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Psilocybin: The Psychedelic Molecule Transforming Mental Health
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Get informed on the science of the psilocybin molecule, magic mushrooms’ psychoactive compound, and learn how it affects the brain here.
Psilocybin, a natural compound found in magic mushrooms, has recently attracted attention from therapists, psychologists, and researchers for its mental health treatment potential.
What is Psilocybin?
Psilocybin is a naturally occurring plant compound found in Psilocybe genus of mushrooms. The substance commonly known as “magic mushrooms” exists in more than 100 mushroom species across the world with different levels of potency1. These mushrooms grow both in the wild and through cultivation, with cultivated varieties containing more potent strains.
When consumed, psilocybin is metabolized into psilocin2, its active compound. It is this chemical conversion of psilocybin into psilocin that creates its psychoactive effects.
Brief History of Psilocybin
The Swiss chemist Albert Hofmann, the same scientist who discovered LSD, extracted psilocybin from Psilocybe mexicana mushrooms for the first time in 1958.
The development of synthetic psilocybin products occurred shortly after its creation and the product remains widely used in present times.
Before scientists discovered its chemical composition, psilocybin served as a sacred substance in indigenous cultures for both religious and healing purposes. The Aztecs named psilocybin-containing mushrooms as “teonanácatl” which translates to “flesh of the gods”, and archaeological evidence shows their use spans across thousands of years.
The Selva Pascuala mural located near Villar del Humo in Spain shows mushroom-like shapes which scientists believe represent Psilocybe hispanica, a psychoactive species found in the region. The artwork dates from approximately 6,000 years ago.
During the 1950s and 1960s, psilocybin became famous in the West after R. Gordon Wasson described his Mazatec shamanic experiences in Mexico.
However, the War on Drugs classified psilocybin as a Schedule I substance in 1970, stopping research for decades. Fast-forward to today, however, and there’s been a renewed scientific interest in its therapeutic applications. In fact, the FDA recently granted “breakthrough therapy” designation for two formulations of psilocybin in the potential treatment of depression.
Today, psilocybin is used for recreational purposes as well as in religious and spiritual ceremonies.
How Does Psilocybin Affect the Brain?
Psilocybin, O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine chemically, is a precursor molecule to psilocin. The term prodrug refers to an inactive substance or less active drug that turns into an active drug after administration into the human body. Essentially, it acts as a precursor to the active substance.
This compound is structurally similar to serotonin, which is a crucial neurotransmitter that helps regulate mood and facilitates communication between different brain regions. Psilocin, however, is more active at the 5-HT2A receptor with weaker effects at 5-HT1A and 5-HT2C receptors3.
5-HT2A receptors located in the cortex and thalamus are key to processing sensory information. This is because when psilocybin binds to these receptors, particularly in the thalamus, it interferes with sensory input. Effects usually start within 20 to 40 minutes and last between 3–6 hours, and a typical dose is about 40 mcg per kg of body weight.
Psilocybin binding to serotonin receptors produces altered perception, heightened introspection, and deep emotional experiences.
The thalamus and sensory-motor regions of the brain are connected more tightly by neuroimaging studies when psilocybin is used while the activity in the Default Mode Network (DMN) which is the brain network associated with self-referential thinking, overanalyzing, and rumination is dampened. This may help explain the profound changes in perception and self that people experience on psilocybin.
In clinical trials, it has shown some genuine potential in the treatment of depression, with findings indicating that it decreases the reactivity of the amygdala to emotional stimuli.
At the same time, psilocybin enhances neuroplasticity4, the brain’s ability to adapt and develop new neural connections. This could be the reason for the deep realizations and emotional breakthroughs that numerous people describe having had after taking psilocybin.
Psilocybin as a Therapeutic Agent for Mental Health
Depression and anxiety are important global mental health problems that affect millions of people. It is often treated with a combination of medication and therapy. For example, medication includes SSRIs and monoamine oxidase inhibitors, which increase the levels of neurotransmitters such as serotonin and dopamine that influence mood.
However, they are not always effective5, may have side effects including sexual dysfunction and cardiovascular problems, and have high relapse rates after the patient stops taking the medication. Psychotherapy includes cognitive-behavioral and interpersonal therapy among others and is useful in changing negative thought patterns; however, it also has high relapse and dropout rates. However, many patients continue to have symptoms, with only about 25% improving to full recovery by the eighth week and about 75% still having symptoms at the end of 24 weeks.6
Therefore, psilocybin and other serotonergic psychedelics are being investigated in clinical and therapeutic trials for the treatment of mental health disorders including depression, anxiety, PTSD, and addiction.
Stimulation of 5-HT2A receptors has been found to be associated with greater efficacy of traditional antidepressants and may play a role in the mechanism of action of SSRIs. Psilocybin has been found to be effective7 in the treatment of major depressive disorder, including treatment-resistant cases, with rapid and sustained results.
Microdosing8, the administration of very low doses of psilocybin, has become popular among individuals who use it to enhance their cognitive functioning, improve their emotional stability, and enhance their creativity.
Furthermore, psilocybin-assisted therapy, which is provided in safe settings with the assistance of trained therapists, is in the process of being developed as a new treatment approach for major depression and PTSD, among other conditions.
Safety research9 on psilocybin did not reveal any increased risk of drug abuse, long-lasting perception alteration, prolonged psychosis, or long-term functional impairment. Side effects were infrequent, brief and primarily associated with higher doses. Participants were followed up for 8 to 16 months after taking psilocybin and no adverse long term consequences were found.
Future Applications
Scientific research into psilocybin has expanded substantially throughout the last years as Johns Hopkins and Imperial College London and MAPS operate as leaders in pioneering investigations.
Psilocybin shows indications of a promising future as public perspectives regarding psychedelics continue to shift.
Scientists are currently investigating psilocybin for its therapeutic applications10 in treating eating disorders and cluster headaches and neurodegenerative diseases.
Synthetic psilocybin derivative development will likely produce more specific and producible treatment options.
With ongoing efforts toward decriminalization and rising public interest, psilocybin has already become a transformative tool in mental health and consciousness exploration, ushering in a new era of psychedelic medicine.
Sources
[1] https://mhc.kglmeridian.com/view/journals/mhcl/7/1/article-p24.xml
[2] https://www.nature.com/articles/s41386-019-0324-9
[3] https://www.jneurosci.org/content/41/5/891
[4] https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2021.724606/full
[5] https://pubmed.ncbi.nlm.nih.gov/10885163/
[6] https://psychiatryonline.org/doi/10.1176/appi.ajp.2011.10111645
[8] https://link.springer.com/article/10.1007/s00213-018-5106-2
[9] https://journals.sagepub.com/doi/10.1177/0269881110382466
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