Delivery to the brain is a challenging task due to its protection by the blood-brain barrier (BBB). Lipids and fatty acids are reported to affect the permeability of the BBB, although this has not been reported following oral administration. Cannabidiol (CBD) has high therapeutic potential in the brain, therefore, this work investigated CBD delivery to anatomical brain regions following oral administration in lipid-based and lipid-free vehicles. All formulations resulted in a short brain Tmax (1 h) and brain-plasma ratios ≥ 3.5, with retention up to 18 h post administration. The highest CBD delivery was observed in the olfactory bulb and striatum, and the medulla pons and cerebellum the lowest. The lipid-free vehicle led to the highest levels of CBD in the whole brain. However, when each anatomical region was assessed individually, the long chain triglyceride-rich rapeseed oil formulation commonly showed optimal performance. The medium chain triglyceride-rich coconut oil formulation did not result in the highest CBD concentration in any brain region. Overall, differences in CBD delivery to the whole brain and various brain regions were observed following administration in different formulations, indicating that the oral formulation selection may be important for optimal delivery to specific regions of the brain.
Keywords: Blood-brain barrier; Brain regions; Cannabidiol; Lipid-based drug delivery; Oral.
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