Anorexia-Cachexia Syndrome

Research Evaluating the Use of Cannabinoids in a Palliative Cancer Care Setting

Anorexia-Cachexia Syndrome Research

For many patients with advanced cancer, weight loss and muscle wasting (cachexia) are prominent features of disease. While decreased appetite and food aversion do occur in cancer, this particular form of weight loss is somewhat different from that of starvation or caloric restriction. Instead, the chronic inflammation associated with cancer truly drives this process. Inflammation results in severe metabolic derangements and high basal energy expenditure that leads to a disproportionate degree of muscle wasting (Evans, Clin Nutr, 2008). This phenomenon is called the anorexia-cachexia syndrome, which can occur with varying degrees of severity. It is no surprise that patients who experience cancer-related weight loss and cachexia often report higher levels of distress and worse quality of life and functional status (Capuano, Support Care Cancer, 2010; Morishita, Support Care Cancer, 2012). Furthermore, cancer-related weight loss and cachexia portend a poor prognosis independent of disease stage, tumor grade, and patient functional status (Dewys, Am J Med, 1980).

The current interventions for anorexia-cachexia syndrome are only minimally effective. Part of the problem is that therapies aim at restoring caloric intake, which does nothing to ameliorate the metabolic derangements characteristic of this disease process (Ovesen, J Clin Oncol, 1993). Nutritional supplementation and lifestyle modifications aimed at improving appetite are attempted first, followed by pharmacologic intervention. The most common drug classes used for cancer-related weight loss are corticosteroids and progesterone analogs, both of which come with their own set of side effects (Ruiz Garcia, Cochrane Database Syst Rev, 2013; Oray, Expert Opin Drug Safe, 2016).

Early studies and common anecdotal reports have suggested that cannabis stimulates appetite and increases caloric intake in healthy individuals (Foltin, Pharmacol Biochem Behav 1986; Vickers, Curr Drug Targets, 2005). For this reason, cannabis was hypothesized to be beneficial in the anorexia-cachexia syndrome. However, clinical trials to date have been conflicting and inconclusive. In one trial, cannabis extract and THC did not significantly improve appetite or patient quality of life compared to placebo (Strasser, J Clin Oncol, 2006), while in another, dronabinol was shown to be inferior to megestrol acetate, a progesterone analog (Jatoi, J Clin Oncol, 2002). Meanwhile, a different randomized, placebo-controlled trial indicated that THC did improve certain quality of life measures, such as sleep and relaxation. Additionally, THC improved patient perception of food taste, appetite, and protein calories consumed (Brisbois, Ann Oncol, 2011). Despite this lack of quality evidence, preclinical studies still indicate that cannabinoids may be beneficial in treating the anorexia-cachexia syndrome due to their interaction with brain areas involved in food reward and appetite (Fride, Exp Biol Med, 2005). Further preclinical and clinical data is greatly needed.