Psilocybe cubensis

coronary artery disease, heart failure, uncontrolled hypertension, arrhythmia

Psilocybin produces transient increases in blood pressure and heart rate via serotonergic sympathomimetic mechanisms. No clinical trials have enrolled patients with established cardiovascular disease. Wsół (2023) notes insufficient data on psilocybin safety in CVD patients. Myocardial injury documented with P. keralensis (a different species) highlights theoretical cardiovascular concern.

schizophrenia, schizoaffective disorder, bipolar I disorder

Personal or family history of psychotic disorders (schizophrenia, schizoaffective disorder, bipolar I with psychotic features) is the primary exclusion criterion in all clinical psilocybin research protocols. 5-HT2A receptor agonism can trigger acute psychotic episodes or unmask latent psychotic vulnerability.

active suicidal ideation, recent suicide attempt

Active suicidal ideation is an exclusion criterion in clinical trials. In the Goodwin et al. 2022 NEJM trial, suicidal ideation or behavior was reported across all dose groups including 1 mg control, consistent with the underlying treatment-resistant depression population rather than a drug-specific effect. The intense emotional amplification during psilocybin experiences could exacerbate pre-existing suicidality.

hepatic impairment, cirrhosis, severe liver disease

Psilocin undergoes hepatic metabolism primarily through CYP2D6 and CYP3A4 pathways. Hepatic impairment could reduce clearance and prolong psilocin exposure, potentially intensifying or extending psychedelic effects. No published clinical data exist in hepatically impaired patients.

pregnancy, breastfeeding

No published human safety or teratogenicity data exist for psilocybin during pregnancy. Serotonin plays critical roles in fetal neurodevelopment, and 5-HT2A agonism during pregnancy represents a theoretical risk. Traditional-use accounts describe adult use only. Avoidance is recommended as a precautionary principle.

age under 18

No clinical trials of psilocybin have been conducted in adolescent or pediatric populations. The developing brain may be more vulnerable to lasting effects of serotonergic perturbation. A published case report documents HPPD in a 16-year-old following psilocybin use (Mori-Kreiner et al. 2025).

MAOI therapy (phenelzine, tranylcypromine, isocarboxazid, selegiline, moclobemide)

Concurrent use of monoamine oxidase inhibitors with psilocybin-containing mushrooms poses risk of hypertensive emergency. P. cubensis contains endogenous β-carboline MAO inhibitors (harmane, norharman); adding an exogenous MAOI creates compounded inhibition of serotonin degradation, potentiating both serotonergic and sympathomimetic effects.

lithium therapy

The lithium-psilocybin combination is flagged as potentially hazardous in published safety guidelines (Johnson et al. 2008). Proposed mechanisms include serotonergic amplification and lithium's pro-convulsant effects. Community reports reference seizure risk, though peer-reviewed case reports specifically documenting lithium-psilocybin seizures were not individually retrieved during research.