Immune Cell Exhaustion and Apoptotic Markers in Major Depressive Disorder: Effects of in Vitro Cannabidiol Administration.

Background: Immune dysregulation is a component of Major Depressive Disorder (MDD). Cannabidiol (CBD) has immunomodulatory and putative antidepressant effects. The relationship between apoptotic and exhaustion immune markers and the clinical features of MDD and the effects of CBD on these markers are still unknown. Objectives: To assess pro-apoptotic (CD95) and T cell exhaustion (TIM3) markers on immune cells in patients with MDD, as well as the impact of in vitro CBD administration on these markers. Methods: We recruited healthy controls and MDD patients and evaluated the immunophenotypes of T/B lymphocytes using flow cytometry in unstimulated and anti-CD3/CD28 stimulated conditions. We evaluated the immune profiles of M1 macrophages, T helper (Th)17 cells, immune-inflammatory response system (IRS), T cell proliferation, and immune-related neurotoxicity (IRN). We investigated the in vitro effects of CBD on immune cell subsets at concentrations of 0.1 ug/mL, 1 ug/mL, and 10.0 ug/mL. Results: The stimulated CD3+CD95+ cell percentages were substantially correlated with the number of depressive episodes, recurrence of illness, and suicidal behaviors. The stimulated CD8+TIM-3+ cell percentages were substantially and inversely associated with the M1, IRS, CIRS, T cell growth, and IRN immune profiles. TIM-3+ bearing CD3+, CD4+, CD8+, and CD20+ cells were significantly suppressed by lower CBD concentrations (0.1 to 1 ug/mL). TIM3+ and all CD95+ bearing cells, with the exception of CD3+CD95+, were suppressed by the higher CBD concentrations. Discussion: Aberrations in immune checkpoint molecular processes impact the features of MDD. CBD significantly impacts apoptotic and exhaustion processes thereby possibly interfering with immune homeostasis.