Psilocybin vs ketamine vs MDMA therapy: which is right for what?

No single one is "right for" everything — and the choice belongs with a licensed clinician. What differs is access: only esketamine (Spravato) is FDA-approved today, for treatment-resistant depression; psilocybin and MDMA are not approved, though psilocybin is in a rolling FDA submission and an MDMA resubmission was reported in August 2026.

"Which one is right for what" is a clinical question, and no website — including this one — can answer it for you. What can be laid out clearly is how these three differ on the things that determine whether you can access them at all: legal status, the strength of the evidence, and how they are given. Status below is as of October 13, 2026; it is moving quickly.

The three at a glance

Ketamine and esketamine: the only one approved today

Esketamine (Spravato) has been FDA-approved for treatment-resistant depression since 2019 and must be given in a certified medical setting under a safety program (REMS). It is covered by major insurers including Medicare Part B and Medicaid, and each treatment visit runs roughly two hours (Psychedelic Beacon tracker; Healing Maps). Generic ketamine, a Schedule III drug, is used off-label by licensed clinicians; that is a prescriber's decision, not an FDA-approved indication.

Psilocybin: approval may be close, but it isn't here

Compass Pathways' synthetic psilocybin (COMP360) is in a rolling FDA submission for treatment-resistant depression. In its second Phase 3 trial (COMP006, 581 participants), Compass reported on July 7, 2026 that the study met its primary endpoint at week 6 and that results held through 26 weeks; serious adverse events were 5.7% in the 25 mg arm and 6.3% in the 1 mg control arm. Compass expects to complete its submission in Q4 2026 and anticipates a launch in the first half of 2027, subject to FDA approval and DEA rescheduling (Compass Pathways, July 7, 2026). That is a company projection, not an FDA decision. FDA granted Compass a national priority voucher in April 2026, which aims for a faster review (Psychedelic Beacon). Until approval and rescheduling happen, psilocybin remains Schedule I outside trials and the Oregon and Colorado state programs. Trial sessions are long — up to about six hours.

MDMA: back at the FDA, no decision

In August 2024 the FDA declined to approve MDMA-assisted therapy for PTSD, asking for more on durability of response, safety characterization, and steps to reduce bias. Resilient Pharmaceuticals (formerly Lykos Therapeutics) was reported on August 9, 2026 to have resubmitted its application without a new Phase 3 trial; neither the company nor the FDA had publicly confirmed it at the time of that report, and the FDA has not announced whether it will review it (Healing Maps, Aug.–Sept. 2026). For now MDMA-assisted therapy is available only in clinical trials.

What the executive order did and didn't do

An April 18, 2026 executive order directs faster FDA review of certain psychedelics. It does not approve any drug or, by itself, change any drug's DEA schedule (NPR).

How to decide, practically

Which option fits a person depends on their diagnosis, medications, health history, and goals — decisions for a licensed prescriber, not a guide or a web page. Each of these has meaningful medication interactions and health screening considerations (see psilocybin and SSRIs). If you are curious about a non-clinical, preparation-and-integration-focused path, a vetted guide can help you think through your questions and your readiness; they do not provide medical care or substances.

Frequently asked questions

Sources

• Compass Pathways: six-month data from second Phase 3 trial (COMP006), July 7, 2026.
• Psychedelic Beacon: Psilocybin FDA approval tracker (updated July 2026).
• Healing Maps: MDMA therapy for PTSD is back at the FDA, without a new Phase 3 trial (Aug.–Sept. 2026).
• Healing Maps: 2026 could be the year psychedelics finally break through.
• NPR: Trump signs order fast-tracking review of psychedelics (Apr. 18, 2026).