Cannabinoid signaling in glial cells

The cannabinoid signaling system is composed of cannabinoid (CB) receptors, their endogenous ligands, the endocannabinoids, and the enzymes that produce and inactivate them. It is well known that neurons communicate between each other through this signaling system. Δ 9 ‐tetrahydrocannabinol, the main psychoactive compound of marijuana, interacts with CB receptors, impinging on this communication and inducing profound behavioral effects such as memory impairment and analgesia. Recent evidence suggests that glial cells also express components of the cannabinoid signaling system and marijuana‐derived compounds act at CB receptors expressed by glial cells, affecting their functions. This review summarizes this evidence, discusses how glial cells might use the cannabinoid signaling system to communicate with neighboring cells, and argues that nonpsychotropic cannabinoids, both marijuana‐derived and synthetic, likely constitute lead compounds for therapy aimed at reducing acute and chronic neuroinflammation, such as occurs in multiple sclerosis. © 2004 Wiley‐Liss, Inc.