Psilocybin & Medication Interactions
Important Safety Information
Please carefully review the information below before participating in a Psyki psilocybin experience.
The following list is not exhaustive. If you take any prescription medication, over-the-counter medication, supplement, recreational substance, or other psychoactive substance that is not listed below, you must disclose it during your health screening and discuss potential interactions with an appropriately qualified medical professional.
Psyki does not provide medical advice and cannot advise you to start, stop, reduce, increase, or otherwise alter prescribed medication.
Never stop or taper prescribed medication solely in order to participate in a psilocybin experience without first consulting the clinician responsible for your medication. Some medications can cause significant or potentially dangerous withdrawal effects if discontinued abruptly.
Psilocybin acts primarily through the serotonin 2A (5-HT2A) receptor, and a number of psychiatric medications also interact with serotonergic systems.
1. Antidepressants
Antidepressants require particular attention because different classes affect serotonin and other neurotransmitter systems in different ways.
SSRIs
Selective serotonin reuptake inhibitors include:
- Citalopram (Celexa, Cipramil)
- Escitalopram (Lexapro, Cipralex)
- Fluoxetine (Prozac, Sarafem)
- Fluvoxamine (Luvox, Faverin)
- Paroxetine (Paxil, Seroxat)
- Sertraline (Zoloft, Lustral)
Research concerning the simultaneous use of SSRIs and psilocybin continues to develop. SSRIs may also alter or reduce the subjective effects of psilocybin. The interaction therefore needs to be considered individually during screening.
Do not discontinue an SSRI without medical supervision.
You can read more about research into SSRIs and psilocybin here:
SSRI Drugs Can Be Used Safely With Psilocybin – Psychedelic Spotlight
Further information about SSRIs:
Mayo Clinic – Selective Serotonin Reuptake Inhibitors (SSRIs)
SNRIs
Serotonin-norepinephrine reuptake inhibitors include:
- Desvenlafaxine (Pristiq, Khedezla)
- Duloxetine (Cymbalta)
- Levomilnacipran (Fetzima)
- Milnacipran (Ixel, Savella)
- Venlafaxine (Effexor XR)
These medications must be disclosed during screening.
MAO Inhibitors
MAOIs substantially affect monoamine metabolism and require particular caution around serotonergic substances.
Examples include:
- Bifemelane (Alnert, Celeport)
- Caroxazone (Surodil, Timostenil)
- Isocarboxazid (Marplan)
- Metralindole (Inkazan)
- Moclobemide (Aurorix, Manerix)
- Phenelzine (Nardil)
- Pirlindole (Pirazidol)
- Selegiline (Eldepryl, Zelapar, Emsam)
- Tranylcypromine (Parnate)
- Toloxatone (Humoryl)
These medications are not accepted in combination with psilocybin at Psyki and must be discussed with the prescribing clinician.
Tricyclic and Tetracyclic Antidepressants
These include:
- Amineptine (Survector, Maneon)
- Amitriptyline (Elavil, Endep)
- Amitriptylinoxide (Amioxid, Ambivalon, Equilibrin)
- Amoxapine (Asendin)
- Clomipramine (Anafranil)
- Desipramine (Norpramin, Pertofrane)
- Dibenzepin (Noveril, Victoril)
- Dimetacrine (Istonil)
- Dosulepin (Prothiaden)
- Doxepin (Adapin, Sinequan)
- Imipramine (Tofranil)
- Lofepramine (Lomont, Gamanil)
- Maprotiline (Ludiomil)
- Melitracen (Dixeran, Melixeran, Trausabun)
- Mianserin (Tolvon)
- Mirtazapine (Remeron)
- Nitroxazepine (Sintamil)
- Nortriptyline (Pamelor, Aventyl)
- Noxiptiline (Agedal, Elronon, Nogedal)
- Opipramol (Insidon)
- Pipofezine (Azafen/Azaphen)
- Protriptyline (Vivactil)
- Setiptiline (Tecipul)
- Tianeptine (Stablon, Coaxil)
- Trimipramine (Surmontil)
These medications may present additional safety concerns and must be disclosed before participation.
NRI/NDRI Medications
These include:
- Atomoxetine (Strattera)
- Bupropion (Wellbutrin)
- Methylphenidate (Ritalin, Concerta)
- Reboxetine (Edronax)
- Teniloxazine (Lucelan, Metatone)
- Viloxazine (Vivalan)
These medications must be disclosed and assessed before participation.
Serotonin Modulators / SARI Medications
These include:
- Trazodone (Desyrel)
- Vilazodone (Viibryd)
- Vortioxetine (Trintellix)
Because these medications interact with serotonergic pathways, Psyki does not recommend combining them with psilocybin without appropriate medical review.
Lithium
Lithium must not be combined with psilocybin at Psyki.
