Direct Cardiodepressant Effects of Cannabinoids

Quit Marijuana The Complete Guide

New Treatment for Cannabis Dependence

Get Instant Access

In contrast to the growing knowledge on the vascular effects of cannabinoids, little is known about cannabinoid-induced direct cardiac effects. The endocannabinoid anandamide (Felder et al. 1996), anandamide amidohydrolase (Bilfinger et al. 1998), and traces of the message for the CBi receptor (Galiegue et al. 1995) have all been detected in the human heart. In a more recent study, the existence of CB1 receptors was confirmed in human atrial myocytes by immunoblotting and immunohistochemistry (Bonz et al. 2003). In the same study, it was demonstrated that anandamide, R-methanandamide, and HU-210 dose-dependently decrease contractile performance in isolated, electrically paced human atrial muscle. A selective and potent CB1 antagonist, AM251 (Gatleyetal. 1997), blocked the negative inotropic effect of all three drugs, and the involvement of CB2 receptor activation, NO, or prostanoid release could all be excluded (Bonz et al. 2003). Consistently with these in vitro results, HU-210 decreases cardiac output in rats in vivo in a CB1 receptor-dependent manner (Wagner et al. 2001b). Previous studies have also demonstrated that anandamide caused SR141716-sensitive coronary vasorelaxation in isolated perfused rat hearts (Randall and Kendall 1997; Fulton and Quilley 1998), implicating cannabinoid receptors. These effects of anandamide were not mimicked by arachidonic acid, indicating that the vasodilator effect was not mediated by arachidonic acid metabolites.

In isolated, perfused, rat Langendorff heart preparations, anandamide and . -methanandamide, but not palmitoylethanolamide or the selective CB2 receptor agonist JWH015, significantly reduced both left ventricular developed and coronary perfusion pressures, indicating decreased myocardial contractile function and coronary vasodilation (Ford et al. 2002). Interestingly, anandamide-mediated vasodilatation and negative inotropy were both sensitive to inhibition by the CB1 antagonist SR141716 and the CB2 antagonist SR144528, but not to the TRPV1 antagonist capsazepine, which led the authors to propose a novel site distinct from classic CB1 and CB2 receptors (Ford et al. 2002).

In agreement with the observations on isolated cardiac preparations, our recent unpublished results using the Millar pressure-volume conductance system (see below and also Figs. 1 and 2) to directly measure cardiac performance in vivo strongly suggest the crucial importance of the cardiac component in the hemo-dynamic effects of cannabinoids. Taken together, the above-mentioned studies suggest that CB1 receptors are present in cardiomyocytes, and cannabinoids may decrease cardiac contractility through both CB1-dependent and CB1-independent mechanisms.

Was this article helpful?

0 0
Dealing With Drugs

Dealing With Drugs

Get All The Support And Guidance You Need To Be A Success At Dealing With Drugs. This Book Is One Of The Most Valuable Resources In The World When It Comes To A Parents Guide To The Drug Talk.

Get My Free Ebook


Post a comment