Acute and chronic cannabis vapor exposure influences basal and stress-induced release of glucocorticoids in male and female rats.

Management of stress and anxiety is often listed as the primary motivation behind cannabis use. Human research has found that chronic cannabis use is associated with increased basal cortisol levels but blunted neuroendocrine responses to stress. Preclinical research has demonstrated mixed effects of Δ-tetrahydrocannabinol (THC; the psychoactive constituent of cannabis), much of which is suggestive of dose-dependent effects; however, the predominance of this work has employed an injection method to deliver cannabis. As inhalation is the most common route of administration in humans, we employed a translationally relevant model of inhaled cannabis vapor exposure to help characterize the extent to which acute and chronic cannabis exposure modulates neuroendocrine responses to stress. Male and female Sprague-Dawley rats were acutely (single day) or chronically (10 days) exposed to cannabis or vehicle vapor, and the stress hormone, corticosterone, was analyzed prior to and following an acute 30-min restraint stress. Our results indicate that initial exposure to the vapor chambers, regardless of vehicle or cannabis exposure, is sufficient to elevate corticosterone levels in male and female rodents. Further, acute cannabis exposure was capable of increasing corticosterone levels in both male and female rats, however, this effect was modified by the habituation to the vapor chambers differentially in males and females. Regardless of sex, chronic cannabis exposure is sufficient to both elevate basal corticosterone levels and blunt stress-induced increases in corticosterone following a restraint stressor. Collectively, these data help characterize the impacts of cannabis vapor exposure on basal and stress-induced activation of the hypothalamic-pituitary-adrenal axis.