SSRI's vs Psilocybin for Mental Health

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Mental health disorders have been drastically on the rise in North America. According to Statistics Canada, more than 5 million people in Canada were categorized in having either a mood or substance disorder in a 2022 statistic, which showed a drastic increase over the past 10 years (Statistics Canada, 2023). One study found, that the number of Canadians who are 15 years and older who have anxiety, have doubled since 2022 (Statistics Canada, 2023). Treatment for mental health can vary from counselling, medication, and lifestyle changes; however, counselling can be out of many peoples budget which leads them to rely on medication to get them back on their feet. A quick search on google saying “top treatments for mental health in Canada”, will first come up with a list of common medications used to treat mental health, rather than an offering of other options. But what if there was another option? What if I told you that there is another type of “natural” drug, that if further studied, could prove to be just as, if not more, effective than the common SSRI medication that is commonly prescribed? What if I told you this “drug” was a fungi substance that has been more commonly known as a “psychedelic”?

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First let’s discuss what an SSRI is and what is does to the body. An SSRI is a “Selective Serotonin Reuptake Inhibitor” that is commonly used to treat moderate to severe depression, anxiety, and mood disorders (NHS, ND). This medication works by binding to the serotonin transporter (SERT), which blocks serotonin from getting reused (NHS, ND). This essentially increases the amount of serotonin in the synapse that allows more messages to be passed between nerve cells. In summary, your nervous system is able to utilize serotonin better, which improves the mood and reduces anxiety levels (NHS, ND). All of this sounds good, but there are also many drawbacks. SSRI’s can take up to 6-8 weeks to feel the full effects—leaving many to discontinue the antidepressant, before it fully starts working, out of impatience or a reaction to adjusting to the side effects (Kalali et al., 2009). The side effects of SSRIs are many, and it can include anxiety, diarrhea, vomiting, loss of libido, dizziness, or difficulty reaching an orgasm (Kalali et al, 2009). In addition, a study done on mice found that long term use of SSRIs may actually dramatically further deplete serotonin from the body (Siesser et al., 2012). Not only may they deplete serotonin over time, they can also deplete Calcium, Vit D, and Sodium levels in the body. These rising concerns could be tied to why a relapse is so evident after antidepressant discontinuation—as when you stop taking the medication, you no longer have the SRRIs support in keeping your remaining serotonin levels within the synapse to support your mood or have adequate levels of Vitamin D in your system to naturally boost more serotonin (Wnorowski, 2023). One of the major problems with going on an SSRI, is that this medication can be incredibly hard to get off once your body becomes reliant on it. Symptoms such as flu-like symptoms, insomnia, shock-like sensations, and aggression are a small list of what is classed to be “discontinuation syndrome” and may even last up to one year (Kalali et al., 2009). In addition, SSRIs are known to only have a 60% response rate, which considering the side effects and reliance issues, may not be worth the try for most people (Watford et al., 2024). This medication may be helpful to those who are in a desperate need to help stabilize their mood disorders, but at what cost? Surely, if there were other options that didn’t risk the long term health or wellbeing of mental health patients, shouldn’t we invest more into performing those studies instead of promoting such drastic medications?

