E M Rock1, L A Parker. 1. Department of Psychology, University of Guelph, Guelph, ON, Canada.
Abstract
BACKGROUND AND PURPOSE: To determine the minimally effective dose of cannabidiolic acid (CBDA) that effectively reduces lithium chloride (LiCl)-induced conditioned gaping reactions (nausea-induced behaviour) in rats and to determine if these low systemic doses of CBDA (5-0.1 μg·kg⁻¹) relative to those of CBD could potentiate the anti-nausea effects of the classic 5-hydroxytryptamine 3 (5-HT₃) receptor antagonist, ondansetron (OND). EXPERIMENTAL APPROACH: We investigated the efficacy of low doses of CBDA to suppress acute nausea, assessed by the establishment of conditioned gaping to a LiCl-paired flavour in rats. The potential of threshold and subthreshold doses of CBDA to enhance the reduction of nausea-induced conditioned gaping by OND were then determined. KEY RESULTS: CBDA (at doses as low as 0.5 μg·kg⁻¹) suppressed nausea-induced conditioned gaping to a flavour. A low dose of OND (1.0 μg·kg⁻¹) alone reduced nausea-induced conditioned gaping, but when it was combined with a subthreshold dose of CBDA (0.1 μg·kg⁻¹) there was an enhancement in the suppression of LiCl-induced conditioned gaping. CONCLUSIONS AND IMPLICATIONS: CBDA potently reduced conditioned gaping in rats, even at low doses and enhanced the anti-nausea effect of a low dose of OND. These findings suggest that combining low doses of CBDA and OND will more effectively treat acute nausea in chemotherapy patients.
BACKGROUND AND PURPOSE: To determine the minimally effective dose of cannabidiolic acid (CBDA) that effectively reduces lithium chloride (LiCl)-induced conditioned gaping reactions (nausea-induced behaviour) in rats and to determine if these low systemic doses of CBDA (5-0.1 μg·kg⁻¹) relative to those of CBD could potentiate the anti-nausea effects of the classic 5-hydroxytryptamine 3 (5-HT₃) receptor antagonist, ondansetron (OND). EXPERIMENTAL APPROACH: We investigated the efficacy of low doses of CBDA to suppress acute nausea, assessed by the establishment of conditioned gaping to a LiCl-paired flavour in rats. The potential of threshold and subthreshold doses of CBDA to enhance the reduction of nausea-induced conditioned gaping by OND were then determined. KEY RESULTS:CBDA (at doses as low as 0.5 μg·kg⁻¹) suppressed nausea-induced conditioned gaping to a flavour. A low dose of OND (1.0 μg·kg⁻¹) alone reduced nausea-induced conditioned gaping, but when it was combined with a subthreshold dose of CBDA (0.1 μg·kg⁻¹) there was an enhancement in the suppression of LiCl-induced conditioned gaping. CONCLUSIONS AND IMPLICATIONS: CBDA potently reduced conditioned gaping in rats, even at low doses and enhanced the anti-nausea effect of a low dose of OND. These findings suggest that combining low doses of CBDA and OND will more effectively treat acute nausea in chemotherapy patients.
Authors: Luciano De Petrocellis; Alessia Ligresti; Aniello Schiano Moriello; Marco Allarà; Tiziana Bisogno; Stefania Petrosino; Colin G Stott; Vincenzo Di Marzo Journal: Br J Pharmacol Date: 2011-08 Impact factor: 8.739
Authors: E M Rock; D Bolognini; C L Limebeer; M G Cascio; S Anavi-Goffer; P J Fletcher; R Mechoulam; R G Pertwee; L A Parker Journal: Br J Pharmacol Date: 2012-04 Impact factor: 8.739
Authors: Erin M Rock; Cheryl L Limebeer; Gavin N Petrie; Lauren A Williams; Raphael Mechoulam; Linda A Parker Journal: Psychopharmacology (Berl) Date: 2017-04-20 Impact factor: 4.530
Authors: Daniel I Brierley; James Samuels; Marnie Duncan; Benjamin J Whalley; Claire M Williams Journal: Psychopharmacology (Berl) Date: 2015-10-06 Impact factor: 4.530
Authors: Roger G Pertwee; Erin M Rock; Kelsey Guenther; Cheryl L Limebeer; Lesley A Stevenson; Christeene Haj; Reem Smoum; Linda A Parker; Raphael Mechoulam Journal: Br J Pharmacol Date: 2017-12-05 Impact factor: 8.739
Authors: Erin M Rock; Megan T Sullivan; Sarah Pravato; Mick Pratt; Cheryl L Limebeer; Linda A Parker Journal: Psychopharmacology (Berl) Date: 2020-01-02 Impact factor: 4.530