title: A comparison of cannabidiolic acid with other treatments for anticipatory nausea using a rat model of contextually elicited conditioned gaping.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Department of Psychology and Collaborative Neuroscience Program, University of Guelph, 50 Stone Rd E, Guelph, ON, N1G 2W1, Canada.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Rock
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Limebeer
authors.forename: Roshan
authors.initials: R
authors.lastname: Navaratnam
authors.forename: Martin A
authors.initials: MA
authors.lastname: Sticht
authors.forename: Natasha
authors.initials: N
authors.lastname: Bonner
authors.forename: Kristin
authors.initials: K
authors.lastname: Engeland
authors.forename: Rachel
authors.initials: R
authors.lastname: Downey
authors.forename: Heather
authors.initials: H
authors.lastname: Morris
authors.forename: Meagan
authors.initials: M
authors.lastname: Jackson
authors.forename: Linda A
authors.initials: LA
authors.lastname: Parker
mesh_terms: D000818:Animals; D059031:Anticipation, Psychological / Q000187:drug effects*; D000932:Antiemetics / Q000494:pharmacology; D002186:Cannabinoids / Q000627:therapeutic use*; D002707:Chlordiazepoxide / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology; D004597:Electroshock; D005239:Fear / Q000187:drug effects / Q000523:psychology; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009325:Nausea / Q000188:drug therapy* / Q000523:psychology*; D017294:Ondansetron / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000932:Antiemetics; D002186:Cannabinoids; D006993:Hypnotics and Sedatives; C524353:delta(1)-tetrahydrocannabinolic acid; D017294:Ondansetron; D002707:Chlordiazepoxide; D013759:Dronabinol; C006884:cannabidiolic acid; D018021:Lithium Chloride