title: Effect of combined oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models.
abstract: The purpose of this study was to evaluate the potential of oral combined cannabis constituents to reduce nausea.
  
  
  
  The objective of this study was to determine the effect of combining subthreshold oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models of conditioned gaping.
  
  
  
  The potential of intragastric (i.g.) administration of THC, CBDA, or combined doses, to interfere with acute nausea-induced conditioned gaping (acute nausea) or the expression of contextually elicited conditioned gaping (anticipatory nausea), was evaluated.
  
  
  
  For acute nausea, i.g. administration of subthreshold doses of THC (0.5 and 1 mg/kg) or CBDA (0.5 and 1 μg/kg) significantly suppressed acute nausea-induced gaping, whereas higher individual doses of both THC and CBDA were maximally effective. Combined i.g. administration of higher doses of THC and CBDA (2.5 mg/kg THC-2.5 μg/kg CBDA; 10 mg/kg THC-10 μg/kg CBDA; 20 mg/kg THC-20 μg/kg CBDA) also enhanced positive hedonic reactions elicited by saccharin solution during conditioning. For anticipatory nausea, combined subthreshold i.g. doses of THC (0.1 mg/kg) and CBDA (0.1 μg/kg) suppressed contextually elicited conditioned gaping. When administered i.g., THC was effective on its own at doses ranging from 1 to 10 mg/kg, but CBDA was only effective at 10 μg/kg. THC alone was equally effective by intraperitoneal (i.p.) and i.g. administration, whereas CBDA alone was more effective by i.p. administration (Rock et al. in Psychopharmacol (Berl) 232:4445-4454, 2015) than by i.g. administration.
  
  
  
  Oral administration of subthreshold doses of THC and CBDA may be an effective new treatment for acute nausea and anticipatory nausea and appetite enhancement in chemotherapy patients.
authors.affiliation: Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, N1G 2W1, Canada.
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: Cassidy
authors.initials: C
authors.lastname: Connolly
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. parkerl@uoguelph.ca.|Department of Psychology, University of Guelph, Guelph, ON, N1G 2W1, Canada. parkerl@uoguelph.ca.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Parker
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002186:Cannabinoids / Q000494:pharmacology*; D003213:Conditioning, Psychological; D013759:Dronabinol / Q000494:pharmacology*; D008297:Male; D009325:Nausea; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002186:Cannabinoids; D013759:Dronabinol; C006884:cannabidiolic acid
keywords: Acute nausea; Anticipatory nausea; CBDA; Conditioned gaping; Hedonic reactions; Locomotor activity; Oral administration; THC