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Role of T and B lymphocyte cannabinoid type 1 and 2 receptors in major depression and suicidal behaviours

Published online by Cambridge University Press:  08 September 2023

Michael Maes*
Department of Psychiatry, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria Research Institute, Medical University Plovdiv, Plovdiv, Bulgaria Kyung Hee University, Seoul, Korea
Muanpetch Rachayon
Department of Psychiatry, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
Ketsupar Jirakran
Department of Psychiatry, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand Department of Pediatrics, Faculty of Medicine, Maximizing Thai Children’s Developmental Potential Research Unit, Chulalongkorn University, Bangkok, Thailand
Atapol Sughondhabirom
Department of Psychiatry, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
Abbas F. Almulla
Department of Psychiatry, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq
Pimpayao Sodsai
Department of Immunology, Faculty of Medicine, Center of Excellence in Immunology and Immune-Mediated Diseases, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
Corresponding author: M. Maes; Email:


Early flow cytometry studies revealed T cell activation in major depressive disorder (MDD). MDD is characterised by activation of the immune-inflammatory response system (IRS) and the compensatory immunoregulatory system (CIRS), including deficits in T regulatory (Treg) cells. This study examines the number of cannabinoid type 1 (CB1) and type 2 (CB2) receptor-bearing T/B lymphocytes in MDD, and the effects of in vitro cannabidiol (CBD) administration on CB1/CB2-bearing immunocytes. Using flow cytometry, we determined the percentage of CD20+CB2+, CD3+CB2+, CD4+CB2+, CD8+CB2+ and FoxP3+CB1+ cells in 19 healthy controls and 29 MDD patients in 5 conditions: baseline, stimulation with anti-CD3/CD28 with or without 0.1 µg/mL, 1.0 µg/mL, or 10.0 µg/mL CBD. CB2+ was significantly higher in CD20+ than CD3+ and CD4+ and CD 8+ cells. Stimulation with anti-CD3/CD8 increases the number of CB2-bearing CD3+, CD4+ and CD8+ cells, as well as CB1-bearing FoxP3+ cells. There was an inverse association between the number of reduced CD4+ CB2+ and IRS profiles, including M1 macrophage, T helper-(Th)-1 and Th-17 phenotypes. MDD is characterised by lowered basal FoxP3+ CB1+% and higher CD20+ CB2+%. 33.2% of the variance in the depression phenome (including severity of depression, anxiety and current suicidal behaviours) is explained by CD20+ CB2+ % (positively) and CD3+ CB2+% (inversely). All five immune cell populations were significantly increased by 10 µg/mL of CBD administration. Reductions in FoxP3+ CB1+% and CD3+ /CD4+ CB2+% contribute to deficits in immune homoeostasis in MDD, while increased CD20+CB2+% may contribute to the pathophysiology of MDD by activating T-independent humoral immunity.

Original Article
© The Author(s), 2023. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology

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