Effect of cannabidiolic acid and Δ
on carrageenan-induced hyperalgesia and edema in a rodent model
of inflammatory pain
Erin M. Rock
&Cheryl L. Limebeer
&Linda A. Parker
Received: 16 January 2018 /Accepted: 7 September 2018 /Published online: 17 September 2018
#Springer-Verlag GmbH Germany, part of Springer Nature 2018
Cannabidiol (CBD), a non-intoxicating component of cannabis, or the psychoactive Δ
-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.
Keywords Inflammation .Hyperalgesia .Δ
-Tetrahydrocannabiol .Cannabidiolic acid .Cannabidiol .Rat .Carrageenan .
Cannabis sativa has been used medicinally for centuries. The
cannabis plant consists of over 100 cannabinoid compounds,
the primary ones being the psychoactive component Δ
hydrocannabinol (THC), and the non-intoxicating component
cannabidiol (CBD). The most frequently reported use of med-
ical cannabis is for pain relief (e.g., Ogborne et al. 2000;
*Linda A. Parker
Department of Psychology and Collaborative Neuroscience
Program, University of Guelph, Guelph, ON N1G2W1, Canada
Psychopharmacology (2018) 235:3259–3271