Mothers Milk , second is the observation that high levels of endocannabinoids in maternal milk are critically important for the initiation of the suckling response in newborns (213). A. Animal studies before the discovery of endocannabinoids Animal models are ideal tools for elucidating the putative mechanism(s) of cannabinoids in the control of energy metabolism. The studies performed in different species to test the orexigenic properties of Δ9-THC up to the discovery of endocannabinoids are summarized in Table 2⇓ (214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244). From a general point of view, one can say that rather contradictory results were obtained in these experiments. The ambiguous data could likely be attributed to differences in the animal model and in the experimental procedures used. Moreover, in early studies using marijuana extracts, comparisons between various experimental data sets are extremely difficult due to the variability of the activity of cannabis derivatives, the dosages, and the routes of administration. In general, early studies using low doses of cannabinoids showed a reliable increase in food intake. When doses of Δ9-THC above 10 mg/kg were used, a concomitant decrease in food intake was observed due to the confounding factors given by the sedative effect of the drug. Studies employing high amounts of Δ9-THC should thus be viewed with caution in terms of effects on appetite and body weight. This is also the reason why, in reviewing the studies published between 1965 and 1975, Abel reported an increased food intake after cannabinoid administration only in 3 of 25 experiments (245). In 1998, Williams et al. (246) provided a very convincing and well-performed experiment to characterize the orexigenic property of Δ9-THC. The authors maximized the ability to detect hyperphagia by adopting a prefed paradigm in which the animals were characterized by low baseline food intake before drug administration. In this experimental setting, Δ9-THC was given orally at increasing dosage before unrestricted access to a standard diet. The authors observed that the maximum effect of the drug (1.0 mg/kg) was far greater than previously reported results, showing a 4-fold increase in food consumption over 1 h. Importantly, this hyperphagic effect was largely attenuated by pretreatment with the CB1 receptor antagonist SR141716, strongly supporting the notion that CB1 receptor activation mediates the hyperphagic effect of Δ9-THC (247). In this experiment, it was also reported that at doses of Δ9-THC higher than 1.0 mg/kg, the rats become unable to overeat due to the presence of motoric and sedative side effects (246). These results strongly suggest that the anorectic effect of Δ9-THC shown by many previous reports was indirectly due to the sedated state induced by high doses of the drug. View this table: In this window In a new window TABLE 2. Summary of the effects of exogenous cannabinoids on food intake B. Studies in humans with exogenous cannabinoids before the discovery of endocannabinoids Abel (245) also critically reviewed the studies aimed at proving the stimulating effect of cannabis on hunger in humans. However, the lack of scientific thoroughness of these earlier studies led Abel to conclude that the putative cannabis-induced hunger effect was still far from being proven (245). Greenberg et al. (248) were the first to systematically assess, under rigorous experimental conditions, the effect of a well-defined amount of Δ9-THC in terms of changes in feeding behavior and in body weight in humans. Both parameters increased after the first few days of the experiment. However, after this period, body weight continued to rise, averaging 2.3 kg across the whole 21-d period study, whereas a stabilization of energy intake was observed. This pioneer study already suggested that the ability of cannabinoids to stimulate hunger may vanish with time, whereas a possible metabolic effect of the drug may remain active longer (248). Nonetheless, later studies did not investigate the metabolic idea further, preferring to concentrate interest on the ability of cannabis to stimulate hyperphagia and overconsumption of highly palatable food at the central level. In 1986, Foltin et al. (249) noted a relevant increase in frequency and consumption of snack foods induced by marijuana only in the periods of social facilitation and environmental familiarity and not when the subjects were alone, indicating on the one hand a strong link between recreational use of the drug and its orexigenic properties and, on the other hand, the ability of marijuana to drive the tendency for palatable food. This hypothesis was further substantiated by the same group a few years later when increased total food intake particularly related to consumption of palatable food (sweet solid snacks) was observed as a main effect of smoked marijuana (250).
Posted on: Sun, 07 Dec 2014 02:55:57 +0000
Trending Topics
Recently Viewed Topics
© 2015