Abstract
BACKGROUND: Cannabidiol (CBD), main non-psychoactive ingredient of Cannabis sativa L. is known to have anti-ischemic, antidiabetic and neuroprotective effects. Ischemia–reperfusion injury of the retina is reportedly involved in deterioration of its function in diabetic retinopathy. The study was aimed to evaluate the in vivo potential retinoprotective role of CBD in type II diabetes mellitus. METHODS: Zucker Diabetic Fatty (ZDF) rats were treated with CBD orally and electroretinographical analysis was carried out. In order to confirm the disease model and to assess other antidiabetic effects of CBD in ZDF rats, fasting blood glucose, oral glucose tolerance test, weight measurements and histology also took place. RESULTS: Weight and glucose-related analyses supported our used diabetic animal model. CBD reduced diabetic weight gain without affecting glucose levels of ZDF rats, suggesting glucose-independent mechanisms of its retinal actions. CBD treatment selectively increased dark-adapted ERG amplitudes, while leaving light-adapted responses unaffected. It did not alter reduced amplitudes and prolonged implicit times of diabetic oscillatory potentials (OPs), but lowered variability of OP amplitudes and flicker peak intervals. A potential indirect mechanism for its effects beside glutamatergic inhibition is the ability of CBD to decrease thickening of diabetic retina. CONCLUSIONS: CBD exerted glucose-independent retinoprotective effects in ZDF rats by normalizing weight gain and preventing retinal thickening. While glycemic levels were unaffected, CBD selectively enhanced rod-mediated ERG amplitudes and reduced variability indicators of OPs and flickers. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s42238-026-00421-z.