Characterizing the Anxiolytic Potential and Synergistic Efficacy of Cannabidiol and d-limonene
Abstract
Emerging evidence has elucidated the anxiolytic properties of the cannabis-derived phytochemicals cannabidiol (CBD) and d-limonene and the ‘Entourage Effect’ wherein, multiple components of cannabis synergize to produce stronger effects than their pure counterparts. However, no studies have yet explored this effect in combinations of CBD and limonene. Thus, the present thesis investigated the anxiolytic and synergistic potential of concurrently administered intra-nucleus accumbens shell CBD (1 ng/0.5 μl or 5 ng/0.5 μl) and inhaled limonene (200 μl or 2000 μl). Additionally, the role of the 5-HT1A receptor in mediating these effects was examined by co-application of the antagonist NAD299 and by the assessment of downstream molecular biomarkers. Findings from this study demonstrated for the first time that relative to their isolated counterparts, combinations of limonene and CBD more effectively reduces symptoms of anxiety, with the observed reversal of these effects with NAD299 elucidating a role at the 5-HT1A receptor.