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.
Nature Medicine
June 3, 2025
Chloé Pronovost-Morgan, Kyle T. Greenway, Leor Roseman et al.
26 citations
A Delphi consensus study with 89 experts from 17 countries identified 30 extra-pharmacological variables that are important or very important for reporting the setting in psychedelic clinical trials. These variables, forming the ReSPCT guidelines, cover physical environment, dosing session procedure, therapeutic framework and protocol, and subjective experiences. The findings reveal significant ambiguities in current conceptualizations of set and setting. The guidelines provide a new standard for designing and documenting contextual factors in psychedelic research.
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 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 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.
Journal of Psychedelic Studies
May 15, 2025
Sara G. Gloeckler, Julien Thibault Lévesque, Alexandre Lehmann et al.
3 citations
Music is a standard part of psilocybin-assisted psychotherapy, but the role of silence is not well understood. In a compassionate-access program in Canada, two breast cancer patients undergoing psilocybin therapy experienced a 30-minute silent period that included mindfulness exercises and therapist discussion. One patient initially found the absence of music difficult but later found the mindfulness exercises highly meaningful. The other patient reported that music had evoked challenging memories early in the session, which were then productively explored during the silent period. The findings suggest that integrating silent intervals may enhance mindfulness and therapist-patient interactions, offering distinct therapeutic benefits. The authors call for more detailed reporting on session components in psychedelic research.