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Br J Pharmacol. 2020 Jan 24. doi: 10.1111/bph.14997. [Epub ahead of print]

An evaluation of the anti-hyperalgesic effects of cannabidiolic acid-methyl ester (CBDA-ME) in a preclinical model of peripheral neuropathic pain.

Author information

1
Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Ontario, Canada.
2
Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
3
Institute for Cannabinoid Research, Hebrew University Medical Faculty, Jerusalem, Israel.

Abstract

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.

KEYWORDS:

cannabidiolic acid-methyl ester; cannabinoid; dorsal root ganglion; electrophysiology; neuropathic pain; sensory neurons

PMID:
31981216
DOI:
10.1111/bph.14997

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