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2022: Transcriptomic Analysis of Cannabidiol and Tetrahydrocannabivarin Revealed New Molecular Targets for Treatment of Experimental Diabetic Neuropathy

Anil Kumar Kalvala
Florida A&M University

Co-authors: Arvind Bagde1, Mandip Singh Sachdeva1
1Florida A&M University

Purpose: To identify the transcriptomic signatures of Cannabidiol (CBD) and tetrahydrocannabivarin (THCV) in Streptozotocin induced experimental diabetic neuropathy (DN).

Methods: Animals were rendered diabetic using STZ (55 mg/kg, i.p). CBD was administered (10 & 20 mg/ kg, i.p) and THCV (15 & 30 mg/kg, i.p) during the last 4 weeks of 12 week diabetic period. The animals’ pain perception was assessed using the Hargreaves plantar test, hot and cold plate method, vonfrey aesthesiometer, and Randal Sellito apparatus, and nerve functional assessment using the Laser Doppler oxymeter. After the study, the animals’ blood was drawn to measure blood glucose levels and their DRGs were isolated for transcriptomic studies.

Results: Diabetic animals after eight weeks significantly (P<0.001) increased hypersensitivity to thermal and mechanical pain and also significantly (p<0.001) reduced nerve blood flow when compared to the age matched control animals. CBD and THCV treatment reversed these effects in a dose-dependent manner while having no effect on the animals’ body weights or blood glucose levels. Differently expressed genes (transcriptomic analysis) have been discovered in the isolated DRGs of control, diabetic, and treated animals, with 32 genes in the control group, 33 in the THCV group, and 45 in the CBD group, all of which differ from the genes expressed in diabetic animals’ DRGs. These genes regulating nerve function by affecting the RAP1 signaling pathway, MAP kinase signaling pathway, neurotrophin signaling pathway, Parkinson’s disease, Alzheimer’s disease, focal adhesion, insulin signaling pathway, microRNAs in cancer, and others according to KEGG analysis.

Conclusion: Despite the fact that CBD and THCV are non-psychoactive medical marijuana components, they differ in their ability to regulate different genes that contribute to the health of neurons in diabetic condition. More research is needed to understand how these two compounds work together to reduce diabetic pain.

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