Discriminative Stimulus Properties of Phytocannabinoids, Endocannabinoids, and Synthetic Cannabinoids

Psychoactive cannabinoids from the marijuana plant (phytocannabinoids), from the body (endocannabinoids), and from the research lab (synthetic cannabinoids) produce their discriminative stimulus effects by stimulation of CB₁ receptors in the brain. Early discrimination work with phytocannabinoids confirmed that Δ⁹-tetrahydrocannabinol (Δ⁹-THC) is the primary psychoactive constituent of the marijuana plant, with more recent work focusing on characterization of the contribution of the major endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG), to Δ⁹-THC-like internal states. Collectively, these latter studies suggest that endogenous increases in both anandamide and 2-AG seem to be optimal for mimicking Δ⁹-THC's discriminative stimulus effects, although suprathreshold concentrations of anandamide also appear to be Δ⁹-THC-like in discrimination assays. Recently, increased abuse of synthetic cannabinoids (e.g., "fake marijuana") has spurred discrimination studies to inform regulatory authorities by predicting which of the many synthetic compounds on the illicit market are most likely to share Δ⁹-THC's abuse liability. In the absence of a reliable model of cannabinoid self-administration (specifically, Δ⁹-THC self-administration), cannabinoid discrimination represents the most validated and pharmacologically selective animal model of an abuse-related property of cannabinoids - i.e., marijuana's subjective effects. The influx of recent papers in which cannabinoid discrimination is highlighted attests to its continued relevance as a valuable method for scientific study of cannabinoid use and abuse.