✅ Lower Risk ⚠️ Caution 🚫 High Risk 🚫 Avoid Entirely

Risk tiers below are taken directly from the classification already stated on each substance's own combinations page (its "Use Caution", "High Risk", or "Avoid Entirely" heading) — this matrix does not add any new interaction claims. Click a substance name or "Details" to read the full mechanism, harm-reduction guidance, and emergency-help notes for that combination.

Psilocybin vs. 18 substances / medication classes, sorted from highest to lowest risk tier. Source: each substance's own page under /combinations/.
Substance Risk Tier Basis (from substance page) Details
Lithium 🚫 Avoid Entirely Dangerous — avoid entirely Details →
MAOIs 🚫 Avoid Entirely Dangerous — serotonin syndrome risk Details →
Tramadol 🚫 Avoid Entirely Dangerous — seizure and serotonin syndrome risk Details →
Stimulants 🚫 High Risk Cardiovascular stress Details →
MDMA 🚫 High Risk Neurotoxicity and overwhelming effects Details →
Cocaine 🚫 High Risk Cardiovascular stress Details →
Opioids 🚫 High Risk Respiratory depression + impaired judgment Details →
Ketamine 🚫 High Risk High complexity — two reality-altering mechanisms stacked Details →
SSRIs ⚠️ Caution Blocked effects — do not stop unsupervised Details →
Cannabis ⚠️ Caution Unpredictable intensification Details →
Alcohol ⚠️ Caution Generally discouraged Details →
Antipsychotics ⚠️ Caution Moderate risk — blocked effects, underlying condition matters most Details →
Beta-Blockers ⚠️ Caution Situational — generally compatible, discuss with your prescriber Details →
ADHD Medications ⚠️ Caution Discuss with your prescriber, don't decide alone Details →
Caffeine ✅ Lower Risk Generally well tolerated Details →
CBD ✅ Lower Risk Limited data, generally considered mild Details →
Benzodiazepines ✅ Lower Risk Sometimes used as a "trip killer" Details →
NSAIDs ✅ Lower Risk Mainly a GI-comfort consideration Details →

⚠️ Medical Disclaimer

This matrix is for educational and harm-reduction purposes only and does not constitute medical advice. Risk tiers summarize the classification already published on each substance's own combinations page — always read the full page for mechanism, dosing, and emergency guidance before acting, and consult a qualified physician or pharmacist before combining any substance with a prescription or over-the-counter medication.

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