Oromucosal Administration of a Cannabidiol-Enriched Cannabis sp. Extract for 2 Weeks Moderately Reduces Cold...

Chronic neuropathic pain (CNP) involves complex interactions between resident and peripheral immune cells, as well as modulation of the endocannabinoid system. Cannabis-based products have emerged as promising therapeutic options, but their effects on immune cells remain unclear. This study evaluated the effects of a cannabidiol (CBD)-enriched Cannabis sp. extract administered via the oral mucosa in a CNP model.

Two-month-old Wistar rats of both sexes were randomly assigned to four groups. Two groups underwent chronic constriction injury (CCI) of the sciatic nerve, while the remaining groups underwent sham surgery (SHAM). Starting at Day 7 post-CCI, rats received either the CBD-enriched extract (10 mg/kg) or vehicle for 15 days. Mechanical and thermal sensitivity were assessed using the von Frey, acetone and hot plate tests. Ipsilateral spinal cord segments were analysed by flow cytometry, immunohistochemistry and western blotting.

CCI induced thermal hyperalgesia and mechanical allodynia. Treatment with the CBD-enriched extract modestly reduced cold sensitivity in CCI rats of both sexes but did not improve heat sensitivity and had a significant but minor effect on mechanical thresholds. CCI increased spinal cord microglial cell numbers, particularly in females, an effect not modulated by treatment. No significant changes were detected in immune cell infiltration or CB1R, CB2R, or TRPV1 protein expression across groups.

Oromucosal treatment with a CBD-enriched extract modestly alleviates cold hypersensitivity in both sexes. Neuroimmune alterations in the spinal cord at 22 days post-CCI indicate a predominance of microglia, with no detectable peripheral immune cell infiltration, regardless of treatment.

This manuscript contributes to addressing gaps in the literature regarding preclinical models evaluating Cannabis sp. based products using treatment protocols that more closely reflect patient use, as commercially available cannabidiol-enriched extract and the oromucosal route, consistent with the route commonly used by patients. In addition, all experiments were conducted in animals of both sexes, addressing a well-recognised limitation of many preclinical studies in chronic pain research. Notably, the International Association for the Study of Pain has emphasised the need for further research in this area before endorsing the use of Cannabis sp. based products for the treatment of chronic pain.