Synthetic cannabinoids (CBs) are marketed and used as alternatives to cannabis. Synthetic CBs appear to have effects similar to those of Δ9-tetrahydrocannabinol (Δ9-THC), the drug primarily responsible for the behavioral effects of cannabis. However, some synthetic CBs have been shown to have higher CB1 receptor agonist efficacy. This study was designed to test whether high-efficacy compounds have greater tolerance after multiple days of dosing versus low-efficacy compounds. Rhesus monkeys were trained to discriminate Δ9-THC from vehicle. After 14 days of dosing Δ9-THC, it took a higher dose of all CB1 agonists for the animals to discriminate the drug from vehicle. However, the more potent CB1 agonists had the smallest change in sensitivity. In addition, 3 days of dosing Δ9-THC did not produce a significant tolerance to the more potent CB1 agonists. In contrast, previous work has shown that 3 days of dosing decreased sensitivity of the less efficacious Δ9-THC. The greater loss of sensitivity to Δ9-THC relative to the more efficacious CB1 agonists suggests that differences in receptor efficacy are important in vivo. It is hypothesized that this difference might partially explain differences in dependence liability and adverse effects of the synthetic cannabinoids.
See article at J Pharmacol Exp Ther 2012, 342:843–849.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics