The role of cannabinoids in inflammatory modulation of allergic respiratory disorders, inflammatory pain and ischemic stroke.

Abstract

This review is intended to offer updated information on the involvement of cannabinoids in the process of inflammation, focusing on immune/allergic reactions, inflammatory pain and neuroinflammation and discussing the interactions among endocannabinoid metabolism, prostanoids and nitric oxide. Two types of cannabinoid receptors, CB1 and CB2, which belong to the G protein-coupled receptor family, have been identified and are targeted by numerous exogenous and endogenous ligands. The activation of CB2 receptors on mast cells has direct antiinflammatory effects, causing decreased release of pro-inflammatory mediators by these cells. The activation of CB1 receptors on bronchial nerve endings has bronchodilator effects by acting on the airway smooth muscle and may be beneficial in airway hyperreactivity and asthma. Moreover, pharmacologic interference with endocannabinoid metabolism has been demonstrated to result in anti-nociceptive activity, mediated by CB1 and CB2 receptors, in animal models of inflammatory pain. The presence of endocannabinoid machinery in the central nervous system, together with high levels of CB1 expression, suggests that the endocannabinoid system is an important modulator of neuroinflammation and a possible drug target. In selected conditions, the activation of CB1 receptors in cerebral blood vessels can have beneficial antiischemic effects. However, as endocannabinoids can also bind to vanilloid receptors, they may also mediate neurotoxic effects.