Food intake behaviour in advanced cancer -- Implications of taste and smell alterations, orosensory reward, and cannabinoid therapy

Food intake is regulated by both appetite and orosensory reward systems. Appetite systems stimulate or reduce hunger, while orosensory reward motivates consumption of high fat sweet foods, resulting in food enjoyment. The majority of advanced cancer patients suffer from malnutrition and wasting, which may be caused by a loss of appetite due to physiological changes or a hindered orosensory reward system due to taste and smell (chemosensory) changes or both. Orosensory reward systems were hypothesized to be impaired in advanced cancer. To understand the influence of chemosensory alterations on food intake and enjoyment, the nature (intensity) of chemosensory alterations in cancer patients and their relationship with ingestive behaviour and quality of life (QOL) were investigated (study 1). Advanced cancer patients (n=192) more frequently self-reported tastes and odours to be heightened rather than diminished (p=0.035). Patients with perceived chemosensory alterations had poorer QOL (p=0.0176) and lower caloric intake (p=0.0018) compared to patients with no alterations. Cannabinoids (e.g. Delta-9-tetrahydrocannabinol, Delta-9-THC) increase food intake by stimulating both appetite and orosensory reward systems as well as potentially enhancing chemosensory function. To palliate chemosensory alterations and poor appetite, advanced cancer patients (n=21, study 2) with these symptoms were randomized to receive either Delta-9-THC (2.5mg) or placebo oral capsules twice daily for 18 days. Compared to patients receiving placebo, Delta-9-THC-treated patients reported that food tasted better (p=0.04), they had improved chemosensory perception (p=0.026), increased preference and intake of high protein foods (p=0.008), and improved appetite (p=0.05), quality of sleep (p=0.025), and relaxation (p=0.045). Like cancer patients, tumour-bearing rats appeared to experience a loss of orosensory reward, showing tumour-associated anorexia when fed a rewarding diet to the same degree as on a usual diet ( study 3). Delta-9-THC significantly increased caloric intake compared to vehicle for both tumour-bearing (p=0.0146) and healthy rats (p=0.0004), suggesting endocannabinoid-mediated appetite systems are functioning in this tumour model. The findings of this thesis suggest orosensory reward systems to be impaired in advanced cancer, decreasing the liking and motivation to eat. Delta-9-THC treatment may help to palliate perceived chemosensory alterations and loss of appetite and food enjoyment in advanced cancer.