Vapor inhalation of cannabidiol (CBD) in rats

Abstract Cannabidiol (CBD) is increasingly available in e-cigarette liquids and other products. CBD use has been promoted for numerous purported benefits which have not been rigorously assessed in preclinical studies. The objective of this study was to further validate an inhalation model to assess CBD effects in the rat. The primary goal was to determine plasma CBD levels after vapor inhalation and compare that with the levels observed after injection. Secondary goals were to determine if hypothermia is produced in male Sprague-Dawley rats and if CBD affects nociception measured by the warm water tail-withdrawal assay. Blood samples were collected from rats exposed for 30 minutes to vapor generated by an e-cigarette device using CBD (100, 400 mg/mL in the propylene glycol vehicle). Separate experiments assessed the body temperature response to CBD in combination with nicotine (30 mg/mL) and the anti-nociceptive response to CBD. Vapor inhalation of CBD produced concentration-related plasma CBD levels in male and female Wistar rats that were within the range of levels produced by 10 or 30 mg/kg, CBD, i.p.. Dose-related hypothermia was produced by CBD in male Sprague-Dawley rats and this was partially attenuated by 5-HT1a receptor blockade. Nicotine (30 mg/mL) inhalation enhanced the effect of CBD. CBD inhalation had no effect on anti-nociception alone or in combination with Δ 9 -tetrahydrocannabinol inhalation. The vapor-inhalation approach is a suitable pre-clinical model for the investigation of the effects of inhaled CBD. This route of administration produces hypothermia in rats, while i.p. injection does not at comparable plasma CBD levels.