Brain imaging of cannabinoid type I (CB ) receptors in women with cannabis use disorder and male and female healthy controls.

Cannabis effects are predominantly mediated by pharmacological actions on cannabinoid type 1 (CB ) receptors. Prior positron emission tomography (PET) studies in individuals who use cannabis included almost exclusively males. PET studies in females are needed because there are sex differences in cannabis effects, progression to cannabis use disorder (CUD), and withdrawal symptom severity. Females with CUD (N = 10) completed two double-blind cannabis smoking sessions (Session 1: placebo; Session 2: active), and acute cannabis effects were assessed. After Session 2, participants underwent 3 days of monitored cannabis abstinence; mood, craving, and withdrawal symptoms were assessed and a PET scan (radiotracer: [ C]OMAR) followed. [ C]OMAR Distribution volume (V ) from these participants was compared with V of age/BMI-similar female non-users of cannabis ("healthy controls"; N = 10). V was also compared between female and male healthy controls (N = 7). Females with CUD displayed significantly lower V than female healthy controls in specific brain regions (hippocampus, amygdala, cingulate, and insula). Amygdala V was negatively correlated with mood changes (anger/hostility) during abstinence, but V was not correlated with other withdrawal symptoms or cannabis effects. Among healthy controls, females had significantly higher V than males in all brain regions examined. Chronic cannabis use appears to foster downregulation of CB receptors in women, as observed previously in men, and there are inherent sex differences in CB availability. Future studies should elucidate the time course of CB downregulation among females who use cannabis and examine the relation between CB availability and cannabis effects among other populations (e.g., infrequent users; medicinal users).