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PsiloAtlas

Research by condition

Treatment-resistant depression

Depression that has not improved after at least two standard treatments. Psilocybin and 5-MeO-DMT have each been tested in separate trials; neither is an approved treatment.

PsiloAtlas editorial · AI-assisted research summary. Not clinical or medical review. How we research and review

First published · Last substantive update · Cited sources checked

What each study tested

Each study is listed with the substance it tested. Results for one substance do not apply to another.

Psilocybin

Goodwin et al., New England Journal of Medicine, 2022

Design
Phase 2, randomized, double-blind trial of a single dose of a synthetic psilocybin formulation (25 mg, 10 mg or 1 mg as control) with psychological support. Funded by COMPASS Pathfinder.
Who took part
233 adults with treatment-resistant depression.
Findings
At week 3, the 25 mg dose reduced depression scores (MADRS) by 6.6 points more than 1 mg. The 10 mg dose did not differ significantly from 1 mg.
Limitations
Sustained response at 12 weeks did not support the week 3 result. 77% of participants had adverse events such as headache, nausea and dizziness, and suicidal ideation, behavior or self-injury occurred in all dose groups. The authors call for larger, longer trials compared with existing treatments.

5-MeO-DMT (mebufotenin)

Feifel et al., JAMA, 2026 (intranasal mebufotenin)

Design
Phase 2b, randomized, double-blind trial at 38 sites in Australia, Europe and the US. One intranasal dose of mebufotenin benzoate (8 mg, 12 mg or a 0.3 mg low-dose comparator) with psychological support, followed for 8 weeks.
Who took part
193 adults aged 18 to 75 with moderate to severe major depression that had not responded to 2 to 5 antidepressants in the current episode.
Findings
At day 29, depression scores (MADRS) fell 5.3 points more with 12 mg and 6.2 points more with 8 mg than with 0.3 mg, with significant differences at every time point from day 2 to day 57. Most participants were ready for discharge within 2 hours.
Limitations
Adverse events were reported in 73% to 85% of each group, nearly all mild or moderate. Follow-up lasted 8 weeks. Several authors report ties to the sponsor. We checked the published abstract; the full paper was not reviewed.

Approval and access, by substance

Research results are not the same as approved or available treatment.

Psilocybin

Not approved by the FDA for any use, and listed in federal Schedule I. Legal adult access in the US exists through Oregon's licensed service centers and Colorado's licensed healing centers, and through clinical trials. Those state programs are not medical treatment programs and do not diagnose or treat conditions. Some countries have separate legal pathways; see the Legal section.

Sources: US Code of Federal Regulations, 21 CFR 1308.11 (Schedule I); Oregon Health Authority, Oregon Psilocybin Services; Colorado Natural Medicine Division, accessing regulated natural medicine

5-MeO-DMT (mebufotenin)

Not approved by the FDA, and listed in federal Schedule I. It is not part of Oregon's psilocybin program or Colorado's regulated healing-center program. The study above tested an investigational nasal spray. Outside clinical trials, PsiloAtlas has not documented a legal US access pathway for this use.

Sources: US Code of Federal Regulations, 21 CFR 1308.11 (Schedule I)

Next steps

General information, not medical advice. Talk to a doctor before any treatment, especially if you take medication or have heart or mental-health conditions.