Expert Review of Clinical Pharmacology
June 1, 2020
Kyle T. Greenway, Nicolas Garel, Lisa Jerome et al.
87 citations
Combinations of psychotherapy with antidepressants and psychedelic-assisted psychotherapy both work through complex, interactional mechanisms. A review of therapeutic mechanisms behind conventional and psychedelic paradigms, including the evolution of this knowledge and explanatory frameworks, finds that the contextual model of common factors in psychotherapy provides a powerful perspective on psychotherapy, antidepressants, psychedelics, MDMA, and ketamine. Conventional antidepressants and especially psychedelics may improve psychotherapy's efficacy via neurochemical changes and increased environmental sensitivity. Combined treatments hold significant promise for advancing knowledge and treatment of many forms of psychopathology.
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.
International Journal of Mental Health and Addiction
April 1, 2024
Joseph T. Torre, Mehdi Mahammadli, Sonya C. Faber et al.
31 citations
Experts in psychiatry, clinical psychology, and psychedelic research agree that excluding people with personal or family histories of psychosis, bipolar disorder, or similar conditions from psychedelic clinical trials may be justified only when protocols offer minimal psychological support. In interviews with 12 experts, themes derived from interpretative phenomenological analysis indicated that psychedelic-, ketamine-, and MDMA-assisted psychotherapy with high levels of support are not necessarily contraindicated for all such individuals and may benefit some. Factors like specific symptoms, illness duration, severity, therapeutic alliance, trauma's role, and available supports could help predict outcomes. More research is needed to develop a safe protocol for this population.
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.
Research Square (Research Square)
January 25, 2022
Joseph T. la Torre, Mehdi Mahammadli, Kyle T. Greenway et al.
18 citations
Experts agree that excluding people with personal or familial histories of psychotic symptoms from psychedelic-assisted psychotherapy may be justified only when protocols provide insufficient psychological support. With highly supportive therapy, such treatment is not necessarily contraindicated and may benefit individuals experiencing psychotic symptoms. Key factors for predicting outcomes include specific symptoms, illness duration, severity, therapeutic alliance quality, trauma's role, and the client's social supports.
Journal of Psychoactive Drugs
September 18, 2023
Emmy Manson, Erin Ryding, Wes Taylor et al.
13 citations
A pilot program offered group-based therapy with three ketamine sessions at a psychedelic dose to eight Indigenous participants and two Elders, in partnership between Roots to Thrive and the Snuneymuxw First Nation. Thematic analysis of interviews and feedback revealed that participants experienced significant benefits, including the importance of Indigenous team members, traditional healing approaches, and authentic relationships. Challenges were also noted. The work highlights the need to address colonial legacies and integrate Indigenous Ways of Knowing for culturally safe psychedelic therapies.
International Clinical Psychopharmacology
April 23, 2021
Kyle T. Greenway, N. Garel, N. Goyette et al.
12 citations
Intravenous ketamine effectively treats bipolar depression, but its side-effect of dissociation can be distressing and treatment-limiting. Two patients with bipolar 1 disorder and severe depression received their first ketamine infusion without music and chose music for subsequent infusions. They reported that music improved tolerance of dissociative symptoms, reducing distress and aiding further treatments. Both achieved remission from treatment-resistant depression after six infusions. This is the first report of music's benefits with ketamine for bipolar 1 depression, building on prior research with psychedelics. Principles of music selection from that paradigm may apply to unipolar and bipolar depression, warranting further research.
Psychedelic Med (New Rochelle)
December 2, 2024
Sara G. Gloeckler, Alexandre Lehmann, Sara de la Salle et al.
4 citations
A survey of over 2,000 people who used psychedelic substances in non-clinical settings found that most reported therapeutic benefits and enjoyment from combining music with their experiences, though the degree of benefit varied by substance. Contrary to clinical guidelines that recommend unfamiliar, lyric-free music, only 10% of respondents agreed music should be unfamiliar and only 22% agreed it should lack understandable lyrics. The data also suggest that psychedelic experiences without music may offer unique benefits, especially with the shortest- and longest-acting substances. These findings indicate that current music selection guidelines for psychedelic therapy may need more nuanced, substance-specific research.
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.
December 4, 2025
Avery Ostrand, Matthew M. Nour, Christopher Timmermann et al.
2 citations
preprint
The term 'psychedelic' was coined in 1956 from Greek roots meaning 'soul-manifesting' or 'soul-illuminating,' intended to name a drug category defined by its ability to induce a characteristic subjective state. This study examined the main subjective effects of psilocybin, ketamine, and MDMA. Over two hundred participants rated items about their experiences with all three drugs. Factor analyses revealed three or four independent dimensions of subjective experience. A machine learning classifier successfully predicted which drug a person had taken from the effects reported, confirming that the three drugs produce categorically distinct experiences: psilocybin induces visions and psychological insight, ketamine induces dissociation, and MDMA induces pro-social feelings such as love. Psilocybin is thus an exemplar psychedelic drug, definable by its induction of a psychedelic state characterized by visions and insight.
J Psychopharmacol
October 27, 2025
David J. Nutt, Celia Morgan, David Erritzøe et al.
2 citations
Ketamine, originally developed as an anesthetic, has emerged as a promising treatment for severe depression and other psychiatric conditions, particularly in patients who have not responded to traditional therapies. The compound can provide rapid relief from depressive symptoms, often within hours, which contrasts with conventional antidepressants that may take weeks to work. This surprising discovery has opened a new frontier in mental health treatment, offering hope for those with challenging mood disorders. However, the use of ketamine in psychiatry also raises concerns about its potential for abuse and long-term side effects, necessitating careful clinical oversight.
Research Square
November 18, 2024
Chloé Pronovost-Morgan, Kyle T. Greenway, Leor Roseman
2 citations
A large international Delphi consensus study with 89 experts from 17 countries developed guidelines for reporting the setting in psychedelic clinical trials. The process identified 770 potential setting variables, synthesized into 49 items, and refined through four rounds of surveys and debates. Thirty extra-pharmacological variables reached consensus as important or very important for reporting, forming the ReSPCT guidelines. These 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, and the guidelines aim to improve methodological rigor in psychedelic research.
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.
Universität Zürich, ZORA
July 1, 2025
Chloé Pronovost-Morgan, Kyle T. Greenway, Leor Roseman et al.
An international Delphi consensus study involving 89 experts from 17 countries generated guidelines for reporting contextual variables in psychedelic clinical research. Over four rounds, 770 responses were synthesized into 49 items, with 30 reaching consensus as important or very important for at least 70% of experts. These items form the Reporting of Setting in Psychedelic Clinical Trials (ReSPCT) guidelines, covering physical environment, dosing session procedure, therapeutic framework and protocol, and subjective experiences. The findings reveal significant ambiguities in current conceptualizations of set and setting, and the guidelines provide a new standard for documenting extra-pharmacological factors in psychedelic research.