Exploring the Role of Cannabidiol-Monoterpene Formulations in Modulating Anxiety Symptoms

Richard Leu, The University of Western Ontario

Abstract

While cannabidiol (CBD) has been documented to elicit anxiolytic effects, only recently have studies been conducted demonstrating the anxiolytic efficacy of the aromatic monoterpene, linalool. Pa

While cannabidiol (CBD) has been documented to elicit anxiolytic effects, only recently have studies demonstrated the anxiolytic efficacy of the aromatic monoterpene, linalool. Past research involving phytocannabinoid-phytocannabinoid formulations has shown that CBD may yield superior anxiolytic efficacy when administered alongside other cannabis compounds, with this phenomenon termed the “Entourage Effect” (EE); however, this EE has not been investigated in phytocannabinoid-terpene formulations. Furthermore, investigations involving intra-cranial CBD administration have shown the nucleus accumbens shell, known for affective processing, to be a therapeutic target of interest. Thus, using treatment interventions in behavioral and molecular assays, this thesis investigated the possibility of EE-potentiated anxiolysis within linalool-CBD formulations through olfactory and intra-NAcSh routes of concurrent acute administration, focusing on GABA_AR and ERK signaling mech

While cannabidiol (CBD) has been documented to elicit anxiolytic effects, only recently have studies demonstrated the anxiolytic efficacy of the aromatic monoterpene, linalool. Past research involving phytocannabinoid-phytocannabinoid formulations has shown that CBD may yield superior anxiolytic efficacy when administered alongside other cannabis compounds, with this phenomenon termed the “Entourage Effect” (EE); however, this EE has not been investigated in phytocannabinoid-terpene formulations. Furthermore, investigations involving intra-cranial CBD administration have shown the nucleus accumbens shell, known for affective processing, to be a therapeutic target of interest. Thus, using treatment interventions in behavioral and molecular assays, this thesis investigated the possibility of EE-potentiated anxiolysis within linalool-CBD formulations through olfactory and intra-NAcSh routes of concurrent acute administration, focusing on GABA_AR and ERK signaling mechanisms previously shown to be mediated by linalool and CBD. Altogether, findings ultimately suggest that linalool-CBD formulations elicit EE-potentiated anxiolysis through GABA

_ttAR- and ERK-dependent mechanisms capable of reversing chronic stress-induced anxiety.

anisms previously shown to be mediated by linalool and CBD. Altogether, findings ultimately suggest that linalool-CBD formulations elicit EE-potentiated anxiolysis through GABA_AR- and ERK-dependent mechanisms capable of reversing chronic stress-induced anxiety.

st research involving phytocannabinoid-phytocannabinoid formulations has shown that CBD may yield superior anxiolytic efficacy when administered alongside other cannabis compounds, with this phenomenon termed the “Entourage Effect” (EE); however, this EE has yet to be investigated in phytocannabinoid-terpene formulations. Furthermore, investigations involving intra-cranial CBD administration have shown the shell region of the nucleus accumbens (NAcSh), located within the mesocorticolimbic pathway and known for affective processing, to be a therapeutic target of interest. Thus, using treatment interventions in behavioral and molecular assays, this thesis investigated the possibility of EE-potentiated anxiolysis between linalool and CBD formulations through olfactory and intra-NAcSh routes of concurrent acute administration. Altogether, the findings ultimately suggest that linalool-CBD formulations elicit EE-potentiated anxiolysis through GABA_AR- and ERK-dependent mechanisms capable of reversing chronic stress-induced anxiety.