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Cue Psilocybin, a psychedelic compound found in many fungi species that the body converts into psilocin—creating a mind altering effect. The Alkaloid “Psilocybin”, belongs to the “Tryptamine” family and is known to enhance the release of serotonin, dopamine, and norepinephrine, but mainly works as a predominant agonist system at 5-HT 1a and 2a receptors (Watford et al., 2024). Both receptors bound with different affinity, the 5-HT 1a promotes the antidepressant, anxiolytic, and antipsychotic effects, while 2a promotes the hallucinogenic, derealization, changes in perception , and depersonalization effects (Watford et al., 2024). It’s because of the former, that Psilocybin is beginning to gain traction in the mental health field, and even scientific communities, as a possible treatment for mental health disorders. The mechanism of action shapes the same as an SSRI, inhibiting serotonin re-uptake, causing increased serotonin levels in the synaptic cleft and improving mood (Watford et al., 2024). Compared to SSRIs, Psilocybin has a low toxicity rate and if dosed in a monitored and safe environment has a very low chance of risk (Watford et al., 2024). Side effects have only been recorded to occur during the 6-8 hour “trip”, and include minimal side effects such as transient anxiety, nausea, and headaches; however, these symptoms do not extend beyond this dosing period (Watford et al., 2024). There have also been no lasting evidence found in any longitude studies for any persistent use of the drug, which demonstrates low potential for harm and addiction (Watford et al., 2024). Studies show that after administration of Psilocybin, cerebral blood flow to the prefrontal cortex and posterior cingulate cortex reduce impacting beneficially upon mood, memory, and the perception of self (Watford et al., 2024). This may be due to the fact that amygdala and posterior cingulate cortex and both hyperactive during major depressive disorder (Watford et al., 2024). Studies also show that Psilocybin can increase communication in more segregated brain regions in areas of the cortex that resemble conjunction maps of the networks associated with hyper and hypo-activity in the default mode network— helping to modulate the mood (Watford et al., 2024). By binding the 5HT2A receptors, these networks become more functionally interconnected and flexible by the result— which can lead to long term changes and possibly long lasting anti-depressant effects (Watford et al., 2024).

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As SSRIs can lead to undesired long term side effects, reliance, and discontinuation syndrome, Psilocybin offers short term side effects, possible long term improvement, as well as a spiritual experience which can help distance you from your depressive symptoms and connect you to the larger picture in life. With more funding towards the benefits of psychedelic therapy for mental health, it would be interesting to see the clinical results of the long term impact and benefits of consuming Psilocybin compared to an SSRI. Hopefully in the future we will begin to see a new industry arise that can address the spiritual and psychological hindrance associated with mental health disorders.

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References

Watford, T., and Masood, N. (2024, Feb 29). “Psilocybin, an Effective Treatment for Major Depressive Disorder in Adults - A Systemic Review”. National Library of Medicine. https://pmc.ncbi.nlm.nih.gov/articles/PMC10811389/

Cascade, E., Kalali, A., and Kennedy, S. (2009, Feb 6). “Real-World Data on SSRI Antidepressant Side Effects”. National Library of Medicine. https:// pmc.ncbi.nlm.nih.gov/articles/PMC2719451/

“Overview - Selective Serotonin Reuptake Inhibitors”. (ND). NHS. https://www.nhs.uk/ mental-health/talking-therapies-medicine-treatments/medicines-and-psychiatry/ssri- antidepressants/overview/ #:~:text=After%20carrying%20a%20message%2C%20serotonin,messages%20betwee n%20nearby%20nerve%20cells.

Siesser, W., Sachs, B., Ramsey, A., et al. (2012, Oct 1). “Chronic SSRI Treatment Exacerbates Serotonin Deficiency in Humanized Tph2 Mutant Mice”. National Library of Medicine. https://pmc.ncbi.nlm.nih.gov/articles/PMC3547473/ #:~:text=Chronic%20treatment%20with%20SSRIs%20(fluoxetine,effects%20in%20wil d%2Dtype%20controls.

Wnorowski, T. (2023, Jan 30). “Medications Deplete Essential Vitamins and Minerals, Here’s How to Protect Yourself”. Body Bio. https://bodybio.com/blogs/blog/drug- induced-nutrient-depletion? srsltid=AfmBOopIiFbTLiEhiZElS7O02JtlWEQe1b0gN3HBEABTXYhvD2GQDShy

Gabriel, M., and Sharma, V. (2017, May.29). “Antidepressant Discontinuation Syndrome”. National Library of Medicine. https://pmc.ncbi.nlm.nih.gov/articles/ PMC5449237/

Lowe, H., Toyang, N., Steele, B., at al. (2021, May 15). “The Therapeutic Potential of Psilocybin”. National Library of Medicine. https://pmc.ncbi.nlm.nih.gov/articles/ PMC8156539/

“Study: Mental disorders and access to mental healthcare”. (2023, Sept 22). Statistics Canada. https://www150.statcan.gc.ca/n1/daily-quotidien/230922/dq230922b- eng.htm