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BEHAVIORAL PHARMACOLOGY

Cannabimimetic Properties of Ajulemic Acid

Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia

Side effects of marijuana-based drugs and synthetic analogs of ⁹-tetrahydrocannabinol (⁹-THC), including sedation and dysphoria, have limited their therapeutic application. Ajulemic acid (AJA), a side-chain synthetic analog of ⁸-THC-11-oic acid, has been reported to have anti-inflammatory properties without producing undesired psychoactive effects. Moreover, it has been suggested that AJA does not interact with cannabinoid receptors to produce its pharmacological effects. The aim of the present study was to conduct a thorough evaluation of the pharmacological effects of AJA then to determine whether actions at cannabinoid receptor (CB)₁ mediated these effects. This study evaluated the psychoactive and analgesic effects of AJA by examining its cannabimimetic properties in ICR mice (i.e., antinociception, catalepsy, hypothermia, and hypomobility), its discriminative stimulus effects in Long Evans rats trained in a two-lever ⁹-THC (3.0 mg/kg) versus vehicle drug discrimination procedure, and its antihyperalgesia effects in a rat model of inflammatory pain [complete Freund's adjuvant (CFA)-induced mechanical hyperalgesia]. Lastly, antagonism tests with SR 141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride], CB₁ receptor antagonist, were conducted. These studies demonstrated that AJA shares a number of CB₁-mediated pharmacological properties with ⁹-THC, including cannabimimetic, discriminative stimulus, and antihyperalgesic effects. Furthermore, a separation between doses that produced antinociception and those that produced the other pharmacological effects in mice was not observed. Moreover, AJA showed nearly equipotency for therapeutic efficacy in the CFA model and for substitution in ⁹-THC discrimination. In summary, this study shows that AJA, like ⁹-THC, exhibits psychoactive and therapeutic effects at nearly equal doses in preclinical models, suggesting similar limitations in their putative therapeutic profiles.

Address correspondence to: Dr. Robert E. Vann, Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 North 12th Street, P.O. Box 980613, Richmond, VA 23298-0613. E-mail: revann{at}vcu.edu

This article has been cited by other articles:

				M. Karst Comments on "Cannabimimetic Properties of Ajulemic Acid" J. Pharmacol. Exp. Ther., July 1, 2007; 322(1): 420 - 421. [Full Text] [PDF]