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Neuromotor tolerability and behavioural characterisation of cannabidiolic acid, a phytocannabinoid with therapeutic potential for anticipatory nausea

Brierley, D., Samuels, J., Duncan, M., Whalley, B. and Williams, C. (2016) Neuromotor tolerability and behavioural characterisation of cannabidiolic acid, a phytocannabinoid with therapeutic potential for anticipatory nausea. Psychopharmacology, 233 (2). pp. 243-254. ISSN 1432-2072

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To link to this item DOI: 10.1007/s00213-015-4100-1

Abstract/Summary

Rationale: Anticipatory nausea (AN) is a poorly controlled side-effect experienced by chemotherapy patients. Currently, pharmacotherapy is restricted to benzodiazepine anxiolytics, which have limited efficacy, 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. Objectives: 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-supressed 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.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Psychology and Clinical Language Sciences > Department of Psychology
Faculty of Life Sciences > School of Psychology and Clinical Language Sciences > Neuroscience
Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
Faculty of Life Sciences > School of Psychology and Clinical Language Sciences > Nutrition and Health
ID Code:46344
Uncontrolled Keywords:Cannabidiolic acid; cannabinoid; WAY-100,635; anticipatory nausea; chemotherapy; tolerability; appetite; anxiety; open field; novelty-suppressed feeding.
Publisher:Springer

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