The endogenous cannabinoid anandamide shares discriminative stimulus effects with ∆(9)-tetrahydrocannabinol in fatty acid amide hydrolase knockout mice.
D Matthew Walentiny, Thomas F Gamage, Jonathan A Warner, Thanh K Nguyen, Darren B Grainger, Jenny L Wiley, Robert E Vann
European Journal of Pharmacology April 10, 2011 DOI: 10.1016/j.ejphar.2011.01.056 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical drug discrimination study Peer reviewed |
|---|---|
| Population | Transgenic mice lacking fatty acid amide hydrolase (FAAH -/- mice) |
| Interventions | Anandamide (AEA) THC oleamide rimonabant |
| Dose | 6mg/kg AEA |
| Topics | Cannabis |
| Key points | AEA functioned as a discriminative stimulus in FAAH -/- mice, with THC producing full AEA-like responding and oleamide failing to substitute. Rimonabant attenuated both AEA- and THC-induced responding, indicating CB1 receptor mediation. The authors suggest that without FAAH, AEA produces intoxication comparable to THC and marijuana. |
Abstract
The endogenous cannabinoid system has been noted for its therapeutic potential, as well as the psychoactivity of cannabinoids such as Δ9-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 CB(1) mediation of AEA's discriminative stimulus. Mice readily discriminated between 6mg/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 CB(1) antagonist rimonabant attenuated AEA- and THC-induced AEA-appropriate responding, demonstrating CB(1) 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.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 5
- Discriminative Stimulus Properties of Phytocannabinoids, Endocannabinoids, and Synthetic Cannabinoids. Current Topics in Behavioral Neurosciences 2018
- Inhibition of the endocannabinoid-regulating enzyme monoacylglycerol lipase elicits a CB1 receptor-mediated discriminative stimulus in mice. Neuropharmacology October 2017
- Just add water: cannabinoid discrimination in a water T-maze with FAAH(-/-) and FAAH(+/+) mice. Behavioural Pharmacology August 2016
- Phenotypic assessment of THC discriminative stimulus properties in fatty acid amide hydrolase knockout and wildtype mice. Neuropharmacology June 2015
- Endocannabinoid contribution to Δ9-tetrahydrocannabinol discrimination in rodents. European Journal of Pharmacology August 15, 2014
Cites 17
- Kappa opioid mediation of cannabinoid effects of the potent hallucinogen, salvinorin A, in rodents. Psychopharmacology June 1, 2010
- Discriminative stimulus properties of delta9-tetrahydrocannabinol (THC) in C57Bl/6J mice. European Journal of Pharmacology August 1, 2009
- Apparent affinity estimates of rimonabant in combination with anandamide and chemical analogs of anandamide in rhesus monkeys discriminating Delta9-tetrahydrocannabinol. Psychopharmacology April 2009
- Cannabinoid agonists differentially substitute for the discriminative stimulus effects of Delta(9)-tetrahydrocannabinol in C57BL/6J mice. Psychopharmacology July 2008
- Divergent effects of cannabidiol on the discriminative stimulus and place conditioning effects of Delta(9)-tetrahydrocannabinol. Drug and Alcohol Dependence April 1, 2008
and 12 more in the library