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.

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.

• Authors: Erin M Rock, Cheryl L Limebeer, Linda A Parker
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 232 Issue 24 Pg. 4445-54 (Dec 2015) ISSN: 1432-2072 [Electronic] Germany
• PMID: 26381155 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiemetics
• Cannabinoids
• Dronabinol
• cannabidiolic acid
• Saccharin
• Lithium Chloride

Topics

• Animals
• Antiemetics (pharmacology, therapeutic use)
• Cannabinoids (pharmacology, therapeutic use)
• Conditioning, Psychological (drug effects)
• Disease Models, Animal
• Dronabinol (pharmacology, therapeutic use)
• Drug Therapy, Combination
• Lithium Chloride
• Male
• Nausea (chemically induced, drug therapy)
• Rats
• Rats, Sprague-Dawley
• Saccharin