CARDIOVASCULAR ACTIONS OF CANNABINOIDS AND THEIR GENERATION DURING SHOCK

Marijuana is a widely abused recreational drug well known for its psyc hoactive properties. Cannabinoids, the active ingredients of marijuana , elicit their neurobehavioral effects by interacting with the CB1 can nabinoid receptor subtype, expressed primarily in the brain but also p resent in some peripheral tissues. A second receptor subtype, the CB2 receptor, is expressed on cells of the immune system and is thought to be responsible for the immunosuppressant effects of cannabinoids, Rec ently, endogenous lipidlike substances have been identified, including arachidonyl ethanolamide (anandamide) and 2-arachidonyl glyceride, th at bind to cannabinoid receptors and mimic many of the neurobehavioral effects of plant-derived cannabinoids. Both plant-derived cannabinoid s and the endogenous ligands have been shown to elicit hypotension and bradycardia via activation of peripherally located CB1 receptors. Pos sible underlying mechanisms include presynaptic CB1 receptor mediated inhibition of norepinephrine release from peripheral sympathetic nerve terminals, and/or direct vasodilation via activation of vascular cann abinoid receptors. The latter may also be the target of endocannabinoi ds of vascular endothelial origin. Recent studies indicate that a peri pheral endogenous cannabinoid system in circulating macrophages and pl atelets is activated in hemorrhagic and septic shock and may contribut e to the hypotension associated with these conditions via activation o f vascular cannabinoid receptors. The potential role of this mechanism in human shock conditions is under investigation.