While there are no conclusive scientificstudies determining whether a psilocybin journey may affect anti-depressants,we think it’s best to take a precautionary approach.

If it is possible and agreed by your doctor(and of course for some people we know it is not), try and wean yourself offyour medication two weeks before your planned psilocybin experience.

Psilocybin is a consciousness-enhancingsubstance and for one, anti-depressants which tend to numb all sensations willlikely reduce the effectiveness of the journey.

What Is psilocybin and how does it work?

Psilocybin is a natural serotonin receptor agonist found in some very special mushrooms, including magic truffles (which is the underground part of these mushrooms).


Psilocybin works by binding to your serotonin receptors and raising your serotonin levels (the happy hormone). Psilocybin also normalizes your amygdala hyperactivity. This helps to reduce your bad moods and increase your good moods.

Taking psilocybintransforms your brain patterns, bringing about mystical and spiritualexperiences which can help you find relief from stress, pain, trauma, ordepression. This change doesn’t occur with regular antidepressants or any othermedication.

As more research is published confirming the effectinveness of psilcybin for treating depression, it is becoming more mainstream and investors are now starting to finance pharmaceutical companies looking to test and develop drugs based on its healing properties.

Quote on psilocybin science by Roland Griffiths
Find more research on the positive effects of psilocybin from our research page.

Psilocybin and antidepressants

From the researchconducted so far, there is strong evidence that psilocybin can significantlyalleivate depression. However, there is little conclusive research availableyet on how psilocybin interacts with antidepressants. We are not medicalpractioners and so can only report the evidence of studies conducted by expertsand we are still in the middle ages when it comes to matters of the mind.

We do know that mostantidepressants have some overlap with the functions of psilocybin because theyboth work with your serotonin receptors and levels.

The possible worst[CB1] case scenario of mixing antidepressants and psychedelics, including psilocybin, is that you would experience serotonin syndrome. Symptoms of serotonin syndrome are:

  • High blood plessure
  • Confusion
  • Agitaion
  • Diarrhea
  • Rapid heartbeat
  • Tremors
  • Shivering
  • Sweating
  • Dilated pupils
  • Nausea and / or vomiting

In more seriouscases of serotonin syndrome, symptoms may be more severe or possibly evenlife-threatening, including: high fever, seizures, irregular heartbeats andunconsciousness.

Serotonin syndrome is thought to be rare with only 2 cases reported out of 19,000 in one study of people mixing serotonergic drugs with triptan drugs.

However, we reiterate that we are not doctors and therefore, recommend discussing this with a specialist before booking a retreat with Truffles Therapy, if you are taking antidepressants. It is possible to wean yourself off your antidepressants under the supervision of your doctor in the weeks prior to your psilocybin journey.

Psilocybin and SSRIs

SSRIs are one ofthe most commonly used antidepressants. Selective Serotonin Re-uptakeInhibitors are prescribed for depression, PTSD, OCD, and other anxietydisorders.

Some common SSRIsare:

  • Dapoxetine (Priligy)
  • Escitalopram (Cipralex, Lexapro)
  • Fluoxetine (Prozac, Sarafem)
  • Citalopram (Cipramil)
  • Sertraline (Zoloft, Lustral)
  • Fluvoxamine (Faverin, Luvox)
  • Vortioxetine (Viibryd)

SSRIs work bychanging and balancing the serotonin levels in your brain. They inhibit the re-uptakeof serotonin by nerve cells so that more serotonin is available, creating aboost of this happy hormone. SSRIs work well for people whose serotonin re-uptakeprocess occurs too quickly, which depletes them of serotonin.

Given that SSRIsblock serotonin receptors while psilocybin binds to the receptors, it ispossible that these antidepressants will reduce the effect of psilocybin. One study confirmed that the interaction betweenserotonergic antidepressants and the hallucinogenic LSD, reduces thepsychedelic’s effect.

Psilocybin and SNRI

Serotonin-NorepinephrineRe-uptake Inhibitors work similarly to SSRIs. They are prescribed fordepression, some anxiety disorders, and even chronic pain.

The differencebetween the two is that SNRIs also boost norepinephrine levels in the brain. Therefore,SNRIs block the re-uptake of serotonin andnorepinephrine,  temporarily boostingboth chemicals.

Some common SNRIsare:

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

The effects ofSNRIs are expected to overlap and reduce the effects of psilocybin, asconfirmed by the same study mentioned previously.  

Psilocybin and MAOIs

Monoamine OxidaseInhibitors are antidepressants that work with three chemicals and receptors inthe brain: serotonin, norepinephrine, and dopamine. MAOIs prevent the enzymemonoamine oxidase removing these three chemicals from the brain, balancingtheir levels.

MAOIs treat depressive disorders as well as other diseases, such as Parkinson’sdisease.

