Pharmacological Profile Of Endocannabinoids

The endogenous ligands for the cannabinoid receptors discovered thus far (the "endocannabinoids"), include the "anandamides" (Devane et al., 1992; Hanus et al., 1993), 2-arachidonoyl glycerol (2-AG, Mechoulam et al., 1995) and noladin ether (Hanus et al., 2001). Thus far, the prototypical anandamide, arachidonoyl ethanol amide (Devane et al., 1992) is the most thoroughly studied endocannabinoid. Although the overall pharmacological activity is similar to the psychoactive plant constituent A8-THC (Fride and Mechoulam, 1993; Mechoulam and Fride, 1995), it is clear that differences between anadamide and plant-derived and synthetic cannabinoids are present too (Fride et al., 1995; Mechoulam and Fride, 1995; Mackie et al., 1993; Smith et al., 1994; Welch et al., 1995). Behaviorally, it was clear from the initial description of anandamide's effects in the tetrad, that it has partial effects for some of its components (hypothermia and analgesia, see Figure 6.1) (Fride and Mechoulam, 1993; Mechoulam and Fride, 1995). Moreover, when different routes of administering anandamide were compared, a complex pattern of full and partial activities was observed (Smith et al., 1994). Further, A9-THC but not anandamide produced conditioned place avoidance (Mallet and Beninger, 1998a).

Additional behavioral differences include the effects of very low doses of anand-amides (0.0001-0.01 mg/kg).

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