Psilocybin Contraindications: Who Should Not Do Psychedelic Therapy

Psilocybin-assisted therapy has a strong safety profile when conducted in appropriate settings with careful screening — but it is not for everyone, and responsible facilitators decline to work with people in certain medical, psychiatric, and pharmacological situations. This post lays out the contraindications that matter, why they matter, and what the screening process actually looks like in a responsible practice.

If you are considering psilocybin therapy, reviewing this list is a useful exercise. If something on this page applies to you, it doesn’t necessarily mean you cannot ever pursue psilocybin therapy — many of these are relative rather than absolute contraindications, and context matters. But it does mean the conversation with your facilitator will need to be more detailed.

This post is educational and does not substitute for a clinical screening conversation with a licensed provider.

Absolute Psychiatric Contraindications

Some psychiatric conditions represent firm contraindications to psilocybin therapy. The concern in these cases is not that psilocybin is dangerous per se, but that the experience itself — with its capacity to destabilize ego structure, blur the boundary between inner and outer experience, and surface powerful emotional material — can trigger or worsen the underlying condition.

Personal history of primary psychotic disorders. Schizophrenia, schizoaffective disorder, and related primary psychotic illnesses are generally considered absolute contraindications. The concern is clear: psilocybin can temporarily produce experiences that resemble features of psychosis — thought disorganization, unusual perceptions, altered sense of self — and in someone with an underlying psychotic disorder, this can exacerbate symptoms or, rarely, trigger a more sustained psychotic episode.

Active mania or bipolar I disorder. Psilocybin can precipitate or worsen manic states in people with bipolar I disorder. Bipolar II and cyclothymia present more nuanced pictures but are usually treated with caution. This is a category where it’s particularly important to be honest during screening, including about family history — a first-degree relative with bipolar I or schizophrenia substantially raises the risk profile.

Active suicidality with intent or plan. People in acute suicidal crisis need urgent stabilization care, not an elective psychedelic experience. This is not a judgment about the person; it is a matter of what kind of intervention is actually appropriate in the moment. Psilocybin therapy can be part of a longer-arc treatment for depression with suicidal features, but only once the acute crisis is stabilized.

Medical Contraindications

Uncontrolled cardiovascular disease. Psilocybin modestly elevates blood pressure and heart rate during the acute phase of the experience. For people with well-controlled cardiovascular conditions this is usually not problematic, but uncontrolled hypertension, recent cardiac events, significant arrhythmias, or known structural heart disease represent situations where the cardiovascular burden is too concerning. Anyone with significant cardiovascular history should have cardiology input before considering psilocybin therapy.

Seizure disorders. The evidence on psilocybin and seizures in people without a seizure disorder is reassuring, but psilocybin is typically avoided in people with epilepsy or other seizure disorders. The interaction risk with certain anticonvulsants is also a consideration.

Pregnancy. Psilocybin therapy is not offered during pregnancy. The evidence base in pregnant populations is essentially nonexistent, and there is no responsible reason to proceed in the absence of that evidence.

Severe liver disease. Psilocin is metabolized through the liver, and severe hepatic impairment can alter the pharmacokinetics in unpredictable ways. Significant liver disease should be evaluated before proceeding.

Very recent head trauma or neurosurgery. A full recovery window should be observed before psychedelic therapy is considered.

Medication Contraindications

Specific medications represent hard contraindications regardless of other circumstances.

Lithium. Case reports have documented seizures when psilocybin or LSD are combined with lithium. This is a firm contraindication in essentially all clinical protocols. Discontinuing lithium is a serious clinical decision that must be made with your prescriber, not your facilitator.

MAOIs. Monoamine oxidase inhibitors — both prescription (phenelzine, tranylcypromine, isocarboxazid, selegiline) and natural (Syrian rue, ayahuasca’s Banisteriopsis caapi) — can dangerously potentiate psilocybin’s effects and are firm contraindications.

Tramadol. Tramadol is both serotonergic and lowers the seizure threshold. Combining it with psilocybin is not recommended.

Medications That Require Tapering or Careful Screening

These are not absolute contraindications but require a thoughtful approach.

SSRIs and SNRIs. These medications downregulate the 5-HT2A receptor that psilocybin acts on, which can blunt the therapeutic experience. Many protocols recommend tapering under prescriber supervision before a psilocybin session, though ongoing use during therapy is sometimes clinically appropriate. Read our detailed post on psilocybin and SSRIs for the full picture.

Mirtazapine (Remeron). Mirtazapine has 5-HT2A antagonist activity that directly opposes psilocybin’s primary mechanism. Typically tapered before a session.

