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We investigated how the biodistribution of cannabidiol (CBD) within the central nervous system (CNS) is influenced by two different formulations, an oil-in-water (O/W) nanoemulsion and polymer-coated nanoparticles (PCNPs). We observed that both CBD formulations administered were preferentially retained in the spinal cord, with high concentrations reaching the brain within 10 mins of administration. The CBD nanoemulsion reached C_max in the brain at 210 ng/g within 120 mins (T_max), whereas the CBD PCNPs had a C_max of 94 ng/g at 30 mins (T_max), indicating that rapid brain delivery can be achieved through the use of PCNPs. Moreover, the AUC_{0–4 h} of CBD in the brain was increased 3.7-fold through the delivery of the nanoemulsion as opposed to the PCNPs, indicating higher retention of CBD at this site. Both formulations exhibited immediate anti-nociceptive effects in comparison to the respective …