A SMALL BUT POWERFUL MUSHROOM  

Since 2019, the spread of a new nondenominational church, known as the Church of Ambrosia, has sparked nationwide controversy. This church has made headlines for using entheogenic (or psychedelic experience-inducing) plants for spiritual and personal improvement. What entheogenic plants are they referring to? Psilocybin, also known as Magic Mushrooms. 

As of 2021, 6.6% of adults between the age of 19 to 30 have used magic mushrooms, a percentage that is steadily growing.¹ Many individuals who regularly consume magic mushrooms report feeling happier, clearer, and better connected with themselves for days or and sometimes even months after their initial dose. These anecdotal claims have catalyzed a new branch of medicine that explores the intersection of psychedelics and mental health in a modern, Western context. Dr. Ryan Mariano, a medical toxicologist at University Hospitals, claims that “psilocybin appears to increase the brain’s capacity to change, to become more adaptive, and to break out of habits and negative thought patterns. Hence psilocybin’s great potential in helping people with problems like depression, anxiety, OCD and addiction.”² 

Although psilocybin is a Schedule I drug, meaning it is federally illegal in the United States, it is generally safe for consumption under medically regulated doses. It is also physiologically non-addictive, meaning that the human body will not become chemically dependent on the drug. In fact, regulated psilocybin purchase is decriminalized in six US cities and soon-to-be fully legal within the state of Colorado.³ Similar to marijuana, many medical professionals advocate for psilocybin legalization for its therapeutic effects on the human brain, particularly its potential to treat depression. 

HOW THE BRAIN COMMUNICATES

Psilocybin targets symptoms of mental health disorders through altering the brain’s main communicative pathways (or the ways in which brain cells, called neurons, can communicate with one another). The human brain is divided into six main lobes with a variety of functions, ranging from language processing, to memory building, to emotional responses. Each region of the brain communicates with the others via a network of neural connections. The frontmost lobe, known as the frontal lobe, contains the prefrontal cortex (PFC), which is also known as the “personality center.” The PFC actively communicates with other lobes of the cerebral cortex to influence specific actions, thoughts, and emotions in response to sensory stimuli. This communication occurs with the help of neurons that release chemical messengers called neurotransmitters after being electrically stimulated. These neurotransmitters bind to other neurons and relay signals throughout the body that ultimately influence how we feel. A well-studied neurotransmitter is serotonin, which regulates long-lasting feelings of happiness and mood regulation. In fact, researchers theorize that a root cause of depression is low serotonin levels.  

THE SCIENCE OF MUSHROOMS IN DEPRESSION PATIENTS

Psilocybin is a fungal metabolite found in many mushroom species that belongs to a class of serotonergic (affecting serotonin-activated neural pathways) psychedelics. These types of drugs alter synaptic plasticity, or the ability for neurons to modify their connections to and rates of communication with other neurons.⁴ When metabolized, psilocybin is converted into psilocin: a compound that is very structurally similar to serotonin. Thus, psilocin has the capability to recognize and bind to serotonin-specific receptors on neurons. For example, psilocin binds to serotonin 5-HT2A receptors on cortical pyramidal cells. These pyramidal cells are “the major computational units of the brain… [they help us] put together our picture of what reality is,” says Purdue Professor David Nichols.⁵ By activating these receptors, psilocin can influence cognitive function and perception, establishing new neural connections between the PFC and other brain regions. Essentially, psilocin unites and excites previously quieted regions of the brain and connects regions of the brain that do not usually communicate. These connections work against depressive symptoms to produce a sense of emotional contemplation and openness in patients. 

MEDICAL OUTLOOK & CLINICAL TRIALS

Microdosing, or the use of sub-perceptual doses of psilocybin for extended periods of time, has emerged as a new facet of clinical psychology research. Sub-perceptual means that the dosage of psilocybin consumed is not perceptually noticeable nor strong enough to cause the visual hallucinations typically associated with magic mushrooms. Usually, individuals who microdose take about 100-300 milligrams of dried mushrooms or mushroom pills, which is about 10% of a standard dose.⁶ There are many different regimens for these pills, such as taking one small dose daily or a larger dose weekly. Controlled studies have revealed that psilocybin has the potential to reduce depression symptom severity, including in people with treatment-resistant depression (cases in which typical antidepressant treatments do not improve depressive symptoms). For example, a recent Phase 2, double-blind trial revealed that a single 25 mg dose of psilocybin coupled with psychotherapy significantly lowered depressive symptoms over a few weeks as patients reported having an improved outlook on life.⁷ This particular clinical trial was run by the company COMPASS Pathways, in hopes of securing FDA regulatory approval for psilocybin pills by 2025.

