The Canadian Journal of Psychiatry
August 17, 2022
Joshua D. Rosenblat, Muhammad Ishrat Husain, Yena Lee et al.
58 citations
Serotonergic psychedelics are being reconsidered as potential treatments for major depressive disorder. A Canadian task force systematically reviewed clinical trials from 1990 to 2021 and found that only psilocybin and ayahuasca have been tested in contemporary studies. Two pilot studies of single-dose ayahuasca for treatment-resistant depression showed preliminary positive effects (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy for major depressive disorder showed superiority to waitlist controls and comparable efficacy and safety to escitalopram with supportive psychotherapy, with additional trials showing efficacy in cancer-related depression (Level 3 evidence).
Frontiers in Psychiatry
September 19, 2023
Nicolas Garel, Jessica Drury, Julien Thibault Lévesque et al.
32 citations
A biopsychosocial approach to ketamine for treatment-resistant depression, called the Montreal model, pairs ketamine infusions with structured psychiatric care and psychotherapy. Developed over six years in public healthcare settings, the model conceptualizes ketamine as a brief intervention that creates windows of opportunity for enhanced care and psychological growth. It combines six ketamine infusions with psychedelic-inspired nonpharmacological adjuncts, including preparative and integrative psychological support. The model aims to bridge biomedical and psychedelic perspectives, offering a standardized yet flexible approach for severe, real-world patients. Further research is needed to assess its effectiveness and hypothesized psychological mechanisms.
Frontiers in Human Neuroscience
July 18, 2023
Nicolas Garel, Julien Thibault Lévesque, Dasha A. Sandra et al.
29 citations
Past environmental exposures can significantly shape psychedelic drug experiences and their therapeutic outcomes, a concept the authors call 'imprinting.' In a clinical trial of ketamine for treatment-resistant depression, two patients' subjective experiences were altered by the type and amount of digital media they consumed in the days before treatment: higher media exposure reduced mystical and emotional qualities of the ketamine experience, overriding standard intention-setting practices and changing therapeutic results. Eight additional patients spontaneously reported past environmental exposures manifesting as visual hallucinations during ketamine sessions. Similar imprinting effects appear in historical reports of other psychedelic drugs and in dreaming. The authors propose expanding the contextual model of psychedelic action to include imprinting, which may help clinicians and researchers better understand these drug effects.
Addiction
January 11, 2024
Nicolas Garel, Steven Tate, Kristin Nash et al.
23 citations
Hallucinogen-related emergency department visits in California rose 54% from 2016 to 2022 (2260 to 3476 visits), while alcohol-related visits fell 20% and cannabis-related visits rose 15%. Hallucinogen-related hospitalizations increased 55% (2556 to 3965), compared with a 1% increase for both alcohol and cannabis. These trends were statistically different from those for alcohol and cannabis. The absolute numbers remain small, but the relative increase is large.
Scientific reports
July 17, 2024
Sara de la Salle, Hannes Kettner, Julien Thibault Lévesque et al.
21 citations
A prospective longitudinal survey of eight Canadians with cancer who received legal psilocybin-assisted psychotherapy under Section 56 exemptions found significant improvements in anxiety, depression, pain, fear of COVID-19, quality of life, and spiritual well-being two weeks after the session. Attitudes toward death, medical assistance in dying, and desire for hastened death remained unchanged. Most participants found the sessions highly meaningful, though one reported a substantial decrease in well-being. These preliminary data suggest that real-world psilocybin-assisted psychotherapy can produce psychiatric benefits similar to those in clinical trials, but limited enrollment and negative experiences indicate a need for formal real-world evaluation programs.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
November 1, 2023
Nicolas Garel, Kyle T Greenway, Lê-Anh L Dinh-Williams et al.
10 citations
A course of six sub-anesthetic ketamine infusions over four weeks helped patients with treatment-resistant depression discontinue long-term benzodiazepine or z-drug use. Of 22 patients, 91% (20/22) successfully stopped all such medications by the end of the infusions, confirmed by urine tests. Fewer than 25% experienced significant worsening of anxiety, depression, sleep problems, or suicidality during withdrawal. Over a mean follow-up of one year, 64% (14/22) remained abstinent. These preliminary results suggest ketamine infusions may facilitate benzodiazepine deprescription even in patients with active depression and significant comorbidity.
The British Journal of Psychiatry
June 18, 2025
Kyle T Greenway, Nicolas Garel, Lê-Anh L Dinh-Williams et al.
