Metabolic and respiratory alterations following acute exposure to high-THC and high-CBD cannabis smoke in female mice

Abstract Background Cannabis use has increased in recent years due to legalization. Smoking cannabis leads to inhalation of ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD), in addition to other particles and gas in the smoke matrix as a result of combustion. The effect of THC on breathing pattern and metabolism has been characterized, but the influence of CBD and the smoke matrix on breathing pattern and metabolism has not been documented. In our study, we investigated the effects of placebo smoke, high-CBD smoke, and high-THC smoke on body temperature, breathing pattern, and metabolism. We also assessed whether there were latent effects of cannabidiol exposure on respiratory control and recovery dynamics by using an acute hypoxia breathing challenge. Methods Acute hypoxia challenges were conducted on each mouse before and after smoke treatment (20 min), with mice exposed to normoxia (21% O 2 ) and acute hypoxia (16% O 2 ) for 20 min each. Plethysmography and respirometry were used to assess breathing pattern and metabolism, with rectal temperature measured at the beginning and end of each hypoxia challenge. Results We found that body temperature depression was influenced by all treatments, suggesting that placebo smoke and high-CBD smoke have additive effects on top of the high-THC smoke treatment. In contrast, the increases in total ventilation and tidal volume with high-THC smoke appeared to be predominantly modulated by high-THC smoke, with a small effect of placebo smoke. We also found that body temperature, breathing pattern, and metabolism recovery was not impacted by cannabidiol exposure, as these measurements returned to similar levels as in the control mice. Conclusions Not all physiological responses of high-THC smoke were strictly due to THC itself, as the smoke matrix and CBD also contribute.