Psilocybin and Brain Function
Introduction
Imagine consuming a compound that can unlock new dimensions of the mind by altering the very synchronization of your brain waves. These compounds, known as psychoactive substances, directly and variably affect the central nervous system (CNS), interacting at different sites and subsequently causing changes in an individual’s mood, behavior and cognition. In general, the compounds typically fall into one of the following classes: opioids, hallucinogens, stimulants, and depressants. Each of these classes contains a number of compounds that act on different neural components (e.g. stimulants and the dopaminergic system) eliciting atypical activity of the brain. Though these compounds often get a bad rap, recent research has shown that some of these substances can have a beneficial impact. For example, certain hallucinogens, which act via the serotonergic 2A receptor, have been shown to have clinical effects in individuals with depress, anxiety, and addiction. One such hallucinogen, psilocybin, is currently being studied in depth to see exactly how it impacts brain function. A recent publication in Nature by Siegel et al. (2024) delves into the implications of psilocybin-induced desynchronization on brain function and mental health [1].
Image of Psilocybe mexicana adapted from https://mushroomobserver.org/account/login/new and is covered under CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0/deed.en) .
Understanding Psilocybin
Psilocybin is a naturally occurring psychedelic compound found in certain species of mushrooms, commonly referred to as "magic mushrooms" or "shrooms." Psilocybin is known for its ability to induce altered states of consciousness, including changes in perception, mood, and thought. Once consumed, psilocybin is broken down into psilocin, which is the active component that alters brain function via the serotonergic 2A receptor. Some species that contain psilocybin include Psilocybe cubensis, Psilocybe cyanescens, Psilocybe weilii, and Psilocybe mexicana (pictured above). These mushrooms are found in various regions, but often emerge in tropical and temperate environments.
Psilocybin has a long history of use, particularly in spiritual, religious, and healing practices among indigenous cultures. The earliest known use of psilocybin-containing mushrooms dates back thousands of years, with evidence suggesting that these mushrooms played a significant role in the rituals and ceremonies of ancient civilizations in Mesoamerica. Psilocybin was seemingly first described by the Spanish Franciscan friar, Bernadino de Sahagún, who visited Mesoamerica in the 1500’s. In Sahagún’s work, “General History of Things of New Spain”, he describes the teonancatl, or “God’s Flesh”, referring to the sacred mushrooms of this region [2]. These mushrooms were later rediscovered by an American banker who traveled to Mexico and participated in a traditional mushroom ceremony, later writing about his experience. This piece attracted the attention of researchers such as Albert Hoffmann who isolated and synthesized psilocybin in 1958, paving the way for research efforts into the effect and potential therapeutic use of psilocybin.
The Concept of Brain Synchronization
Brain synchronization works much like an orchestrated symphony with varying parts of the brain working together seamlessly to control movement, perception, memory, attention, and other cognitive processes. The brain produces electrical rhythms, known as neural oscillations (brain waves) which are associated with different types of neural activity [3]. These rhythms include alpha, beta, theta, delta, and gamma waves, each linked to specific cognitive states, such as alertness, relaxation, or deep sleep. For the brain to function effectively, these oscillations need to be synchronized across different brain regions. This synchronization allows for the integration of information, enabling different areas of the brain to process data simultaneously and share information in a coordinated manner.
Synchronization of the brain is vital for neural function, however, there are numerous cognitive/neurological disorders or diseases that cause disruption to typical neuronal activity. Certain impairments that cause this neural dysregulation include schizophrenia, Alzheimer’s, Parkinson’s, anxiety, epilepsy and autism. Each of these diseases or disorders causes changes in normal synchronizations within the brain subsequently producing abnormal synchronization patterns, leading to altered perception, memory, and other cognitive functions. Understanding the basis of how these disorders impair brain synchronization is key to creating effective treatments that can potentially restore normal cognition and processing.
Key Findings from the New Research
In a recent publication titled “Psilocybin desynchronizes the human brain” in the journal Nature, collaborating researchers delved into how psilocybin, the active component in magic mushrooms, longitudinally alters brain activity. The primary objective of the study was to determine changes of neural connectivity and function of the brain after a high dose of psilocybin had been administered. Subjects for this study consisted of young, healthy individuals who received 25 mg of psilocybin and 40 mg of methylphenidate (Ritalin) one to two weeks apart. During this time span, individuals underwent functional MRI’s before, during, between, and after being administered the compounds. Data from these scans were extrapolated and statistically analyzed to determine effects of psilocybin administration on the functional connectivity of the brain. While in the scanner, participants completed a simple auditory-visual matching task which gauged whether or not the brain functionally processed these stimuli differently when under the effect of psilocybin. Additionally, the researchers were able to compare subjective psychedelic experiences using a self-assessment tool that measures the “intensity and quality of mystical experiences, including feelings of connectedness, transcendence of time and space, and a sense of awe”.
Results and Implications
The primary findings of the study revealed that psilocybin disrupts brain synchronization, causing widespread and profound changes in the brain’s functional connectivity. The researchers found that the greatest psilocybin-associated change occurred in the association cortex (an area of the brain that performs complex cognitive functions such as attention), followed by the primary cortex and subcortical areas. In comparison, methylphenidate primarily caused effects in the sensorimotor systems with an overall lesser effect on brain functional connectivity (psilocybin had a more than threefold larger effect on synchronization). Psilocybin administration caused a reduction in the interaction of the dorsal mode network (DMN) with other networks such as the frontoparietal (supports modulation of sensory neurons) and salience (neural components involved in identifying important stimuli and responding to them) systems. Long term effects of psilocybin administration were also assessed and evidence of brain desynchronization was present up to 6-12 months post drug administration.
