Cannabis sativa and the Endogenous Cannabinoid System: Therapeutic Potential for Appetite Regulation

Abstract

The herb Cannabis sativa (C. sativa) has been used in China and on the Indian subcontinent for thousands of years as a medicine. However, since it was brought to the UK and then the rest of the western world in the late 19th century, its use has been a source of controversy. Indeed, its psychotropic side effects are well reported but only relatively recently has scientific endeavour begun to find valuable uses for either the whole plant or its individual components. Here, we discuss evidence describing the endocannabinoid system, its endogenous and exogenous ligands and their varied effects on feeding cycles and meal patterns. Furthermore we also critically consider the mounting evidence which suggests non‐Δ9tetrahydrocannabinol phytocannabinoids play a vital role in C. sativa‐induced feeding pattern changes. Indeed, given the wide range of phytocannabinoids present in C. sativa and their equally wide range of intra‐, inter‐ and extra‐cellular mechanisms of action, we demonstrate that non‐Δ9tetrahydrocannabinol phytocannabinoids retain an important and, as yet, untapped clinical potential. Copyright © 2011 John Wiley & Sons, Ltd.

Dissociable Effects of the Cannabinoid Receptor Agonists Δ9-Tetrahydrocannabinol and CP55940 on Pain-Stimulated Versus Pain-Depressed Behavior in Rats

“…Second, the effects of THC and CP55940 were evaluated in an assay of acid-induced depression of feeding (Stevenson et al, 2006). Feeding is reliably stimulated by THC and other cannabinoid agonists in the absence of pain (Williams et al, 1998;Miller et al, 2004;Jä rbe and DiPatrizio, 2005;Farrimond et al, 2011), suggesting that cannabinoids might be more effective in blocking acid-induced depression of feeding than acid-induced depression of ICSS. The nonsteroidal antiinflammatory drug (NSAID) and clinically effective analgesic ketoprofen (Flecknell, 2009;Sarzi-Puttini et al, 2010) was tested as a positive control in assays of acid-stimulated and acid-depressed behavior.…”

Theoretical Explanation for Reduced Body Mass Index and Obesity Rates in <em>Cannabis</em> Users

“…It stimulates the appetite centers of the brain, leading to hyperphagia and favoring fat accumulation in adipose tissue. At the same time, CB1R activation reduces energy expenditures (Simopoulos, 2002, DiPatrizio and Piomelli, 2012, Freitas et al, 2017, Mazier et al, 2015, Engeli, 2008, Bisogno and Maccarrone, 2014, Alvheim et al, 2014, Khan et al, 2014a, Cota et al, 2003a, Cota et al, 2003b, Farrimond et al, 2011. These actions contribute to homeostasis in the context of a hunter-gatherer diet of plants, plant-feeding animals, and fish.…”

“…The central role of CB1R in appetite, energy intake, energy conservation, and diet-induced obesity (Freitas et al, 2017, Mazier et al, 2015, Alvheim et al, 2014, Engeli et al, 2005, Engeli, 2008, Cota et al, 2003a, Cota et al, 2003b, Cardinal et al, 2012, DiPatrizio and Piomelli, 2012, Matias and Di Marzo, 2007, Matias et al, 2008, Pagotto et al, 2006, and the hyperphagia and hypothermia resulting from acute stimulation of CB1R by THC (Farrimond et al, 2011, Borgen et al, 1973, makes CB1R a prime suspect for a causative role in the effects of Cannabis use on BMI.…”

Chemotherapy‐induced cachexia dysregulates hypothalamic and systemic lipoamines and is attenuated by cannabigerol

“…However, these failed to demonstrate efficacy, in part due to dose‐limiting psychoactive side effects . In addition to Δ 9 ‐THC, there are now known to be over 100 other phytocannabinoids in C. sativa , the majority of which are non‐psychoactive, some of which have appetite‐modulating effects . We have recently shown that cannabigerol (CBG), a non‐psychoactive phytocannabinoid, increases food intake in healthy rats without eliciting neuromotor side effects .…”

“…15,16 In addition to Δ 9 -THC, there are now known to be over 100 other phytocannabinoids in C. sativa, the majority of which are non-psychoactive, some of which have appetite-modulating effects. [17][18][19][20] We have recently shown that cannabigerol (CBG), a non-psychoactive phytocannabinoid, increases food intake in healthy rats without eliciting neuromotor side effects. 21,22 Given that patients undergoing chemotherapy commonly report appetite loss, altered food palatability, and early satiety, [23][24][25][26] CBG may have potential to attenuate these anorectic side effects.…”