# Role of CB1 Receptors in Opioid Tolerance During Pain

> **NIH NIH R00** · LEGACY EMANUEL HOSPITAL AND HEALTH CENTER · 2020 · $249,000

## Abstract

PROJECT SUMMARY
The goal of this research is to characterize the interaction between the mu-opioid and CB1-cannabinoid
receptors during pain. The analgesic properties of opioids are well known, and because of the recent
legalization of medicinal cannabis in many US states, cannabis is increasingly being utilized as an
analgesic. A growing body of evidence suggests that the cannabinoid and opioid systems interact in several
ways that could be of significant therapeutic utility. However, the mechanisms of cannabinoid/opioid
interactions, and the abuse potential of combined cannabinoid/opioid administration have yet to be
elucidated. Therefore, we propose to characterize the interaction between opioids and cannabinoids in
conditions during which these drugs might be used for their analgesic properties; specifically, in
inflammatory and neuropathic pain. This five-year, Pathway to Independence project has three Specific
Aims. The first Aim (during the mentored K99 phase) will characterize pain-induced adaptations in the CB1
receptor system. The second Aim (during the R00 phase) will determine the efficacy and safety of combined
cannabinoid/opioid treatment of inflammatory and neuropathic pain. While the studies in Aim 2 will provide
important clinical insight, safe implementation of novel analgesic strategies requires a thorough
understanding of the neural mechanisms underlying cannabinoid/opioid interactions. These mechanisms
will be uncovered in the third Aim of this proposal, and the experiments therein provide an added benefit of
mapping the relatively nebulous periaqueductal gray, using cutting edge optogenetic techniques. The
studies in these independent Aims seamlessly blend the skills I propose to acquire with my extensive
expertise in the behavioral pharmacology and in vitro physiology of chronic morphine-induced adaptations
in the descending pain pathway. The completion of the proposed studies will allow me to accomplish my
immediate goal of further characterizing cannabinoid/opioid interactions. It also directly contributes to my
long-term goal of developing novel therapies that maximize analgesia while minimizing negative side
effects. This Pathway to Independence project also provides me with the critical opportunity to transition
from mentored trainee to tenure-track independent investigator. The mentor Jose Moron-Concepcion is the
ideal supervisor for this project, as his experience with motivated behavior and molecular biochemistry is
critical in carrying my work into the future. As a world leader in the chronic pain field and an innovator in in
vitro optogenetics, the co-mentor Robert Gereau is equally well suited to expand my skills to include cutting
edge elements that will significantly elevate the impact of my work. Furthermore, the world-class facilities at
Washington University will provide an impeccable training environment in which I can complete my goals
and successfully transition to independence.

## Key facts

- **NIH application ID:** 10013187
- **Project number:** 5R00DA041467-04
- **Recipient organization:** LEGACY EMANUEL HOSPITAL AND HEALTH CENTER
- **Principal Investigator:** Adrianne Rae Wilson-Poe
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2019-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10013187

## Citation

> US National Institutes of Health, RePORTER application 10013187, Role of CB1 Receptors in Opioid Tolerance During Pain (5R00DA041467-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10013187. Licensed CC0.

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