# Exploring the mechanisms underlying the analgesic effect of Cannabidiol using Proton Magnetic Resonance Spectroscopy.

> **NIH NIH R21** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $152,500

## Abstract

Project Summary/Abstract: Chronic pain is a prevalent disorder affecting approximately 100 million Americans.
Treatment of chronic pain has heavily relied on opioid drugs, however; the use of opioids is accompanied with
significant shortcomings including lack of efficacy in the long term and the risk for dependence that has
contributed significantly to the national opioid epidemic. Thus, development and identification of novel
strategies for pain management in chronic pain is a critical unmet need. A burgeoning body of literature
suggests that the Cannabis plant has analgesic properties, with reported therapeutic effects ranging from
substantial to conclusive in both preclinical and clinical studies. The main psychoactive constituent in the
cannabis plant, tetrahydrocannabinol (THC) has demonstrated analgesic effects, however; its use is limited by
adverse psychoactive and cognitive effects. However, not all isomers of THC demonstrate psychoactive
effects. For example, cannabidiol (CBD) has been shown to demonstrate analgesic properties without
psychoactive effects. The biological mechanisms underlying the analgesic efficacy of CBD are relatively
unexplored and hence mechanistic studies investigating this research question are needed. CBD has a
complex pharmacology with agonist and antagonist activity at several receptors including but not limited to
endocannabinoid CB1 and CB2 receptors, serotonin 5-HT1A receptors, gamma-amino butyric acid receptors
(GABA-A), and vanilloid receptors. In addition, CBD is a potent anti-inflammatory and has shown to decrease
levels of cytokines and other pro-inflammatory signaling molecules. The goal of the proposed study, which
responds to RFA-AT-19-009, is to evaluate changes in brain chemistry after a short-term (5-day) administration
of a cannabis extract enriched in CBD using proton magnetic resonance spectroscopy (1H-MRS). 1H-MRS
allows the measurement of in vivo levels of brain metabolites such as N-acetylaspartate, creatine, lactate,
glutamate, GABA, glutamine (Gln), and myoinositol (mI). MRS studies of chronic pain have demonstrated
changes in glutamate and GABA signaling in critical pain-processing regions of the brain. Furthermore, chronic
pain has also been associated with increased levels of pro-inflammatory signaling molecules. Thus,
pharmacological agents that can modulate central glutamate and GABAergic tone may exhibit potent analgesic
activity. With the proposed study, we aim to investigate whether a short-term administration of a cannabis
extract enriched in CBD can modulate glutamate and GABAergic signaling in critical pain-processing regions of
the brain such as the anterior cingulate cortex (ACC) and insula. Furthermore, we plan to investigate the
effects of CBD on peripheral and neural markers of inflammation. The successful completion of the study will
advance the evidence-based application of CBD as a potential treatment for pain conditions and will also
provide substrates that can be targe...

## Key facts

- **NIH application ID:** 10017872
- **Project number:** 5R21AT010736-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** PERRY FRANKLIN RENSHAW
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $152,500
- **Award type:** 5
- **Project period:** 2019-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017872

## Citation

> US National Institutes of Health, RePORTER application 10017872, Exploring the mechanisms underlying the analgesic effect of Cannabidiol using Proton Magnetic Resonance Spectroscopy. (5R21AT010736-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10017872. Licensed CC0.

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