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Psychopharmacology (Berl). 2015 Dec;232(24):4445-54. doi: 10.1007/s00213-015-4080-1. Epub 2015 Sep 18.

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.

Author information

1
Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, N1G 2W1, Canada. erock@uoguelph.ca.
2
Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, N1G 2W1, Canada.

Abstract

RATIONALE:

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.

MATERIALS AND 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.

KEYWORDS:

Acute nausea; Anticipatory nausea; CBDA; Conditioned taste avoidance; Locomotor activity; THC

PMID:
26381155
DOI:
10.1007/s00213-015-4080-1
[Indexed for MEDLINE]

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