InvestigationalNot FDA approved

Psilocybin: what it is and how we study it

What psilocybin is, how it acts in the brain, what it has been studied for, and how our team gives it safely in clinical trials.

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What is psilocybin?

Psilocybin is a naturally occurring compound found in more than 100 species of mushrooms.

The psilocybin used in research is made in a laboratory to pharmaceutical standards, so every capsule holds a precise, verified dose. In the United States, psilocybin is a Schedule I controlled substance. It is not approved by the FDA for any condition and is available only through authorized research.

How psilocybin works

Psilocybin itself is inactive. After it is swallowed, the body converts it into psilocin, the form that acts on the brain.

Psilocin attaches mainly to the brain's serotonin 2A (5-HT2A) receptors, which are concentrated in areas involved in perception, thinking and sense of self.1 Effects begin within about 30 to 60 minutes and fade over four to six hours. Researchers are studying three ways this may lead to lasting change:

During the sessionBrain networks shiftBrain imaging shows that the usual patterns of communication between brain networks loosen while psilocin is active.4
Days to weeksNew connections formIn laboratory and animal studies, psychedelics including psilocybin promote the growth of new connections between nerve cells.23 Whether the same happens in people is being studied.
With supportA window for changeResearchers think these changes may make it easier to step out of rigid patterns of thinking, which preparation and integration sessions help put to use.

These are working explanations. Exactly how psilocybin produces lasting benefit is still an open research question.

Conditions psilocybin has been studied to treat

Psilocybin is not approved to treat any condition. These are the main areas where clinical trials have tested it:

DepressionIncluding depression that has not responded to standard care. Randomized trials have found reduced symptoms after a single supported dose, and larger Phase 3 trials are under way.567
Anxiety and depression with serious illnessIn people facing life-threatening cancer, trials found lasting reductions in anxiety and depression.89
Alcohol and tobacco useA randomized trial found fewer heavy drinking days, and a pilot study tested psilocybin to help people quit smoking.1011
Obsessive-compulsive disorderEarly evidence comes from small studies. Our team's trials are designed to test it more rigorously.12

Studies are also under way in other areas, including opioid use disorder, depression in Parkinson's disease and overlapping mental health symptoms. See our current studies.

Effects of psilocybin

Effects vary with the dose, the person and the setting. During a session, people may experience:

  • Changes in perception. Altered vision, sound and sense of time, often more vivid with eyes closed.
  • Strong emotions. Feelings can be intense, ranging from joy and connection to grief or fear.
  • New perspective. Many people describe insights into their lives, relationships and patterns of thinking.
  • Physical effects. Temporary rises in blood pressure and heart rate, nausea and headache are common and usually short-lived.1

Some sessions are difficult. That is why preparation and in-session support matter, and why psilocybin should only be taken in a controlled clinical setting.

How psilocybin is given in studies

  • Oral capsule. People in our studies swallow a capsule with water. Our studies have used a fixed 25 mg dose, and our first OCD trial used a dose based on body weight.
  • One or two sessions. Most of our studies use a single dose. Our repeated-dosing OCD study gives two doses one week apart.
  • Supported sessions. Each dosing day lasts about eight hours in a private, comfortable room. Two trained facilitators stay with the person throughout, and a study physician is on call.
  • Before and after. Preparation sessions come before dosing, and an integration session follows soon after, with follow-up visits over the following weeks and months.

Our studies run on an outpatient basis at 40 Temple Street in New Haven. People go home the same day once they are medically cleared. The FDA has issued guidance on how these trials should be designed and run.13

Safety considerations

  • Psilocybin is experimental and not approved for medical use.
  • Using psilocybin outside a controlled clinical setting can be dangerous and is illegal under federal law.
  • It can interact with other medications, and it may not be safe for people with certain mental health conditions, such as a personal or family history of psychosis or bipolar I disorder, or with heart conditions.
  • Everyone in our studies is screened medically and psychiatrically, monitored throughout the session and followed afterward. An independent board reviews safety data.

Always talk with a healthcare professional before considering any new kind of care, including joining a clinical trial.

Our work

Our team began with obsessive-compulsive disorder, where an early pilot study had suggested psilocybin could reduce symptoms,12 and has since widened the question to people whose symptoms cross diagnostic lines.

  1. CompletedPhase 1Study page ClinicalTrials (opens in a new tab)

    Psilocybin for Treatment-Resistant OCD — NIMH K23

    A randomized, double-blind trial comparing psilocybin with an active placebo (niacin), with brain imaging before and after. Completed in 2024. Funded by the Yale Center for Clinical Investigation (YCCI) and philanthropic support.

  2. NIMH career development award

    A K23 award, the first career development award for psychedelic research since 1967, supporting our OCD and neuroimaging work.

