Lyman Support Centers LLC. - (303) 591-1960 - Join our email list!

Address; 800 W. 8th Ave #110 Denver Colorado - 2-6:45 PM Tuesday - Saturday

- Darren Lyman - (303) 591-1960 - Twitter | Facebook | LinkedIn

Contraindications of Psilocybin Mushrooms with Prescription Medications and Over The Counter (OTC):

Pharmacological Mechanism of Psilocybin:

•Psilocybin is a naturally occurring prodrug found in psychedelic mushrooms.

•After ingestion, psilocybin is rapidly dephosphorylated to psilocin, the active compound.

•Psilocin is a partial agonist at 5-HT2A receptors, with additional activity at 5-HT1A, 5-HT2C, and dopamine D2 receptors.

•Metabolized primarily by hepatic cytochrome P450 enzymes, especially CYP3A4, and also influenced by monoamine oxidase A (MAO-A).

•Effects include altered perception, mood, and cognition, as well as changes in heart rate, blood pressure, and body temperature.

Contraindicated Drug Classes:

Selective Serotonin Reuptake Inhibitors (SSRIs)

•Examples: Fluoxetine, Sertraline, Citalopram, Paroxetine, Escitalopram

•Mechanism: SSRIs increase extracellular serotonin by blocking reuptake; chronic use causes 5-HT2A receptor downregulation.

•Risks:

•Serotonin Syndrome if combined with high doses of psilocybin (rare but serious).

•Blunted psychedelic response due to receptor desensitization.

•Clinical Note: Tapering off SSRIs prior to psychedelic therapy is sometimes recommended under medical supervision.

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

•Examples: Venlafaxine, Duloxetine, Desvenlafaxine

•Mechanism: Dual reuptake inhibition increases both serotonin and norepinephrine levels.

•Risks:

•Heightened adrenergic activity (elevated blood pressure, anxiety).

•Serotonin Syndrome in polypharmacy settings.

Monoamine Oxidase Inhibitors (MAOIs)

•Examples: Phenelzine, Tranylcypromine, Isocarboxazid

•Mechanism: Inhibit MAO-A and/or MAO-B, preventing serotonin degradation.

•Risks:

•Hypertensive crisis due to tyramine accumulation or excessive serotonin.

•Potentiation of psilocin, leading to dangerous overstimulation.

Tricyclic Antidepressants (TCAs)

•Examples: Amitriptyline, Nortriptyline, Imipramine

•Risks:

•Lowered seizure threshold.

•Increased anticholinergic load (confusion, dry mouth, tachycardia).

•Potential cardiovascular instability.

Mood Stabilizers

•Lithium and Carbamazepine: Documented to cause seizures or severe neurological reactions when combined with psilocybin or LSD.

•Valproate: May interfere with psilocybin metabolism; risk data limited.

Antipsychotic Medications:

Typical and Atypical Antipsychotics

•Examples: Haloperidol, Risperidone, Olanzapine, Quetiapine

•Mechanism: Antagonize D2 and 5-HT2A receptors.

•Risks:

•Blunting of psychedelic experience by receptor blockade.

•Potential extrapyramidal symptoms if combined with serotonergic agents.

•Use in emergency trip termination due to antagonistic effects on 5-HT2A.

Anxiolytics and Sedatives:

Benzodiazepines

•Examples: Diazepam, Lorazepam, Clonazepam, Alprazolam

•Mechanism: Enhance GABA-A activity.

•Clinical Use: Often used to reduce or abort an overwhelming psychedelic experience.

•Risks:

•May cause memory impairment or excessive sedation.

•No major toxic interaction but may reduce introspective benefits of therapy.

Z-Drugs (Sedative-Hypnotics)

•Examples: Zolpidem, Eszopiclone

•Risks: Confusion, sleepwalking, amnesia if mixed with psilocybin.

Over-the-Counter Medications (OTC):

Antihistamines

•Diphenhydramine (Benadryl): Increases CNS depression and anticholinergic burden.

•Cetirizine, Loratadine (non-drowsy): Minimal interaction.

NSAIDs

•Ibuprofen, Naproxen, Aspirin: Low direct interaction; caution with stomach irritation or dehydration.

