Protocol to prepare inclusion complex-enhanced cannabinoid nano-micelles for behavioral pharmacology and in vivo neurophysiology in mice

Abstract Cannabinoids have significant therapeutic potential but are limited by hydrophobicity and low bioavailability. Here, we present a protocol for preparing a nano-micellar cannabidiol formulation (CBD-IN) using CBD, (2-hydroxypropyl)-β-cyclodextrin, and polysorbate 80. We describe the steps to produce 16–32 nm micelles that markedly enhance cannabinoid water solubility. We detail quality-control procedures using liquid chromatography-mass spectrometry and cryo-transmission electron microscopy. This protocol applies to real-time mouse behavioral pharmacology and in vivo neurophysiology studies through rapid systemic delivery and central nervous system