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Effect of combined doses of Δ9-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea using rat (Sprague- Dawley) models of conditioned gaping

Abstract

Rationale

Δ9-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.

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Acknowledgments

This work was supported by a Natural Sciences and Engineering Research Council of Canada (NSERC) Engage Grant (EGP #470199-14) to LAP in partnership with Prairie Plant Systems Inc, as well as grants to LAP from NSERC (92056) and Canadian Institute of Health Research (137122).

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Correspondence to Erin M. Rock.

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Rock, E.M., Limebeer, C.L. & Parker, L.A. Effect of combined doses of Δ9-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea using rat (Sprague- Dawley) models of conditioned gaping. Psychopharmacology 232, 4445–4454 (2015). https://doi.org/10.1007/s00213-015-4080-1

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Keywords

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