Who should avoid psilocybin? What clinical trials exclude

The short answer

Across the eight psilocybin trials we checked, researchers repeatedly excluded people with a personal history of psychosis, schizophrenia or bipolar disorder, a close relative with one of those, recent suicidal behavior, heart disease, uncontrolled high blood pressure or a long QT interval, epilepsy, pregnancy or breastfeeding, moderate or severe liver disease, or a current substance use disorder.¹ They also required people to come off antidepressants, antipsychotics, MAOIs, stimulants and other psychiatric medicines first, under supervision, or left them out.² Being excluded from a trial doesn't prove psilocybin would harm you. It means no one has shown it's safe for you, and for some groups the research shows real warning signs.

How trials screen people

We read the eligibility criteria for eight trials on ClinicalTrials.gov, plus the full protocols posted for three of them.¹² COMP001's registry entry lists almost no criteria, so its exclusions here come from its posted protocol. COMP005 and COMP006 list only key criteria in the registry, so their full lists may be longer.

Screening went well beyond a questionnaire. Depending on the trial, it included a structured suicide-risk interview (the C-SSRS), several blood pressure readings (the Johns Hopkins cancer trial averaged four or more over at least two days), an ECG to measure the QT interval, liver tests, and in COMP001 and Usona's trials a urine drug test.¹² Investigators could also exclude anyone they judged at risk. The Johns Hopkins safety guidelines for hallucinogen research explain the reasoning behind several of these exclusions, including psychosis risk and medicines such as lithium.³

Which exclusions apply to you? A private checklist

For each item you tick, the checklist shows what the trials did about it and why, with sources. With JavaScript off, every item is listed in full.

If you take any prescription medicine, our psilocybin interaction checker covers 26 medicine and drug classes. Never stop or change a prescribed medicine on your own.

What psilocybin does to blood pressure and the heart

Psilocybin raises blood pressure and heart rate during a session. These figures come from people who had already passed heart screening, in clinics with staff watching.

A modeling study estimated an average change in corrected QT of 2.1 ms at a clinical trial dose, with an upper 90% bound of 6.6 ms.⁸ In a controlled study of 23 healthy volunteers, psilocybin didn't change average QTc, but the longest single readings were 509 ms after escitalopram pretreatment and 481 ms after placebo, and one person fainted (vasovagal syncope).⁹ Trials set QTc limits between 440 and 470 ms.¹

Trials excluded heart disease and uncontrolled blood pressure, so these figures say nothing about people with those conditions. If you have either, ask your doctor.

Mental health history: psychosis, bipolar disorder and suicide risk

The Johns Hopkins guidelines give two reasons for excluding a personal or family history of psychosis: schizophrenia has a genetic component, and prolonged psychosis after hallucinogens appears to occur mostly in people with an illness that was already present.³ In a US sample of 2,822 adults, representative by sex, age and ethnicity, psychotic symptoms were highest among people who had used psychedelics and also had a family history of psychotic or bipolar disorders.¹⁰ In Ontario, among 9,244,292 people, an emergency visit involving hallucinogens was followed by a schizophrenia spectrum diagnosis within 3 years in 3.99% (208 of 5,217), against 0.15% of the general population; that study covered all hallucinogens and shows an association, not a cause.¹¹

For bipolar disorder, a survey of 541 people with self-reported bipolar disorder who had used psilocybin found 32.2% reported new or worse symptoms afterward, most often mania symptoms, sleep problems and anxiety; 3.3% used emergency services.¹² A small open-label trial in 15 people with bipolar II depression found no significant change on a mania rating scale, but its participants were carefully selected and supervised.¹³

Suicide risk is screened hard, and still showed up. In COMP001, serious suicidal behavior occurred in 3 of 79 people in the highest-dose group, against 0 of 75 and 0 of 79 in the other two groups, and serious self-injury occurred in all three groups.¹⁴ Those participants had treatment-resistant depression and had tapered off antidepressants first. Across 114 studies of classic psychedelics (3,504 participants), serious adverse events occurred in none of the healthy participants and in about 4% of those with pre-existing psychiatric or neurological conditions.¹⁵ Several trials also excluded borderline and other personality disorders.¹ If you're having thoughts of suicide, call or text 988.

Pregnancy and breastfeeding

All six trials that published full criteria excluded pregnancy and breastfeeding and required effective contraception, and four of them also explicitly excluded people planning a pregnancy.¹ Our research found no human safety data on psilocybin in pregnancy or breastfeeding. The only data are from animals: in mice given psilocybin after giving birth, the mothers were more anxious weeks later, and pups exposed through nursing showed anhedonia (lost interest in rewards) as adults.¹⁶ How that applies to people is unknown. If you're pregnant or breastfeeding, talk to your obstetrician, midwife or doctor.

What a clear checklist does not mean

Ticking nothing above isn't a green light. Trials screen with physical exams, ECGs, lab tests and interviews that a checklist can't replace, and investigators turn people away for reasons no list captures. Even screened participants have side effects: in COMP001, 179 of 233 participants (77%) had an adverse event, with headache the most common.¹⁴ Reporting is patchy too: only 16 of 68 psychedelic studies since 2005 described a systematic way of collecting adverse events.¹⁵

Trials also gave a measured amount of a pure compound to people with medical staff present. Mushrooms vary widely in strength (see our potency data), and no checklist covers your setting, your state of mind or what else is in your system. If something does go wrong, our help page covers what to do, and the overdose and warning signs page lists the signs that mean calling 911.