Evaluation of the potential of the phytocannabinoids, cannabidivarin (CBDV) and Δ(9) -tetrahydrocannabivarin (THCV), to produce CB1 receptor inverse agonism symptoms of nausea in rats

Br J Pharmacol. 2013 Oct;170(3):671-8. doi: 10.1111/bph.12322.

Abstract

Background and purpose: The cannabinoid 1 (CB1 ) receptor inverse agonists/antagonists, rimonabant (SR141716, SR) and AM251, produce nausea and potentiate toxin-induced nausea by inverse agonism (rather than antagonism) of the CB1 receptor. Here, we evaluated two phytocannabinoids, cannabidivarin (CBDV) and Δ(9) -tetrahydrocannabivarin (THCV), for their ability to produce these behavioural effect characteristics of CB1 receptor inverse agonism in rats.

Experimental approach: In experiment 1, we investigated the potential of THCV and CBDV to produce conditioned gaping (measure of nausea-induced behaviour) in the same manner as SR and AM251. In experiment 2, we investigated the potential of THCV and CBDV to enhance conditioned gaping produced by a toxin in the same manner as CB1 receptor inverse agonists.

Key results: SR (10 and 20 mg·kg(-1) ) and AM251 (10 mg·kg(-1) ) produced conditioned gaping; however, THCV (10 or 20 mg·kg(-1) ) and CBDV (10 or 200 mg·kg(-1) ) did not. At a subthreshold dose for producing nausea, SR (2.5 mg·kg(-1) ) enhanced lithium chloride (LiCl)-induced conditioned gaping, whereas Δ(9) -tetrahydrocannabinol (THC, 2.5 and 10 mg·kg(-1) ), THCV (2.5 or 10 mg·kg(-1) ) and CBDV (2.5 or 200 mg·kg(-1) ) did not; in fact, THC (2.5 and 10 mg·kg(-1) ), THCV (10 mg·kg(-1) ) and CBDV (200 mg·kg(-1) ) suppressed LiCl-induced conditioned gaping, suggesting anti-nausea potential.

Conclusions and implications: The pattern of findings indicates that neither THCV nor CBDV produced a behavioural profile characteristic of CB1 receptor inverse agonists. As well, these compounds may have therapeutic potential in reducing nausea.

Keywords: CB1 receptor antagonism; CB1 receptor inverse agonism; THC; anhedonia; cannabidivarin; depression; nausea; rimonabant; tetrahydrocannabivarin.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Cannabinoid Receptor Agonists / pharmacology*
  • Cannabinoid Receptor Agonists / toxicity
  • Cannabinoids / pharmacology*
  • Cannabinoids / toxicity
  • Disease Models, Animal
  • Dronabinol / analogs & derivatives*
  • Dronabinol / pharmacology
  • Dronabinol / toxicity
  • Drug Partial Agonism
  • Lithium Chloride
  • Male
  • Nausea / chemically induced
  • Nausea / metabolism
  • Nausea / prevention & control*
  • Nausea / psychology
  • Phytochemicals / pharmacology*
  • Phytochemicals / toxicity
  • Piperidines / toxicity
  • Pyrazoles / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / agonists*
  • Receptor, Cannabinoid, CB1 / metabolism
  • Rimonabant

Substances

  • Cannabinoid Receptor Agonists
  • Cannabinoids
  • Cnr1 protein, rat
  • Phytochemicals
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • tetrahydrocannabivarin 9
  • AM 251
  • Dronabinol
  • Lithium Chloride
  • cannabidivarin
  • Rimonabant