You’re in a hut in the jungle, the music of wildlife and aroma of smoking herbs permeating the air. The shaman, dressed in traditional Amazonian garb, hands you the brownish sludgy concoction called ayahuasca. As you drink it – the nastiest, most foul-smelling thing you’ve ever had – the shaman begins singing, calling out to the “spirits of the jungle”. The purging begins: your stomach churns, you sweat profusely and vomit intensely, your skin burning like literal hell. And then it hits. You see yourself melting away, dissolving into the universe, and you relive your life, re-experiencing all your childhood traumas and repressed emotions, the past fusing with the present, until there is no more sense of time nor self. In what feels like multiple lifetimes, you finally awaken a few hours later with a sense of overwhelming tranquility and bliss the likes of which you’ve never felt before…

Such an experience may seem an unconventional and perhaps “unscientific” method of treatment for mental health disorders. Yet psychedelic drugs have recently garnered renewed interest in both the public and scientific communities for their potential therapeutic effects on major depressive disorders (MDD), anxiety disorders, and addictions. The allure of these “enlightenment” drugs is certainly understandable, given the growing incidence and awareness of mental health disorders coupled with the inefficacy of current medications.

The difficulty in finding effective medication for mental health disorders stems from our weak understanding of the pathophysiology of these conditions. For example, there currently exist multiple theories for depression, including monoamine deficiency, neuroinflammation, and dysfunction of the neuroendocrine system. Medications aim to address each of these biological pathways in a rather reductive manner. Despite their low efficacy and plethora of adverse effects, selective serotonin reuptake inhibitors (SSRIs) are still the first line treatment for MDD. In fact, traditional antidepressants have either no effect or adverse ones in a whopping 1 of every 3 patients. Furthermore, depression is not simply a neurological disorder; social and psychological determinants play a significant, if not primary, role in its pathogenesis. Studies have shown strong correlations between childhood trauma and adult onset MDD, as psychologists suggest that patients develop ingrained behavioural patterns that contribute to depression. Certainly, the heterogeneity of depression itself presents additional challenges not only in how we diagnose it, but also in patients’ responses to different treatments.

Enter psychedelic drugs, which proponents tout as a potential cure for mental health disorders. In contrast to harmful drugs such as alcohol, cocaine, or heroin, psychedelics are neither addictive nor acutely toxic. Human brain functional magnetic resonance imaging (fMRI) studies indicate that psychedelics function by fundamentally changing the architecture of the prefrontal cortex via neurogenesis and induction of novel neural pathways. However, how these changes alter mood and induce hallucinations remains unclear. Some studies suggest neuronal excitation creating transient neural scaffolds is involved, while others demonstrate decreased activity in the brain’s key connector hubs to enable unrestrained cognition.

Of course, the hallmark of psychedelic drugs lies not in its pharmacological actions, but in its phenomenological effects on the user. Despite their similar mechanisms, each type of psychedelic has different methods of administration, hallucinogenic effects, and public perceptions, all of which influence the experience itself and post-trip outcomes. It is important, then, to differentiate the history and uses of each drug for a more nuanced understanding of their therapeutic potential in different mental health disorders.

Lysergic acid diethylamide (LSD), or “acid”, was first synthesized in 1938 by Swiss chemist Albert Hofmann. Its psychedelic effects were uncovered after the chemist accidentally ingested it, and in 1947, LSD was introduced as a psychiatric drug to treat alcoholism, neurosis, and schizophrenia. Since then, the drug has been used in an infamous CIA mind control program Project MKUltra, endorsed as a route towards consciousness expansion, touted as “the next big thing” in psychiatry, and prominently featured in the arts and music scene of the 1960s. During this period, LSD became a popular recreational drug, and its association with the counterculture hippie movement prompted the United States government to outlaw the drug in 1968, despite its therapeutic potential and lack of harm or abuse risk. The turn of the 21st century saw a resurgence of research into LSD for psychedelic therapy.

LSD is typically processed into strips that can be placed on the tongue for ingestion. Trips start within 20-30 minutes of ingestion and can last from 6 to 12 hours in a dose-dependent manner. While trips are highly variable and context-dependent, an early clinical study describes them as “psychic states in which the subject becomes aware of repressed memories and other unconscious material”, and anecdotal reports include descriptions of visual hallucinations, synesthesia, and ego dissolution. In terms of medical efficacy, randomized controlled trials have shown beneficial effects of LSD-assisted psychotherapy on alcoholism and on anxiety associated with life-threatening diseases, without any acute or chronic side effects.

Of course, LSD can sometimes provoke “bad trips”, during which users commonly experience anxiety, panic, and despair. Such experiences sometimes induce psychotic reactions and suicide attempts. In recent years LSD microdosing became a popular method of avoiding bad trips while still harnessing the drug’s stimulatory effects. While the jury is still out on the effectiveness of microdosing, anecdotal reports describe it as enhancing overall wellbeing, reducing stress and anxiety, and improving creativity and concentration. What this also implies though is that LSD’s synthetic nature will make it easier to administer in purified form and accurately measure dosage, thereby enabling a potentially smoother transition towards becoming a prescription drug.

