Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury

Abstract

Cannabidiol (CBD) is a major, nonpsychoactive Cannabis constituent with anti-inflammatory activity mediated by enhancing adenosine signaling. Inasmuch as adenosine receptors are promising pharmaceutical targets for ischemic heart diseases, we tested the effect of CBD on ischemic rat hearts. For the in vivo studies, the left anterior descending coronary artery was transiently ligated for 30 min, and the rats were treated for 7 days with CBD (5 mg/kg ip) or vehicle. Cardiac function was studied by echocardiography. Infarcts were examined morphometrically and histologically. For ex vivo evaluation, CBD was administered 24 and 1 h before the animals were killed, and hearts were harvested for physiological measurements. In vivo studies showed preservation of shortening fraction in CBD-treated animals: from 48 +/- 8 to 39 +/- 8% and from 44 +/- 5 to 32 +/- 9% in CBD-treated and control rats, respectively (n = 14, P < 0.05). Infarct size was reduced by 66% in CBD-treated animals, despite nearly identical areas at risk (9.6 +/- 3.9 and 28.2 +/- 7.0% in CBD and controls, respectively, P < 0.001) and granulation tissue proportion as assessed qualitatively. Infarcts in CBD-treated animals were associated with reduced myocardial inflammation and reduced IL-6 levels (254 +/- 22 and 2,812 +/- 500 pg/ml in CBD and control rats, respectively, P < 0.01). In isolated hearts, no significant difference in infarct size, left ventricular developed pressures during ischemia and reperfusion, or coronary flow could be detected between CBD-treated and control hearts. Our study shows that CBD induces a substantial in vivo cardioprotective effect from ischemia that is not observed ex vivo. Inasmuch as CBD has previously been administered to humans without causing side effects, it may represent a promising novel treatment for myocardial ischemia.

Neuroprotective Effects of the Nonpsychoactive Cannabinoid Cannabidiol in Hypoxic-Ischemic Newborn Piglets

“…Although myocardial ischemia was greater in the CBD than the VEH group, as indicated by the higher cTnT levels at drug administration, CBD blunted subsequent rises of cTnT at both 3 h and 6 h after HI. Protective effects of CBD against myocardial ischemic reperfusion injury have also been detected in adult rats (30). Mechanical ventilation progressively damaged piglet lung, as shown by the decrease in lung compliance observed in SHAM piglets throughout the experiment; a similar decrease was observed in HIϩVEH.…”

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

“…CBD produces antinecrotic effects in ischemic hearts (815) and reduces infarct size in models of ischemia-reperfusion in rats (233) and rabbits (255). It decreases myocardial inflammation by attenuating lipid peroxidation and reduced glutathione levels and by decreasing iNOS expression in the myocardium (327).…”

Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action

“…95 CBD has been studied for ischemic heart diseases in rats. 96 The left anterior descending coronary artery was transiently obstructed for 30 min, and the rats were treated for 7 days with CBD (5 mg/kg, ip) or vehicle. Cardiac function was studied by echocardiography and showed preservation of shortening fraction in CBD-treated animals.…”