8 citations
In a clinical trial of ketamine combined with psychotherapy for severe treatment-resistant depression, 32 participants received six ketamine infusions with psychological support, either with or without music. Both groups showed large and sustained reductions in depression, anxiety, and suicidality at four weeks, fully maintained at eight-week follow-up. The ketamine experiences were highly emotional and mystical, comparable to those seen with psilocybin. Converging analyses suggested that mystical-like experiences contributed to the immediate and lasting antidepressant effects. Music did not enhance outcomes or psychedelic experiences.
Expert review of clinical pharmacology
March 1, 2025
Danny Diep, Sara de la Salle, Julien Thibault Lévesque et al.
8 citations
Ketamine's subjective effects have been interpreted in three major ways since its 1962 synthesis: as dissociative, dream-like, or psychedelic, depending on the clinical context and dose. Biomedical frameworks often label its effects as dissociative or psychotomimetic, while psychedelic paradigms highlight potential therapeutic benefits. Factors such as language, dose, and environmental setting influence both the drug's effects and treatment outcomes. The authors argue that ketamine is best understood as a chameleon whose effects shift with context, rather than a tiger to be tamed. A nuanced, interdisciplinary approach is needed to maximize its clinical potential.
International clinical psychopharmacology
September 1, 2023
Nicolas Garel, Michka Nazon, Kamran Naghi et al.
7 citations
A Canadian patient with severe, prolonged treatment-resistant depression who was actively requesting Medical Assistance in Dying (MAiD) experienced remission after a course of intravenous ketamine infusions. This is the first reported case of any intervention yielding remission in a patient who would otherwise likely have been eligible for MAiD for depression. The case raises questions about evaluating MAiD requests for psychiatric disorders, particularly regarding the definition of irremediability—whether a patient lacks any reasonable prospect for recovery. The authors suggest that a trial of ketamine warrants consideration in similar cases.
Palliative & Supportive Care
January 1, 2025
Houman Farzin, Brigita Koren, Helen Ferrier et al.
1 citation
A 51-year-old man with metastatic lung cancer and a prognosis of less than 6 months experienced depression and anxiety linked to demoralization and existential distress, which persisted despite psychotherapy and 100 mg of sertraline. Through Health Canada’s Special Access Program, he received 25 mg of oral psilocybin in a homecare setting, with preparative and integrative therapy before and after the session. The treatment was well tolerated, and the patient reported a sustained reduction in suffering and improved well-being at 2 months post-intervention. Psilocybin-assisted therapy may be safely delivered at home and offer lasting relief for anxiety and depression associated with existential distress in palliative care.
Healthcare (Basel, Switzerland)
June 3, 2026
Michel Dorval, Virginie Audet-Croteau, Sue-Ling Chang et al.
After one year of offering psilocybin-assisted therapy (PAT) at a Canadian university-affiliated tertiary care center, no patients had received the treatment despite clinicians and managers viewing it favorably. Interviews with ten professionals identified administrative and regulatory procedures, along with logistical constraints, as key barriers, while perceived clinical relevance and institutional leadership were facilitators. The estimated cost of delivering a complete PAT intervention ranged from 2,648 to 5,827 Canadian dollars per patient, excluding the cost of psilocybin itself. The gap between regulatory authorization and actual service uptake highlights the need for structured implementation strategies, sustained institutional support, and alignment between regulatory frameworks and clinical workflows.
Psychological medicine
May 8, 2026
Lou-Anne Chavigny, Véronique Desbeaumes Jodoin, Nicolas Garel et al.
A systematic review of 21 studies involving approximately 900–1,180 participants with treatment-resistant depression found that low-dose intravenous ketamine preserves and enhances certain cognitive functions. Improvements were frequently observed in processing speed and working memory, while attention remained stable or modestly improved. Results for verbal and visual memory varied across studies. Executive control, especially inhibitory performance on Stroop tasks, improved in several trials. No cognitive worsening was reported. Two studies directly examined cognition in relation to suicidal behaviors, suggesting that procognitive effects, particularly in executive control, may mediate ketamine's antisuicidal action. Standardized longitudinal studies are needed to clarify durability and clinical significance.
BMJ Open
March 1, 2026
Christina Mcanulty, Philippe Lavoie, Samuel Cyr et al.
A new treatment combining ketamine infusions with acceptance and commitment therapy (ACT) may be feasible for people who have both alcohol use disorder and treatment-resistant depression. In an open-label trial at a Montreal hospital, 30 participants will receive six ketamine infusions plus eight weekly therapy sessions, either in person or online. The study primarily tests whether the combined approach is practical and acceptable by measuring completion rates, safety, and data quality. Exploratory measures will track changes in depressive symptoms, alcohol use, and quality of life. Some participants will also be interviewed about their experiences.