Cannabidiol improves short-term memory in a Streptozotocin-induced animal model of Alzheimer’s disease

Alzheimer's disease (AD) is a progressive neurodegenerative pathology and the leading cause of dementia in the elderly. Early impairments in brain glucose metabolism and insulin signaling pathway may contribute to neurodegeneration, promoting oxidative stress, increased amyloid-beta (Aβ) production, Tau hyperphosphorylation, mitochondrial dysfunction, neuroinflammation, and neuronal loss. The search for novel therapeutic strategies that can prevent, or slow AD progression remains a major challenge. Cannabidiol (CBD), a phytocannabinoid, has been shown to exert neuroprotective, antioxidant, and anti-inflammatory effect in various experimental models. This study aimed to evaluate the potential neuroprotective effect of CBD in a rat model of AD induced by streptozotocin (STZ, 3 mg/kg, i.c.v.). Wistar rats (6–7 months old) received CBD (10 mg/kg, i.p.) for 14 consecutive days. During treatment, behavioral assessments including the open field, novel object recognition, sucrose preference, and spontaneous alternation tasks were performed, alongside monitoring of body weight and liquid consumption. At the end of the protocol, brains were collected for immunohistochemistry, immunofluorescence, and oxidative stress analysis. STZ-treated animals displayed cognitive deficits, weight loss, and increased Aβ deposition in the hippocampus. CBD treatment prevented short-term memory impairment, reduced Aβ accumulation in the CA1 and dentate gyrus, and decreased microglial activation (Iba-1 immunoreactivity). In addition, CBD attenuated oxidative damage in the striatum. These findings suggest that CBD exerts neuroprotective effects in this pharmacological model of AD, supporting its potential as a candidate for further investigation in the context of neurodegenerative diseases.