Cannabidiol attenuates methamphetamine-induced cardiac inflammatory response through the PKA/CREB pathway in rats.

ABSTRACT

Background: Methamphetamine (MA) abuse is a major global public health problem. However, it is not yet known whether cannabidiol (CBD) has protective effects on MA-induced cardiotoxicity. The present study investigated whether CBD has protective effects on MA-induced cardiac damage in rats via the protein kinase A/cyclic adenosine monophosphate (cAMP)-response element-binding protein (PKA/CREB) pathway. Methods: A total of 30 rats were randomly divided into 5 groups. The rats were administered MA (10 mg/kg) by intraperitoneal (IP) injection once a day for 4 weeks, and with CBD (40 or 80 mg/kg, IP) treatment 1 h before the MA injections. Morphological changes were determined using hematoxylin and eosin and Masson's trichrome staining. The serum levels of interleukin (IL)-6 and IL-10 were detected using enzyme-linked immunoassay kits. The protein expression levels of cardiac troponin I (cTnI), PKA, phospho-PKA (p-PKA), CREB, and phospho-CREB (p-CREB) in the myocardium were detected by Western blot analysis. Results: There was no significant difference in body weight among the groups. Heart weight and the heart-to-body weight ratio were higher in the MA group than the control group, while CBD (80 mg/kg) pretreatment (CBD80 + MA group) reduced the heart weight and the heart-to-body weight ratio compared to the MA group. The chronic administration of MA resulted in a cardiac inflammatory response, the progressive development of fibrosis, and necrosis, while CBD treatment attenuated these lesions. The protein expression levels of PKA, p-PKA, CREB, and p-CREB increased following MA administration, but significantly decreased with CBD treatment. These results indicate that chronic MA administration leads to cardiotoxicity, but these effects can be attenuated by CBD pretreatment. Conclusions: This study was the first to examine the protective effects of CBD on cardiotoxicity elicited by chronic MA exposure in rats. Our research suggests that CBD attenuates the cardiac inflammatory response induced by MA through the PKA/CREB pathway, and CBD may have potential clinical application in the treatment of MA-induced cardiotoxicity.