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

Abstract

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 Δ 9-tetrahydrocannabinol and synthetic cannabinoids (many possessing higher potencies and efficacies than Δ 9-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 cannabinoid 1 receptors. Here, we review the evidence that cannabinoid 1 receptor antagonists, originally developed for indications ranging from obesity to smoking cessation and schizophrenia, provide a molecular approach to treating acute cannabinoid overdose.

Beneficial and harmful effects of CB1 and CB2 receptor antagonists on chronotropic and inotropic effects related to atrial β‐adrenoceptor activation in humans and in rats with primary hypertension

“…The role of cardiac CB‐Rs in pathological conditions is controversial. Therefore, there is evidence that CB 1 ‐R antagonism may be beneficial in impaired cardiac function (for review, see Bátkai and Pacher 18 ) and in the treatment of acute cannabinoid overdose in humans 23 . By contrast, mortality is even increased in rats treated with rimonabant 24 and in CB 1 knockout mice with acute heart failure, 25 whereas WIN55212‐2 improves doxorubicin‐induced atrial dysfunction in mice 26 and another CB‐R agonist, CB13, inhibits electrical remodelling of the rat atrium 27 .…”