An evaluation of the anti-hyperalgesic effects of cannabidiolic acid-methyl ester (CBDA-ME) in a preclinical model of peripheral neuropathic pain.
Br J Pharmacol. 2020 Jan 24;:
Authors: Zhu YF, Linher-Melville K, Niazmand MJ, Sharma M, Shahid A, Zhu KL, Parzei N, Sidhu J, Haj C, Mechoulam R, Singh G
BACKGROUND AND PURPOSE: Chronic neuropathic pain (NEP) is associated with growing therapeutic cannabis use. To promote quality of life without psychotropic effects, cannabinoids other than Δ9-tetrahydrocannabidiol, including cannabidiol and its precursor cannabidiolic acid (CBDA), are being evaluated. Due to its instability, CBDA has been understudied, particularly as an anti-nociceptive agent. Adding a methyl ester group (CBDA-ME) significantly enhances its stability, facilitating analyses of its analgesic effects in vivo. This study examines early treatment efficacy of CBDA-ME in a rat model of peripherally induced NEP and evaluates sex as a biological variable.
EXPERIMENTAL APPROACH: After 14 consecutive days of intraperitoneal CBDA-ME administration at 0.01, 0.1, and 1 μg/kg, commencing one day after surgically implanting a sciatic nerve-constricting cuff to induce NEP, the anti-nociceptive efficacy of this cannabinoid was assessed in male and female Sprague-Dawley rats relative to vehicle-treated counterparts. In females, 2 and 4 μg/kg daily doses of CBDA-ME were also evaluated. Behavioural tests were performed for hind paw mechanical and thermal withdrawal thresholds once a week for eight weeks. At endpoint, in vivo electrophysiological recordings were obtained to characterize soma threshold changes in primary sensory neurons.
KEY RESULTS: In males, CBDA-ME elicited a significant concentration-dependent chronic anti-hyperalgesic effect, also influencing both nociceptive and non-nociceptive mechanoreceptors, which were not observed in females at any of the concentrations tested.
CONCLUSION AND IMPLICATIONS: Initiating treatment of a peripheral nerve injury with CBDA-ME at an early stage post-surgery provides anti-nociception in males, warranting further investigation into potential sexual dimorphisms underlying this response.
PMID: 31981216 [PubMed – as supplied by publisher]