  3. Active, not recruitingPhase 1Study page ClinicalTrials (opens in a new tab)

    Repeated Psilocybin Dosing in OCD

    A randomized, waitlist-controlled trial testing whether a second dose adds benefit. Supported by the Steven & Alexandra Cohen Foundation.

  4. RecruitingPhase 1bStudy page ClinicalTrials (opens in a new tab)

    Psilocybin for Transdiagnostic Psychiatry Symptoms

    An open-label study of a single dose in adults with overlapping symptoms, designed to reflect the patients clinicians see in everyday practice.

Our team also serves as a site for industry-sponsored Phase 3 trials in depression and runs a fellowship in psychedelic medicine for clinicians. See all studies on Research & Trials.

Questions & glossary

Can I get psilocybin from you outside a study?

No. Psilocybin is only available through approved research. Joining a study means being a fit for it, which the study team decides in screening.

Will I know if I receive psilocybin?

It depends on the study. In our open-label transdiagnostic study, everyone receives psilocybin. Some trials compare psilocybin with a placebo, and the people taking part do not know which they received until after the main assessments.

Do I have to stop my current medications?

That varies by study. In our transdiagnostic study, most stable medications and therapy can continue, though some medications are not allowed. The team reviews your medications with you and your provider. Please do not stop any medication on your own to qualify.

How long do the effects last?

The acute effects usually last four to six hours, and people stay on site until they have fully worn off. Whether and how long any benefits last is one of the questions our follow-up visits are designed to answer.

What are the risks?

Common short-term effects include anxiety, nausea, headache and temporary rises in blood pressure and heart rate. Some sessions are emotionally difficult. Rarely, psychological effects can persist. Each study's consent form describes its risks in full, and the team will go through them with you.

Glossary

What do trial phases mean? New medicines are tested in steps before the FDA can consider approving them.

Phase 1
First studies in people. A small group, focused on safety, dosing and early signs of benefit.
Phase 2
A larger group. Tests whether the medicine works for a specific condition and continues to track safety.
Phase 3
Large studies, often at many sites, that confirm benefit and safety. Results support an application for FDA approval.
Phase 4
Studies after approval that follow long-term safety and use in everyday care.
Open-label
Everyone, including the people taking part, knows which study drug is given.
Placebo
An inactive or comparison substance used to judge a medicine's true effect.
Transdiagnostic
Looking across diagnoses at symptoms people share, rather than one condition at a time.
Functional impairment
How much symptoms get in the way of work, relationships and self-care.
Facilitator
A trained clinician who prepares and stays with a person through the session.
Integration
Sessions after dosing that help connect the experience to daily life.
Psilocin
The active form psilocybin is converted into in the body.
5-HT2A receptor
A serotonin receptor in the brain where psilocin mainly acts.
Neuroplasticity
The brain's ability to form and reorganize connections between nerve cells.
Schedule I
The federal category for substances with no accepted medical use; research requires special licenses.
Sources
13 sources
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  2. Ly C, Greb AC, Cameron LP, et al. Psychedelics promote structural and functional neural plasticity. Cell Rep. 2018;23:3170–3182. PubMed (opens in a new tab)
  3. Shao LX, Liao C, Gregg I, et al. Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo. Neuron. 2021;109:2535–2544. PubMed (opens in a new tab)
  4. Siegel JS, Subramanian S, Perry D, et al. Psilocybin desynchronizes the human brain. Nature. 2024;632:131–138. PubMed (opens in a new tab)
  5. Carhart-Harris R, Giribaldi B, Watts R, et al. Trial of psilocybin versus escitalopram for depression. N Engl J Med. 2021;384:1402–1411. PubMed (opens in a new tab)
  6. Goodwin GM, Aaronson ST, Alvarez O, et al. Single-dose psilocybin for a treatment-resistant episode of major depression. N Engl J Med. 2022;387:1637–1648. PubMed (opens in a new tab)
  7. Raison CL, Sanacora G, Woolley J, et al. Single-dose psilocybin treatment for major depressive disorder: a randomized clinical trial. JAMA. 2023;330:843–853. PubMed (opens in a new tab)
  8. Griffiths RR, Johnson MW, Carducci MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J Psychopharmacol. 2016;30:1181–1197. PubMed (opens in a new tab)
  9. Ross S, Bossis A, Guss J, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 2016;30:1165–1180. PubMed (opens in a new tab)
  10. Bogenschutz MP, Ross S, Bhatt S, 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;79:953–962. PubMed (opens in a new tab)
  11. Johnson MW, Garcia-Romeu A, Cosimano MP, Griffiths RR. Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. J Psychopharmacol. 2014;28:983–992. PubMed (opens in a new tab)
  12. Moreno FA, Wiegand CB, Taitano EK, Delgado PL. Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. J Clin Psychiatry. 2006;67:1735–1740. PubMed (opens in a new tab)
  13. US Food and Drug Administration. Psychedelic Drugs: Considerations for Clinical Investigations. Draft guidance for industry. June 2023. FDA (opens in a new tab)