Psilocybin & SSRI's

SSRIs and Psilocybin - Mixing Pharma with Psychedelics.

Psilocybin, and other psychedelic research is only recently beginning again. After many years of being kept in the dark it is finally seeing the light. Psychedelic research and medicines are becoming increasingly popular in mainstream culture. So many of us are seeking greater self-knowledge and advances in health and wellness, and unsurprising psychedelic medicine is rife with just such potential. Through Ceremonial practices with psychedelic plants, to clinical trials and therapies, we are collectively making leaps and bounds closer to a mentally and physically healthier humanity. The more we learn about these medicines and their influential function in our bodies and minds, the closer we come to finding safer alternatives to pharmaceuticals for the deep level of healing so many of us so desperately need.

You may be wondering; “Why is this path taken by so many?” You may even be curious about walking it yourself. Curiosity is a great start. The world of psychedelic medicine is vast with much to learn across many fields. From a research perspective Psychedelics have been approached with the hope of reaching a deeper level of healing. This contrasts to the traditional allopathic approach of pharmaceuticals, which often become coping mechanisms used to lessen symptoms. Pharmacist Ben Malcolm puts it well when he states that pharmaceuticals are a way of “weathering the storm”. [1]. In order to understand psychedelics and the potential they present us, we must first understand the role and importance of Serotonin.

Serotonin is formed from the amino acid L-tryptophan. One amazing characteristic of Serotonin is that, in addition to its regulatory effects on mood, it plays various other important roles throughout our body. Many of our serotonin receptors are actually in the gut, known by most as our second brain, helping to regulate appetite, digestion, gastric activity, nausea and more [2]. There are several mechanisms that regulate the effects of serotonin in our central nervous system. Examples of such mechanisms are: reuptake mechanisms, feedback loops and enzymes (such as monoamine oxidase). [3]. Healthy levels of serotonin in our central nervous system coincide with balances in awareness, behaviour, mood, sexuality, and attention . The effects of serotonin are mediated through 7 different receptor types, and 14 different subtypes [4]. Almost all things in our body and mind are regulated by serotonin and serotonin receptors.

It cannot be understated just how much serotonin does for the body and mind. Psilocybin (psilocin), the psycho-active ingredient in “magic mushrooms” just so happens to share many traits with serotonin. Psychedelics such as LSD and Psilocybin are grouped together pharmacologically because of their ability to act as serotonin receptor agonists. This means that they use the neural pathways of, ‘brain highways,’ to activate the very same receptors of the brain used by serotonin. Substances such as LSD and Psilocybin affect most notably the prefrontal cortex of the brain. This area is responsible for higher thinking such as reasoning and analysis, as well as mood. Psilocybin is the word most are familiar with, however the substance responsible for the notorious effects of mushrooms is psilocin. Psilocin occurs when our body breaks Psilocybin into smaller parts. The neurological effects of psilocybin (psilocin) are powerful when used to treat mental illness due to their ability to increase communication between different parts of the brain. When Psilocin is active in the brain, it decreases the blood flow to the Default Mode Network (DMN), a part of the brain that is largely responsible for thoughts of self, daydreaming, and thinking about the past, present, and future. Depression has been linked to an overactive DMN, thus the therapeutic effects are direct as it decreases activity in the part of the depressive brain responsible for depression or anxiety [5]/[6].

If we intend on using these substances medicinally then it is crucial to understand how they work in our body. This is especially true for anyone using medications like SSRI’s (Selective Serotonin Reuptake Inhibitors). SSRI’s are the most common pharmaceuticals prescribed for disorders such as Generalized Anxiety Disorder, Panic Disorder, Agoraphobia, OCD, Depression, and PTSD. They work by inhibiting serotonin reabsorption in the neuronal synapses. This creates more serotonin left in the synaptic cleft, supposedly improving the transmission of messages between neurons. The effect of SSRIs applies mainly to serotonin, hence the word “Selective” in the name. The most common types of SSRIs are Celexa (Citalopram), Lexapro (Escitalopram), Prozac (Fluoxetine), Paxil (Paroxetine) and Zoloft (Sertraline).