Acetaminophen

•Generally safe unless liver function is impaired or combined with alcohol.

Decongestants

•Pseudoephedrine, Phenylephrine: Can exacerbate tachycardia, anxiety, and hypertension during a psilocybin experience.

Cough Suppressants

•Dextromethorphan (DXM): High risk. Shares serotonergic and NMDA effects—can cause psychosis, serotonin syndrome, and dissociation.

CNS Stimulants (Prescription & OTC):

ADHD Medications

•Examples: Adderall (amphetamine salts), Methylphenidate (Ritalin)

•Risks:

•Cardiovascular overstimulation (tachycardia, hypertension).

•Increased anxiety, restlessness, panic during the trip.

Modafinil

•Theoretical interaction risk due to unknown 5-HT modulation.

•Not well studied in combination.

Opioids and Synthetic Analgesics:

•Morphine, Oxycodone, Hydrocodone: Increased sedation; some users report reduced clarity or intensified nausea.

•Tramadol: Contraindicated due to serotonin syndrome risk.

•Kratom: Unpredictable CNS effects; may mask or distort psilocybin effects.

Cardiovascular Medications:

•Beta-blockers (Propranolol, Atenolol): May mitigate cardiovascular overstimulation and anxiety.

•ACE inhibitors / ARBs: No direct interactions known.

•Antiarrhythmics (Amiodarone, Flecainide): Contraindicated due to unknown electrophysiological interactions with psilocybin.

•Diuretics: Risk of dehydration; monitor fluid intake.

Antibiotics and Antifungals:

•Erythromycin, Fluconazole: Inhibit CYP3A4 → may increase psilocin levels unexpectedly.

•Rifampin: Induces CYP enzymes → may reduce psilocybin effect.

•Ciprofloxacin: Rare reports of CNS excitation or anxiety during co-administration.

Supplements & Natural Products:

•St. John’s Wort: Potent CYP3A4 inducer and serotonergic activity → increases risk of serotonin syndrome and reduces psilocybin potency.

•5-HTP / L-Tryptophan: Precursor loading may overstimulate serotonin pathways.

•Melatonin: Generally safe; may smooth come-up phase in some anecdotal reports.

Physiological and Psychological Contraindications:

•Schizophrenia or Bipolar I (especially with psychotic features): High risk of psychosis induction or exacerbation.

•Seizure disorders: Increased risk of seizure activity, especially with lithium or stimulant co-use.

•Cardiovascular disease: Use with caution—psilocybin transiently increases blood pressure and heart rate.

•Liver disease: Psilocybin is hepatically metabolized; impaired liver function may increase active metabolite duration.

•Pregnancy: Not studied—contraindicated until more data are available.

Clinical Risk Summary:

•Most dangerous combinations:

•MAOIs

•Lithium

•Tramadol

•Dextromethorphan

•SSRIs/SNRIs (due to serotonin syndrome or blunted response)

•Safe or moderate risk (when supervised):

•NSAIDs, Beta-blockers, Non-drowsy antihistamines, Benzodiazepines (rescue only)

•Unpredictable interactions:

•Polypharmacy regimens, especially involving CNS-active agents, should be approached with caution.

References:

1. Johnson, M. W., Richards, W. A., & Griffiths, R. R. (2008). Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology.

2. Gable, R. S. (2004). Comparison of acute lethal toxicity of commonly abused psychoactive substances. Addiction.

3. Carhart-Harris, R. L., et al. (2012). Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. PNAS.

4. Studerus, E., et al. (2011). Acute, subacute and long-term subjective effects of psilocybin in healthy humans. Journal of Psychopharmacology.

5. Nichols, D. E. (2016). Psychedelics. Pharmacological Reviews.

6. Orsolini, L., et al. (2019). Serotonin syndrome: a narrative review of clinical pharmacology, clinical symptoms and diagnosis. Therapeutics and Clinical Risk Management.

7. Brown, T. K., & Nicholas, C. R. (2020). Safety and tolerability of psychedelics for therapeutic use: focus on ayahuasca, psilocybin, and LSD. Expert Opinion on Drug Safety.

Thanks for reading and sharing! Call or text anytime.

800 W. 8th Ave #110 Denver Colorado - (303) 591-1960 - Join our email list!