title: Effect of combined doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea using rat (Sprague- Dawley) models of conditioned gaping.
abstract: BACKGROUND
  Δ(9)-Tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) found in cannabis both reduce the distressing symptom of nausea, but their combined effects are not understood.
  
  
  OBJECTIVE
  The potential of combined doses of THC and CBDA to reduce acute nausea and anticipatory nausea in rodent models was assessed.
  
  
  METHODS
  For acute nausea, the potential of cannabinoid pretreatment(s) to reduce LiCl-induced nausea paired with saccharin was evaluated in a subsequent drug free taste reactivity test, followed by a taste avoidance test. For anticipatory nausea, the potential of the cannabinoid pretreatment(s) to reduce the expression of LiCl-induced contextually elicited conditioned gaping was evaluated.
  
  
  RESULTS
  Combined subthreshold doses of THC (0.01 and 0.1 mg/kg) and CBDA (0.01 and 0.1 μg/kg) reduced acute nausea. Higher doses of THC (1.0, 10 mg/kg) or CBDA (1.0, 10 μg/kg) alone, as well as these combined doses also reduced acute nausea. THC (10 mg/kg) interfered with conditioned taste avoidance, an effect attenuated by CBDA (10 μg/kg). On the other hand, combined subthreshold doses of THC (0.01 and 0.1 mg/kg) and CBDA (0.01 and 0.1 μg/kg) did not suppress contextually elicited conditioned gaping in a test for anticipatory nausea. However, higher doses of THC (1.0, 10 mg/kg) or CBDA (1.0, 10 μg/kg) alone, as well as these combined doses, also reduced anticipatory nausea. Only at the highest dose (10 mg/kg) did THC impair locomotor activity, but CBDA did not at any dose.
  
  
  CONCLUSIONS
  Combined subthreshold doses of THC:CBDA are particularly effective as a treatment for acute nausea. At higher doses, CBDA may attenuate THC-induced interference with learning.
authors.affiliation: Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, N1G 2W1, Canada. erock@uoguelph.ca.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Rock
authors.affiliation: Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, N1G 2W1, Canada.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Limebeer
authors.affiliation: Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, N1G 2W1, Canada.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Parker
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000494:pharmacology* / Q000627:therapeutic use; D002186:Cannabinoids / Q000494:pharmacology* / Q000627:therapeutic use; D003213:Conditioning, Psychological / Q000187:drug effects*; D004195:Disease Models, Animal; D013759:Dronabinol / Q000494:pharmacology* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D018021:Lithium Chloride; D008297:Male; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012439:Saccharin
chemical_list: D000932:Antiemetics; D002186:Cannabinoids; D013759:Dronabinol; C006884:cannabidiolic acid; D012439:Saccharin; D018021:Lithium Chloride
keywords: Acute nausea; Anticipatory nausea; CBDA; Conditioned taste avoidance; Locomotor activity; THC