Psychedelic mushrooms, colloquially known as mushrooms or shrooms, are a group of fungi that contain psychoactive compounds such as psilocybin, psilocin, and baeocystin. Mushrooms became popularized in modern Western culture after the American mycologist R. Gordon Wasson participated in an indigenous psilocybin ritual in Mexico and publicized his experience in 1957. As with LSD, psilocybin was heavily studied in the 1960s for its therapeutic potential and similarly outlawed by the end of the decade.

In contrast to LSD, psilocybin induces different hallucinogenic experiences. Mushrooms are typically eaten, brewed into tea, or taken in pill form, with trips lasting 3 to 6 hours. Shroom trips have been described as “more giggly than LSD”, during which visions are more saturated, “mundane aspects of life can become comical”, and one’s sense of self disintegrates. Given its relatively mild psychedelic effects and weaker social stigma, it is not surprising then that the scientific community is now turning its head towards psilocybin. Recently, open-label feasibility studies indicate one to two doses of psilocybin in conjunction with therapy can assist in treatment of alcohol dependence and treatment-resistant depression for up to nine months. Similar results were found on patients with anxiety associated with advanced-stage cancer, obsessive-compulsive disorder, and substance addictions. Nevertheless, these studies have extremely small sample sizes, and definitive conclusions cannot be made due to their absence of placebo-controlled groups. To address these issues, Imperial College London has recently established a Psychedelic Research Group, with upcoming double-blind randomized controlled trials on psilocybin treatment for MDD.

Ayahuasca, Quechuan for “vine of the spirit”, is a psychotropic brew traditionally used for spiritual and therapeutic purposes in Amazonian indigenous populations. The concoction, made from the Banisteriopsis caapi vine boiled with leaves from the Psychotria viridis shrub, contains the powerful hallucinogen N,N-dimethyltryptamine (DMT) and monoamine oxidase A (MAO-A) inhibitors, which allow the former to bypass gastrointestinal degradation and enter the circulation and central nervous system. Interestingly, DMT is the only known psychoactive compound that is naturally found, albeit at low levels, in the human brain.

Unlike LSD and mushrooms, ayahuasca-induced psychedelic experiences seem much stronger and more spiritual in nature, with stories of users going through “hell”, seeing horrific visions, reliving traumas, and talking to the plant itself, before emerging with a sense of bliss and newfound understanding of one’s place in the world. Physically, ayahuasca users usually undergo vomiting, diarrhea, and tachycardia, considered to be a necessary purging. Although the ayahuasca experience may not appear to be a very pleasant one, multiple self-reports of long-lasting psychological improvements suggest the plant may be worth a deeper look.

Psychological guidance is a major part of Ayahuasca ceremonies, with a shaman typically guiding users physically and emotionally. This guidance throughout and after the ayahuasca experience is vital for the healing process and has been implemented in the clinic. In 2010-2011, Canadian physician Dr. Gabor Mate successfully treated multiple addiction patients at his Vancouver-based clinic with ayahuasca and guided therapy, helping them to work out their past traumas to get to what he believes is the root cause of many addictions. This approach is widely used in many ayahuasca retreats in South America, where the drug is legal for spiritual use. To date, researchers from the University of Barcelona and University of São Paulo have found significant improvements in addiction patients who received ayahuasca treatment in preliminary studies. These findings have prompted neuroscientists in the United States to seek government approval to bring this traditional brew to patients in North America.

While preliminary research into psychedelic therapy looks promising, these results should not be interpreted as an endorsement for psychedelic drugs as self-medication nor as recreational use. Most studies so far have been small open-label trials that often do not include placebo controls, have extensive exclusion criteria, and have not measured the long-term outcomes of psychedelic treatment. Appropriate administration, psychological guidance, and extensive support, both during and after the experience, are extremely important; it’s been shown that the psychological context and expectations during the acute psychedelic experience can predict long-term outcomes on mental health.

What this ultimately points to, however, is the need for further research, which is currently restricted by social stigma and the legal status of these drugs. A common thread in the most researched psychedelic drugs is the experience of reliving past traumas and integrating those reflections into reinventing oneself. It is crucial that we look past preconceived notions of these psychotropic plants, which have arguably co-existed with, and helped, us since prehistoric times. In a society that is growing evermore disconnected with the world, perhaps it is time we look deep into our roots and journey back into our interconnected experience of life with nature.


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Pailin Chiaranunt

Pailin is a PhD student in the Department of Immunology at the University of Toronto. She works in Dr. Arthur Mortha's laboratory on creating a high-dimensional map of host-microbiome interactions in the intestine. In her spare time, Pailin enjoys traveling, reading philosophy, and dabbling in martial arts and languages.

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