Interactions between Psilocybin and Medications


Please do not use or consume the following medications in combination with psilocybin:

If you decide to taper off on your own accord, please make sure to always do this under supervision of a licensed medical professional.


1. Antidepressants and psilocybin

Please check with your doctor if your antidepressant is a tricyclic antidepressant, an SNRI, a SMS or Sari, NRI/NDRI, MAOI, lithium or a SSRI. We only in rare cases allow the use of SSRIs at your own risk.



SSRIs work by preventing the clearance of excess serotonin from the brain, meaning that serotonin levels are temporarily boosted. While in rare cases, it has been hypothesized that this can lead to serotonin syndrome.

There have been recent studies that have shown the opposite to be true: that SSRIs and Psilocybin can be taken together safely with no risk, but more studies need to be done to be certain of that. However, we invite all our participants to do their own research and if they feel like they would like to go ahead anyway while on the SSRI we can proceed once a waiver is signed that the participant takes the responsibility for any possible risk. We have worked with people who wanted to stay on their medicine in the past and it has worked really well, however there is still the risk mentioned above along with the risk of the substance having no effect.

Here is a link to an article about the study.

SSRI medication include:
• Citalopram (Celexa, Cipramil)
• Escitalopram (Lexapro, Cipralex)
• Fluoxetine (Prozac, Sarafem)
• Fluvoxamine (Luvox, Faverin)
• Paroxetine (Paxil, Seroxat)
• Sertraline (Zoloft, Lustral)

Here is a list of antidepressants that we do not work with in combination with Psilocybin:


b. Tricyclic antidepressants:

• 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)


C.  SNRI medication:

•Desvenlafaxine (Pristiq, Khedezla)
• Duloxetine (Cymbalta)
• Levomilnacipran (Fetzima)
• Milnacipran (Ixel, Savella)
• Venlafaxine (Effexor XR)


D.  MAOIs:

Monoamine oxidase inhibitors (MAOIs) are a class of drugs that are used to treat depression and anxiety. They work by blocking the enzyme monoamine oxidase, which is responsible for breaking down certain neurotransmitters in the brain. When psilocybin is taken with an MAOI, it can lead to a dangerous increase in serotonin levels, which can cause a condition known as serotonin syndrome. Symptoms of serotonin syndrome include agitation, confusion, rapid heart rate, high blood pressure, and fever. In severe cases, serotonin syndrome can lead to seizures, coma, and even death.

Common MAOI medications 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)



Some classic NRIs and NDRIs include:

  • Bupropion (Wellbutrin)
  • Methylphenidate (Ritalin, Concerta)
  • Reboxetine (Edronax)
  • Teniloxazine (Lucelan, Metatone)
  • Viloxazine (Vivalan)

It is unknown if psilocybin and NRIs/NDRIs interact. As far as we know, psilocybin does not significantly affect the norepinephrinergic or dopaminergic neurotransmitter systems. However, to be safe, do not combine psilocybin with an NDRI.



Some SMS/SARI include:

  • Trazodone (Desyrel)
  • Vilazodone (Viibryd)
  • Vortioxetine (Trintellix)

Since these substances will affect the serotonin system in a potentially less predictable way than SSRIs. To be safe, we do not recommend combining these with psilocybin.


G.   TCAs and TeCAs

TCAs and TeCAs work in a similar way to SNRIs, by boosting the levels of serotonin and norepinephrine in the brain. However they also activate a wide range of additional receptors, and also block some ion channels, creating dangerous side effect.

Some of the most well-known TCAs and TeCAs are:

  • 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)


H. Lithium

Lithium is often given as a mediator in combination with TCAs.

Numerous reports suggest that Lithium, when mixed with psychedelics, can cause fatal seizures or heart attacks. Do not mix psilocybin and Lithium.


2.  Supplements that may affect serotonergic function And Psilocybin

Supplements such as 5 HTP, St John’s Wort or others should not be combined with Psilocybin.


3.   Depressants And Psilocybin

Please do not consume any cannabis, alcohol or opioids for at least 72h before a Psilocybin session.


