Cannabis constituents modulate ∆9-tetrahydrocannabinol-induced hyperphagia in rats

Abstract

All Delta9THC compounds displayed classical Delta9THC effects on feeding, significantly increasing shortterm intake whilst decreasing latency to the first meal. We propose that the subtle adjustment to the meal patterns seen between the purified Delta9THC and Delta9THC-BDS are due to non-Delta9THC cannabinoids present in Delta9THC-BDS. These compounds and other non-cannabinoids have an emerging and diverse pharmacology and can modulate Delta9THC-induced hyperphagia, making them worth further investigation for their therapeutic potential.

Neuromotor tolerability and behavioural characterisation of cannabidiolic acid, a phytocannabinoid with therapeutic potential for anticipatory nausea

“…The acute feeding test in pre-satiated rats has been utilised in many previous studies in our lab to sensitively determine hyperphagic actions of pharmacological compounds, providing detailed information on both food intake and the microstructure of meal patterns (Williams et al 1998;Williams and Kirkham 2002;Farrimond et al 2010a;Farrimond et al 2010b;Farrimond et al 2012a). In vehicle-dosed rats, feeding behaviour during the test period is minimal, typically comprising one to two small meals with a total consumption of ≤1 g, occurring after 90 min (Farrimond et al 2012b).…”

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

“…Thirty‐six pre‐satiated, male, Lister‐hooded rats received a purified, C. sativa ‐derived Δ 9 THC (hereafter purified Δ 9 THC), a synthetic Δ 9 THC and a high‐Δ 9 THC standardized botanical drug substance (BDS), similar in composition to that used in Sativex and containing a typical array of non‐Δ 9 THC pCBs (high‐Δ 9 THC BDS; all treatments were dose matched for Δ 9 THC content; 0.00, 0.34, 0.67, 1.34 and 2.68 mg/kg; p.o. ; Farrimond et al , ). Synthetic and purified Δ 9 THC administration induced classical Δ 9 THC hyperphagia in this study: the latency to the first meal was reduced and both the first hour intake and first meal duration were increased versus vehicle treatments.…”

“…When these two studies are considered together (Farrimond et al ), a number of suggestions can be made: firstly, since the observed effects of the non‐Δ 9 THC components of the extracts administered reduced hyperphagia when presented in one ratio and increased hyperphagia when presented in a different ratio, it is highly unlikely that the plant matter also present was responsible for these effects, given that its content did not change between the two tests. Secondly, it is possible that the pCBs present in both studies did not act in isolation such that more than one compound induced the observed effects.…”

“…Whilst a definitive mechanism underlying the findings reported by Farrimond et al . () remains unknown, the naturally occurring pCB and CB 1 R neutral antagonist Δ 9 THCV, which was also present in the extracts employed in Farrimond et al, has been considered alone and shown to exert hypophagic actions (Riedel et al , ). Indeed, given the difficulties associated with the use of the highly specific and potent CB 1 R antagonist/inverse agonist SR141716A in the clinic, the use of Δ 9 THCV, as a neutral antagonist, to reduce food intake may be of therapeutic value.…”

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 .…”