A Trip to the Therapeutic World of Psychedelic Mushrooms
Rory Thompson
Illustrations by Ayane Garrison
“I saw a liquor bottle in the middle of a desert … all of a sudden it disintegrates into the sand. And I thought that was pretty obvious symbolism for my alcoholism leaving me… At that point, I, kind of, felt free from my addiction,” reflects Jon Kostas, contemplating his experience taking psychedelic mushrooms [1]. Kostas struggled with alcoholism since he was a teen, and it got to the point where he had “nothing to lose” except for his life. After three doses of the psychedelic compound psilocybin, along with psychotherapy, Kostas began his journey into seven years of sobriety, emphasizing how he had “no words to explain how crazy and shocking this is.” Kostas is just one of many individuals whose drinking was reduced long-term after receiving psilocybin-assisted therapy [2].
What is this drug that has succeeded in treating psychiatric disorders where modern Western medicine has historically failed [1]? Psilocybin is a natural psychedelic compound produced by fungi colloquially termed “magic mushrooms.” Humans have ingested psilocybin for millions of years; in fact, psilocybin-containing mushrooms are present across all major habitable regions of Earth [3]. In Cuenca, Spain, the Selva Pascuala mural of rock art — thought to be from 4000 B.C.E. — portrays mushroom figures [4]. Further, in 1910, anthropologists found rock carvings in the Tassili caves in the south of Algeria depicting dancing figures with mushroom heads holding mushroom-like objects [5]. Lines carved from the objects to the heads of the dancers are thought to reflect the states of consciousness induced by psychedelic mushrooms, while the postures of the figures depict the associated ritual dances. These carvings suggest that psilocybin use has been widespread in Africa and the Middle East since ancient times [6].
Psilocybin was often ingested in religious practices for healing purposes [5, 7]. In many parts of the world, including ancient Europe and Asia, shamanistic practices incorporated the use of hallucinogenic mushrooms to enhance healing abilities by connecting shamans with the spiritual world [5, 7]. Psilocybin allows shamans to “see” the causes of illness, and healing is assisted by spirits, referred to as “power animals,” “guardians,” or “helpers” [8]. Hindu practices may have also incorporated the use of psilocybin. Soma, a drink that was believed to be consumed by the Hindu gods and their ancient priests, has been theorized to originate from hallucinogenic mushrooms [9, 10]. Its consumption was thought to heal illness, promote positive emotions, and bring humans closer to the divine.
Given psilocybin’s use in healing by indigenous communities for thousands of years, researchers today are investigating its ability to treat psychiatric disorders. Psilocybin-assisted therapy has been identified as a potential treatment option for conditions including major depressive disorder, generalized anxiety disorder, and addiction [11]. Unfortunately, the use of psychedelics as therapeutics is often met with controversy because of their complex and politicized past [12, 13]. As a result, much is still unknown about how psilocybin acts on the brain to produce healing effects. Dismantling the negative stigmatization surrounding psilocybin has the potential to make alternative treatments for debilitating psychological disorders more accessible.
A Trip to the Past: Overcoming Historical Stigmas Surrounding Psychedelics
The indigenous peoples of Mesoamerica consumed psychedelic mushrooms during therapeutic and religious rituals for many centuries before the arrival of Christopher Columbus [14]. Spanish missionary Fray Bernardino de Sahagún first mentioned these practices in an account from 1530: “The first thing they ate in a feast, were some black mushrooms… that make you drunk and make you see visions” [15]. However, many indigenous groups were forced to stop consuming mushrooms during the colonial era due to laws imposed by Christian missionaries which forbade the use of psilocybin, even for medicinal and religious purposes [14]. Christians believed that using hallucinogens allowed individuals to communicate with the devil [16]. They associated mind-altering substances with supernatural forces they feared, such as witches and the demonically possessed [17]. Prohibition began with Columbus's presence in Mesoamerica and continued until the 20th century, as Catholic and Evangelical Protestant missionaries discouraged the use of hallucinogenic mushrooms in religious rituals.
In the 1960s, scientific and popular interest in psychedelic compounds resurged [18]. Unfortunately, the increased interest exacerbated preexisting negative biases towards these substances within law enforcement and scientific institutions. Initially, the renewed use of psychedelics prompted hundreds of studies on hallucinogenic substances worldwide. At the same time, the distribution of illicitly manufactured psychedelics led to use in uncontrolled settings and increased reports of “bad trips,” or psychedelic experiences involving overwhelming anxiety that can turn into panic, anger, and depression with suicidal thoughts. The rare but highly publicized suicide cases following these kinds of psychedelic experiences led to social backlash, resulting in the discontinuation of research on psilocybin [18]. The use of psychedelics by anti-Vietnam War activists also led government officials to associate psychedelic use with anti-war sentiment [19]. The stigma surrounding psychedelics contributed to the commencement of the War on Drugs and the enactment of the Controlled Substances Act of 1970, formally classifying these substances as dangerous drugs with a high potential for abuse [20].
Despite these efforts to vilify psilocybin, its use is gradually becoming more accepted. In November 2022, a vote by Denver, Colorado resulted in the decriminalization of psilocybin for recreational use [21]. Additionally, four in ten adults surveyed in the United States feel that psilocybin should be legal, at least under some circumstances [22]. This change in perspective can be attributed to new evidence demonstrating that psilocybin has many therapeutic benefits and little potential for abuse or dependence; in healthy participants, the short-term and long-term effects of psilocybin are safe and tolerable [23, 24, 25]. These findings challenge negative stigma around psilocybin created by colonial leaders, religious figures, and pro-Vietnam war advocates, demonstrating that psychedelics are safe and medically effective drugs.