Lithium in combination with psychedelics has been associated with serious adverse effects, including seizures.
2. Supplements Affecting Serotonin
Please disclose supplements and herbal preparations, particularly those that may influence serotonin or other neurotransmitter systems.
These include:
- 5-HTP
- St John’s Wort
- Yohimbe
- Other supplements marketed for mood, serotonin, or neurotransmitter support
These products may interact unpredictably with psilocybin and should always be disclosed during screening.
3. Opioids and Other Depressants
Please disclose all opioid medications and recreational opioid use.
Of particular concern are:
- Tramadol
- Pethidine
- Meperidine
Do not consume alcohol, cannabis, or recreational opioids for at least 72 hours before your Psyki session.
4. Stimulants
Stimulants can affect heart rate, blood pressure, body temperature, anxiety, and psychological arousal.
These include:
- Cocaine
- Amphetamines
- Methamphetamine
- Methylphenidate
- Phentermine
- Diethylpropion
- MDMA
- Other prescription or recreational stimulants
These substances must be disclosed before participation.
5. Other Psychedelics and Psychoactive Substances
Do not combine a Psyki psilocybin experience with other psychedelics or psychoactive drugs unless this has specifically been medically assessed.
This includes:
- LSD
- MDMA
- Amphetamines
- Other psychedelic substances
6. Antihistamines
Certain antihistamines may contribute to sedation, dizziness, confusion, or other central nervous system effects.
These include:
- Diphenhydramine (Benadryl)
- Chlorpheniramine (Chlor-Trimeton)
Please disclose regular or recent antihistamine use during screening.
7. Anticonvulsant and Anti-Epileptic Medication
Please disclose anticonvulsant or anti-epileptic medications, including:
- Gabapentin (Neurontin)
- Topiramate (Topamax)
- Other anticonvulsant medications
The effects and possible interactions of these medications need to be assessed individually.
8. Migraine Medications and Triptans
Please disclose the use of triptans or other migraine medication.
Examples include:
- Sumatriptan (Imitrex, Imigran) injections
- Sumatriptan (Imitrex, Imigran) tablets
- Sumatriptan (Imitrex, Imigran) nasal spray
- Zolmitriptan (Zomig)
- Zolmitriptan ODT (Zomig-ZMT)
- Naratriptan (Amerge, Naramig)
- Rizatriptan (Maxalt)
- Rizatriptan ODT (Maxalt-MLT)
- Almotriptan (Axert)
- Frovatriptan (Frova)
- Eletriptan (Relpax)
These medications must be disclosed during screening.
9. Other Medications Requiring Disclosure
The following medications or medication classes should also be disclosed before participating:
- Buspirone
- Linezolid
- Dextromethorphan
- Montelukast
- Haloperidol
- Ondansetron (Zofran)
- Prochlorperazine (Compazine)
- Ritonavir
- Indinavir
- Prednisone
- Levothyroxine (Synthroid)
- Benzodiazepines and tranquillisers such as alprazolam (Xanax) and diazepam (Valium)
- Hormonal medications or medications affecting hormone production
- Any other psychiatric or mood-altering medication
Serotonin Syndrome
Serotonin syndrome is a potentially serious condition caused by excessive serotonergic activity.
Possible signs and symptoms can include:
- Agitation or restlessness
- Confusion
- Sweating
- Tremor
- Loss of coordination
- Rapid heart rate
- Significant changes in blood pressure
- High body temperature
Suspected serotonin syndrome requires urgent medical assessment.
Before Your Psyki Experience
During your health screening, please provide us with a complete and accurate list of all medications, supplements, and recreational substances you currently use or have recently used.
Do not stop taking medication simply because it appears on this page. If a medication may make participation unsuitable, we will discuss this with you as part of the screening process and may ask you to consult your prescribing doctor.
Psyki does not instruct participants to discontinue, reduce, or taper prescribed medication. Any medication changes must be decided between you and an appropriately qualified medical professional.
This page is intended as screening and harm-reduction information and is not a substitute for individual medical advice.
Further Information & Resources
For additional information about psilocybin, antidepressants, and drug interactions, you may wish to consult the following resources:
Drug Combination Chart
TripSit – Guide to Drug Combinations
Psilocybin & Antidepressant Interactions
Synthesis – Psilocybin and SSRI/SNRI Interactions
Drug Interaction Information
Essence – Drug Interaction Information
SSRIs
Mayo Clinic – Selective Serotonin Reuptake Inhibitors
Research on Psilocybin and SSRIs
Psychedelic Spotlight – SSRI Drugs Can Be Used Safely With Psilocybin
Psychedelic Safety Research
Johnson, M. W., Richards, W. A., & Griffiths, R. R. (2008). Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology, 22(6), 603–620.