Cannabinoids in Eating Disorders and Obesity

Abstract

Cannabinoid system is a crucial mechanism in regulating food intake and energy metabolism. It is involved in central and peripheral mechanisms regulating such behavior, interacting with many other signaling systems with a role in metabolic regulation. Cannabinoid agonists promote food intake, and soon a cannabinoid antagonist, rimonabant, will be marketed for the treatment of obesity. It not only causes weight loss, but also alleviates metabolic syndrome. We present a review of current knowledge on this subject, along with data from our own research: genetic studies on this system in eating disorders and obesity and studies locating cannabinoid receptors in areas related to food intake. Such studies suggest cannabinoid hyperactivity in obesity, and this excessive activity may have prognostic implications.

Dietary conditions and highly palatable food access alter rat cannabinoid receptor expression and binding density

“…Long-term treatment with a CB1 receptor antagonist/ inverse agonist (SR141617A; rimonabant) led to effective sustained weight loss in rodent studies and human clinical trials, but a large number (26%) of the treated clinical population reported a profile of psychiatric side effects (including depression, anxiety, and agitation) [2,21]. Rodent models offer the advantage of assessing various aspects of eating behavior and diet without the constraints of the complex cognitive attributes that often accompany multifactorial human eating pathologies [33,73].…”

“…For instance, diet-induced obesity produced a down-regulation of the CB1 receptor in several brain regions [13,14,16,17], whereas prolonged treatment with a CB1 antagonist or disruptions in the CB1 receptor gene reduce food intake and adiposity, and prevents the development of diet-induced obesity [18-20]. As a result, normalization of the endogenous cannabinoid system by reducing CB1 signaling has generated considerable therapeutic interest for the treatment of obesity [21,22]. …”

Endocrine disrupters as obesogens

“…A third major circuit for appetite and body weight regulation that is a candidate for obesogenic disruption involves the endocannabinoid system (ECS) pathway (reviewed in [136]). Endogenous or dietary agonists of the cannabinoid receptor type 1 (CB1), including the lipid derivatives anandamide (AEA) and 2-arachidonyl glycerol (2-AG), have central orexigenic effects in the hypothalamus, even in satiated animals [137], and impact metabolic functions in peripheral tissues including adipose.…”

A nonsynonymous polymorphism in cannabinoid CB2 receptor gene is associated with eating disorders in humans and food intake is modified in mice by its ligands

“…Although several classes of drugs including cannabinoids, (Corey, 2005;Rockwell et al, 1984;Volicer et al, 1997) have been tried as therapy for anorexia nervosa, to date no medication, alone or in combination with other therapies, has been demonstrated to be effective in the treatment of the primary disorder (Israel, 2005). However, anorexia, marked by decreased food intake has been reported as one of the withdrawal effects in over 50% of individuals who smoke marijuana repeatedly through out the day, 6-7 days per week in laboratory and clinical studies (Haney et al, 2008;Horcajadas, 2007). In one study, Haney et al, (2008) reported that a combination of THC and lofexidine, a centrally acting a 2 -agonist, produced the most robust improvements in marijuana withdrawal effects relative to either medication alone (Haney et al, 2008;Horcajadas, 2007).…”