Cannabidiolic acid prevents vomiting in Suncus murinus and nausea‐induced behaviour in rats by enhancing 5‐HT1A receptor activation. (25th February 2013)

• Record Type: Journal Article
• Authors: Bolognini, D; Rock, EM; Cluny, NL; Cascio, MG; Limebeer, CL; Duncan, M; Stott, CG; Javid, FA; Parker, LA; Pertwee, RG
• Is Part Of: British journal of pharmacology. Volume 168:Number 6(2013:Mar.)
• Page Start: 1456
• Page End: 1470
• Publication Date: 2013-02-25
• Subjects: Pharmacology -- Periodicals; Chemotherapy -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/bph.12043
• Languages: English
• ISSNs: 0007-1188

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bph12043-sec-0001" sec-type="section"> <title>Background and Purpose</title> <p>To evaluate the ability of cannabidiolic acid (CBDA) to reduce nausea and vomiting and enhance 5‐HT<sub>1A</sub> receptor activation in animal models.</p> </sec> <sec id="bph12043-sec-0002" sec-type="section"> <title>Experimental Approach</title> <p>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 (<italic>Suncus murinus</italic>); and (iv) rat brainstem 5‐HT<sub>1A</sub> receptor activation by 8‐hydroxy‐2‐(di‐<italic>n</italic>‐propylamino)tetralin (8‐OH‐DPAT) and mouse whole brain CB<sub>1</sub> receptor activation by CP55940, using [<sup>35</sup>S]GTPγS‐binding assays.</p> </sec> <sec id="bph12043-sec-0003" sec-type="section"> <title>Key Results</title> <p>In shrews, CBDA (0.1 and/or 0.5 mg·kg<sup>−1</sup> 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<sup>−1</sup> i.p.) suppressed LiCl‐ and context‐induced conditioned gaping, effects that were blocked by the 5‐HT<sub>1A</sub> receptor antagonist, WAY100635 (0.1 mg·kg<sup>−1</sup> i.p.), and, at 0.01 mg·kg<sup>−1</sup> i.p., enhanced saccharin palatability. CBDA‐induced suppression of LiCl‐induced conditioned gaping was unaffected by the CB<sub>1</sub> receptor antagonist, SR141716A (1 mg·kg<sup>−1</sup> i.p.). <italic>In vitro</italic>, CBDA (0.1–100 nM) increased the <italic>E</italic><sub>max</sub> of 8‐OH‐DPAT.</p> </sec> <sec id="bph12043-sec-0004" sec-type="section"> <title>Conclusions and Implications</title> <p>Compared with cannabidiol, CBDA displays significantly greater potency at inhibiting vomiting in shrews and nausea in rats, and at enhancing 5‐HT<sub>1A</sub> 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.</p> </sec> </abstract>