, Volume 235, Issue 11, pp 3259–3271 | Cite as

Effect of cannabidiolic acid and ∆9-tetrahydrocannabinol on carrageenan-induced hyperalgesia and edema in a rodent model of inflammatory pain

  • Erin M. Rock
  • Cheryl L. Limebeer
  • Linda A. ParkerEmail author
Original Investigation



Cannabidiol (CBD), a non-intoxicating component of cannabis, or the psychoactive Δ9-tetrahydrocannabiol (THC), shows anti-hyperalgesia and anti-inflammatory properties.


The present study evaluates the anti-inflammatory and anti-hyperalgesia effects of CBD’s potent acidic precursor, cannabidiolic acid (CBDA), in a rodent model of carrageenan-induced acute inflammation in the rat hind paw, when administered systemically (intraperitoneal, i.p.) or orally before and/or after carrageenan. In addition, we assess the effects of oral administration of THC or CBDA, their mechanism of action, and the efficacy of combined ineffective doses of THC and CBDA in this model. Finally, we compare the efficacy of CBD and CBDA.


CBDA given i.p. 60 min prior to carrageenan (but not 60 min after carrageenan) produced dose-dependent anti-hyperalgesia and anti-inflammatory effects. In addition, THC or CBDA given by oral gavage 60 min prior to carrageenan produced anti-hyperalgesia effects, and THC reduced inflammation. The anti-hyperalgesia effects of THC were blocked by SR141716 (a cannabinoid 1 receptor antagonist), while CBDA’s effects were blocked by AMG9810 (a transient receptor potential cation channel subfamily V member 1 antagonist). In comparison to CBDA, an equivalent low dose of CBD did not reduce hyperalgesia, suggesting that CBDA is more potent than CBD for this indication. Interestingly, when ineffective doses of CBDA or THC alone were combined, this combination produced an anti-hyperalgesia effect and reduced inflammation.


CBDA or THC alone, as well as very low doses of combined CBDA and THC, has anti-inflammatory and anti-hyperalgesia effects in this animal model of acute inflammation.


Inflammation Hyperalgesia Δ9-Tetrahydrocannabiol Cannabidiolic acid Cannabidiol Rat Carrageenan SR141716 AMG9810 



This work was supported by a Natural Sciences and Engineering Research Council of Canada (NSERC) Collaborative Research and Development Grant (CRDPJ 476416-14) to LAP in partnership with Prairie Plant Systems Inc., as well as a grant to LAP from NSERC (92056) and from Canadian Institute of Health Research (137122).

Compliance with ethical standards

All animal procedures complied with the Canadian Council on Animal Care and were approved by the Institutional Animal Care Committee (accredited by the Canadian Council on Animal Care).

Conflict of interest

The authors declare that they have no conflict of interest.


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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Psychology and Collaborative Neuroscience ProgramUniversity of GuelphGuelphCanada

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