INVESTIGATOR: Catherine Cahill, Ph.D.

STUDY LOCATION: University of California, Los Angeles

PROJECT TITLE: Terpenes as novel analgesics - preclinical study 

FUNDING SOURCE: Center for Medicinal Cannabis Research

PROJECT TYPE: Preclinical Study

STATUS: Active 

ABSTRACT:

The United States is in the midst of a nationwide opioid epidemic; 128 Americans fatally overdosed daily on an opioid drug in 2021. The majority of those that develop an Opioid Use Disorder started with prescription opioid analgesics, highlighting the need to identify new pain treatments. Cannabinoids and terpenes derived from the cannabis plant hold promise as novel pharmacotherapeutic strategies to reduce reliance on opioids for pain management. While delta-9-tetrahydrocannabinol (THC) and cannabidiol have been primary targets for understanding the therapeutic effects of cannabis, accumulating evidence suggests that terpenes, non-intoxicating constituents of the cannabis plant, play an important role in the treatment of pain. Myrcene and ß-caryophyllene are two terpenes shown to have analgesic efficacy in preclinical studies, but these studies are limited to various acute pain assays that are purely sensory in nature or formalin inflammatory pain models. The predictive validity of these nociceptive measures has been questioned with the failure of multiple novel analgesic clinical trials. Given that sensory pain is less likely to impact quality of life compared to the emotional affective component of pain, the proposed studies probing the analgesic potential of terpenes will focus on targeting these emotional affective pain states. To do this, in preclinical models of prolonged pain we will assess the effects of terpenes on the affective-motivational component of pain using assays well-established in our lab. As there is evidence terpenes engage endogenous opioid systems, we will investigate the necessity of the this system in terpene-induced changes in both sensory and affective measures of pain by using knockout mice. One of the primary targets of ß-caryophyllene is the cannabinoid 2 receptor, where activation reduces inflammatory processes. We will use microPET/CT imaging to understand the extent ß-caryophyllene reduces neuroinflammation associated with chronic pain. For all experiments, experimenters handling rodents will be blind to surgery, genotype, sex, and drug treatment. All behavioral data will be analyzed by Factorial ANOVA analyses. These data will provide strong evidence to support the potential of terpenes in pain management as well as inform mechanisms and circuits by which they engage endogenous opioid systems.