A comparison of cannabidiolic acid with other treatments for anticipatory nausea using a rat model of contextually elicited conditioned gaping

Psychopharmacology (Berl). 2014 Aug;231(16):3207-15. doi: 10.1007/s00213-014-3498-1. Epub 2014 Mar 5.


Rationale: The effectiveness of cannabidiolic acid (CBDA) was compared with other potential treatments for anticipatory nausea (AN), using a rat model of contextually elicited conditioned gaping reactions.

Objective: The potential of ondansetron (OND), Δ(9)-tetrahydrocannabinol (THC), chlordiazepoxide (CDP), CBDA, and co-administration of CBDA and tetrahydrocannabinolic acid (THCA) to reduce AN and modify locomotor activity was evaluated.

Materials and methods: Following four pairings of a novel context with lithium chloride (LiCl), the rats were given a test for AN. On the test trial, they received pretreatment injections of the following: vehicle, OND (0.1 or 1.0 mg/kg), THC (0.5 mg/kg), CBDA (0.0001, 0.001, 0.01, 0.1 mg/kg or 1.0 mg/kg), CDP (1, 5, or 10 mg/kg) or co-administration of subthreshold doses of CBDA (0.1 μg/kg), and THCA (5 μg/kg). Immediately following the AN test trial in all experiments, rats were given a 15 min locomotor activity test. Finally, the potential of CBDA (0.001, 0.01, 0.1, and 1 mg/kg) to attenuate conditioned freezing to a shock-paired tone was assessed.

Results: THC, CBDA, and CDP, but not OND, reduced contextually elicited gaping reactions. Co-administration of subthreshold doses of CBDA and THCA also suppressed AN, and this effect was blocked by pretreatment with either a cannabinoid receptor 1 (CB1) receptor antagonist or a 5-hydroxytryptamine 1A (5-HT1A) receptor antagonist. CDP (but not CBDA, THC or CBDA and THCA) also suppressed locomotor activity at effective doses. CBDA did not modify the expression of conditioned fear.

Conclusions: CBDA has therapeutic potential as a highly potent and selective treatment for AN without psychoactive or locomotor effects.

Publication types

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

MeSH terms

  • Animals
  • Anticipation, Psychological / drug effects*
  • Antiemetics / pharmacology
  • Cannabinoids / therapeutic use*
  • Chlordiazepoxide / pharmacology
  • Conditioning, Psychological / drug effects
  • Dronabinol / analogs & derivatives
  • Dronabinol / pharmacology
  • Electroshock
  • Fear / drug effects
  • Fear / psychology
  • Hypnotics and Sedatives / pharmacology
  • Lithium Chloride / pharmacology
  • Male
  • Motor Activity / drug effects
  • Nausea / drug therapy*
  • Nausea / psychology*
  • Ondansetron / pharmacology
  • Rats
  • Rats, Sprague-Dawley


  • Antiemetics
  • Cannabinoids
  • Hypnotics and Sedatives
  • delta(1)-tetrahydrocannabinolic acid
  • Ondansetron
  • Chlordiazepoxide
  • Dronabinol
  • cannabidiolic acid
  • Lithium Chloride