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How Microdosing Psilocybin Interacts With Other Medications?

Microdosing Mushrooms for Migraines

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When you start a medication or buy shrooms, Canada experts suggest checking for drug-drug-interactions.

As research and anecdotal evidence mounts, more and more scientists and researchers alike begin to vie for a better understanding of psychedelics and their promising effect on mental health issues. However, as social stigma and long-standing litigation make it difficult to both study and obtain quality source materials, there is still little research regarding the overall efficacy of the drugs. However, there is an overwhelmingly positive response that comes from communities of self-reporting microdosers that give good reason to suggest that the drug is incredibly safe.

According to the Global Drug Survey, in 2017 out of 120,000 participants, 28,000 admitted to using psilocybin-containing mushrooms. Of those, few reported any serious side effects, and only 0.2% required medical treatment. Magic mushrooms have long been considered the safest recreational drug to take, with a high therapeutic index and incredibly rare rate of overdose. In fact, one report suggests that the worst complication of taking “magic mushrooms” is incorrectly identifying them, and ingesting a toxic fungus instead.

However, within any drug or medication, it’s always wise to discuss the possible interactions and contraindications with your healthcare professional prior to use. Specifically if you’re already taking regular medications.


What is known for certain, is that psilocybin interacts directly with serotonin receptors in the brain- which is why it is considered to be a favorable treatment for many mental problems. Because of low risk of toxicity and largely positive responses in populations tested or polled, microdosing psilocybin is considered safe, particularly in the low doses that are referenced in the microdosing guide.

There are some fears that because psilocybin interacts with serotonin, taking it in conjunction with other serotonin affective drugs could present possible side effects, with the most serious complication being considered serotonin syndrome. However, perhaps the most commonly reported issue is that psilocybin may render traditional antidepressants ineffective, which could be a resounding positive to some. Again, always check with a healthcare provider, specifically if you’re planning on stopping a regularly scheduled medication- as many common antidepressants could have serious consequences if abruptly cessated.


Selective Serotonin Reuptake Inhibitors (SSRIs) are perhaps the most commonly prescribed antidepressant medication in the world.

  • Citalopram
  • Fluoxetine
  • Escitalopram
  • Fluvoxamine
  • Paroxetine
  • Sertraline

These encompass some of the most well known SSRIs that are prescribed. As both SSRIs and Psilocybin interact with serotonin receptors, it’s possible that there may be some overlap should a use be ingesting both simultaneously. There have been reports that SSRIs dampen the experience of psychedelics, but no hard evidence has been found.


Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) are less often prescribed, but still a somewhat common choice for healthcare providers. Some of the most well known SNRIs include:

  • Desvenlafaxine
  • Duloxetine
  • Levomilnacipran
  • Milnacipran
  • Venlafaxine

Again, these drugs work similarly to the SSRIs mentioned above. No confirmed reports of serious interaction with microdosing have been noted, but it’s something to consider before you buy shrooms. Canada is amongst a few countries that are hoping to trial psilocybin as an adjunct to mental health issues in place of both SSRIs and SNRIs


Tricyclic Antidepressants (TCAs) are far less commonly prescribed than the medications mentioned above. This is largely because they have a litany of serious and potentially fatal side effects. Largely because of the inherent risk that these medications pose on their own, it’s not suggested that users take these medications while microdosing. Guide yourself to your nearest pharmacist or healthcare professional to find out more.


Monoamine Oxidase Inhibitors (MAOIs) are another class of antidepressants that are used largely to medicate anxiety, however, due to their inherent and serious side effects, MAOIs are prescribed with extreme caution. MAOIs work by preventing the breakdown of many neurotransmitters, such as serotonin, dopamine, and norepinephrine. Ideally boosting the levels of these neurotransmitters in the synaptic space.

As mentioned before, any medication that affects the serotonergic system of the brain, it’s always best to take a cautious approach when microdosing psilocybin. As microdosing in and of itself means taking small, sub-hallucinogenic amounts of psilocybin, interactions are likely to be mild, if present at all. But always be aware of possible complications.


Norepinephrine Reuptake Inhibitors (NRIs) and Norepinephrine-Dopamine Reuptake Inhibitors (NDRIs) are newer medications that are just starting to become an on-trend prescription for certain presentations of depression and anxiety. Commonly prescribed NRIs and NDRIs are:

  • Atomoxetine
  • Bupropion
  • Methylphenidate
  • Reboxetine
  • Teniloxazine
  • Viloxazine

The effectiveness of many NRIs and NDRIs is fairly contentious, with some showing little more effect than that of placebo. However, as these drugs primarily affect the norepinephrine and dopamine systems, it’s unlikely that they will interact with psilocybin, particularly at a microdose.

Other Medications

There are a few other medications that may present interactions when taken in conjunction with psilocybin. If you have a shroom dispensary, or buy shrooms Canada, talk with whomever is providing you with your materials. Find out the content of psilocybin or psilocin and bring this information to your healthcare professional.


Lithium is a medication that is often given alongside many TCAs, however, it’s prescription is becoming more and more rare as time marches on and the pharmaceutical community is faced with fielding multiple problems with the drug. Lithium can be an incredibly dangerous medication to take on its own and should never be mixed with psychedelics.


May increase the risk of rapid speech, anxiety, aggressiveness, and others, as Carbidopa interacts with dopamine systems.


Dextromethorphan, a drug commonly found in cold medicine also influences serotonin systems. As mentioned above, taking medication that interacts with serotonin systems in conjunction with psilocybin may increase the risk of serotonin syndrome.


A type of opioid analgesic, pentazocine has been largely discontinued due to extreme and serious side effects. However, it is still prescribed in some areas and may increase the likelihood of serotonin syndrome when combined with psilocybin.


Both opioid pain relievers, tramadol and meperidine (Demerol) can interact with serotonin systems and increase the likelihood of serotonin syndrome. However, there is no hard evidence suggesting this to be the case, caution is advised purely on a hypothetical basis.

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Microdosing Guide

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Essential Guide to Microdosing

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Essential Guide to Microdosing
Microdosing Guide

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Essential Guide to Microdosing

Heal trauma, overcome fear, improve performance and transform your life in just 90 days.

Essential Guide to Microdosing