title: Neuromotor tolerability and behavioural characterisation of cannabidiolic acid, a phytocannabinoid with therapeutic potential for anticipatory nausea.
abstract: BACKGROUND
  Anticipatory nausea (AN) is a poorly controlled side effect experienced by chemotherapy patients. Currently, pharmacotherapy is restricted to benzodiazepine anxiolytics, which have limited efficacy, have significant sedative effects and induce dependency. The non-psychoactive phytocannabinoid, cannabidiolic acid (CBDA), has shown considerable efficacy in pre-clinical AN models, however determination of its neuromotor tolerability profile is crucial to justify clinical investigation. Provisional evidence for appetite-stimulating properties also requires detailed investigation.
  
  
  OBJECTIVE
  This study aims to assess the tolerability of CBDA in locomotor activity, motor coordination and muscular strength tests, and additionally for ability to modulate feeding behaviours.
  
  
  METHODS
  Male Lister Hooded rats administered CBDA (0.05-5 mg/kg; p.o.) were assessed in habituated open field (for locomotor activity), static beam and grip strength tests. A further study investigated whether these CBDA doses modulated normal feeding behaviour. Finally, evidence of anxiolytic-like effects in the habituated open field prompted testing of 5 mg/kg CBDA for anxiolytic-like activity in unhabituated open field, light/dark box and novelty-suppressed feeding (NSF) tests.
  
  
  RESULTS
  CBDA had no adverse effects upon performance in any neuromotor tolerability test, however anxiolytic-like behaviour was observed in the habituated open field. Normal feeding behaviours were unaffected by any dose. CBDA (5 mg/kg) abolished the increased feeding latency in the NSF test induced by the 5-HT1AR antagonist, WAY-100,635, indicative of anxiolytic-like effects, but had no effect on anxiety-like behaviour in the novel open field or light/dark box.
  
  
  CONCLUSIONS
  CBDA is very well tolerated and devoid of the sedative side effect profile of benzodiazepines, justifying its clinical investigation as a novel AN treatment.
authors.affiliation: School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK.|School of Chemistry, Food and Nutritional Sciences, and Pharmacy, University of Reading, Reading, UK.
authors.forename: Daniel I
authors.identifier: http://orcid.org/0000-0002-4360-2648
authors.initials: DI
authors.lastname: Brierley
authors.affiliation: School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK.
authors.forename: James
authors.initials: J
authors.lastname: Samuels
authors.affiliation: GW Pharmaceuticals Ltd, Cambridge, UK.
authors.forename: Marnie
authors.initials: M
authors.lastname: Duncan
authors.affiliation: School of Chemistry, Food and Nutritional Sciences, and Pharmacy, University of Reading, Reading, UK.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Whalley
authors.affiliation: School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK. claire.williams@reading.ac.uk.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Williams
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000517:prevention & control / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D002186:Cannabinoids / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects; D018737:Hand Strength; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D053580:Muscle Strength / Q000187:drug effects; D009325:Nausea / Q000517:prevention & control* / Q000523:psychology; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology
chemical_list: D014151:Anti-Anxiety Agents; D002186:Cannabinoids; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C006884:cannabidiolic acid
keywords: Anticipatory nausea; Anxiety; Appetite; Cannabidiolic acid; Cannabinoid; Chemotherapy; Novelty-suppressed feeding; Open field; Tolerability; WAY-100,635