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Psychopharmacology (Berl). 2014 Aug;231(16):3207-15. doi: 10.1007/s00213-014-3498-1. Epub 2014 Mar 5.

A comparison of cannabidiolic acid with other treatments for anticipatory nausea using a rat model of contextually elicited conditioned gaping.

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1
Department of Psychology and Collaborative Neuroscience Program, University of Guelph, 50 Stone Rd E, Guelph, ON, N1G 2W1, Canada.

Abstract

RATIONALE:

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.

MATERIALS AND 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.

PMID:
24595502
DOI:
10.1007/s00213-014-3498-1
[Indexed for MEDLINE]
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