Neural desynchronization after psilocybin administration was most prominent in DMN, and area often noted with neuropsychiatric disorders, and the anteromedial hippocampal region, an area involved in self perception [1]. Both of these regions are important in disorders like depression, and psilocybin likely has a therapeutic effect (anti-depressive), but would need to be confirmed using a subject population involving individuals with depression.
Practical Applications and Future Research
Current and potential future applications of psilocybin in mental health treatment. In recent years, psilocybin has gained traction as a potential therapeutic agent in western health care. Though heavily restricted, psilocybin has been approved by the U.S. FDA to be used in treatment resistant depression [5]. Unfortunately, due to its restrictions, there has not been adequate research to readily support psilocybin for therapeutic use in other disorders or diseases. However, preliminary research has shown potential benefits of psilocybin in alcohol/tobacco addiction, migraines, and obsessive compulsive disorder. Current clinical trials are being conducted to determine what beneficial effects psilocybin may have on other conditions (e.g. bipolar disorder, OCD, anxiety, depression). Future research should delve into potential long term effects and optimal dosing levels of psilocybin as well as any drug-drug interactions and acute adverse events that may occur.
Ethical and Legal Considerations
Current legal status of psilocybin in various regions. Psilocybin and magic mushrooms were first banned in 1971 by the United Nations after the Convention on Psychotropic Substances [4]. Due to this convention, psilocybin became a Schedule 1 substance in many countries including the United States, Australia, the United Kingdom and most of Asia, Africa and parts of Europe. More recently, several states in the the U.S. have begun decriminalizing and even legalizing psilocybin for medical use. Colorado and Oregon are the only states that allow the use of psilocybin for medical treatments while other states (California, Minnesota, Washington, Michigan, Maine, and Pennsylvania) have decriminalized psilocybin.
The use of psilocybin in therapy and research presents several ethical challenges such as ensuring informed consent, particularly given the unpredictable nature of psychedelic experiences, and managing the psychological risks associated with psilocybin use. There's also the issue of equitable access to treatment, as well as the need for cultural sensitivity towards traditionally indigenous practices. Legal and regulatory complexities add another layer of ethical consideration. Finally, the potential for shifting societal views on drug use and the risk of commodifying psychedelic therapy emphasize the need for rigorous standards and ongoing ethical dialogue.
Conclusion
Psilocybin, a naturally occurring psychedelic compound in certain mushrooms that has been historically used in spiritual practices and is now gaining attention for its potential therapeutic applications. Recent research reveals that psilocybin disrupts brain synchronization, significantly altering connectivity in brain regions associated with complex cognitive functions and neuropsychiatric disorders like depression. These findings highlight psilocybin's promise in treating conditions such as treatment-resistant depression, though its legal status and ethical considerations remain complex. Ongoing studies aim to better understand its long-term effects and optimal therapeutic use.
As researchers further explore the potential use of psilocybin, they offer hope in creating additional avenues for treating crippling neuropsychiatric disorders such as depression, anxiety, obsessive-compulsive disorder, and bipolar disorder. Several states in the U.S. have legalized psilocybin for medical use, giving support to treatment options for these disorders.
I encourage you to stay informed about the exciting research unfolding around psilocybin. As new studies continue to reveal its potential benefits for mental health, your awareness and understanding can make a real difference. By staying engaged, you can be part of the conversation that shapes how psilocybin is viewed and used in therapy. Your voice matters in advocating for evidence-based policies that ensure this compound is used safely and ethically. Together, we can help guide the future of mental health treatment toward more informed and compassionate solutions..
Additional Resources
For those seeking to delve deeper into psilocybin and its effects on the brain, there are several valuable resources available. "How to Change Your Mind" by Michael Pollan offers an insightful exploration of the history, science, and personal experiences related to psychedelics, including psilocybin. The book "The Psilocybin Solution: The Role of Sacred Mushrooms in the Treatment of Depression" by Simon G. Powell provides a comprehensive look at psilocybin's potential therapeutic benefits. For academic articles, the journal Frontiers in Psychology frequently publishes research on psychedelics and their impact on mental health. Websites like the Multidisciplinary Association for Psychedelic Studies (MAPS) and the Beckley Foundation offer extensive information and research updates on psilocybin and its effects. These resources offer a thorough understanding of psilocybin’s mechanisms, historical context, and emerging research.
References
[1] Siegel, J.S., Subramanian, S., Perry, D. et al. Psilocybin desynchronizes the human brain. Nature 632, 131–138 (2024). https://doi.org/10.1038/s41586-024-07624-5
[2] Nichols D. E. (2020). Psilocybin: from ancient magic to modern medicine. The Journal of antibiotics, 73(10), 679–686. https://doi.org/10.1038/s41429-020-0311-8
[3] Grover S, Nguyen JA, Reinhart RMG. Synchronizing Brain Rhythms to Improve Cognition. Annu Rev Med. 2021 Jan 27;72:29-43. doi: 10.1146/annurev-med-060619-022857. Epub 2020 Oct 9. PMID: 33035432; PMCID: PMC10068593.
[4] Psilocybin Laws: A Country-by-Country Magic Mushrooms Legal Guide - Psilocybin
[5] MacCallum CA, Lo LA, Pistawka CA, Deol JK. Therapeutic use of psilocybin: Practical considerations for dosing and administration. Front Psychiatry. 2022 Dec 1;13:1040217. doi: 10.3389/fpsyt.2022.1040217. PMID: 36532184; PMCID: PMC9751063.
Footnote
The article discussed herein is titled “Psilocybin desynchronizes the human brain” by Siegel et al., 2024, can be found in the journal Nature and is covered by CC-BY 4.0 International.
