Features of (+)-trans-cannabidiol-2-hydroxy pentyl and applications to disease: A focus on usage in diabetic nephropathy

Two isomers of cannabidiol (CBD) exist; the natural (−)-CBD and the synthetic enantiomer (+)-trans-CBD. (+)-CBD and its derivatives have an increased affinity to the cannabinoid type 1 and type 2 receptors (CB1R and CB2R), binding in the nanomolar range. A novel (+)-trans enantiomer, (+)-trans-cannabidiol-2-hydroxy-pentyl ((+)-CBD-HPE) acts as a CB1R antagonist and a CB2R agonist with very high affinity for both receptors. The cannabinoid receptors have an impact on metabolic disorders with concomitant inflammation, such as type 1 diabetes and its complications, including diabetic nephropathy. (+)-CBD-HPE protects insulin-producing beta cells from STZ-induced insulitis, preserving their viability and function, thus preventing hyperglycemia. Also, (+)-CBD-HPE prevents renal inflammation and fibrosis in STZ-challenged mice, reducing renal lesions and glomerular hypertrophy, hence preserving renal function. Potential therapeutic applications of (+)-CBD-HPE are broad, including other forms of nephropathy and diabetes and pathologies associated with chronic inflammation and fibrosis for which CB1R and CB2R play a role.