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. 2023 Jan;68(1):5-21.
doi: 10.1177/07067437221111371. Epub 2022 Aug 17.

The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Report: Serotonergic Psychedelic Treatments for Major Depressive Disorder

Joshua D Rosenblat  1   2 , M Ishrat Husain  1   3 , Yena Lee  2 , Roger S McIntyre  1   2 , Rodrigo B Mansur  1   2 , David Castle  1   3 , Hilary Offman  1 , Sagar V Parikh  1   4 , Benicio N Frey  5 , Ayal Schaffer  1   6 , Kyle T Greenway  7 , Nicolas Garel  7 , Serge Beaulieu  7 , Sidney H Kennedy  1   2 , Raymond W Lam  8 , Roumen Milev  9 , Arun V Ravindran  1   3 , Valerie Tourjman  10 , Michael Van Ameringen  11 , Lakshmi N Yatham  8 , Valerie Taylor  1   2
Affiliations

The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Report: Serotonergic Psychedelic Treatments for Major Depressive Disorder

Joshua D Rosenblat et al. Can J Psychiatry. 2023 Jan.

Abstract

Objective: Serotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence and provide a consensus recommendation for the clinical use of psychedelic treatments for major depressive disorder.

Methods: A systematic review was conducted to identify contemporary clinical trials of serotonergic psychedelics for the treatment of major depressive disorder and cancer-related depression. Studies published between January 1990 and July 2021 were identified using combinations of search terms, inspection of bibliographies and review of other psychedelic reviews and consensus statements. The levels of evidence for efficacy were graded according to the Canadian Network for Mood and Anxiety Treatments criteria.

Results: Only psilocybin and ayahuasca have contemporary clinical trials evaluating antidepressant effects. Two pilot studies showed preliminary positive effects of single-dose ayahuasca for treatment-resistant depression (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy and safety to an active comparator (escitalopram with supportive psychotherapy) in major depressive disorder, with additional randomized controlled trials showing efficacy specifically in cancer-related depression (Level 3 evidence). There was only one open-label trial of psilocybin in treatment-resistant unipolar depression (Level 4 evidence). Small sample sizes and functional unblinding were major limitations in all studies. Adverse events associated with psychedelics, including psychological (e.g., psychotomimetic effects) and physical (e.g., nausea, emesis and headaches) effects, were generally transient.

Conclusions: There is currently only low-level evidence to support the efficacy and safety of psychedelics for major depressive disorder. In Canada, as of 2022, psilocybin remains an experimental option that is only available through clinical trials or the special access program. As such, Canadian Network for Mood and Anxiety Treatments considers psilocybin an experimental treatment and recommends its use primarily within clinical trials, or, less commonly, through the special access program in rare, special circumstances.

Keywords: N; N-dimethyltryptamine; antidepressants; ayahuasca; clinical practice guidelines; lysergic acid diethylamide; major depressive disorder; mescaline; psilocybin; psychophamacology; psychotherapy.

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Conflict of interest statement

The author(s) declared the following potential conflicts of interest:

Joshua D. Rosenblat has received research grant support from the Canadian Institute of Health Research (CIHR), Physician Services Inc. (PSI) Foundation, Labatt Brain Health Network, Brain and Cognition Discovery Foundation (BCDF), Canadian Cancer Society, Canadian Psychiatric Association, Academic Scholars Award, American Psychiatric Association, American Society of Psychopharmacology, University of Toronto, University Health Network Centre for Mental Health, Joseph M. West Family Memorial Fund and Timeposters Fellowship and industry funding for speaker/consultation/research fees from Janssen, Allergan, Lundbeck, Sunovion and COMPASS. He is the Chief Medical and Scientific Officer of Braxia Scientific Corp and the Medical Director of Braxia Health.

M. Ishrat Husain reports grants from the Brain and Behavior Research Foundation, CAMH Foundation, Canadian Institutes of Health Research, Physicians Services Incorporated Foundation and University of Toronto. Dr Husain has been a PI for a trial sponsored by COMPASS Pathways Limited and is on the advisory boards of MindSet Pharma Inc., Wake Network Inc. and PsychEd Therapeutics. He owns shares of MindSet Pharma Inc.

Yena Lee was previously the Chief Research Officer of Braxia Scientific Corp.

