Authors:
Durst R, Danenberg H, Gallily R, Mechoulam R, Meir K, Grad E, Beeri R, Pugatsch T, Tarsish E, Lotan C.
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.