Abstract
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, 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.
Objectives
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.
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Abbreviations
- CBDA:
-
Cannabidiolic acid
- CBD:
-
Cannabidiol
- pCB:
-
Phytocannabinoid
- CINV:
-
Chemotherapy-induced nausea and vomiting
- AN:
-
Anticipatory nausea
- CDP:
-
Chlordiazepoxide
- NK1:
-
Neurokinin 1
- 5-HT:
-
5-Hydroxytryptamine
- 5-HT1AR:
-
5-Hydroxytryptamine receptor type 1A
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Acknowledgments
This research was supported by grants to CMW and BJW by GW Pharmaceuticals and Otsuka Pharmaceuticals, and in part by the University of Reading Research Endowment Trust Fund to DIB.
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The work reported was funded in part by grants to BJW and CMW from GW Pharmaceuticals and Otsuka Pharmaceuticals. The original study concept was discussed with the sponsor (GW Pharmaceuticals) although all subsequent study design, data collection, analysis and interpretation were conducted independently by the authors. The report was approved by the sponsor company prior to submission, and the authors retain full control of all primary data.
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Brierley, D.I., Samuels, J., Duncan, M. et al. Neuromotor tolerability and behavioural characterisation of cannabidiolic acid, a phytocannabinoid with therapeutic potential for anticipatory nausea. Psychopharmacology 233, 243–254 (2016). https://doi.org/10.1007/s00213-015-4100-1
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DOI: https://doi.org/10.1007/s00213-015-4100-1