Roger McIntyre has received research grant support from Global Alliance for Chronic Diseases/Canadian Institutes of Health Research (CIHR)/National Natural Science Foundation of China's Mental Health Team Grant; speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Abbvie. He is the CEO of Braxia Scientific Corp.

Rodrigo B. Mansur has received research grant support from the Canadian Institute of Health Research (CIHR), Physician Services Inc. (PSI) Foundation, Baszucki Brain Research Fund, and an Academic Scholars Award from the University of Toronto, Department of Psychiatry.

David Castle has received grant monies for research from Eli Lilly, Janssen Cilag, Roche, Allergen, Bristol-Myers Squibb, Pfizer, Lundbeck, Astra Zeneca, Hospira; Travel Support and Honoraria for Talks and Consultancy from Eli Lilly, Bristol-Myers Squibb, Astra Zeneca, Lundbeck, Janssen Cilag, Pfizer, Organon, Sanofi-Aventis, Wyeth, Hospira, Servier, Seqirus; and is a current or past Advisory Board Member for Lu AA21004: Lundbeck; Varenicline: Pfizer; Asenapine: Lundbeck; Aripiprazole LAI: Lundbeck; Lisdexamfetamine: Shire; Lurasidone: Servier; Brexpiprazole: Lundbeck; Treatment-Resistant Depression: LivaNova; Cariprazine: Seqirus. He is a founder of the Optimal Health Program (OHP), and holds 50% of the IP for OHP; and is part owner of Clarity Healthcare. He is on the scientific advisory of The Mental Health Foundation of Australia. He does not knowingly have stocks or shares in any pharmaceutical company.

Hilary Offman has received consulting fees from Braxia Scientific Corp.

Sagar V. Parikh has received honoraria or research funds from Assurex, Takeda, Janssen, Mensante, Aifred, Sage.

Benicio N. Frey has no disclosures.

Ayal Schaffer has received funding (past 3 years) from AbbVie, GlaxoSmithKline, Janssen, Lundbeck, Otsuka, Sunovion.

Kyle T. Greenway has served as an instructor for psychedelic support and an uncompensated scientific advisor for Wake Network, Inc. and grant support from the Quebec Network on Suicide, Mood Disorders and Related Disorders; the Northern Ontario Academic Medicine Association; and the Foundation for Psychocultural Research

Nicolas Garel has no disclosures.

Serge Beaulieu has received honoraria or research funds from CIHR, Pfizer, Otsuka, Lundbeck, Sunovion, Allergan, Abbvie, Janssen-Ortho and Takeda.

Sidney H. Kennedy has received grants from Abbott, Allergan, Brain Canada, Canadian Institutes for Health Research (CIHR), Janssen, Lundbeck, Ontario Brain Institute, Ontario Research Fund(ORF), Otsuka, Pfizer, Servier, Sunovion and Xian-Janssen and consulting fees or honorarium from Abbott, Alkermes, Allergan, Boehringer Ingelheim, Brain Canada, Canadian Institutes for Health Research (CIHR), Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute, Ontario Research and has Stock/Stock Options from Field Trip Health

Raymond W. Lam has received honoraria for ad hoc speaking or advising/consulting, or received research funds, from Allergan, Asia-Pacific Economic Cooperation, BC Leading Edge Foundation, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Healthy Minds Canada, Janssen, Lundbeck, Lundbeck Institute, Michael Smith Foundation for Health Research, MITACS, Myriad Neuroscience, Ontario Brain Institute, Otsuka, Unity Health, Vancouver Coastal Health Research Institute, Viatris and VGH-UBCH Foundation.

Roumen V. Milev has received honoraria or research funds from Ontario Brain Institute, Allergan, Janssen, Lallemand, Kye, Lundbeck, Nubiyota, Otsuka, Pfizer and Sunovion.

Arun V. Ravindran has received grants from Janssen.

Valerie Tourjman has no disclosures.

Michael van Ameringen has received honoraria or research funds from Allergan, Almatica, Brainsway, Lundbeck, Myriad Neuroscience, Otsuka, Purdue, Janssen, Canadian Foundation for Innovation, Hamilton Academic Health Sciences Organization and Pfizer.

Lakshmi N. Yatham has received honoraria or research grants from Allergan, CANMAT, Lundbeck Institute, Otsuka, DSP and Sanofi.

Valerie H. Taylor has received honoraria or research funds from Optmi, DiaMentis, Janssen, Lundbeck, Otsuka, Purdue, Shire and Takeda.

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