Cannabidiolic acid prevents vomiting in Suncus murinus and nausea‐induced behaviour in rats by enhancing 5‐HT_1A receptor activation

Abstract

Compared with cannabidiol, CBDA displays significantly greater potency at inhibiting vomiting in shrews and nausea in rats, and at enhancing 5-HT(1A) receptor activation, an action that accounts for its ability to attenuate conditioned gaping in rats. Consequently, CBDA shows promise as a treatment for nausea and vomiting, including anticipatory nausea for which no specific therapy is currently available.

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

“…In studies using CBDA, low doses (0.01-0.5 mg/kg; i.p.) attenuated acute vomiting in shrews, and both acute and anticipatory nausea in rats, with the latter effect blocked by the 5-HT 1A R antagonist WAY-100,635 (Bolognini et al 2013). The same study reported an enhancement of saccharin palatability, as measured by unconditioned hedonic reactions.…”

“…Recently, a number of pre-clinical studies have identified the non-psychoactive phytocannabinoid, cannabidiolic acid (CBDA), as a potential novel pharmacotherapy for the treatment of AN (Bolognini et al 2013;Rock and Parker 2013a;Rock and Parker 2013b;Rock et al 2014a). Parker and colleagues assessed the ability of CBDA and a number of other phytocannabinoids to prevent cisplatin-or lithium chloride (LiCl)-induced vomiting (a model of acute vomiting) in house musk shrews and in rats to prevent LiCl-induced gaping (a model of acute nausea) or context-induced gaping (a conditioned model of AN).…”

“…During our battery of locomotor tasks, there was the suggestion of putative anxiolytic-like effects seen in the habituated open field test. As a final experiment therefore, using three tests of anxiety-like behaviour, CBDA was assessed alone and in combination with WAY-100,635, a 5-HT 1A R silent antagonist, as this receptor has previously been shown to block the effects of CBDA in models of acute and anticipatory nausea (Bolognini et al 2013). …”

Down-regulation of cyclooxygenase-2 (COX-2) by cannabidiolic acid in human breast cancer cells

“…The specific use of the acidic cannabinoid as an active pharmaceutical ingredient has not yet been achieved because CBDA is recognized as the pharmacologically inactive form (Yamauchi et al, 1967;Razdan, 1986;Burstein, 1999). However, recent studies including ours demonstrated that, in addition to CBD, CBDA by itself exhibits biological actions, such as antibacterial effects (Appendino et al, 2008), the inhibition of cyclooxygenase-2 (COX-2) (Takeda et al, 2008), and anti-nausea/emetic effects (Bolognini et al, 2013;Rock et al, 2013).…”

Gastrointestinal Safety Pharmacology in Drug Discovery and Development

“…In those species, conditioned taste aversion has been reported as a potential model of emesis (Limebeer et al 2008). The musk shrew (Suncus murinus) has also been described as a suitable experimental model to evaluate drug-induced vomiting (Ueno et al 2002;Bolognini et al 2013). However, its poor availability as laboratory animal limits its use in research and development.…”