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  • Title: Effect of combined oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models.
    Author: Rock EM, Connolly C, Limebeer CL, Parker LA.
    Journal: Psychopharmacology (Berl); 2016 Sep; 233(18):3353-60. PubMed ID: 27438607.
    Abstract:
    RATIONALE: The purpose of this study was to evaluate the potential of oral combined cannabis constituents to reduce nausea. OBJECTIVE: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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