Psilocybin Could Win FDA Approval by Early 2027

Psilocybin therapy for treatment-resistant depression could be legal in the U.S. by early 2027, after biotechnology company Compass Pathways reported two consecutively positive Phase 3 trials for its COMP360 psilocybin therapy. If approved, COMP360 would become the first classic psychedelic — a drug acting on a particular serotonin receptor in the brain — ever cleared by the FDA.

The FDA currently classifies psilocybin as a Schedule I controlled substance, meaning it is considered to have no medical use and a high potential for abuse. Oregon and Colorado have already moved ahead: psilocybin is legal there for treating mental health conditions in certain settings. Australia, New Zealand and Switzerland permit therapeutic use for some mental health conditions.

What does the clinical evidence show?

An unaffiliated 2026 study published in the journal Nature Medicine found that people with treatment-resistant depression given COMP360's formulation of psilocybin had lower depression scores than those treated with a placebo. A Johns Hopkins Medicine study in the Journal of Psychopharmacology showed in 2022 that the antidepressant effects of psilocybin therapy, combined with supportive psychotherapy, may last a full year.

Around 2.8 million people have treatment-resistant depression, according to the Journal of Clinical Psychiatry. The FDA defines the condition medically as having tried two different antidepressants with limited improvement, though no consensus exists on that definition.

Christopher Pittenger, MD, PhD, the Elizabeth Mears and House Jameson professor of psychiatry at Yale School of Medicine, points to two theories for how psilocybin could help them. "One is that it increases brain plasticity," he says. A depressed brain struggles to form new connections; psilocybin may make it more pliable. A second theory holds that psilocybin alters brain circuits — including the default mode network — allowing patients to view themselves differently.

Jay Godfrey, co-founder and CEO of Nushama, billed as the world's largest psychedelic wellness center in New York City, describes the mechanism in psychological terms. "There is a theory that psilocybin causes a quieting of an area of our brain called the default mode network, where your ego is housed," he says. "Psilocybin creates what we call ego dissolution: You get to observe yourself in the absence of your judgment, opinions, and all the walls that are around you that keep you safe."

How would treatment work?

Unlike daily SSRIs, dosing would be rare. "You're taking one to four doses per year," says Myriam Barthes, co-founder and CEO of Journey Clinical, the largest psychedelic-assisted psychotherapy platform in the United States. "The experience itself will last about five to seven hours." Godfrey estimates a standard dose at 25 milligrams.

Unlike marijuana, psilocybin would likely be regulated as a pharmaceutical drug, with each session taking place in a clinic under a trained medical professional. Lief Fenno, MD, PhD, chair of the American Psychiatric Association Council on Addiction Psychiatry, rules out take-home prescriptions. "Patient safety is paramount, so these are highly controlled situations with trained professionals," Fenno says. "That's very different than you simply taking a bunch of mushrooms or dropping acid."

What are the risks and open questions?

Trial side effects include headaches, nausea, anxiety, dizziness, elevated blood pressure and a slight blood pressure increase — people with hypertension should likely avoid the drug. Pittenger's main worry: psilocybin could trigger psychosis in people already at risk, such as those with a personal or family history of schizophrenia or bipolar disorder. A full medical and psychiatric evaluation should precede treatment.

Blinding poses a scientific problem. "Patients in the trials know whether or not they're getting a compound that creates an altered state of consciousness, or if they're getting a neutral placebo," Fenno says. Trials are ongoing to determine how much of the therapeutic effect comes from psilocybin itself.

A recent RAND survey put public support for legalized psilocybin at 23 percent — nearly matching support for cannabis in the mid-1990s. Joshua C. Black, PhD, a statistical scientist who analyzed Oregon and Colorado for the American Medical Association, found a cautionary signal: "We showed that with decriminalization, the number of adults using psilocybin about doubled in each state." He notes prescription access will be far tighter: "FDA-approved drugs will have substantial controls over manufacturing and distribution, and I don't think that would generate the same pattern."

For Fenno, the conversation itself matters. "One of the most exciting parts about all of this research is that it's got the entire country talking about mental illness, and new treatments for it," he says. Shroom chocolates at dinner parties will stay illegal — but for 2.8 million people with treatment-resistant depression, a medically supervised option may arrive within two years.

If you or someone you know is experiencing a mental health crisis, dial 988 or (800) 662-HELP.

By Rebecca Stone