CBD May Help Reverse Cognitive Decline Linked to Olanzapine and High-Fat Diet, Finds New Study

New research published in Archives of Physiology and Biochemistry finds that cannabidiol (CBD) may help counteract cognitive decline associated with antipsychotic use and a high-fat diet, with effects comparable to a commonly prescribed metabolic drug.

The study, conducted by researchers from Babcock University and the University of Rwanda, examined the impact of CBD on adult male rats exposed to both olanzapine, an antipsychotic medication, and a high-fat diet—two factors known to impair cognitive function.

Over a two-week period, the combination of olanzapine and a high-fat diet led to a sharp decline in memory performance. Object location memory dropped from 3.5% to −39%, while object recognition memory fell from 21.47% to −30.30%. These changes were accompanied by increased levels of amyloid beta 1–42 and heightened expression of GFAP in key brain regions, indicators commonly associated with neurodegeneration and inflammation.

Rats treated with CBD at doses of 10 mg/kg and 25 mg/kg showed significant improvement in cognitive performance, with results comparable to those treated with metformin, a drug often used to manage metabolic side effects. The findings suggest that CBD helped preserve memory function while also reducing biochemical markers tied to brain damage.

Researchers found that CBD’s protective effects were linked to a reduction in lipid peroxidation, a process that damages cells through oxidative stress, as well as the downregulation of pathways involving GFAP and acetylcholinesterase (AChE), both of which play roles in neuroinflammation and cognitive decline.

The study concludes that CBD demonstrates strong neuroprotective potential in this model, particularly in mitigating memory impairment caused by combined pharmaceutical and dietary stressors.

The study’s full abstract can be found below:

The present study investigates the neuroprotective effects of Cannabidiol (CBD) in olanzapine/high-fat diet (HFD) treated adult male Wistar rats. Animals weighing 160-180 g were divided into five groups (n = 7). They include Untreated, HFD+Olan, Met + HFD+Olan, CBD (10 mg/kg)+HFD+Olan, and CBD (25 mg/kg)+HFD + Olan. Olanzapine and metformin were administered as 5 mg/kg and 20 mg/kg, respectively. Cognitive functions, brain biochemical markers, histology and immunohistochemistry were determined. 2 weeks cotreatment of olanzapine/HFD induced cognitive impairment evidenced by significant reduction in Object location memory (OLM) from 3.5 ± 0.75 to -39 ± 8.57% and Object recognition memory (ORM) indices from 21.47 ± 12.68 to -30.30 ± 4.29%, increased serum amyloid beta 1-42 and GFAP hypothalamic and prefrontal cortex expressions. CBD comparable to metformin ameliorated the induced cognitive impairment. CBD possesses remarkable cognitive preserving activity which is associated with decreased lipid peroxidation and down regulation of GFAP/ACHE pathway.