Cannabinoid₁ (CB-1) receptor antagonists: a molecular approach to treating acute cannabinoid overdose

The legalization of cannabis for both recreational and medical use in the USA has resulted in a dramatic increase in the number of emergency department visits and hospital admissions for acute cannabinoid overdose (also referred to as cannabis intoxication and cannabis poisoning). Both "edibles" (often sold as brownies, cookies, and candies) containing large amounts of Δ⁹-tetrahydrocannabinol and synthetic cannabinoids (many possessing higher potencies and efficacies than Δ⁹-tetrahydrocannabinol) are responsible for a disproportionate number of emergency department visits relative to smoked cannabis. Symptoms of acute cannabinoid overdose range from extreme lethargy, ataxia, and generalized psychomotor impairment to feelings of panic and anxiety, agitation, hallucinations, and psychosis. Treatment of acute cannabinoid overdose is currently supportive and symptom driven. Converging lines of evidence indicating many of the symptoms which can precipitate an emergency department visit are mediated through activation of cannabinoid₁ receptors. Here, we review the evidence that cannabinoid₁ receptor antagonists, originally developed for indications ranging from obesity to smoking cessation and schizophrenia, provide a molecular approach to treating acute cannabinoid overdose.