3. Umbruch 4.4..2005 - Online Pot

Cannabinoids in appetite and obesity 221
Of particular interest are the experiments conducted with anandamide and
2-arachidonoyl glycerol (2-AG), the endogenous ligands for cannabinoid
receptors. Subcutaneous injection of anandamide (0.5–10 mg/kg) induced significant
overeating in pre-satiated male rats [20]. Subsequent studies have
shown that very low doses of anandamide [0.001 mg/kg, administered
intraperitoneally (i.p.)] also increased food intake in female mice while higher
doses were not active in this paradigm [21]. Direct injection of anandamide
(50 ng in 0.5 µl) into the ventromedial hypothalamus also initiated food intake
in rats [22]. Similarly, injection of 2-AG into the nucleus accumbens shell, a
limbic forebrain area strongly linked to eating motivation, potently and
dose-dependently stimulated feeding in rats [23]. This effect was blocked by
pre-treatment with the cannabinoid antagonist SR-141716 (Fig. 1), indicating
the involvement of the cannabinoid CB 1 receptor.
These experiments clearly demonstrated that activation of central cannabinoid
receptors by endocannabinoids stimulates eating behavior, and provided
important evidence for the involvement of a central cannabinoid system in the
normal control of feeding.
Interestingly, the selectivity for sweet or palatable food observed in humans
was also observed in animal experiments. The potent synthetic cannabinoid
agonist CP-55,940 (0.01–0.05 mg/kg i.p.) was shown to increase motivation
for beer and for a sucrose solution in rats [24]. ∆ 9 -THC (0.5–2.5 mg/kg i.p.)
also selectively increased the consumption of a high-fat or high-fat sweetened
diet versus standard chow in free-feeding Lewis rats [16].
Recent studies also suggested that the endocannabinoid 2-AG present in
milk may play a vital role in the initiation of milk suckling, and hence in
growth and development during the early stages of mouse life [25, 26].
Cannabinoid antagonists and obesity
The first potent and selective CB 1 cannabinoid antagonist, SR-141716, was
described in 1994 [27]. This compound was able to reverse the hyperphagia
Figure 1. Selected cannabinoid CB1 antagonists acting on food intake.