Effects of Cannabidiol on Diabetes Outcomes and Chronic Cerebral Hypoperfusion Comorbidities in Middle-Aged Rats

Neurotox Res. 2019 Feb;35(2):463-474. doi: 10.1007/s12640-018-9972-5. Epub 2018 Nov 14.


Diabetes and aging are risk factors for cognitive impairments after chronic cerebral hypoperfusion (CCH). Cannabidiol (CBD) is a phytocannabinoid present in the Cannabis sativa plant. It has beneficial effects on both cerebral ischemic diseases and diabetes. We have recently reported that diabetes interacted synergistically with aging to increase neuroinflammation and memory deficits in rats subjected to CCH. The present study investigated whether CBD would alleviate cognitive decline and affect markers of inflammation and neuroplasticity in the hippocampus in middle-aged diabetic rats submitted to CCH. Diabetes was induced in middle-aged rats (14 months old) by intravenous streptozotocin (SZT) administration. Thirty days later, the diabetic animals were subjected to sham or CCH surgeries and treated with CBD (10 mg/kg, once a day) during 30 days. Diabetes exacerbated cognitive deficits induced by CCH in middle-aged rats. Repeated CBD treatment decreased body weight in both sham- and CCH-operated animals. Cannabidiol improved memory performance and reduced hippocampal levels of inflammation markers (inducible nitric oxide synthase, ionized calcium-binding adapter molecule 1, glial fibrillary acidic protein, and arginase 1). Cannabidiol attenuated the decrease in hippocampal levels of brain-derived neurotrophic factor induced by CCH in diabetic animals, but it did not affect the levels of neuroplasticity markers (growth-associated protein-43 and synaptophysin) in middle-aged diabetic rats. These results suggest that the neuroprotective effects of CBD in middle-aged diabetic rats subjected to CCH are related to a reduction in neuroinflammation. However, they seemed to occur independently of hippocampal neuroplasticity changes.

Keywords: Brain ischemia; Cannabidiol; Diabetes; Middle-aged rats; Neuroprotection.

MeSH terms

  • Age Factors
  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Brain / blood supply*
  • Brain / drug effects*
  • Brain / metabolism
  • Cannabidiol / pharmacology
  • Cannabidiol / therapeutic use*
  • Cerebrovascular Circulation / drug effects*
  • Cerebrovascular Circulation / physiology
  • Chronic Disease
  • Comorbidity
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy*
  • Male
  • Rats
  • Rats, Wistar
  • Treatment Outcome


  • Blood Glucose
  • Cannabidiol