Abstract
RationaleThe appetite-stimulating properties of cannabis are well documented and have been predominantly attributed to the hyperphagic activity of the psychoactive phytocannabinoid, ∆9-tetrahydrocannabinol (∆9-THC). However, we have previously shown that a cannabis extract devoid of ∆9-THC still stimulates appetite, indicating that other phytocannabinoids also elicit hyperphagia. One possible candidate is the non-psychoactive phytocannabinoid cannabigerol (CBG), which has affinity for several molecular targets with known involvement in the regulation of feeding behaviour.ObjectivesThe objective of the study was to assess the effects of CBG on food intake and feeding pattern microstructure.MethodsMale Lister hooded rats were administered CBG (30–120 mg/kg, per ora (p.o.)) or placebo and assessed in open field, static beam and grip strength tests to determine a neuromotor tolerability profile for this cannabinoid. Subsequently, CBG (at 30–240 mg/kg, p.o.) or placebo was administered to a further group of pre-satiated rats, and hourly intake and meal pattern data were recorded over 2 h.ResultsCBG produced no adverse effects on any parameter in the neuromotor tolerability test battery. In the feeding assay, 120–240 mg/kg CBG more than doubled total food intake and increased the number of meals consumed, and at 240 mg/kg reduced latency to feed. However, the sizes or durations of individual meals were not significantly increased.ConclusionsHere, we demonstrate for the first time that CBG elicits hyperphagia, by reducing latency to feed and increasing meal frequency, without producing negative neuromotor side effects. Investigation of the therapeutic potential of CBG for conditions such as cachexia and other disorders of eating and body weight regulation is thus warranted.
Highlights
IntroductionCannabis sativa L. has been utilised for medicinal and recreational purposes for millennia and is increasingly being recognised as a valuable source of unique compounds (phytocannabinoids) with a multitude of potential therapeutic applications (Deiana et al 2012)
Cannabis sativa L. has been utilised for medicinal and recreational purposes for millennia and is increasingly being recognised as a valuable source of unique compounds with a multitude of potential therapeutic applications (Deiana et al 2012)
The main psychoactive constituent of C. sativa, Δ9-tetrahydrocannabinol (Δ9-THC), was Psychopharmacology (2016) 233:3603–3613 first isolated and characterised in the 1960s (Mechoulam & Gaoni 1965; Gaoni & Mechoulam 1971), and this has been followed by the discovery of numerous additional phytocannabinoids over the last two decades
Summary
Cannabis sativa L. has been utilised for medicinal and recreational purposes for millennia and is increasingly being recognised as a valuable source of unique compounds (phytocannabinoids) with a multitude of potential therapeutic applications (Deiana et al 2012). One of the better known properties of C. sativa is its ability to stimulate appetite (hyperphagia), which has been described anecdotally by recreational users and demonstrated under laboratory conditions (Hollister 1971; Mattes et al 1994). Our laboratory has shown that oral administration of Δ9-THC to pre-satiated rats produced significant shortterm hyperphagia (Williams et al 1998), characterised by a marked reduction in latency to begin feeding (Williams and Kirkham 2002a), an effect that was reversed by coadministration of the selective CB1 receptor (CB1R) antagonist SR141716 (Williams and Kirkham 2002b). In the latter study, we demonstrated altered brain levels of AEA and 2-AG during fasting and feeding states, implicating eCBs in the control of appetite
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