, updated
FDA finalizes its guidance for clinical trials of psychedelic drugs
FDA has finalized its guidance on how companies should run clinical trials of psychedelic drugs, three years after its 2023 draft. The final version, announced on July 14, 2026, names interactions with SSRIs, lithium and tricyclic antidepressants that trial sponsors should plan for.
What FDA published
FDA announced the final guidance, "Psychedelic Drugs: Considerations for Clinical Investigations", in the Federal Register on July 14, 2026 (91 FR 43101, Docket No. FDA-2023-D-1987). It finalizes the draft published on June 26, 2023 (88 FR 41407).1 The guidance itself is a 16-page document dated July 2026.23
It is written for sponsors, the companies and researchers who run trials. Its pages are headed "Contains Nonbinding Recommendations", and FDA notes that its guidance documents "do not establish legally enforceable responsibilities".2 It is not advice for individuals.
The drug interactions it names
FDA tells sponsors to consider how other medicines affect both safety and how trial results can be read. "Although more research is needed", it lists these potential interactions:2
| Medicine and length of use | What the guidance says |
|---|---|
| SSRIs, SNRIs or MAOIs for 3 weeks or more | "may reduce the subjective effects of psychedelic drugs" |
| Tricyclic antidepressants or lithium for 3 weeks or more | "may potentiate the subjective effects of psychedelic drugs, creating a potential psychiatric safety concern" |
| SSRIs, SNRIs or MAOIs for less than 3 weeks | "may also potentiate the subjective effects" |
| MAOIs with MDMA or other amphetamine-based psychedelics | "can produce a life-threatening hypertensive crisis" |
The lithium entry lines up with other evidence. In an analysis of online experience reports, 47% of 62 reports of lithium taken with a classic psychedelic (such as LSD or psilocybin) described seizures. Those were self-selected reports with no count of everyone who combined the two.4 Our psilocybin interactions reference sets out what is known for each medicine class.
What it says about dose and mushroom material
Dose-response. Sponsors "should plan to characterize the dose-response relationship for both safety and efficacy early in the drug development program". FDA suggests pairing a trial of a low, middle and high dose without placebo with a placebo-controlled trial.2
Mushroom-based products. A product made from plant material, algae or "macroscopic fungi" may be considered a botanical under FDA's botanical drug guidance. Highly purified substances, or ones made by fermentation, are not.2
Heart valves. Because long-term exposure to drugs with 5-HT2B agonism "may induce cardiac valve stiffening", FDA recommends excluding people with existing valvulopathy or pulmonary hypertension from multiple-dose studies of such drugs until the risk is better understood.2 Our page on who should avoid psilocybin covers the conditions trials screen out.
Why it matters if you read dose claims
This is FDA's current written position, and it treats three things as open questions that must be measured: how response changes with dose, how other medicines change the effect, and how to handle material made from whole mushrooms. Online dose calculators assume answers to all three. In our audit of 36 online calculators, 8 named lithium, and 22 named none of lithium, SSRIs or MAOIs. A trial sponsor working with an exactly measured compound still has to establish each answer with data; a calculator working from untested mushrooms has less to go on.
Sources
- Psychedelic Drugs: Considerations for Clinical Investigations; Guidance for Industry; Availability, 91 FR 43101. Food and Drug Administration, Federal Register, July 14, 2026.
- Psychedelic Drugs: Considerations for Clinical Investigations, guidance for industry (PDF). U.S. Food and Drug Administration, July 2026.
- Guidance document page: Psychedelic Drugs: Considerations for Clinical Investigations. U.S. Food and Drug Administration, 2026.
- Nayak SM, et al. Classic psychedelic coadministration with lithium, but not lamotrigine, is associated with seizures: an analysis of online psychedelic experience reports. Pharmacopsychiatry, 2021;54(5):240-245. PMID 34348413.
- Considerations for Potential Future Therapeutic Use of Psychedelic Drugs; Public Hearing; Request for Comments, 91 FR 43095. Food and Drug Administration, Federal Register, July 14, 2026.
- Compass Pathways press release on COMP005 52-week data. Compass Pathways, September 9, 2026.
Keep reading
Psilocybin drug interactions: lithium, SSRIs, MAOIs and 23 more26 medicine and drug classes: what research found when each met psilocybin, and how strong the evidence is.
Who should avoid psilocybin? What clinical trials excludeWhat 8 psilocybin trials screened out and why, with a private checklist that explains each exclusion.
FDA holds a public hearing on how approved psychedelic drugs could be usedFDA asked how clinics and state programs should record drug, dosage and setting the same way.
Written and checked by the Dosage Calculator editors. Every figure on this page links to its source. Found an error? Tell us and we'll correct it in the open, as our editorial standards describe. Magic Mushroom Dosage Calculator is published by the team that runs My Mushroom Dispensary, an online shop. We sell no advertising and nothing on this site.