Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5- HT1A receptor activation.

Background and Purpose To evaluate the ability of cannabidiolic acid ( CBDA) to reduce nausea and vomiting and enhance 5- HT_1A receptor activation in animal models. Experimental Approach We investigated the effect of CBDA on (i) lithium chloride ( LiCl)-induced conditioned gaping to a flavour (nausea-induced behaviour) or a context (model of anticipatory nausea) in rats; (ii) saccharin palatability in rats; (iii) motion-, LiCl- or cisplatin-induced vomiting in house musk shrews ( Suncus murinus); and (iv) rat brainstem 5- HT_1A receptor activation by 8-hydroxy-2-(di- n-propylamino)tetralin (8- OH-DPAT) and mouse whole brain CB₁ receptor activation by CP55940, using [³⁵ S] GTPγ S-binding assays. Key Results In shrews, CBDA (0.1 and/or 0.5 mg·kg⁻¹ i.p.) reduced toxin- and motion-induced vomiting, and increased the onset latency of the first motion-induced emetic episode. In rats, CBDA (0.01 and 0.1 mg·kg⁻¹ i.p.) suppressed LiCl- and context-induced conditioned gaping, effects that were blocked by the 5- HT_1A receptor antagonist, WAY100635 (0.1 mg·kg⁻¹ i.p.), and, at 0.01 mg·kg⁻¹ i.p., enhanced saccharin palatability. C BDA-induced suppression of LiCl-induced conditioned gaping was unaffected by the CB₁ receptor antagonist, SR141716A (1 mg·kg⁻¹ i.p.). In vitro, CBDA (0.1-100 nM) increased the E_max of 8- OH-DPAT. Conclusions and Implications 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. [ABSTRACT FROM AUTHOR]