Brain imaging of cannabinoid type I (CB₁) 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 (CB₁) 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: [¹¹C]OMAR) followed. [¹¹C]OMAR Distribution volume (V_T) from these participants was compared with V_T of age/BMI-similar female non-users of cannabis (“healthy controls”; N = 10). V_T was also compared between female and male healthy controls (N = 7). Females with CUD displayed significantly lower V_T than female healthy controls in specific brain regions (hippocampus, amygdala, cingulate, and insula). Amygdala V_T was negatively correlated with mood changes (anger/hostility) during abstinence, but V_T was not correlated with other withdrawal symptoms or cannabis effects. Among healthy controls, females had significantly higher V_T than males in all brain regions examined. Chronic cannabis use appears to foster downregulation of CB₁ receptors in women, as observed previously in men, and there are inherent sex differences in CB₁ availability. Future studies should elucidate the time course of CB₁ downregulation among females who use cannabis and examine the relation between CB₁ availability and cannabis effects among other populations (e.g., infrequent users; medicinal users).