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

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.

• Authors: Daniel I Brierley, James Samuels, Marnie Duncan, Benjamin J Whalley, Claire M Williams
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 233 Issue 2 Pg. 243-54 (Jan 2016) ISSN: 1432-2072 [Electronic] Germany
• PMID: 26439367 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Anxiety Agents
• Cannabinoids
• Serotonin 5-HT1 Receptor Antagonists
• Receptor, Serotonin, 5-HT1A
• cannabidiolic acid

Topics

• Animals
• Anti-Anxiety Agents (pharmacology)
• Anxiety (prevention & control, psychology)
• Behavior, Animal (drug effects)
• Cannabinoids (adverse effects, pharmacology)
• Dose-Response Relationship, Drug
• Feeding Behavior (drug effects)
• Hand Strength
• Male
• Motor Activity (drug effects)
• Muscle Strength (drug effects)
• Nausea (prevention & control, psychology)
• Psychomotor Performance (drug effects)
• Rats
• Receptor, Serotonin, 5-HT1A (drug effects)
• Serotonin 5-HT1 Receptor Antagonists (pharmacology)