By Tiffany Chien, Avni Bhargava, and Nicole Chu

Graphic design by Raymond Zhang  

Once dismissed as relics of counterculture, psychedelics are now being studied in some of the world’s leading research institutes. While headlines often celebrate these substances as “miracle cures,” the clinical reality is far more nuanced.¹ Emerging clinical trials across Canada are gradually changing the longstanding reputation psychedelics had as illicit drugs, as researchers increasingly explore their potential as promising candidates for the treatment of mental illness.

Psychedelics refer to a class of drugs that alter feelings, perception, and self-awareness.² Classical psychedelic drugs are serotonin 2A receptor agonists such as lysergide D-tartrate (LSD), mescaline, psilocybin, as well as more potent and fast-acting compounds like Dimethyltryptamine (DMT) and 5-MeO-DMT. These drugs have gained significant traction for their potential therapeutic effects at low doses.² In contrast to macrodosing, where individuals take enough of the drug to experience a “trip”, microdosing involves taking small amounts regularly, without experiencing hallucinations.³

Psychedelic research gained early momentum in the 1960s but came to an abrupt halt amid political and public concerns about recreational drug use. By the early 1970s, psychedelics were classified as Schedule I under United States federal law–a category reserved for drugs considered to have no accepted medical use and a high potential for abuse.⁴ Research stalled and psychedelics became symbols of rebellion rather than subjects of rigorous medical study. In the early 2000s, improved ethical frameworks and renewed interest in novel mental health treatments sparked interest in resuming psychedelic research. Substances once pushed to the margins of medicine are now at the centre of cutting-edge conversations about mental health, trauma, pain management, and end of life care. This resurgence of interest is largely driven by limitations of existing treatment options and the need for novel therapeutic approaches to improve patient outcomes.

Current treatments for neuropsychiatric disorders, including mood and anxiety disorders, primarily involve the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs). While effective, approximately 30% to 50% of patients experience only partial relief, and 10% to 30% of patients are treatment-resistant.⁵ The gap in treatment efficacy has led to renewed interest in exploring psychedelic-assisted therapy, which has shown promising results, including sustained antidepressant effects among patients with major depressive disorder, treatment-resistant depression, and cancer patients dealing with psychological distress. ⁵

Across North America, several clinical trials are on the brink of discovering psychedelic treatments to target common neuropsychiatric disorders such as Major depression, treatment resistant depression (TRD), post-traumatic stress disorder (PTSD), anxiety disorders, and substance abuse.⁶ Depression, PTSD, and addiction have high comorbidity and common pathophysiology that involve changes in the same brain areas, particularly the shrinkage and loss of neurons in the prefrontal cortex.⁷ Studies have shown that the antidepressant and anxiolytic effects of psychedelics are attributable to their ability to promote rapid structural and functional neuronal growth.⁷

While psilocybin, the active ingredient found in “magic mushrooms”, remains illegal in many parts of the world, the trend of decriminalization across the United States is slowly expanding in Canada through the Health Canada Special Access Program.^8,9 It is expected that the FDA will approve these hallucinogenic drugs for treating psychiatric disorders in the upcoming year. Compass Pathways, a UK biotechnology company, has developed a drug candidate called COMP360, a psilocybin for the treatment of TRD.¹⁰ Additionally, Definium Therapeutics (formerly MindMed), a New York-based biotechnology company, is currently in its second phase 3 clinical trial evaluating the safety and efficacy of DT120 (formerly MM120), an LSD treatment for generalized anxiety disorder, is underway.^11,12 

Since psychedelics can produce intense alterations in perception, cognition, and emotion, especially when used outside of controlled settings, the therapeutic benefits observed in trials may not be the same as effects of recreational psychedelic use, which may carry risks such as psychological distress, adverse reactions, and unpredictable outcomes. As such, increasing evidence suggests that sustained benefits may arise not from the psychedelic compound alone, but from its integration within a structured psychotherapeutic framework.¹³

Several studies have demonstrated the therapeutic potential of psychedelics in combination with psychotherapy to reduce distress and improve quality of life.¹⁴ Patients suffering from life-threatening illnesses often experience distress, depression, and anxiety related to the loss of meaning of. The Psychedelic Psychotherapy Research Group at the University Health Network (UHN) have developed ongoing studies, specifically the Psilocybin-assisted Existential, Attachment and Relational (PEARL) study, for helping patients with advanced cancer and their caregivers ease end-of-life existential distress, mortality-related anxiety, and depression.¹⁵ 

On episode 138 of Raw Talk Podcast, a graduate student-run initiative at the University of Toronto, we spoke with Dr. Emma Hapke, Co-Founder and Associate Director at the UHN Psychedelic Psychotherapy Research Group emphasized the importance of providing support to both patients and their caregivers because end-of-life distress in patients with advanced cancer, chronic and life-threatening illnesses “affect the whole family […] and [caregivers are] often overlooked in the system that’s really focused on the patient,” says Dr. Hapke.

In recent years, private clinics, biotechnology companies, and investors have increasingly entered the psychedelic space, hoping to translate promising research into new treatments. While this momentum has accelerated innovation, it has also raised important questions about regulation, equitable access, and whether commercial enthusiasm may outpace scientific evidence. As scientific interest in psychedelics continues to grow, we also enter a period termed “the psychedelic gold rush,” where private clinics and biotech startups want to capitalize on public fascination.¹⁶ Ultimately, as the field matures, it must contend with the reality that these interventions are not one size fits all and require regulations that prioritize patient safety over market velocity. 

Acknowledgements

To learn more about psychedelics and psychedelic assisted therapies, we invite readers to check out episode #137 and 138 of Raw Talk Podcast. We would like to acknowledge the efforts, creativity, and dedication of the episode team: Avni Bhargava and Swapna Mylabathula served as Show Hosts, Bellinda Yin was our content creator, Victoria Li was our audio engineer, and Nicole Chu was our Executive Producer.

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