Feeding And Appetite

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Marijuana or its major psychotropic constituent A9-THC is used clinically to enhance appetite in acquired immunodeficiency syndrome (AIDS) (Beal et al., 1997; Mattes et al., 1994; Plasse et al., 1991; Struwe et al., 1993; Mechoulam et al., 1998a). The rationale for such use is based both on anecdotal and scientific evidence. Thus cannabis, A9-THC as well as endocannabinoids enhance appetite (Mechoulam et al., 1998b; Gallate et al, 1999; Williams et al, 1998; Williams and Kirkham, 1999), although no effect (Graceffo and Robinson, 1998) or reductions in food intake (Miczek and Dixit, 1980; Sofia and Knobloch, 1976; Compton et al., 1996) have also been reported, mainly in earlier studies (see Compton et al., 1996). These opposite effects on food intake may be explained by a masking anxiogenic effect of the cannabinoids. Indeed, in a recent report (Giuliani et al., 2000b), HU-210 (a very potent CB receptor agonist)-induced reductions in food intake were noted, which may be ascribed to the stress induced by HU-210 (Rodriguez de Fonseca et al., 1996; Giuliani et al., 2000a, see "Stress and Anxiety").

Chronic administration of low doses of anandamide (presumably without stress effects), enhanced food intake in food deprived mice (Hao et al., 2000). Conversely, further support for an appetite-enhancing effect of cannabinoids comes from studies where appetite suppression and weight loss were reported using the CBX receptor antagonist SR141716A (Arnone et al., 1997; Colombo et al., 1998). Thus the evidence is clearly tilted - unless masked by an anxiety-induced loss of appetite - toward an appetite-enhancing effect of cannabinoids and resulting weight gain. It has been suggested that the increase in appetite is either socially induced and/or nmol/g tissue

PREFRONTAL CORTEX HIPPOCAMPUS

Figure 6.2 Anandamide levels in the prefrontal cortex and hippocampus of acutely stressed (30min of bell noise) female Sabra mice were measured by GC-MS using SIM (selective ion monitoring) mode with deuterated anandamide as internal standard (Fride et al., 1998). The - preliminary - data presented here, suggest a selective, almost 4-fold increase in anandamide levels in the PFC as a result of stress.

PREFRONTAL CORTEX HIPPOCAMPUS

Figure 6.2 Anandamide levels in the prefrontal cortex and hippocampus of acutely stressed (30min of bell noise) female Sabra mice were measured by GC-MS using SIM (selective ion monitoring) mode with deuterated anandamide as internal standard (Fride et al., 1998). The - preliminary - data presented here, suggest a selective, almost 4-fold increase in anandamide levels in the PFC as a result of stress.

related to an increased craving for sweets and carbohydrate-rich drinks (Compton et al., 1996). Thus, in an experimental situation, human subjects were prone to eat more snack foods when smoking marijuana in social circles, while subjects smoking marijuana in isolation, did not alter food intake (Foltin et al., 1986).

In accordance with a stimulatory effect of cannabinoids on feeding, a hypothalamo-collicular pathway involved in feeding-related behaviors and disinhibited upon activation of CBX receptors has been suggested (see Sanudo-Pena and Fride, this book). Be that as it may, the potential for weight gain in conditions such as AIDS and cancer deserves further exploration.

Endocannabinoids and other A-acylethanolamines (NAPE) have been detected in several foods including chocolate (di Tomaso et al., 1996), milk, oatmeal, hazelnuts, millet and soy beans (Di Marzo et al., 1998b). The presence of endocannabinoids in chocolate is especially interesting and has been investigated further. Although the endocannabinoid concentrations in chocolate are far too low to induce visible marijuana-like euphoriant effects when taken orally (Di Marzo et al., 1998b), two alternative biological explanations may explain the phenomenon of "chocolate craving". First, there may be enough endocannabinoids present in chocolate to activate the mesolimbic reward system (see "Addiction") required for craving. Intriguingly, the smell of chocolate reduced theta brain waves, presumably reducing attention and promoting a sense of relaxation (Martin, 1998). Second, non-cannabinoid NAPE's found in chocolate, with "entourage" properties (see "Pharmacological profile of endocannabinoids"), i.e., which do not bind the cannabinoid receptor but inhibit the degradation of endocannabinoids and/or potentiate endocannabinoid binding to the CBX receptors (Ben-Shabbat et al., 1998), may amplify the activities of the endocannabinoids present in chocolate (Fride et al., 1997). Indeed, oleoyl ethanol amide and lineoyl ethanol amide, both present in chocolate (di Tomaso et al., 1996; Di Marzo et al., 1998b) exhibit psychotropic effects in the "tetrad", presumably by potentiating endocannabinoid activity (Fride et al, 1997).

In summary, the well known appetite enhancing effect of cannabis may be clinically exploited to enhance appetite in AIDS, cancer patients or other patients suffering from wasting diseases. However, the importance of the presence of endocannabinoids in milk may transcend the subtle effects on appetite, mentioned above. Rather, being present in milk, their physiologic importance may lie in their potential role during the neonatal period, when endocannabinoids may play a crucial role in the well being of the newborn. Indeed, initial evidence has accumulated in support of such hypothesis, which will be discussed below (see "Function of the endocannabinoid system in the neonate").

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With all the stresses and strains of modern living, panic attacks are become a common problem for many people. Panic attacks occur when the pressure we are living under starts to creep up and overwhelm us. Often it's a result of running on the treadmill of life and forgetting to watch the signs and symptoms of the effects of excessive stress on our bodies. Thankfully panic attacks are very treatable. Often it is just a matter of learning to recognize the symptoms and learn simple but effective techniques that help you release yourself from the crippling effects a panic attack can bring.

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