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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 <jats:italic>in vitro<\/jats:italic> 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 \u00b5g\/mL, 1.0 \u00b5g\/mL, or 10.0 \u00b5g\/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 \u00b5g\/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.<\/jats:p>","DOI":"10.1017\/neu.2023.35","type":"journal-article","created":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T11:11:01Z","timestamp":1694171461000},"page":"287-298","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":9,"title":["Role of T and B lymphocyte cannabinoid type 1 and 2 receptors in major depression and suicidal behaviours"],"prefix":"10.1017","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2012-871X","authenticated-orcid":false,"given":"Michael","family":"Maes","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muanpetch","family":"Rachayon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ketsupar","family":"Jirakran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atapol","family":"Sughondhabirom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7667-6731","authenticated-orcid":false,"given":"Abbas F.","family":"Almulla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pimpayao","family":"Sodsai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2023,9,8]]},"reference":[{"key":"S0924270823000352_ref28","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1600-065X.1996.tb00921.x","article-title":"The role of CD40 ligand in costimulation and T-cell activation","volume":"153","author":"Grewal","year":"1996","journal-title":"Immunol Rev"},{"key":"S0924270823000352_ref47","doi-asserted-by":"crossref","first-page":"3302","DOI":"10.1038\/s41380-020-00867-4","article-title":"The longitudinal associations of inflammatory biomarkers and depression revisited: systematic review, meta-analysis, and meta-regression","volume":"26","author":"Mac Giollabhui","year":"2021","journal-title":"Mol Psychiatry"},{"key":"S0924270823000352_ref44","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3390\/ijms22010019","article-title":"CB2 receptor in microglia: the guardian of self-control","volume":"22","author":"Komorowska-M\u00fcller","year":"2020","journal-title":"Int J Mol Sci"},{"key":"S0924270823000352_ref65","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/nm1561","article-title":"Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells","volume":"13","author":"Maresz","year":"2007","journal-title":"Nat Med"},{"key":"S0924270823000352_ref7","doi-asserted-by":"crossref","first-page":"5720","DOI":"10.4049\/jimmunol.1102195","article-title":"Cannabinoid receptor 2 is critical for the homing and retention of marginal zone B lineage cells and for efficient T-independent immune responses","volume":"187","author":"Basu","year":"2011","journal-title":"J Immunol"},{"key":"S0924270823000352_ref69","doi-asserted-by":"crossref","first-page":"104408","DOI":"10.1016\/j.phrs.2019.104408","article-title":"Emerging role of innate B1 cells in the pathophysiology of autoimmune and neuroimmune diseases: association with inflammation, oxidative and nitrosative stress and autoimmune responses","volume":"148","author":"Morris","year":"2019","journal-title":"Pharmacol Res"},{"key":"S0924270823000352_ref77","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.clim.2016.04.007","article-title":"IgM antibodies against malondialdehyde and phosphorylcholine are together strong protection markers for atherosclerosis in systemic lupus erythematosus: regulation and underlying mechanisms","volume":"166","author":"Rahman","year":"2016","journal-title":"Clin Immunol"},{"key":"S0924270823000352_ref83","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.niox.2020.11.001","article-title":"Construction of a nitro-oxidative stress-driven, mechanistic model of mood disorders: a nomothetic network approach","volume":"106","author":"Simeonova","year":"2021","journal-title":"Nitric Oxide"},{"key":"S0924270823000352_ref85","volume-title":"State-Trait Anxiety Inventory for Adults (STAI-AD.) 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