compass Pathways ran a large Phase 2b trial of COMP360, a synthetic psilocybin formulation, in treatment-resistant depression (TRD), published in the New England Journal of Medicine in 2022. It compared three dose levels. The 25 mg dose showed a significantly greater reduction in depression scores at week 3 than the 1 mg control, while the 10 mg dose did not show meaningful efficacy. Some participants had adverse events including suicidal behaviour, which prompted close monitoring in later trials.

The Phase 3 program

Compass reported on February 17, 2026 that both of its Phase 3 trials, COMP005 and COMP006, met their primary endpoints in TRD. In July 2026 it reported 26-week data from COMP006 in nearly 600 patients:

• About 39% of patients receiving two 25 mg doses achieved a clinically meaningful response (a reduction of at least 25% on a depression rating scale) by week 6, with the response maintained through week 26.
• That compared with about 25% response after a single dose in COMP005.
• Almost 30% of responders reached remission during the treatment interval.
• Serious adverse events were about 5.7% in the 25 mg arm and 6.3% in the 1 mg control arm over 26 weeks.

Compass says it is completing a rolling New Drug Application with the FDA, with final submission expected in Q4 2026 and a possible launch in the first half of 2027 if approved. Those are company projections and not regulatory decisions.

Reading the numbers carefully

Response is not remission. A 25% reduction in symptoms is a lower bar than being symptom-free. Many participants who responded still had symptoms.

The population is very difficult. These patients had long-lasting depressive episodes (averaging over three years in COMP006) and had not responded to multiple treatments. A 39% response in that group is meaningful, but it is also not a cure for most.

Blinding remains an issue. Psychedelic effects are obvious. Trials use a low-dose active control to improve blinding, but participants often guess correctly.

Therapy is part of the package. Trials include preparation and support. Whether the drug alone produces the effect, or how much of it is therapeutic, is still debated.

Company-reported data. Press-release results are not the same as peer-reviewed publication. Wait for the full papers and for FDA review.

Safety considerations

Common effects in trials include headache, nausea, anxiety, and temporary increases in blood pressure. Participants with a personal or family history of psychosis or bipolar disorder are generally excluded, because psychedelics may trigger episodes in vulnerable people. Anyone considering these treatments should talk with a clinician rather than self-medicating, particularly if they take antidepressants or other psychiatric medications.

What to watch

• The FDA’s review of COMP360, including how it handles unblinding.
• Independent trials from academic groups.
• Whether regulators require specific therapist training and monitoring.
• Pricing and access, since the session-based model is resource-intensive.

The takeaway

Psilocybin has moved from small pilot studies to large Phase 3 trials with positive headline results in treatment-resistant depression. Regulatory approval is plausible but unconfirmed, and the details of effect size, durability, and safety will shape how it is used.

Sources: Compass Pathways announcements (Feb and July 2026) as reported by PharmaTimes, BusinessWire, and trade press; Johns Hopkins (JAMA Psychiatry 2021) and Compass Phase 2b (NEJM 2022) publications.