Your Brain on Magic Mushrooms: A Potential New Therapy for Mental Disorders

Human usage of psychedelic mushrooms may date back thousand of years, from mentions in ancient cave wall murals in the Sahara Desert to their use by Indigenous Central and South American shamans¹. Research on the use of psychedelic mushrooms in therapy began in the 1950s and was significantly furthered by the discovery of the molecules psilocybin and psilocin as the major psychoactive components. After this breakthrough, clinical studies accelerated, with research in the 60s and 70s largely focusing on the short-term effects of the drug and potential therapeutic uses. Unfortunately, the rise in recreational use led to the classification of psilocybin as a Schedule 1 drug in 1970, which made possession illegal and research far more difficult¹. Despite their controversial nature, psychedelic mushrooms are now being investigated for their potential uses in therapy for depression, substance use disorders, anxiety, and obsessive-compulsive disorder (OCD)².

The exact mechanisms of action of psilocybin and psilocin are still poorly understood and a large area of ongoing research. Psilocybin is a prodrug for psilocin, meaning the psilocybin molecule itself cannot affect the brain until it is processed by the body and turned into psilocin¹. Psilocin can then enter the brain and exert its psychedelic effects. Psilocin mimics the structure of serotonin, a neurotransmitter that plays an important role in regulating behaviour, mood, and memory³. It acts as a serotonin receptor agonist, meaning it activates serotonin receptors across the brain¹. The unique psychedelic effects of psilocybin come from the specific subtypes of serotonin receptors with which it can interact. Improper serotonin receptor function has been associated with a range of mental disorders, particularly depression⁴. The agonist properties of psilocin make it a potential treatment for patients experiencing depression that does not improve when treated with more common serotonin agonists or through psychotherapy⁵.

Short-term effects of psychedelic mushrooms include a distorted sense of reality, synesthesia (mixed-up senses, such as seeing colours when hearing sounds), and an altered sense of time². One study that analyzed both short- and long-term effects of the drug identified decreased negative mood, amplified positive mood, and decreased amygdala response to negative stimuli as the primary acute effects. The amygdala is the part of the brain responsible for fear and negative emotion, and it has been implicated in mental disorders including depression and alcohol use disorder⁶. This suggests that psilocybin may be a useful therapeutic in treating these disorders.

Ongoing clinical trials are attempting to analyze the short- and long-term therapeutic potential of psilocybin, as well as its safety. A phase 2 clinical trial studied the ability of psilocybin doses and psychological support to treat major depressive disorder (MDD). It found that psilocybin treatment was associated with significantly reduced scores of depressive symptoms on a self-reported scale. This randomized, placebo-controlled study compared the effects of a 25 mg dose of psilocybin to a niacin (a form of vitamin B) placebo, both of which were administered with psychological support. 104 adults aged 21–65 years were included, all of whom had an MDD diagnosis and were on no other treatments. Drug administration was identical for placebo and treatment groups and consisted of 6–8 hours of preparatory sessions with two facilitators before dosing, a 7–10 hour dosing session under the supervision of the same facilitators, and 4 hours of post-dosing discussion with facilitators. One limitation of studies like this one is possible patient bias, as patients can distinguish which drug they received based on the effects; psilocybin has psychoactive effects while niacin does not. After dosing, assessments of depressive symptoms were done on days 2, 8, 15, 29, and 43 in the form of The Montgomery–Åsberg Depression Rating Scale (MADRS), where a higher score indicated more severe depression. Most significantly, this trial found that the psilocybin group showed larger decreases in MADRS score compared to the control group at all four time points⁵. This suggests that psilocybin has a long-term antidepressive effect that outlasts the actual presence of the drug in the body. Similar trials have been conducted to look at the effect of psilocybin in alcohol use disorder, where 2 doses were found to decrease the amount of heavy drinking in a 32-week period⁷.

With a rich history of use and a resurgence of interest in clinical studies, psilocybin’s unique mechanism of action offers hope for individuals struggling with conditions like depression and substance use disorders. As research progresses, it is crucial to prioritize rigorous scientific study and focus on gaining an understanding of long-term effects. The evolving understanding of psilocybin could mark a turning point in mental health treatment that could benefit many, highlighting the need for continued exploration in this area.