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To evaluate the ability of cannabidiolic acid (CBDA) to reduce nausea and vomiting and enhance 5‐HT_1A receptor activation in animal models.

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 [³⁵S]GTPγS‐binding assays.

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 …