The cannabinoid system and immune modulation

Abstract

Studies on the effects of marijuana smoking have evolved into the discovery and description of the endocannabinoid system. To date, this system is composed of two receptors, CB1 and CB2, and endogenous ligands including anandamide, 2-arachidonoyl glycerol, and others. CB1 receptors and ligands are found in the brain as well as immune and other peripheral tissues. Conversely, CB2 receptors and ligands are found primarily in the periphery, especially in immune cells. Cannabinoid receptors are G protein-coupled receptors, and they have been linked to signaling pathways and gene activities in common with this receptor family. In addition, cannabinoids have been shown to modulate a variety of immune cell functions in humans and animals and more recently, have been shown to modulate T helper cell development, chemotaxis, and tumor development. Many of these drug effects occur through cannabinoid receptor signaling mechanisms and the modulation of cytokines and other gene products. It appears the immunocannabinoid system is involved in regulating the brain-immune axis and might be exploited in future therapies for chronic diseases and immune deficiency.

Peripheral Endocannabinoid System Dysregulation in First-Episode Psychosis

“…Although both receptors have a role to restore homeostasis mechanisms, CB1 receptors perform their function mainly in the CNS, whereas CB2 receptors do it mainly at the peripheral level. Some authors have reported CB1 expression in human PBMCs, but its levels are much lower than CB2 and considerable work is still needed to define its relevance and regulatory mechanism/s (Klein et al, 2003). Second, 81.1% of the patients were receiving antipsychotic treatment.…”

Cannabinoids and neuroinflammation

“…In human peripheral blood cells, CB 1 receptor mRNA and protein are expressed, in decreasing rank order, by B cells, NK cells, neutrophils, CD8 þ T cells, monocytes, and CD4 þ T cells (Galiegue et al, 1995). CB 1 and CB 2 receptors are expressed by human peripheral blood cell-derived dendritic cells (DCs) (Matias et al, 2002), and mRNA for both CB 1 and CB 2 receptors is expressed in mouse bone marrow-derived DC (Klein et al, 2003). Mouse peritoneal macrophages and rodent macrophage cell lines express CB 2 receptor mRNA, and this message is more abundant than the message for CB 1 (Carlisle et al, 2002).…”

CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: Potential role for CB2-selective ligands as immunosuppressive agents

“…It is generally believed that cannabinoids alter the immune functions through their ability to mediate an effect on cytokine production and to exert anti-proliferative properties [15] (Review). Recent studies from our laboratory suggested that the anti-proliferative activity of THC may result from its ability to trigger apoptosis in immune cells [16].…”