Some common MAOIsare:

  • Isocarboxazid (Marplan)
  • Phenelzine (Nardil)
  • Selegiline (Emsam)
  • Tranylcypromine (Parnate)

MAOI antidepressants need to be treated with extreme caution as they can cause dangerously high blood pressure in combination with certain foods or medications.

For this reason, we don’t recommend going on a magic truffles journey while on MAOIs or without your doctor’s approval. We want your experience with psilocybin to be safe, healing and enlightening.

Pharmaceutical pills flying over a scale

Psilocybin and TCA / TECA

TCA, or Tricyclic Antidepressants, act on many receptors in the brain, in addition to serotonin and norepinephrine. TCA / TECA also inhibit ion channels.

They tend to have quite a lot of side effects and are usually replaced with new-generation antidepressants such as SSRIs and SNRIs.

Some common TCA /TECA are:

  • Amitriptyline
  • Amoxapine
  • Desipramine (Norpramin)
  • Imipramine (Tofranil)
  • Nortriptyline (Pamelor)
  • Protriptyline (Vivactil)
  • Trimipramine (Surmontil)

It is notrecommended that you go on a psilocybin journey if you are taking theseantidepressants.

Psilocybin and NRI / NDRI

Norepinephrine Re-uptakeInhibitors and Norepinephrine-Dopamine Re-uptake Inhibitors act on thenorepinephrine and dopamine receptors in your brain. Similar to SSRIs and SNRIs,they block receptors from absorbing these chemicals.

NRIs and NDRIsare used to treat depression, anxiety disorders and also to boost cognitiveperformances.

More recently developed, antidepressants have an impact on the amygdala, while NRIs and NDRis do not.

Some common NRIs/ NDRIs are:

  • Bupropion (Wellbutrin / Zyban)
  • Dexmethylphenidate (Focalin)
  • Diphenylprolinol (D2PM)
  • Ethylphenidate (EPH)
  • Pipradrol (Meratran)

We do not knowexactly how NRI / NDRI antidepressants would interact with psilocybin. Sincethese antidepressants don’t work on the serotonin receptors, there might not bean overlap.

We recommend you discuss with your doctor beforehand and if you join us onretreat we would start with a low dose of psilocybin for your journey.

Psilocybin and SMS / SARI

Serotoninmodulators and stimulants / Serotonin antagonists and re-uptake inhibitors area new-generation of antidepressants that follow SSRIs and SNRIs. They, too, areused to treat depressive and anxiety disorders.

SMS / SARI work with serotonin receptors and chemicals but in a different way.SARIs not only block serotonin receptors but also guide serotonin particles inthe right direction. SMSs work similarly by blocking some receptors andmodulating them or others at the same time.

Even though SSRIs are much more commonly used than SMS / SARIs, they are regarded as just as effective, or more so, and are beginning to be prescribed more often.

Some common SMS / SARIs:

  • Vortioxetine (Trintellix)
  • Trazodone (Desyrel)
  • Milnacipran (Savella)
  • Venlafaxine (Effexor)

Since SMS /SARIs are relatively new in the treatment for depression, we do not know howthey would interact with psilocybin. We assume some overlap would occur, asboth affect serotonin levels and receptors.

Please discuss with your doctor before planning a psilocybin journey and we canoffer you a small dose for your mystical journey.

Psilocybin and Lithium

Lithium isoften used to treat mania. It is also used as a mediator with certain types ofantidepressants, such as TCA, in the treatment of depression. Unfortunately,doctors limited understanding of how Lithium works, but it is believed tostrengthen nerve cell connections.

Reports from users mixing lithium and psychedelics are not positive. One study showed people taking Lithium had an increased response to LSD – which might be similar in the case of psilocybin.

We do notrecommend psilocybin be taken while on a Lithium treatment.

Do you think this experience is for you or still have questions? Great, we’re here to help!

We havetried to bring you all the information currently available on psilocybin andantidepressants. Unfortunately, there is still limited research on takingpsilocybin while on antidepressants, so we suggest being extremely cautious ifconsidering it. This is sure to change in the coming years, as more and moremental health practitioners and scientists recognize the value of psychedelicson the human psyche and conduct more research.

We here at Truffles Therapy offer experienced and safe guided psilocybin journeys. Our retreats in the beautiful Netherlands countryside are one of the best places to experience psilocybin in a controlled environment.

During the retreat, you will also get to enjoy yoga and meditation sessions, healthy vegan food, walks in nature and sharing your mystical experiences on psilocybin. The entire staff is highly experienced and loving, caring for your every need.

We will make sure your experience is as safe as possible so you can get the mystical experience and transformation you seek. If you have any doubts, please don’t hesitate to arrange a call with us so we can discuss your individual circumstances.

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