Cannabinoids as Novel Anti-Inflammatory Drugs

Abstract

Cannabinoids are a group of compounds that mediate their effects through cannabinoid receptors. The discovery of Δ9-tetrahydrocannabinol (THC) as the major psychoactive principle in marijuana, as well as the identification of cannabinoid receptors and their endogenous ligands, has led to a significant growth in research aimed at understanding the physiological functions of cannabinoids. Cannabinoid receptors include CB1, which is predominantly expressed in the brain, and CB2, which is primarily found on the cells of the immune system. The fact that both CB1 and CB2 receptors have been found on immune cells suggests that cannabinoids play an important role in the regulation of the immune system. Recent studies demonstrated that administration of THC into mice triggered marked apoptosis in T cells and dendritic cells, resulting in immunosuppression. In addition, several studies showed that cannabinoids downregulate cytokine and chemokine production and, in some models, upregulate T-regulatory cells (Tregs) as a mechanism to suppress inflammatory responses. The endocannabinoid system is also involved in immunoregulation. For example, administration of endocannabinoids or use of inhibitors of enzymes that break down the endocannabinoids, led to immunosuppression and recovery from immune-mediated injury to organs such as the liver. Manipulation of endocannabinoids and/or use of exogenous cannabinoids in vivo can constitute a potent treatment modality against inflammatory disorders. This review will focus on the potential use of cannabinoids as a new class of anti-inflammatory agents against a number of inflammatory and autoimmune diseases that are primarily triggered by activated T cells or other cellular immune components.

Histone Modifications Are Associated with Δ9-Tetrahydrocannabinol-mediated Alterations in Antigen-specific T Cell Responses

“…THC has been shown to have anti-inflammatory and immunosuppression properties and to induce apoptosis of immune cells (40). Indeed, the size of the popliteal lymph node was FIGURE 4.…”

The Endocannabinoid/Endovanilloid N-Arachidonoyl Dopamine (NADA) and Synthetic Cannabinoid WIN55,212-2 Abate the Inflammatory Activation of Human Endothelial Cells

“…NADA and WIN55,212-2 Negatively Regulate EC Inflammatory Activation-Cannabinoids have been reported to modulate the inflammatory activation of leukocytes, but their effects on endothelial inflammation have not been thoroughly investigated (16,17). Because the inflammatory activation of ECs also plays a central role in recruiting leukocytes and mounting immune responses, we decided to test a panel of synthetic cannabinoids, phytocannabinoids and eCBs, including the TRPV1-activating compound CAP, for their ability to regulate the secretion of IL-6 and IL-8 from HMVEC-lung activated with the pro-inflammatory agonists FSL-1 (TLR2/6 ligand), LPS (TLR4 ligand), or TNF␣.…”

“…In particular, CB 2 R is expressed at relatively high levels, especially in B-cells, natural killer cells, and monocytes, and its activation can dampen the inflammatory response to infection (9 -12). In fact, targeting CB 2 R in leukocytes has been suggested as a therapy for inflammatory disorders such as sepsis (13)(14)(15)(16). Although it is clear that several plant-derived (i.e.…”

“…Using a panel of synthetic cannabinoids, phytocannabinoids, and eCBs, we found that the synthetic cannabinoid WIN55,212-2 and the eCB NADA have the ability to dampen the activation of primary human lung microvascular ECs (HMVEC-lung) by a variety of inflammatory agonists, including bacterial lipopeptides (TLR2 agonist), lipopolysaccharide (LPS) (TLR4 agonist), and TNF␣. Although the anti-inflammatory properties of WIN55,212-2 have previously been described, only a few reports have described the physiological functions of NADA, including its role in inflammation (16,(25)(26)(27)(28)(29)(30)(31)(32).…”

Cannabinoids and their medicinal potential

“…20 In a survey in 112 humans with MS in USA and UK, who took cannabis as self medication, it was seen that cannabis improved spasticity, pain, tremors, depression in majority of the patients. 20,26 Another large multicentric study conducted in MS patients who received either synthetic THC or a Cannabis or placebo, recorded significant improvements in spasticity, pain and sleep quality of the patients. The 12 month follow up also showed a remarkable decrease in spasticity.…”