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

Psychopharmacology (Berl). 2016 Jan;233(2):243-54. doi: 10.1007/s00213-015-4100-1. Epub 2015 Oct 6.

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.

Keywords: Anticipatory nausea; Anxiety; Appetite; Cannabidiolic acid; Cannabinoid; Chemotherapy; Novelty-suppressed feeding; Open field; Tolerability; WAY-100,635.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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