Unravelling a potential therapeutic effect of polymeric lipid-core nanoencapsulated cannabidiol on anxiety- and panic-like behaviours elicited by Bothrops jararaca lancehead pit vipers.

The burgeoning interest in cannabinoid-based therapies for mental disorders motivates research into their efficacy. This study investigates the acute effects of nanoencapsulated Cannabidiol (CBD) on panic attack-like defensive responses elicited in mice by the venomous snake Bothrops jararaca in polygonal arenas validated as a panic attack experimental model. The aim of this work was to investigate if polymeric lipid core-nanoencapsulated CBD at low doses was able to cause antiaversive effects in comparison to non-encapsulated CBD at a higher dose. Mice were habituated in the enriched polygonal arena during three days and treated with either CBD in a dose already demonstrated to cause antiaversive effects (3 mg/kg), used as a positive control, or nanostructured CBD at much lower doses before snake confrontation. Both non-encapsulated and nanoencapsulated CBD significantly attenuated antipredatory responses in mice. Interestingly. Polymeric lipid core-nanoencapsulated CBD, particularly at lower doses, attenuated panic-like responses, including defensive attention, flat back approach, and escape behaviours to safe places after reaching limbic system structures. Additionally, rhodamine-labeled polymeric lipid core-nanoencapsulated CBD, administered either intraperitoneally or intranasally, effectively crossed the blood-brain barrier, with fluorescence observed in multiple limbic and paralimbic brain structures implicated in the elaboration of defensive/antipredatory behavioural responses. These findings indicate that nanoencapsulation improves the bioavailability of CBD and its targeting of the central nervous system, thereby supporting its potential for low-dose therapeutic applications in the treatment of anxiety and panic disorders.