4.   Stimulants And Psilocybin

Stimulants such as cocaine, amphetamines, and even caffeine can increase heart rate, blood pressure, and body temperature.

When taken with Psilocybin, they can increase the risk of cardiovascular complications, such as heart attack and stroke. In addition, stimulants can also worsen the negative effects of Psilocybin, such as anxiety and paranoia.


5.  Antihistamines and psilocybin

Antihistamines such as diphenhydramine (Benadryl) and chlorpheniramine (Chlor-Trimeton) are commonly used to treat allergies and insomnia.

When taken with psilocybin, they can increase the risk of dizziness, confusion, and hallucinations.

In addition, antihistamines can also worsen the negative effects of psilocybin, such as anxiety and paranoia.


6.   Other Medications:

• Antibiotics:  There are many ways that psychotropic drugs and antibiotics interact. For example, the action of psychotropic drugs on the body can be affected by certain antibiotics, and this can cause some harmful side effects. According to the US National Institutes of Health (NIH), psychotropic and antibiotic drugs have some specific side effects and mechanisms of action. This makes the interactions between both substances have variations, which depend on the drugs involved.

Taking the two substances concurrently could cause harm to the liver. Even though this is a rare occurrence, it’s worth noting that antibiotics can cause damage to the liver or liver failure. On the other hand, psychotropic drugs have the potential to increase liver enzymes, which could potentially cause liver damage.

The liver plays a major role in breaking down medications in the body. A combination of both substances could trigger different adverse reactions and liver damage. This is because they are both metabolized by liver enzymes, and the combination of both substances can go beyond the capacity of the liver.

•  Anti-convulsants or anti-epileptic medications such as Neurontin(gabapentin) and Topamax(topiramate). The exact mechanism by which topiramate works, for example, is still unknown, so it is impossible to even guess whether or not it will interfere with psilocybin.

•  Medications which are either synthetic analogs of certain hormones or which regulate hormone production: Prednisone and Synthroid, for example. There is no direct evidence to suggest that these drugs will interact with psilocybin, but hormones have a very complex and inter-related effect on numerous body systems. We have seen a few reports suggesting that thyroid levels play a part in cluster headaches

•  Tranquilizers and mood-altering medications such as Xanax, Valium, Prozac and Wellbutrin.

•  Ondansetron (Zofran) and Compazine(prochlorperazine)

•   Imitrex (and associated triptans): In relation to migraine headaches based upon many reports, triptans are one of the most likely medications to block the clusterbusting effects of psychedelics. We recommend to avoid them both before, during and after, beginning psychedelic treatments for cluster headaches.

•   Sumatriptan (Imitrex®, Imigran®) injections

•   Sumatriptan (Imitrex®, Imigran®) tablets

•   Zolmitriptan (Zomig®) tablets

•   Sumatriptan (Imitrex®, Imigran®) nasal spray

•   Naratriptan (Amerge®, Naramig®) tablets

•   Rizatriptan (Maxalt®) tablets and rizatriptan orally dissolvable
(Maxalt-MLT®) tablets

•   Zolmitriptan orally dissolvable (Zomig-ZMT®) tablets

•   Almotriptan (Axert®) tablets

•   Frovatriptan (Frova®) tablets

•   Eletriptan (Relpax®) tablets

•  Ritonavir/Indinavir

•  Haloperidol

•  Omeprazole (Prilosec):  One of the side effects that is difficult to notice and could cause severe problems is that the use of Omeprazole can cause low magnesium blood levels. Magnesium deficiencies enhance the reactivity of arteries to vasoconstriction. One of the side effects of Psilocybin is vasoconstriction.

•  Carvedilol:  The adrenergic receptor antagonist carvedilol interacts with serotonin 2A receptors both in vitro and in vivo.

•  Oxycodone:  There has been little research into the interaction of psilocybin and opioids. But it’s thought that psilocybin could increase opioids’ depressing effect on the central nervous system (CNS). In mild cases, this could mean loss of coordination, confusion, and drowsiness, More dangerously, it could mean the user’s breathing and heart slow or even stop.


For more drug interactions, please check out this chart:





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