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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on November 14, 2006; DOI: 10.1124/jpet.106.111625

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Received for publication July 27, 2006.
Revised November 10, 2006.
Accepted for publication November 10, 2006.

Cannabimimetic Properties of Ajulemic Acid

Robert E. Vann 1*, Charles D. Cook 1, Billy R. Martin 1, Jenny L. Wiley 1

1 Virginia Commonwealth University

* Address correspondence to: E-mail: revann{at}vcu.edu

Abstract

Side effects of marijuana-based drugs and synthetic analogs of {Delta}9-tetrahydrocannabinol ({Delta}9-THC), including sedation and dysphoria, have limited their therapeutic application. Ajulemic acid (AJA), a side-chain synthetic analog of {Delta}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 CB1 cannabinoid receptors 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 {Delta}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 SR141716A, CB1 receptor antagonist, were conducted. These studies demonstrated that AJA shares a number of CB1-mediated pharmacological properties with {Delta}9-THC, including cannabimimetic, discriminative stimulus, and antihyperalgesic effects. Further, 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 {Delta}9-THC discrimination. In summary this study shows that AJA, like {Delta}9-THC, exhibits psychoactive and therapeutic effects at nearly equal doses in preclinical models, suggesting similar limitations in their putative therapeutic profiles.


Key words: Ajulemic Acid, THC, antinociception, cannabinoid, drug discrimination, neuropathic pain


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Comments on "Cannabimimetic Properties of Ajulemic Acid"
J. Pharmacol. Exp. Ther., July 1, 2007; 322(1): 420 - 421.
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