A Trip Into the Brain: How Does Psilocybin Treatment Work?
The War on Drugs and the resulting halt in psilocybin research have limited our understanding of how this psychedelic acts on the brain [26]. One widely accepted theory for the brain mechanisms underlying psilocybin’s effects is that they occur largely through the stimulation of serotonin receptors [26]. Serotonin is a chemical in our brains known to modulate mood, cognition, reward, learning, and memory [27]. Psilocybin’s chemical structure is similar to that of serotonin, allowing it to activate serotonin receptors [28]. Let us imagine the serotonin receptor as a baseball player catching a baseball, the serotonin molecule. The shape of the player’s glove is created specifically to catch a baseball. If a basketball were thrown at the player, they would not be able to catch it with the glove. However, if a ball that is similar in structure to the baseball is thrown, such as a softball, the glove would be able to catch it equally as well. Like the similar shapes and sizes of the softball and baseball, psilocybin and serotonin can both be “caught” by serotonin receptors [26].
Why is it important to understand psilocybin's underlying mechanisms? Psilocybin may be a viable treatment option for mental health disorders [11]. Especially effective in tandem with psychotherapy, psilocybin can help individuals with alcohol dependence reduce their alcohol consumption [2, 29]. Similar positive results were found for persons experiencing tobacco addiction—psilocybin treatment led to greater rates of smoking cessation than other behavioral therapies such as nicotine replacement therapy [30, 31]. Psilocybin doesn’t just counteract a specific drug dependency but may interrupt the neurological pathways of addiction by improving a person’s ability to change ingrained behaviors [32]. This can support their agency to alter drug-use behaviors, but more research into this topic needs to be done [33, 34, 35]. Individuals with substance dependence also have impairments in their emotional processes controlled by the amygdala, the brain area involved in memory, decision making, and emotional responses [36]. Hyperactivity and a disturbed balance in serotonin receptors in the amygdala have been thought to contribute to emotional distress seen in substance use disorder [28]. Psilocybin’s actions on serotonin receptors decrease amygdala activity, which can be useful in treating emotional dysregulation found in drug users [37].
Along with psilocybin’s positive effects on substance use disorders, it holds large therapeutic potential in treating major depressive disorder and generalized anxiety disorder [38, 39, 40]. Psilocybin leads to rapid and long-term antidepressant effects [39]. Similarly to substance dependence, these positive effects appear to be mediated by a decrease in amygdala activity [41]. Additionally, individuals with depression often demonstrate increased communication between the hippocampus, a brain region important for memory encoding and retrieval, and the prefrontal cortex — an area involved in high-order cognitive processes such as decision making, reasoning, personality expression, and social cognition. After psilocybin treatment, communication between these regions decreases [41]. Major depressive disorder, generalized anxiety disorder, and substance use disorder are all associated with increased connectivity between brain regions in a large-scale network that is active when the brain is at rest [11]. The network is primarily composed of the dorsal medial prefrontal cortex, posterior cingulate cortex, and angular gyrus [42]. When completing a cognitive task, this network is typically inactive, but increased connectivity between the brain regions involved renders the network overactive, which can impair cognitive performance [43]. Psilocybin appears to disrupt this impaired neural network by decreasing communication between brain areas after its consumption [11, 44]. Psilocybin demonstrates high therapeutic potential in treating these psychiatric disorders, but because it is still classified as a dangerous drug according to legislation, it cannot be prescribed for treatment until it is reclassified as a medication [20].
A Trip to the Future: The Growing Acceptance of Psilocybin Therapy
Although psilocybin demonstrates potential efficacy in treating mental health disorders, negative stigmatization continues to impact the amount of psychedelic research being conducted [12, 13]. In Australia and New Zealand, for example, psychedelics are still viewed as addictive and dangerous with no therapeutic applications, so academic institutions are hesitant to become involved in this field of research. These countries are top leaders in medical research and could contribute to the advances being made in psychedelic therapy, but due to the continued perception of these drugs as harmful substances, they are falling behind in psychedelic research [12, 13]. Many other countries are adopting the use of psychedelics in therapy, and now, there are hundreds of ongoing psychedelic research trials [45]. The Netherlands, in particular, has legalized psychedelics and is home to world-class psychedelic therapy centers, embracing them as a medical treatment [46]. Examples of legalization, such as the case in the Netherlands, may provide a potential avenue for other countries to follow suit.
While results on psilocybin-assisted therapy are promising, it is important to note many of these studies report small sample sizes [38]. Large sample sizes are a necessity if we want to more closely approximate how the larger population would react to this type of treatment [47]. Since psychedelics are becoming increasingly accepted around the world, a greater number of studies with larger sample sizes have been conducted. For example, a recent study on treatment-resistant depression had 230 participants, the largest population in a psychedelic study to date, and reported a concrete reduction in depressive symptoms [48]. With a large sample size like this one, we can better predict the effects on a range of people, as well as check for any adverse symptoms that may have not been present in smaller groups [48]. If more studies with larger sample sizes are conducted, we may be able to see a future where psilocybin is accepted as a medical treatment. Individuals who are suffering from mental illnesses could experience a life-changing moment like Jon Kostas did when he realized, after only his second psilocybin session, that he was “killing off the addiction, the alcoholism and starting with a clean slate” [1].
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