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Molecule guide

Psilocybin: what the research shows

The key compound in 'magic mushrooms', now in late-stage trials for depression. How it works, what it's been studied for, and how strong the evidence is.

ReviewedLast updated September 25, 2026

Also known as Psilocin (active form), COMP360, Magic mushrooms

At a glance

Type
Classic psychedelic (a tryptamine), found in many species of mushroom.
How it acts
The body converts it to psilocin, which activates serotonin 2A receptors.
Approved uses
None in Canada or the US. Australia allows authorised psychiatrists to prescribe it for treatment-resistant depression (since 2023).
Legal status
Schedule III in Canada, with limited medical access through the Special Access Program. Schedule I in the US federally.
How it's given in research
One or two supervised oral doses, with psychological support before, during and after.
Strongest evidence
Depression, including treatment-resistant depression, from several randomised trials.
Biggest open question
How long benefits last, and how much comes from the drug versus the therapy and expectations around it.

Evidence by condition

How strong the research is for each use, on our four-level evidence scale.

Major depression Moderate

Randomised trials (24 to 104 people) show large, fast reductions in symptoms after one or two doses with support. A head-to-head trial against the SSRI escitalopram found no significant difference on its main measure.

Treatment-resistant depression Moderate

A 233-person phase 2 trial found a single 25 mg dose beat a 1 mg control at three weeks, but not at 12 weeks. Two phase 3 trials have been reported as positive by the company running them.

Anxiety and depression with life-threatening cancer Moderate

Two randomised crossover trials (51 and 29 people) found rapid improvements, with most participants still improved six months later.

Alcohol use disorder Low

One 95-person randomised trial found fewer heavy drinking days over 32 weeks than an active placebo, both given alongside therapy.

Tobacco addiction Very low

An open-label pilot of 15 smokers found 12 were abstinent at six months. There was no control group.

What it is

Psilocybin is the main psychoactive compound in many species of mushroom, often called “magic mushrooms”. These mushrooms have been used in ceremonial settings in Mesoamerica for centuries. Psilocybin was first isolated and made in a lab in the late 1950s.10

Research slowed for decades after psychedelics were banned around 1970. It restarted in the 2000s, and psilocybin is now one of the most-studied psychedelics in medicine. Trials give a measured dose of pure, often synthetic, psilocybin in a controlled room, with trained staff present. Participants also have preparation sessions beforehand and “integration” sessions afterwards to make sense of the experience.

How it works in the brain

After it’s swallowed, psilocybin is converted to psilocin, which activates the serotonin 2A receptor. That’s the same target as LSD and other classic psychedelics.10 The effects last several hours, which is why sessions take most of a day.

Researchers think this temporarily loosens rigid patterns of brain activity and thinking, and may promote new connections between brain cells. Brain-imaging studies show changes in how brain networks communicate, including the “default mode network” linked to self-focused thought.

Key studies

Treatment-resistant depression, 2022. In the largest trial published so far, 233 adults received a single dose of 25 mg, 10 mg or 1 mg (the control) with psychological support. At three weeks, the 25 mg dose reduced depression scores significantly more than 1 mg. The difference wasn’t sustained at 12 weeks.2

Major depression, 2023. In a 104-person trial, a single dose of psilocybin reduced depression scores much more than an active placebo (niacin), from day 8 through day 43, with no serious adverse events.3 An earlier 24-person trial found large improvements after two sessions.4

Psilocybin vs an SSRI, 2021. In a 59-person trial, two doses of psilocybin were compared with six weeks of the antidepressant escitalopram. There was no significant difference on the main depression measure. Some secondary measures favoured psilocybin, but the trial wasn’t designed to test them.1

Cancer-related distress, 2016. Two randomised crossover trials, with 51 and 29 people with life-threatening cancer, found rapid drops in depression and anxiety. About 60–80% of participants still had clinically meaningful improvements six months later.56

Alcohol use disorder, 2022. In a 95-person trial, two psilocybin sessions alongside 12 weeks of therapy cut the share of heavy drinking days to 9.7%, compared with 23.6% on an active placebo.7

Smoking, 2014. In an open-label pilot study, 12 of 15 smokers were abstinent six months after psilocybin sessions within a quit program.8 With no control group, this is early evidence only.

Safety and risks reported in research

In trials, common short-term effects include headache, nausea, anxiety and raised blood pressure and heart rate during the session. In the largest depression trial, 77% of participants had at least one side effect, mostly headache, nausea and dizziness.2

  • Canada: Schedule III under the Controlled Drugs and Substances Act.12 Since January 2022, physicians can request psilocybin for individual patients with serious or life-threatening conditions through Health Canada’s Special Access Program, case by case.13
  • United States: Schedule I federally. Oregon (2020) and Colorado (2022) have created state-licensed programs for supervised psilocybin services.15
  • Australia: Since July 2023, authorised psychiatrists can prescribe psilocybin for treatment-resistant depression.14

History in brief

  • Centuries ago: Psilocybin mushrooms used in ceremonial settings in Mesoamerica.10
  • Late 1950s: Psilocybin isolated and synthesised in a lab.10
  • Around 1970: Research largely stops as psychedelics are banned.
  • 2000s: Modern clinical research resumes, led by centres such as Johns Hopkins.4
  • 2016: Two randomised trials in people with cancer published.56
  • 2022: Largest treatment-resistant depression trial published. Canada reopens Special Access Program requests.213
  • 2023: Australia allows authorised psychiatrists to prescribe it.14
  • 2025: First phase 3 results announced.9

Myths vs evidence

The claim“Psilocybin is proven to cure depression.”

