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Combining Psilocybin Mushrooms & Antidepressants

Last updated on June 20th, 2023

If you’re thinking about taking magic mushrooms with antidepressants, read this post.

What is Psilocybin?

Psilocybin is the main psychoactive component of psychedelic mushrooms. Once ingested, psilocybin is converted to psilocin, which has the ability to cross the blood-brain barrier. Psilocin works by bringing a partial agonist effect on mainly the 5-HT 1A receptors.

Psilocin has the ability to activate serotonergic receptors, which causes a flow of excitatory activity in the brain. This wave spreads throughout the main perceptual centers of the brain and can alter normal waking consciousness.

Reported effects:

  1. Unusual and colourful visuals with eyes open or closed
  2. Disintegration of ‘self’ or ‘ego’
  3. Unconstrained explorative thinking, cognitive, affective and perceptual changes
  4. Sense of connectedness to self, others and the world

Therapeutic benefits of psilocybin

There’s more and more research indicating the positive benefits of psilocybin in a therapeutic context. Psilocybin has been shown to significantly reduce symptoms in people suffering from severe depression. Also, psilocybin seems to prolong these positive effects more than typical treatments, especially when combined with therapeutic integration programs.

In addition to depression, psilocybin has been shown to reduce symptoms of anxiety, PTSD, substance abuse and end-of-life distress (people struggling with terminal diseases).

Can you take psilocybin while on antidepressants?

Like psilocybin, most typical antidepressants work on the serotonergic system . Mixing antidepressants and psilocybin could lead to an overstimulation of serotonin, known as the serotonin syndrome.

Serotonin is a natural chemical that helps regulate many different functions, such as: mood, sleep, digestion, sexual desire, among others. Depression has been linked to an imbalance of serotonin in the brain, but too much serotonin is no good either.

Symptoms of serotonin syndrome:

Serotonin syndrome symptoms usually occur within several hours of taking a new drug or increasing the dose of a drug you’re already taking.


  1. Agitation or restlessness
  2. Insomnia
  3. Confusion
  4. Rapid heart rate and high blood pressure
  5. Dilated pupils
  6. Loss of muscle coordination or twitching muscles
  7. High blood pressure
  8. Muscle rigidity
  9. Heavy sweating
  10. Diarrhea
  11. Headache
  12. Shivering
  13. Goose bumps

Severe serotonin syndrome can be life-threatening.

Severe Symptoms:

  1. High fever
  2. Tremor
  3. Seizures
  4. Irregular heartbeat
  5. Unconsciousness

Serotonin syndrome generally doesn’t cause any problems once serotonin levels are back to their original levels. It often resolves within 24 hours of discontinuing the serotonergic agent. Attention with drugs with long half-lives or active metabolites as they may cause symptoms to persist. Irreversible monoamine oxidase inhibitors (MAOIs) carry the greatest risk, and symptoms can persist for several days.

SSRI & Psilocybin:

Selective Serotonin Reuptake Inhibitors (SSRIs) are the most commonly prescribed medications for depression, OCD, PTSD, and other anxiety disorders. Some of the most well-known SSRIs include:

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

While in rare cases, it has been hypothesized that this can lead to serotonin syndrome. With proper dosage, guidance and supervision, such risks can be mitigated. Treatment programs tend to accepts individuals on SSRIs, usually taking into account their medical history, and other factors.

SNRI & Psilocybin:

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) boost both serotonin and norepinephrine levels in the brain. Some typically prescribed SNRIs are:

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

Just like with SSRIs, we would expect SNRIs to overlap with the effects of psilocybin. However, there are no reports of serious adverse effects of combining the two. There’s data suggesting that SNRIs actually reduce the effect of psychedelics.

MAOIs & Psilocybin:

Monoamine Oxidase Inhibitors (MAOIs) work by preventing the breakdown of monoamine neurotransmitters (dopamine, serotonin, and norepinephrine) and thus, boosting their levels.
Common MAOI medications include:

  • Bifemelane (Alnert, Celeport)
  • Caroxazone (Surodil, Timostenil)
  • Isocarboxazid (Marplan)
  • Metralindole (Inkazan)
  • Moclobemide (Aurorix, Manerix)

There is the small possibility of serotonin syndrome if MAOIs are combined with psilocybin. It is advised to avoid taking large doses of psilocybin if you are taking MAOIs. However, some people have reported that combining MAOIs with classic psychedelics reduces the effect of the psychedelic. As always, it is recommended to start with small doses.

*Attention! Mixing MAOIs with MDMA has potentially fatal effects as the risk of serotonin syndrome is much higher. Do not mix MAOIs with MDMA.

Least Common Medication Combined with Psilocybin for Depression:

TCA/TeCA: Data suggest that they can cause death by their effects on the heart. Is not recommended to mix these with psilocybin.

NRI/NDRI: There’s not enough research to know what the interaction would be between psilocybin and NRIs/NDRIs, thus, is better not to combine them.

SMS/SAR: work on the serotonin system in a potentially less predictable way than SSRIs (activating and deactivating specific receptors). Thus, is not recommended to mix these substances.

Lithium: Its mode of action is not completely understood, but there is research indicating that Lithium is a dangerous substance to combine with psychedelics. It has been reported to cause seizures, heart failure, and even death.