Turning Over a New Leaf: Cannabinoid and Endocannabinoid Modulation of Immune Function

Abstract

Cannabis is a complex substance that harbors terpenoid-like compounds referred to as phytocannabinoids. The major psychoactive phytocannabinoid found in cannabis ∆9-tetrahydrocannabinol (THC) produces the majority of its pharmacological effects through two cannabinoid receptors, termed CB1 and CB2. The discovery of these receptors as linked functionally to distinct biological effects of THC, and the subsequent development of synthetic cannabinoids, precipitated discovery of the endogenous cannabinoid (or endocannabinoid) system. This system consists of the endogenous lipid ligands N- arachidonoylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG), their biosynthetic and degradative enzymes, and the CB1 and CB2 receptors that they activate. Endocannabinoids have been identified in immune cells such as monocytes, macrophages, basophils, lymphocytes, and dendritic cells and are believed to be enzymatically produced and released “on demand” in a similar fashion as the eicosanoids. It is now recognized that other phytocannabinoids such as cannabidiol (CBD) and cannabinol (CBN) can alter the functional activities of the immune system. This special edition of the Journal of Neuroimmune Pharmacology (JNIP) presents a collection of cutting edge original research and review articles on the medical implications of phytocannabinoids and the endocannabinoid system. The goal of this special edition is to provide an unbiased assessment of the state of research related to this topic from leading researchers in the field. The potential untoward effects as well as beneficial uses of marijuana, its phytocannabinoid composition, and synthesized cannabinoid analogs are discussed. In addition, the role of the endocannabinoid system and approaches to its manipulation to treat select human disease processes are addressed.

Determination of ∆-9-Tetrahydrocannabinol (THC), 11-hydroxy-THC, 11-nor-9-carboxy-THC and Cannabidiol in Human Plasma using Gas Chromatography–Tandem Mass Spectrometry

“…Both THC and CBD have been approved for treatment of medical conditions; THC most notably for treatment of nausea during chemotherapy and loss of appetite among AIDS patients, and CBD for treatment of epileptic syndromes (5-7). Cannabinoids, particularly CBD are also being espoused as potential treatments for immune dysfunctions (8,9), diabetes (10), addictive behavior (11) and cancer (12).…”

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

“…104), ⌬ 9 -THC modulates cytokine (e.g., TNF-␣, IL-1␤, IL-6, IL-12, and IL-10) and chemokine production, the expression of adhesion molecules, and the migration, proliferation, and apoptosis of inflammatory cells (439, 899).…”

The Pharmacological Basis of Cannabis Therapy for Epilepsy

“…It is principally accountable for the psychoactive effects associated with THC, and stimulation of this receptor also plays a role in regulating stress responses, pain, lipogenesis, and energy regulation. In contrast, the CB 2 receptors are predominantly expressed throughout the immune system, though sparsely expressed within the CNS as well, generally located on microglial cells (Cabral et al, 2015). The complexity of the endocannabinoid system throughout the CNS and the periphery may offer various targets to modulate the endocannabinoid signaling Häring et al, 2011;Iannotti et al, 2014;Naderi et al, 2015).…”