A low-?9tetrahydrocannabinol cannabis extract induces hyperphagia in rats
ABSTRACT Appetite stimulation via partial agonism of cannabinoid type 1 receptors by Δ9tetrahydrocannabinol (Δ9THC) is well documented and can be modulated by non-Δ9THC phytocannabinoids. Δ9THC concentrations sufficient to elicit hyperphagia induce changes to both appetitive (reduced latency to feed) and consummatory (increased meal one size and duration) behaviours. Here, we show that a cannabis extract containing too little Δ9THC to stimulate appetite can induce hyperphagia solely by increasing appetitive behaviours. Twelve, male Lister hooded rats were presatiated before treatment with a low-Δ9THC cannabis extract (0.5, 1.0, 2.0 and 4.0 mg/kg). Hourly intake and meal pattern data were recorded and analyzed using one-way analyses of variance followed by Bonferroni post-hoc tests. The cannabis extract significantly increased food intake during the first hour of testing (at 4.0 mg/kg) and significantly reduced the latency to feed versus vehicle treatments (at doses ≥1.0 mg/kg). Meal size and duration were unaffected. These results show only the increase in appetitive behaviours, which could be attributed to non-Δ9THC phytocannabinoids in the extract rather than Δ9THC. Although further study is required to determine the constituents responsible for these effects, these results support the presence of non-Δ9THC cannabis constituent(s) that exert a stimulatory effect on appetite and likely lack the detrimental psychoactive effects of Δ9THC.
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ABSTRACT: BACKGROUND AND PURPOSE Endocannabinoid systems are strongly implicated in the physiological control of appetite and eating behaviour, with cannabinoid CB(1) receptor agonists and antagonists, respectively, increasing or decreasing food intake. This study examined the acute actions of the putative endocannabinoid noladin ether on food intake and eating motivation, assessing how it affects the amount of work expended by animals to obtain food. EXPERIMENTAL APPROACH Non-deprived male rats were injected systemically with noladin ether to assess its acute effects on ad libitum feeding of a standard laboratory diet. Additionally, the effects of noladin on lever pressing for palatable food were determined using a progressive ratio (PR) operant paradigm. KEY RESULTS Noladin dose dependently increased 2 h food intake, with a significant effect over 1 h after a dose of 0.5 mg·kg(-1). In the PR test, this hyperphagic dose of noladin ether promoted sustained high rates of responding and significantly increased the total number of lever presses and break-point. These latter effects were prevented by pretreatment with 1.0 mg·kg(-1) of the selective CB(1) antagonist surinabant (SR147778), that alone had no effect on responding. CONCLUSIONS AND IMPLICATIONS This is the first report of hyperphagia induced by acute noladin administration, and the first description of behavioural actions in rats. Consistent with prevailing notions about the role of endocannabinoids in appetite, a hyperphagic dose of noladin markedly increased efforts expended by animals to obtain food. Thus, noladin exerts a specific action on eating motivation; possibly promoting eating by increasing the incentive value of food.British Journal of Pharmacology 02/2012; 166(6):1815-21. · 5.07 Impact Factor
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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-Δ(9) tetrahydrocannabinol 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-Δ(9) tetrahydrocannabinol phytocannabinoids retain an important and, as yet, untapped clinical potential.Phytotherapy Research 02/2011; 25(2):170-88. · 2.07 Impact Factor
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ABSTRACT: Increased food consumption following ∆(9)-tetrahydrocannabinol-induced cannabinoid type 1 receptor agonism is well documented. However, possible non-∆(9)-tetrahydrocannabinol phytocannabinoid-induced feeding effects have yet to be fully investigated. Therefore, we have assessed the effects of the individual phytocannabinoids, cannabigerol, cannabidiol and cannabinol, upon feeding behaviors. Adult male rats were treated (p.o.) with cannabigerol, cannabidiol, cannabinol or cannabinol plus the CB(1)R antagonist, SR141716A. Prior to treatment, rats were satiated and food intake recorded following drug administration. Data were analyzed for hourly intake and meal microstructure. Cannabinol induced a CB(1)R-mediated increase in appetitive behaviors via significant reductions in the latency to feed and increases in consummatory behaviors via increases in meal 1 size and duration. Cannabinol also significantly increased the intake during hour 1 and total chow consumed during the test. Conversely, cannabidiol significantly reduced total chow consumption over the test period. Cannabigerol administration induced no changes to feeding behavior. This is the first time cannabinol has been shown to increase feeding. Therefore, cannabinol could, in the future, provide an alternative to the currently used and psychotropic ∆(9)-tetrahydrocannabinol-based medicines since cannabinol is currently considered to be non-psychotropic. Furthermore, cannabidiol reduced food intake in line with some existing reports, supporting the need for further mechanistic and behavioral work examining possible anti-obesity effects of cannabidiol.Psychopharmacology 04/2012; 223(1):117-29. · 4.06 Impact Factor