What the evidence says Misleading

Trials are promising, but psilocybin isn't approved in Canada or the US. In the 233-person trial, the benefit of a single dose was clear at three weeks but not sustained at 12 weeks.2 Against the antidepressant escitalopram, psilocybin didn't show a significant difference on the main measure.1

The claim“Magic mushrooms are addictive.”

What the evidence says False

Classic psychedelics like psilocybin are generally not considered to cause dependence or addiction.10 That doesn't make them risk-free: the main risks are psychological, and trials screen people carefully.11

The claim“Psilocybin is legal in Canada now.”

What the evidence says Misleading

Psilocybin remains a Schedule III controlled substance.12 Since 2022, doctors can request it for individual patients with serious conditions through Health Canada's Special Access Program, case by case.13 Dispensaries selling mushrooms are not legal.

See all myths vs evidence →

Frequently asked questions

What is the difference between psilocybin and psilocin?

Psilocybin is the compound found in the mushrooms. After it's swallowed, the body converts it to psilocin, which is the form that acts on the brain.

Is psilocybin therapy just taking mushrooms?

No. In trials, participants take a measured dose of pure psilocybin in a controlled setting, with trained staff present. They also have preparation sessions beforehand and support sessions afterwards. Results from those settings may not apply to unsupervised use.

How long do the effects of psilocybin therapy last?

It varies by study. In the cancer trials, most participants still had improvements six months later. In the largest treatment-resistant depression trial, the difference from control wasn't sustained at 12 weeks. Durability is one of the main questions researchers are working on.

Who is usually excluded from psilocybin trials?

Trials commonly exclude people with a history of psychosis or mania, active substance use disorders, a history of serious suicide attempts, or current suicidal thoughts with intent.34 That means results may not apply to everyone.

Can you access psilocybin therapy legally in Canada?

Only in limited ways. A physician can apply to Health Canada's Special Access Program for an individual patient with a serious condition, and clinical trials are running. Talk to a qualified health professional about your own situation.

Clinical trials

Showing 8 of 162 active trials in our tracker.

See all trials in the tracker →

References

  1. Carhart-Harris R, et al. Trial of psilocybin versus escitalopram for depression. New England Journal of Medicine. 2021;384(15):1402–1411. Source
  2. Goodwin GM, et al. Single-dose psilocybin for a treatment-resistant episode of major depression. New England Journal of Medicine. 2022;387(18):1637–1648. Source
  3. Raison CL, et al. Single-dose psilocybin treatment for major depressive disorder: a randomized clinical trial. JAMA. 2023;330(9):843–853. Source
  4. Davis AK, et al. Effects of psilocybin-assisted therapy on major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2021;78(5):481–489. Source
  5. Griffiths RR, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. Journal of Psychopharmacology. 2016;30(12):1181–1197. Source
  6. Ross S, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of Psychopharmacology. 2016;30(12):1165–1180. Source
  7. Bogenschutz MP, et al. Percentage of heavy drinking days following psilocybin-assisted psychotherapy vs placebo in the treatment of adult patients with alcohol use disorder: a randomized clinical trial. JAMA Psychiatry. 2022;79(10):953–962. Source
  8. Johnson MW, et al. Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. Journal of Psychopharmacology. 2014;28(11):983–992. Source
  9. Compass Pathways. Compass Pathways successfully achieves primary endpoint in first phase 3 trial evaluating COMP360 psilocybin for treatment-resistant depression. Company announcement, 2025. Source
  10. Nichols DE. Psychedelics. Pharmacological Reviews. 2016;68(2):264–355. Source
  11. Johnson MW, Richards WA, Griffiths RR. Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology. 2008;22(6):603–620. Source
  12. Government of Canada. Controlled Drugs and Substances Act (S.C. 1996, c. 19), Schedule III. Source
  13. Canada Gazette, Part II. Regulations Amending Certain Regulations Relating to Restricted Drugs (Special Access Program), SOR/2021-271. January 5, 2022. Source
  14. Therapeutic Goods Administration (Australia). Change to classification of psilocybin and MDMA to enable prescribing by authorised psychiatrists. 2023. Source
  15. Ballotpedia. Colorado Proposition 122, Decriminalization and Regulated Access Program for Certain Psychedelic Plants and Fungi Initiative (2022), including comparison with Oregon Measure 109 (2020). Source