How to read these pages
Every interaction page opens with a color-coded verdict so you can take a position in seconds:
No known dangerous interaction
Routine combinations with low theoretical and clinical risk.
Reduced effect or moderate risk
Combination changes outcomes or carries manageable risk that needs planning.
Serious risk of harm
Documented adverse events. Avoid unless under medical supervision.
Hard no
Lethal or severely harmful pathway. Do not combine, ever.
Pages in this section
Cards display verdict color at a glance. New pages appear here automatically when published.
ADHD Stimulants and Psilocybin: Cardiovascular Load and Anxiety Stacking
Adderall, Vyvanse, Ritalin, and Concerta are some of the most commonly prescribed psychiatric medications. Their interaction with psilocybin is not life-threatening in healthy adults
Alcohol and Psilocybin: Why It Blunts the Trip and Stacks the Risks
Alcohol and psilocybin is the most common combination people ask about because both are widely used. Pharmacologically the picture is unflattering: alcohol blunts the
Anti-Epileptics and Psilocybin: A Per-Drug Answer for AED Interactions
Anti-epileptic drugs (AEDs) are not a single class with a shared mechanism. Valproate is a broad GABA and sodium-channel modulator that also inhibits UGT
Antihistamines and Psilocybin
Antihistamines split sharply into two groups. First-generation (diphenhydramine / Benadryl, doxylamine / Unisom, hydroxyzine, promethazine) are sedating and strongly anticholinergic. Combining them with psilocybin
Antipsychotics and Psilocybin: Receptor Block, Diagnosis Caution
Most atypical antipsychotics (olanzapine, quetiapine, risperidone, aripiprazole) are 5-HT2A antagonists. That is the same receptor psilocin activates. The result is predictable: they blunt or
Benzodiazepines and Psilocybin: Trip Killer, Rescue Tool, and the Daily-Use Trap
Benzodiazepines (Xanax, Klonopin, Ativan, Valium) are the most reliable way to shorten or abort a difficult psilocybin experience, which is exactly why therapists keep
Beta-Blockers and Psilocybin: Likely Safe, Sometimes Useful for the Cardiovascular Rise
Beta-blockers (propranolol, metoprolol, atenolol, bisoprolol, carvedilol, nebivolol) block β1 and β2 adrenergic receptors. They reduce heart rate and blood pressure. They do not touch
Birth Control and Psilocybin: No Pharmacological Interaction, with Practical Notes
Hormonal contraceptives (combined oral pills, progestin-only pills, hormonal IUDs, implants, vaginal rings, patches, depot injections) act on estrogen and progesterone receptor pathways. They do
Bupropion and Psilocybin: The Non-Serotonergic Antidepressant That Still Wants a Pause
Bupropion (Wellbutrin, Zyban) is the antidepressant people most often hope is safe to combine with psilocybin, because it is not serotonergic. The good news
Cannabis and Psilocybin: Common, Not Catastrophic, Sometimes Counterproductive
The most asked combination in microdosing forums after SSRIs. The interaction is not life-threatening but can amplify anxiety, intensify the trip, and undermine integration.
DXM and Psilocybin: Serotonin Syndrome Risk From an Over-the-Counter Cough Medicine
Dextromethorphan is the cough suppressant in Robitussin, Delsym, NyQuil, and dozens of OTC combination products. It is also a serotonin reuptake inhibitor and an
Gabapentinoids and Psilocybin: No Serotonin Pathway, Sedation and Blunting Concerns, Hard Rules Against Abrupt Stopping
Gabapentin and pregabalin (Lyrica) bind the α2δ subunit of voltage-gated calcium channels. They do not touch serotonin, MAO, or 5-HT2A. The pharmacological interaction with
Ketamine and Psilocybin: Different Receptor Systems, Real Cardiovascular and Psychological Stacking
Ketamine is an NMDA antagonist and a dissociative. Psilocybin is a 5-HT2A agonist and a classical psychedelic. There is no shared serotonergic pathway, so
Lamotrigine and Psilocybin: A Mood Stabilizer That Quiets the Glutamate Echo
Lamotrigine (Lamictal) is a sodium-channel blocker that suppresses glutamate release. Psilocybin produces much of its cortical signal through 5-HT2A activation that triggers a downstream
Lithium and Psilocybin: The Most Documented Dangerous Combination
Of all psychedelic drug interactions, this one has the largest case series and the most consistent signal. Seizures, prolonged psychotic reactions, hospitalizations. The combination
MAOIs and LSD: Real Serotonin Syndrome Risk
MAOIs flood the brain with serotonin. LSD activates the receptors that flood is hitting. The combination has well-documented case reports of severe serotonin syndrome,
MDMA and Psilocybin: Hippie Flipping and the Real Risks
"Hippie flipping" is a real combination with a long recreational history. Pharmacologically the picture is more complicated than either alone: serotonin demand spikes, neurotoxicity
NSAIDs and Psilocybin: Likely Safe with GI and Hydration Notes
NSAIDs (ibuprofen, naproxen, aspirin, diclofenac, celecoxib) inhibit cyclooxygenase. They do not touch serotonin receptors and do not interact pharmacologically with psilocybin in any meaningful
Opioids and Psilocybin: Lower Acute Risk Than Tramadol, Real Practical Problems
Pure mu-opioid agonists like oxycodone, hydrocodone, morphine, and fentanyl do not share tramadol's serotonergic mechanism. Acute pharmacology is largely additive sedation, not serotonin syndrome.
PPIs and Psilocybin
Proton pump inhibitors (omeprazole, esomeprazole, pantoprazole, lansoprazole, rabeprazole, dexlansoprazole) suppress gastric acid by blocking the H+/K+ ATPase in stomach parietal cells. They do not
Psilocybin Plus MDMA Plus Amphetamine Stack: The Three-Way Combination Risk Profile
The two-substance combination of psilocybin and MDMA, sometimes called hippie flipping, has a substantial recreational history and modest documented harm profile when both substances
SSRIs and Psilocybin: Why Serotonin Syndrome Theory Diverges From Clinical Reality
The textbook warning is serotonin syndrome. The clinical data tells a different story: most SSRIs blunt the psilocybin experience rather than amplify it. Here
Statins and Psilocybin: A Cholesterol Drug Talking to a Liver Pathway That Does Not Matter for Psilocin
Statins (atorvastatin, rosuvastatin, simvastatin, pravastatin, pitavastatin, lovastatin, fluvastatin) lower LDL by blocking HMG-CoA reductase, the rate-limiting enzyme of hepatic cholesterol synthesis. They do not
Thyroid Medication and Psilocybin: Replacing a Hormone Does Not Touch the Serotonin System, with a Note on Untreated Hyperthyroidism
Levothyroxine (Synthroid, Eltroxin, Euthyrox, Tirosint) and liothyronine (Cytomel) are hormone replacements for an underactive thyroid. They restore physiological levels of T4 and T3 and
Tramadol and Psilocybin: Underestimated Serotonin Syndrome Risk
Tramadol looks like a benign opioid analgesic. It is also a serotonin reuptake inhibitor with a meaningful seizure-threshold effect. Combined with psilocybin, the case
Trazodone and Psilocybin: The Sleep Aid That Camps on the Receptor You Need
Trazodone is a SARI (serotonin antagonist and reuptake inhibitor) with high affinity for 5-HT2A as an antagonist. That is the same receptor psilocin needs
Sources we use
Tripsit drug interaction chart, DrugBank, PubMed case reports, MAPS protocols, Halman et al. (2024) lithium review, Sarparast et al. (2022) psychedelic-medication interaction systematic review.
