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

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 exposure. For complete details on the use and execution of this protocol, please refer to Feng et al. 1