In 2017 about 970 million people, which is roughly one in every eight people, were living with a mental health disorder or substance use disorder, with the greatest prevalence being anxiety followed by depression. A mental health disorder (MHD) is a clinical condition that is significantly impacting one's cognition, emotional regulation or behaviour. Unfortunately, individuals taking medication to treat their MHD aren't always compliant with taking the medicine for various reasons like adverse drug reactions (for example, headaches, diarrhoea), drug tolerance, the drug being ineffective or having to take the drug several times a day. But what if someone told you that there is an alternative natural option, one that is more effective, non-addictive and non-toxic?
Magic mushrooms (MM) may be the golden key we have been waiting for and may be the first step to moving away from big pharma to natural remedies in managing MHD. MM come from a genus of fungi-forming mushrooms called Psilocybe. These mushrooms have a compound called psilocybin which is a tryptamine alkaloid. Upon being ingested and metabolised it can cause hallucinations and is consequently known as psychedelic/psilocybin mushrooms, booms and shrooms. There are about 200 species of MM globally which vary depending on their phytoconstituents, particularly the concentration of psilocybin which is the main compound responsible for their psychedelic (that is hallucinogenic) effect.
The most common wild MM is Psilocybin cubensis which is found in the United States, Mexico, Central and South America and the West Indies. While MM are identified as being little brown or white mushrooms that can grow in soil, dump, wood or mosses, they mustn't be mistaken for similar poisonous mushrooms which are deadly. MM have a viscid cap when moist and dark purplish spores. In some species, when the mushroom is injured, aged or dried its caps and stems become bruised attaining a green-blue hue. This is indicative of psychedelic compounds.
The consumption of MM for human or religious use dates back to over 6,000 years ago. In fact, in Nahuatl, which was the language of the Aztecs, who ruled Mexico throughout the 14th and 16th centuries, denoted the psilocybin-containing mushrooms as "Teonanácatl" which means "divine flesh". However, it was only in 1958 that further insight into how MM exert its effect on the human body was obtained. Albert Hofmann identified the active metabolite psilocin which is released from psilocybin upon being metabolised. Hofmann then synthesised psilocybin as the synthetic compound indocybin which was marketed in 1959 for psychopharmacological use and therapeutic clinical research. Unfortunately, this new area of exploration brought about hesitance in the medicinal industry. In fact, until the 1990s research on MM's potential as a medicine was significantly reduced due to it gaining popularity as a recreational hallucinogenic since it brought about an altered state of consciousness, mood, perception and thought. Albeit, it is well known that all drugs are poisons and the benefit depends on the dosage. Luckily, over the past few years, human studies involving MM have increased expanding our knowledge of it and unlocking its therapeutic potential in treating neurotic disorders, alcoholism, depression, obsessive-compulsive disorder (OCD), addiction, anxiety and even cluster headaches.
Psilocybin is the prodrug to psilocin, which is produced upon dephosphorylation of psilocybin by an esterase in the intestinal mucosa. The molecular shape of psilocin is similar to that of serotonin and it therefore agonistically binds with serotonin type 2 receptors in the brain instead of serotonin. Upon this binding, a hallucinatory effect is produced since it stimulates frontal hyper-frontality which in turn contributes to its anti-depressant and anti-anxiety effects.
In depression, the medial prefrontal cortex is hyperactive and individuals usually lose responsiveness to emotional stimuli. However, psilocybin is able to modulate the activity of the prefrontal and limbic brain regions. Furthermore, psilocybin-induced alteration in brain connectivity involves the disintegration of associative networks and the integration of sensory function networks. Similarly, psilocybin interacts with various feedback loops between the cortex and thalamus, producing a general activation of the cortex. It is believed that this is why psilocybin results in a state of altered consciousness, cognition and behaviour which can last for four to six hours.