Long term use of SSRIs can cause dependency, and thus may present difficulty when attempting to wean off. Combining different pharmaceuticals with each other or with other substances can be dangerous or lethal. It is imperative to talk to your doctor or pharmacist prior to mixing medication or substances to avoid anything unsafe from happening. When taking pharmaceutical medications such as an SSRI, it is important to always do your own research, direct your questions to a trusted and qualified healthcare practitioner, and always make the choice that feels right for you.

One outcome of combining pharmaceuticals like the ones previously listed with other serotonergic compounds like psilocybin is something called, “Serotonin Syndrome.”

Serotonin Syndrome is an overactivation of the serotonin receptors in your body. It is an extreme increase in the serotonin levels in the brain which can lead to symptoms such as anxiety, high fever, sweating, agitation, extreme confusion, tremors, changes in blood pressure, rapid heart rate, and lack of coordination. Unfortunately, research is lacking on the effects of mixing psilocybin with SSRIs, or serotonin syndrome as a whole. This means that the true level of risk involved with mixing these substances is unknown. However with the knowledge we have of how Psilocybin and SSRIs affect the brain we can theorize on its potential negative effects.

It is rather interesting to note that people using these types of medications do not experience the effects of psychedelics [7]. SSRIs inhibit the enzyme “CYP2D6” which is found in the liver and is responsible for metabolizing xenobiotic substances; things not made naturally by the body. Many psychedelic compounds are also metabolized by this same enzyme. When psychedelics and SSRIs are present in the body at the same time, it means less CYP2D6 is available to metabolize either substance. This can cause a higher blood concentration of serotonergic substances, a symptom associated with serotonin syndrome. [8]

When it comes to mixing substances, it is safe to reason that it is not the best decision. This cited harm reduction chart states numerous dangerous and potentially deadly combinations of substances [9]. When taking any substance or drug, it is important to educate yourself. If you are looking for alternative healing methods such as psilocybin, it is your responsibility to be mindful of any potential contraindications with your prescription medication. It's not uncommon for retreat spaces and ceremonies to recommend that you wean off medication before being permitted to sit with certain psychedelic medicines. Should you choose such activities, reach out to your doctor for information about reducing your dosage.

Psilocybin is continuing to grow as a popular tool for improving mental health, as well as for general well being. The powerful potential of this medicine is only reinforced as more studies are released showing its efficacy in generating lasting healing change when used with intention and mindfulness. If a clinical setting, or large dose seems out of reach for you then it may behoove you to research microdosing. Microdosing may just be the most widely known and frequently used method to use psychedelic medicines. There are centres opening for psychedelic therapies to assist people as the demand for access to this healing substance grows. With that growth comes the decrease of the old stigma of mushrooms and psychedelic medicine. People of all walks of life are now opening their minds to the potential of psychedelics and what they have to offer. Mushrooms have stepped into the spotlight of mental health discovery, and are leading the way to a healthier, happier humanity.


[1] Ben Malcolm, Jan 11, 2021, Coping With Antidepressants and Psychedelics, Paragraph 2

[2] Miles Berger, John A. Gray, Bryan L. Roth, Mar 22, 2018, The Expanded Biology of Serotonin, Introduction and From Brain to Behaviour paragraphs, Serotonin and Vascular Biology graphic

[3] Camile Bahi, Sept 11, 2020, Antidepressants and Psychedelics, Paragraph 3

[4] Anand B. Pithadia and Sunita M. Jain, Jun 21, 2009, Paragraph 1 Abstract

[5] Author Unknown, Microdosing Guide, Paragraph 3, Effects - Link Here

[6] Synthesis Retreat Article, Author Unknown, What is Psilocybin? Section 3, How does psilocybin affect the brain? Link Here

[7] Bonson KR, Buckholtz JW, Murphy DL. June 14, 1996, Chronic administration of serotonergic antidepressants attenuates the subjective effects of LSD in humans. Neuropsychopharmacology

[8] Camile Bahi, Sept 11, 2020, Antidepressants and Psychedelics, Paragraph 10

[9] Harm Reduction Drug Combination Chart, Link Here

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