What trials have excluded

The Johns Hopkins safety guidelines of 2008 name current or past schizophrenia and other psychotic disorders, and bipolar I or II disorder, as the most important conditions to exclude. They also exclude people with a first- or second-degree relative, such as a parent, sibling, grandparent, aunt or uncle, who has one of these disorders. A 2021 Johns Hopkins depression trial also excluded people with a recent substance use disorder, a medically significant suicide attempt or certain heart conditions.

Data from outside trials show why the caution exists: in a survey of 541 people with bipolar disorder who had used psilocybin mushrooms, about one in three reported new or worsening symptoms afterward, most prominently mania.

Heart, blood pressure and medicines

Psilocybin raises blood pressure for several hours. In supervised studies the average rise is about 19 mmHg in systolic pressure and 8.7 in diastolic, largest 60 to 90 minutes after dosing. The Johns Hopkins group excluded volunteers whose resting blood pressure was above 140/90. Among medicines, lithium carries the clearest warning: in 62 online accounts of people combining lithium with a classic psychedelic, 47 percent described seizures. MAO inhibitors are the medicines most linked to serious serotonin toxicity, and common antidepressants can change how a session feels. Trials have also excluded anyone who is pregnant.

Absolute, relative and trial-only

Medical usage distinguishes absolute contraindications, where the risk can be life-threatening, from relative ones, where a clinician may judge that the benefits outweigh a higher risk. Trial criteria are not the same thing: some exist to keep the data clean rather than for safety. A 2025 expert consensus notes that patients in ordinary practice will bring less complete histories than research volunteers, so risk has to be judged with more nuance, case by case.

None of this is a checklist to apply to yourself, and decisions about any medicine belong with the clinician who prescribed it. Our safety and screening page sets out the criteria we use, and a separate page explains whom we decline, and why.

Related terms

Serotonin Syndrome: what the studies of psilocybin with antidepressants found.

Set and Setting: the conditions of the session, a separate safeguard from screening.

Psychedelic Integration: the work after a session.