The Effect of Repeated Administration of Cannabis on the Electrocardiogram and Cardiac Histology in Normal and Epinephrine-treated Rats

Cannabis, recognized as the most prevalent illegal drug globally, has been linked to various acute cardiovascular incidents, including arrhythmias such as premature ventricular contractions, ventricular tachycardia, sinus arrest, and myocardial infarction. We investigated the effect of cannabis extract on electrocardiographic parameters and cardiac histology in anaesthetized normal rats and in epinephrine-induced arrhythmia and myocardial damage anaesthetized rat model. Male Sprague-Dawley rats were treated with cannabis extract (10 or 20 mg/kg  9 -THC) given intraperitoneally (i.p.) for one week prior to intravenous (i.v.) saline or epinephrine. The control group received saline. Results indicated that (i) the repeated administration of cannabis at 10 or 20 mg/kg in normal rats caused dose-dependent and significant bradycardia (heart rate decreased by 15.7% and 24.0%, respectively), and shortened QRS duration by 8% and 16%, respectively. The QTc interval was prolonged by 28.6% and 52.9% and R wave amplitude increased by 30.5% and 38.7% following the administration of 10 and 20 mg/kg cannabis, respectively. The ST segment was depressed after 10 and 20 mg/kg cannabis; (v) In contrast, rats pretreated with cannabis prior to i.v. epinephrine, exhibited increased the heart rate by 46.3% and 91.4%, and decreased P-R interval by 18.6% and 30% compared with the epinephrine control values. Cannabis at 10 and 20 mg significantly decreased the QRS duration by 21.6% and 18.7% while significantly increased the QTc interval by 17.9% and 22.6%, respectively. In addition, cannabis at 10 mg/kg induced a significant inversion of the ST-segment, while the higher dose resulted in significantly raised ST segment, compared with the corresponding epinephrine control; (vi) administration of cannabis was associated with a significant and dose-related suppression of the epinephrine arrhythmia; (vii) cannabis caused disorganization of cardiac muscle fibers, nuclear pyknosis, interstitial inflammatory cell invasion, vacuolar degeneration and hyalinization of muscle fibers. Epinephrine-treated rats showed coagulative necrosis, shrunken nuclei and focal degeneration of cardiac muscle fibers. Notably, rats receiving 20 mg/kg of cannabis prior to epinephrine treatment exhibited extensive degeneration and coagulative necrosis of cardiac muscle fibers. Collectively, these results show that the repeated administration of cannabis in high doses caused bradycardia, QTc prolongation, and ST changes suggestive of myocardial ischaemia. Cannabis caused structural myocardial damage and aggravated that caused by epinephrine. Repeated cannabis administration did not increase epinephrine arrhythmia.