ABSTRACT
SUMMARY. The use of ∆9-THC hemisuccinate (HS) in a suppository formulation is an attempt to develop a cannabinoid possessing possible therapeutic effects with a minimal side effect profile. The purpose of this study was to investigate the antinociceptive and reinforcing effects of rectally administered ∆9-THC-HS in rats. Tests were conducted in two groups of animals: Complete Freund’s adjuvant-inflamed animals (CFA)
and non-inflamed controls. A hotplate test was administered to index hyperalgesia and possible analgesic effects of ∆9-THC-HS on thermal nociception. CFA animals demonstrated shorter latencies than non-inflamed animals. The highest dose of ∆9-THC-HS produced longer hotplate latencies. Additionally, the reinforcing properties of ∆9-THC-HS were evaluated using the Conditioned Place Preference (CPP) paradigm. ∆9-THC-HS produced an increase in preference scores in non-inflamed animals (positive reinforcement), but did not affect preference scores in CFA animals. These data suggest that ∆9-THC-HS has therapeutic potential and is unlikely to possess an abuse liability when used in the context of chronic pain. [Article copies available for a fee from The Haworth Document Delivery Service: 1-800-342-9678. E-mail address: <getinfo@ haworthpressinc.com> Website: <https://www.HaworthPress.com>; © 2001 by The Haworth Press, Inc. All rights reserved.]
KEYWORDS. ∆9-THC, adjuvant-inflamed, rat, hotplate, conditioned place preference
INTRODUCTION
The role of cannabinoids (CB) in pain modulation is well documented (Fuentes et al. 1999). Administration of anandamide, ∆9-tetrahydrocannabinoid (∆9-THC), and various selective CB receptor agonists, have shown antinociceptive effects in a variety of acute (Buxbaum 1972; Welch and Stevens 1992) and chronic (Sofia et al. 1973; Smith et al. 1998) models of nociception (for review see Pertwee 2001). These antinociceptive effects are mediated by CB1 receptors located at spinal (Yaksh 1981; Lichtman and Martin 1991; Welsh and Stevens 1992) and supraspinal sites (Lichtman and Martin 1991; Martin et al. 1993) as well as CB1 (Richardson et al. 1998) and CB2 receptors (Jagger et al. 1998) located in peripheral tissues (for review see Pertwee 2001). Although numerous studies suggest otherwise (Onaivi et al. 1990; McGregor et al. 1996; Sanudo-Pena et al. 1997; Tzschentke 1998), several experiments implicate cannabinoid systems in reward. For example, ∆9-THC is self administered in humans (Chait and Burke 1994) and squirrel monkeys (Tanda et al. 2000), lowers intracranial self-stimulation thresholds in rats (Gardner et al. 1988) and produces place preference in rats (Lepore et al. 1995). ∆9-THC has been shown to increase firing of dopamine neurons in the nucleus accumbens (Gessa et al. 1998), as well as increase dopamine levels in the shell of the nucleus accumbens (Tanda et al. 1997). Collectively, these studies suggest that CB reinforcement is likely mediated through the same
mesolimbic dopaminergic systems involved in opioid and psychostimulant reward (Koob and Bloom 1988). While one literature clearly suggests CB receptors present a viable target for analgesic drugs (for review see Pertwee 2001), a second literature suggests these putative analgesic compounds are likely to possess an abuse liability (Gessa et al. 1998).