Although psilocybin and psilocin were listed as a Schedule I drug in 1971 meaning that they cannot be prescribed for medicinal use, a large body of evidence supports their medicinal and therapeutic potential. In fact, in 2018, researchers from Johns Hopkins University recommended that they be reclassified to Schedule IV, which includes drugs with a low potential for abuse. A pilot study had demonstrated that upon administering doses of psilocybin ranging from 0.025 mg/kg to 0.3 mg/kg, to nine individuals with treatment-resistant OCD, their symptoms had significantly improved after four, eight and 24 hours of taking it. Similarly, another study involved 27 participants having a longstanding history of depression some of whom had taken anti-depressant medication at some point. These were subjected to two doses of psilocybin every two weeks for a year-and-a-half. Follow-ups revealed a significant reduction in depression symptoms which remained low for up to 12 months. Likewise, in another study comprising 953 patients that participated in a psilocybin microdosing trial for 30 days, exhibited improvements in mental health and mood over one month compared to those that didn't take small amounts of psilocybin.
Globally, every year, three million deaths are accounted for the misuse of alcohol. Luckily, MM may be the solution to overcoming alcoholism. In one study, 49 participants between the ages of 25 and 65 having alcohol use disorder who experienced at least four heavy drinking days in the 30 days prior to the study were employed. Heavy drinking is defined as consuming four or more drinks daily for women and five or more drinks daily for men. During the study, participants had two day-long medication sessions and 12 psychotherapy sessions over 12 weeks. The participants that were given psilocybin reduced their heavy drinking days by 83% and eight months after the first dose, 48% of them, had stopped drinking completely. On the same tangent, an open-label study found that two to three doses of psilocybin (20 mg/70 kg and 30 mg/70kg) in combination with cognitive behavioural therapy for smoking cessation resulted in an 80% success rate after six months with 12 of 15 participants showing biologically verified smoking abstinence.
About 300 million people around the world suffer from some kind of colour vision deficiency meaning that they have difficulty distinguishing the colours red, green and yellow. Unfortunately, some people cannot see any colour at all making them colour blind which is genetic. Sadly, there is no cure so far for colour blindness. However, a 2021 report revealed that some people having colour deficiencies that consumed MM recreationally were able to see colours clearer. Furthermore, in 2017, out of a cohort of 47 respondents who had colour vision deficiency, 23 had reported that they experienced an improvement in their vision upon psychedelic consumption, like MM. It is believed that this is due to the psychedelics' ability to activate serotonin type 2 receptors. These are responsible for neural plasticity too which in turn helps create new neural connections in the brain.
Although, psilocybin-containing mushrooms exhibit low toxicity, are non-addictive and are thus considered safe, abuse of psilocybin can lead to a "bad trip". This is an undesired or even traumatic physical and emotional experience characterised by altered visual perception, extreme distress, fear, panic attacks and lack of coordination. Furthermore, while MM poisoning is rare and often accidental, it is a risk too. MM poisoning could lead to minor gastrointestinal illness, hypertension and convulsion, requiring medical intervention. In general, psilocybin is documented to have the most favourable safety profile of all psychedelic drugs.
This year, the United States Food and Drug Administration (FDA) approved the first-ever clinical trial studying the effects of naturally derived psychedelic drug candidates in which psilocin and psilocybin are derived from mushrooms rather than having these compounds synthetically produced. This trial is being conducted by the company Filament Health Corp. Seeing this great step forward in psychedelic medicine and how the MM market size is projected to be worth $1.2bn by 2027 with a compounded annual rate of growth (CAGR) of 10.3% between 2022 and 2027, one begs to ask the question, will MM follow the same legalisation blueprint as marijuana?
Furthermore, although MM are seen to be physiologically well tolerated improving mood, mental health and psychomotor ability, further research is still required to obtain a better understanding of MM's physiological mechanisms as well as safety parameters. Thus, one can only wonder what the future beholds.
In conclusion, it is strongly advised not to self-medicate using MM unless under medical supervision. Should one need to seek mental health support, please get in touch with your healthcare provider.
Renald Blundell is a biochemist and biotechnologist with a special interest in Natural and Alternative Medicine. He is a professor at the Faculty of Medicine and Surgery,
University of Malta
Emma Camilleri is currently a medical student at the University of Malta