PROJECT SUMMARY/ABSTRACT
Chronic pain, one of the most common reasons adults seek medical care, has been linked to restrictions in
mobility and daily activities, anxiety and depression, and poor perceived health or reduced quality of life.
Treatment options are limited and often ineffective, contributing to current opioid prescription and abuse issues.
Better outcomes can be achieved by developing new and improved therapeutic approaches or more immediately
by identifying favorable combinations of available or emerging drugs. This research proposal will to test the
effectiveness of a novel pharmacological combination strategy involving a minor cannabinoid (cannabidiol, CBD)
and terpene (Beta-caryophyllene (¿CP) to effectively inhibit chronic pain without abuse potential.
CBD has gained attention as a therapeutic agent over the past several years due to its lack of psychoactivity. A
preclinical dose-response study of the analgesic effect of CBD in a chronic pain model showed that although
CBD has potential in managing chronic pain condition, it exhibited moderate efficacy. However, the beneficial
analgesic effect of CBD was not associated with any of the common side effects of cannabinoids or abuse
potential. Therefore, a strategy is needed to increase the analgesic efficacy of CBD without the potential for
abuse. ¿CP has been approved by the Food and Drug Administration (FDA) as a food additive, known for its
favorable safety profile. Found in plants including basil, black pepper, cloves, and cannabis sativa. BCP is a
natural selective agonist for the cannabinoid type 2 receptor (CB2). In various experimental models, BCP has
an analgesic effect without causing negative psychoactive effects, presumably due to its selectivity to the CB2
receptor; at the same time, BCP does have anti-depressant and anxiolytic effects which are of interest in
addressing common comorbidities of chronic pain. This project will test the novel hypothesis that in comparison
with CBD and BCP alone, CBD and ¿CP in combination produces an enhanced (e.g. synergistic)
analgesic effect in chronic pain without abuse potential. Aim 1 will use behavioral assays and
pharmacological tools to determine the beneficial of CBD and ¿CP in combination in the well-establish chronic
arthritis pain model (Complete Freund’s Adjuvants, CFA). We will use the behavioral assessment of sensory and
affective pain. Isobolographic analysis will demonstrate the nature of interaction (e.g. synergistic). The abuse
potential of CBD and ¿CP in combination will also be tested.
The proposed studies will significantly impact the field of chronic pain management by providing a new
combination therapy, CBD and ¿CP, that is effective and nonaddictive. Furthermore, if effective, this combination
therapy will have a significant impact on the opioid epidemic by offering a safe alternative to opioids that lacks
abuse potential.