Antidote to cannabinoid intoxication: Inverse cannabinoid receptor one (CB1) agonism by N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidse (AM251) reverses the hypothermic effects of cannabinoid receptor one agonism by 1-Naphthalenyl [4-(pentyloxy)-1-naphthalenyl] methanone (CB13) in mice.
Br J Pharmacol
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BACKGROUND & PURPOSE: Cannabis is a recreational drug leading to intoxication, due to cannabinoid receptor one (CB1 ) stimulation. However, more recently herbs mixed with synthetic cannabinoids sometimes known as "Spice" and "Black Mamba" have been increasing used and their high CB1 receptor affinity means not only marked intoxication, but life-threatening complications and an increasing number of deaths. Whilst many studies have indicated that prophylactic CB1 receptor antagonism can block cannabimimetic effects in animals and humans. The aim of the study was to determine whether CB1 antagonism could reverse physical cannabimimetic effects. EXPERIMENTAL APPROACH: Cannabimimetic effects, measured by the hypothermic response following sedation and hypomotility, were induced by 1-Naphthalenyl[4-(pentyloxy)-1-naphthalenyl] methanone (synthetic CB1 agonist) in Biozzi ABH mice. N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251. CB1 antagonist/inverse agonist) was subsequently administered and the influence on cannabimimetic effects assessed. KEY RESULTS: In this study, the pre-existing, central nervous system-related cannabimimetic effects, measured via the hypothermic effect, induced by CB1 receptor agonism where therapeutically treated and were rapidly reversed by CB1 receptor antagonism/inverse agonism. There was also a subjective reversal of visually-evident sedation. CONCLUSIONS & IMPLICATIONS: Cannabinoid receptor antagonists have been used in thousands of people and so may provide a single-dose antidote to cannabinoid intoxication, which may save human life, if the life-threatening effects are mediated by the cannabinoid receptor and not off-target influences of the synthetic cannabinoids or non-cannabinoids within the recreational drug mixture.
AuthorsPryce, G; Baker, D
- College Publications 
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