Individual case studies have also suggested the efficacy of using mushrooms to combat depression. In a case study presented by psychiatrist Dr. Ashley Lyons at Rocky Mountain University, a forty-three year old man was diagnosed with treatment-resistant major depressive disorder (MDD) after failing to positively respond to numerous rounds of medicine and therapy. However, after the patient started self-administering small doses of psilocybin, he experienced immense improvement in his MDD symptoms. Such symptomatic remedies included improvements in sleep patterns, persistent fatigue, daily focus, and feelings of worthlessness.⁸

EXPANDING THE SCOPE 

Beyond microdosing, anecdotal evidence suggests that taking larger doses of psilocybin infrequently may also be beneficial for cognition. With larger doses, users report temporary alterations to their “ego,” resulting in higher self-reflection and new ways of viewing their lives. Under a larger magnitude of psilocybin influx, the brain undergoes greater neurotransmitter activity. Thus, users physiologically and mentally become “better connected” and can view their issues from previously unexplored perspectives. Although the physiological hyperconnectivity of the brain eventually wears off, the psychological sense of clarity has a lasting effect well after the mushroom trip ends. On the other hand, consuming too much psilocybin can have harmful effects on the user. As neural signals become more interconnected and disorganized, multiple sensations can start blurring together and an individual’s grasp on reality can become warped. This is responsible for the common report of synesthesia-like “seeing sound and hearing color” while on a mushroom high. In extreme cases, this sensation can result in intense emotional overload or frightening visual hallucinations. Thus, controlling dosage is key to the safe administering of psilocybin as a drug that supports mental health.

PSILOCYBIN YESTERDAY AND TOMORROW

As depression rates in the United States have climbed to over 17%, new treatments for mental health disorders have become a greater necessity. For centuries, various civilizations have used psilocybin as an integral part of their medicinal culture. For example, the Aztecs in 1,500 BCE Central America used to ingest magic mushrooms as a part of healing rituals and spiritual ceremonies.⁹  Even today, Australia has become the first country in the modern world to legalize the clinical prescribing of psilocybin after being criminalized for many years. Whether or not other countries, such as the United States, will follow suit depends on the country’s ability to become more receptive to the versatile ways in which psychedelics can be used. 

ACKNOWLEDGEMENTS

I would like to offer my sincerest appreciation to Imran Khan, the executive director at the Berkeley Center for the Science of Psychedelics, for reviewing this article and offering insightful feedback.

REFERENCES 

1. De Vise D. (2023, June 19). ‘Magic’ mushroom use by young adults has nearly doubled in three years. The Hill. Retrieved October 30, 2023, from https://thehill.com/policy/healthcare/4054255-magic-mushroom-use-by-young-adults-has-nearly-doubled-in-three-years/
2. University Hospitals. (2022, May 15). “Magic Mushrooms,” Psilocybin and Mental Health. Retrieved October 30, 2023, from https://www.uhhospitals.org/blog/articles/2022/05/magic-mushrooms-psilocybin-and-mental-health
3. Drug Enforcement Administration. (2023). Drug Scheduling. Retrieved October 30, 2023, from https://www.dea.gov/drug-information/drug-scheduling
4. Canal C. E. (2018). Serotonergic Psychedelics: Experimental Approaches for Assessing Mechanisms of Action. Handbook of experimental pharmacology, 252, 227-260. Retrieved October 30, 2023, from https://doi.org/10.1007/164_2018_107
5. American Society for Microbiology. (2023, February 10). Psilocybin and Mental Health: The Magic in the Mushrooms. Retrieved October 20, 2023, from https://asm.org/Articles/2023/February/Psilocybin-and-Mental-Health-The-Magic-in-the-Mush
6. Shukla D. (2022, July 25). Microdoses of psychedelic mushrooms may improve mood and mental health. MedicalNewsToday. Retrieved October 30, 2023, from https://www.medicalnewstoday.com/articles/microdoses-of-psychedelic-mushrooms-may-improve-mood-and-mental-health
7. Goodwin G.M., Aaronson S.T., Alvarez O., Arden P.C., Baker A., Bennett J.C.,… Maliveskaia E. (2022, November 3). Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. The New England Journal of Medicine. Retrieved October 30, 2023, from https://www.nejm.org/doi/10.1056/NEJMoa2206443
8. Lyons A. (2022). Self-administration of Psilocybin in the Setting of Treatment-resistant Depression. Innovations in clinical neuroscience, 19(7-9), 44-47. Retrieved October 30, 2023, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9507144/
9. Dorr A. (2021, December 2). The History of Psilocybin: Magic Mushroom Use Through the Ages. Mushroom Revival. Retrieved October 20, 2023, from https://www.mushroomrevival.com/blogs/blog/the-history-of-psilocybin-magic-mushroom-use-through-the-ages

IMAGE REFERENCES 

Header Image: Volkov A. (2020, September 26). Mexican Psilocybe Cubensis [Image]. iStock. Retrieved October 30, 2023, from https://www.istockphoto.com/photo/the-mexican-magic-mushroom-is-a-psilocybe-cubensis-whose-main-active-elements-are-gm1276620416-376076274

Figure 1: Keim B. (2014, October 31). This is what your brain looks like on magic mushrooms [Image]. WIRED. Retrieved October 30, 2023, from https://www.wired.co.uk/article/what-magic-mushrooms-does-to-your-brain

Figure 2: Coghlan A. (2017, April 19). Psychedelic drugs push the brain to a state never seen before [Image]. New Scientist. Retrieved October 30, 2023, from https://www.newscientist.com/article/2128192-psychedelic-drugs-push-the-brain-to-a-state-never-seen-before/

Figure 3: Altitude Consulting Clinic. (2023, February 15). Psilocybin Mushrooms Lose Potency. Here’s Proof [Photograph]. Altitude Consulting. Retrieved October 30, 2023, from https://altitudeconsultingllc.com/psilocybin-mushrooms-lose-potency-heres-proof/