• Journal Article

Apparent CB1 receptor rimonabant affinity estimates: combination with THC and synthetic cannabinoids in the mouse in vivo triad model

Citation

Grim, T. W., Morales, A. J., Thomas, B. F., Wiley, J. L., Endres, G. W., Negus, S. S., & Lichtman, A. H. (2017). Apparent CB1 receptor rimonabant affinity estimates: combination with THC and synthetic cannabinoids in the mouse in vivo triad model. Journal of Pharmacology and Experimental Therapeutics. DOI: 10.1124/jpet.117.240192

Abstract

Synthetic cannabinoids (SCs) represent an emerging class of abused drugs associated with psychiatric complications and other substantial health risks. These ligands are largely sold over the internet for human consumption presumably because of their high cannabinoid 1 receptor (CB1R) affinity and potency in eliciting similar pharmacological effects as Δ9-tetrahydrocannabinol (THC), while circumventing laws illegalizing this plant. Factors potentially contributing to the increased prevalence of SC abuse and related hospitalizations, such as increased CB1R efficacy and non-CB1R targets, highlight the need for quantitative pharmacological analyses to determine receptor mediation of the pharmacological effects of cannabinoids. Accordingly, the present study used pA2 and pKB analyses for quantitative determination of CB1R mediation in which we utilized the CB1R-selective inverse agonist/antagonist rimonabant to elicit rightward shifts in the dose-response curves of five SCs (i.e., A-834,735D, WIN55,212-2, CP55,950, JWH-073, and CP47,497) and THC in producing common cannabimimetic effects (i.e., catalepsy, antinociception, and hypothermia). The results revealed overall similarity of pA2 and pKB values for these compounds, and suggest that CB1Rs, and not other pharmacological targets, largely mediated these central pharmacological effects. More generally, affinity estimation offers a powerful pharmacological approach to assess potential receptor heterogeneity subserving in vivo pharmacological effects of SCs.