Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury.
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.
Durst
Ronen
R
Cardiology Department, Hadassah Hebrew University Medical Center, Jerusalem, Israel. rdurst@partners.org
Danenberg
Haim
H
Gallily
Ruth
R
Mechoulam
Raphael
R
Meir
Keren
K
Grad
Etty
E
Beeri
Ronen
R
Pugatsch
Thea
T
Tarsish
Elizabet
E
Lotan
Chaim
C
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism; D002185:Cannabidiol / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D002188:Cannabis / Q000737:chemistry; D002317:Cardiovascular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000601:surgery; D004195:Disease Models, Animal; D004452:Echocardiography; D006097:Granulation Tissue / Q000187:drug effects; D015850:Interleukin-6 / Q000097:blood; D008026:Ligation; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D017725:Ventricular Pressure / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D002317:Cardiovascular Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002185:Cannabidiol; D002097:C-Reactive Protein