Tricyclic antidepressants. Similar approach to SSRIs — taper if clinically appropriate, screen carefully.

Antipsychotics. Most antipsychotics — both first-generation and atypicals — block the receptors psilocybin acts on. They are usually incompatible with a therapeutic psilocybin experience. Whether to discontinue them is a serious clinical decision tied to the underlying diagnosis; for many people on antipsychotics, psilocybin therapy is not the right intervention.

Benzodiazepines. Not contraindicated from a safety standpoint, but they blunt psilocybin’s effects. Typically held on the day of the session.

Stimulants (Adderall, Ritalin, Vyvanse). Generally held on the day of the session. The interaction is not especially dangerous but is pharmacologically complicating.

Psychological Factors That Warrant Extra Care

Beyond formal contraindications, several psychological factors warrant an especially careful screening conversation.

Unprocessed major trauma without existing therapeutic support. Psilocybin can surface trauma material powerfully. If you have significant trauma history but no existing relationship with a therapist to support you during and after the psilocybin arc, the work is likely to be more difficult than it needs to be. This isn’t a reason not to do it — but it may be a reason to build that support structure first.

Current severe depression with features of hopelessness or apathy too deep for preparation engagement. Psilocybin therapy requires active engagement in preparation and integration. When someone is too depleted to engage with preparation, the therapeutic arc breaks down.

Dissociative symptoms or depersonalization/derealization disorder. Psilocybin can exacerbate dissociative features. This is a nuanced area that calls for careful individual assessment.

Eating disorders in active acute phase. Active severe eating disorders warrant stabilization first. Psilocybin therapy has shown promise for some eating disorder populations but is not a frontline intervention in acute crisis.

Personality disorders with significant instability. Particularly borderline personality disorder with frequent affective storms or self-harm behaviors. Psilocybin therapy can be part of a longer therapeutic journey in these populations but typically requires extensive stabilization and skilled support.

Family History

Some contraindications extend to family history. A first-degree relative with schizophrenia or bipolar I disorder raises the risk profile enough that many protocols either decline to proceed or proceed only with particularly careful screening and lower doses. This is one reason the preparation conversation can feel more extensive than people expect.

Drug and Alcohol Use

Active addiction to substances requiring medical supervision for withdrawal (alcohol, benzodiazepines, opioids) represents a situation where stabilization usually needs to precede psilocybin work. Psilocybin has clinical evidence for addiction treatment, but it’s not a substitute for acute detox care.

Regular high-intensity stimulant use (including cocaine, methamphetamine) warrants careful cardiovascular evaluation.

Chronic heavy cannabis use is not a contraindication but is worth discussing because it can shape psychedelic experience and integration in specific ways.

Age

Psilocybin therapy under Colorado’s Natural Medicine Health Act is limited to adults 21 and older. This is non-negotiable. Beyond the legal floor, many facilitators apply clinical judgment about whether someone in their early 20s has the life experience and ego development that support productive psychedelic work — this is not a firm rule, but it is a consideration.

On the older end, age itself is not a contraindication. Psilocybin therapy for end-of-life distress is one of the most robust clinical indications, and older adults respond well to the work. Cardiovascular screening becomes more important with age simply because prevalence of cardiovascular disease increases.

How Screening Actually Works

A responsible facilitator’s screening process typically includes a detailed medical history (cardiovascular, neurological, metabolic), a psychiatric history including personal and family mental health history, a full medication review including supplements and recreational substances, a substance use history, an assessment of current life stability and support, and a preparation conversation focused on intentions, expectations, and readiness.

This screening is not bureaucratic gatekeeping. It is the foundational therapeutic phase where your facilitator develops the understanding needed to support you through the arc. A facilitator who skips this work or rushes through it is not offering responsible care.

If Something on This List Applies to You

The presence of a contraindication or a risk factor does not automatically close the door on psilocybin therapy forever. Many of these are contextual — relative rather than absolute, or tied to the current phase of an underlying condition rather than the condition itself. The right move is to have an honest conversation with a licensed facilitator, and often to involve your existing clinical team. Sometimes the answer is not now; sometimes the answer is not without additional support; sometimes the answer is yes, with careful planning.

What is not appropriate is pursuing psilocybin therapy without disclosing relevant medical or psychiatric history. Withheld information undermines the screening process and makes the experience less safe than it should be.

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Questions about whether psilocybin therapy is appropriate for your situation? Get in touch for a confidential conversation, or read our safety guide and five things before psilocybin therapy for more context.