title: Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation.
abstract: OBJECTIVE
  To evaluate the ability of cannabidiolic acid (CBDA) to reduce nausea and vomiting and enhance 5-HT(1A) receptor activation in animal models.
  
  
  METHODS
  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 CB(1) receptor activation by CP55940, using [³⁵S]GTPγS-binding assays.
  
  
  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. CBDA-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
  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.
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: D
authors.initials: D
authors.lastname: Bolognini
authors.forename: E M
authors.initials: EM
authors.lastname: Rock
authors.forename: N L
authors.initials: NL
authors.lastname: Cluny
authors.forename: M G
authors.initials: MG
authors.lastname: Cascio
authors.forename: C L
authors.initials: CL
authors.lastname: Limebeer
authors.forename: M
authors.initials: M
authors.lastname: Duncan
authors.forename: C G
authors.initials: CG
authors.lastname: Stott
authors.forename: F A
authors.initials: FA
authors.lastname: Javid
authors.forename: L A
authors.initials: LA
authors.lastname: Parker
authors.forename: R G
authors.initials: RG
authors.lastname: Pertwee
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002186:Cannabinoids / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D005260:Female; D008297:Male; D051379:Mice; D009041:Motion Sickness / Q000503:physiopathology / Q000517:prevention & control; D009325:Nausea / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000737:chemistry / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D012788:Shrews; D014839:Vomiting / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids; D009419:Nerve Tissue Proteins; D043884:Receptor, Cannabinoid, CB1; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C006884:cannabidiolic acid