CNR1 and Anxiety: Differential effects of cannabinoid type 1 receptor (CB1R) agonists, like THC, observed in long-term vs. acute dosing studies may be a product of increased CB1R binding on cortical glutamatergic neurons due to CB1R downregulation on GABAergic terminals (33, 34); a similar mechanism is implicated in the dose-dependent effects of acute THC exposure on anxiety (33).