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

• Published in: Psychopharmacology Vol. 235; no. 11; pp. 3259 - 3271
• Main Authors: Rock, Erin M., Limebeer, Cheryl L., Parker, Linda A.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2018; Springer Nature B.V
• Subjects: Administration, Oral; Analgesics, Non-Narcotic; Animals; Anti-inflammatory agents; Biomedical and Life Sciences; Biomedicine; Cannabinoids; Cannabinoids - administration & dosage; Cannabis; Carrageenan; Carrageenan - toxicity; Disease Models, Animal; Dose-Response Relationship, Drug; Dronabinol - administration & dosage; Edema; Edema - chemically induced; Edema - drug therapy; Hyperalgesia; Hyperalgesia - chemically induced; Hyperalgesia - drug therapy; Inflammation; Inflammation - chemically induced; Inflammation - drug therapy; Male; Neurosciences; Oral administration; Original Investigation; Pain - chemically induced; Pain - drug therapy; Pain perception; Pharmacology/Toxicology; Psychiatry; Rats; Rats, Sprague-Dawley; Rodents; Tetrahydrocannabinol; Transient receptor potential proteins; Treatment Outcome; Δ; Rat; AMG9810; Cannabidiol; Inflammation; Tetrahydrocannabiol; Cannabidiolic acid; Carrageenan; SR141716; Hyperalgesia; Δ9-Tetrahydrocannabiol
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-018-5034-1

Rationale Cannabidiol (CBD), a non-intoxicating component of cannabis, or the psychoactive Δ 9 -tetrahydrocannabiol (THC), shows anti-hyperalgesia and anti-inflammatory properties. Objectives 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. Results 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. Conclusion 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.