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THC slows progressive weight loss in a rodent model of anorexia nervosa

Alexis Perrini
Florida State University

Objective: Consistent with its complex and poorly understood etiology, the course of anorexia nervosa (AN) is highly variable, effective pharmacotherapies are limited, and relapse is common. Thus, a critical need exists for new drug therapies that target symptoms of AN. In this regard, our group is interested in the endocannabinoid system, based on its involvement in regulating food intake, energy expenditure, and reward processing, all of which are dysregulated in AN. Additionally, clinical studies report impaired cannabinoid signaling in AN patients, and daily treatment with Δ⁹-tetrahydrocannabinol (THC) has been shown to attenuate weight loss in the pre-clinical rodent model of activity-based anorexia (ABA). An important limitation of existing studies showing THC’s ability to attenuate ABA-induced weight loss is that THC treatment is started in healthy animals that have not developed symptoms of ABA.  With respect to developing new pharmacotherapies, a better approach would be to initiate cannabinoid treatment after, rather than before, animals have developed ABA. Here, we tested the hypothesis that treatment with THC would rescue the ABA phenotype and restore normal endocannabinoid function in female rats that had experienced significant weight loss in the ABA paradigm.

Methods: Female rats were exposed to the ABA paradigm, which combines restricted feeding (90 min access to food/day) with unlimited access to running wheels (RWs). Following 15% weight loss, rats received once-daily intraperitoneal injections of THC (1 mg/kg) or vehicle for 7 days. Throughout the experiment, food intake, RW activity, and body weight were monitored daily.

Results: Our analysis of the first cohort of rats (n = 8) revealed similar daily food intake in the THC- and vehicle-treated groups (~4.4g/day). However, THC-treated rats displayed about a 50% decrease in RW activity, relative to vehicle-treated rats (treatment average = 7257 ± 1437 vs. 14051 ± 508 revolutions/day, p < 0.05), and this resulted in a reduction in the rate of weight loss over the treatment period in THC- versus vehicle-treated rats.

Conclusion: These preliminary findings suggest that daily THC treatment helps to rescue the ABA phenotype in underweight, symptomatic female rats primarily through a reduction in energy expenditure. (Funded by the Consortium for Medical Marijuana Clinical Outcomes Research)

Co-authors: Lisa Eckel1
1Florida State University

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