The endogenous cannabinoid anandamide shares discriminative stimulus effects with D9-tetrahydrocannabinol in fatty acid amide hydrolase knockout mice
The endogenous cannabinoid system has been noted for its therapeutic potential, as well as the psychoactivity of cannabinoids such as ?9-tetrahydrocannabinol (THC). However, less is known about the psychoactivity of anandamide (AEA), an endocannabinoid ligand. Thus, the goals of this study were to establish AEA as a discriminative stimulus in transgenic mice lacking fatty acid amide hydrolase (i.e., FAAH ?/? mice unable to rapidly metabolize AEA), evaluate whether THC or oleamide, a fatty acid amide, produced AEA-like responding, and assess for CB1 mediation of AEA's discriminative stimulus. Mice readily discriminated between 6 mg/kg AEA and vehicle in a two-lever drug discrimination task. AEA dose-dependently generalized to itself. THC elicited full AEA-like responding, whereas oleamide failed to substitute. The CB1 antagonist rimonabant attenuated AEA- and THC-induced AEA-appropriate responding, demonstrating CB1 mediation of AEA's discriminative stimulus. These findings suggest that, in the absence of FAAH, AEA produces intoxication comparable to THC, and consequently to marijuana.
Walentiny, D. M., Gamage, T. F., Warner, J. A., Nguyen, T. K., Grainger, D. B., Wiley, J., & Vann, R. E. (2011). The endogenous cannabinoid anandamide shares discriminative stimulus effects with D9-tetrahydrocannabinol in fatty acid amide hydrolase knockout mice. European Journal of Pharmacology, 656(1-3), 63-67. DOI: 10.1016/j.ejphar.2011.01.056