# Evaluation of Cannabidiol for Reduction of Brain Neuroinflammation

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $753,349

## Abstract

Millions of individuals in the United States suffer from chronic pain and co-morbid depression,
conditions that are debilitating and complex to manage. A reason for the scarcity of safe and efficacious
therapies for these conditions is our limited knowledge of viable targets. Preclinical models of pain have shown
that microglia and astrocytes play a key role in the establishment and/or maintenance of pain and depressive
behaviors. Additionally, patients with chronic low back pain (cLBP) demonstrate “pain-related” and
“depression-related” elevated levels of the glial marker 18kDa translocator protein (TSPO), suggesting that
pain and depressive symptoms may be mediated / maintained by neuroinflammatory mechanisms
 In this proposal, we will study whether cannabidiol (CBD), the primary centrally and peripherally active
non-intoxicating compound in the cannabis plant, exerts anti-neuroinflammatory effects in patients with cLBP
with mild-to-moderate depression. In animals, CBD induces analgesic and antidepressant effects, via a
complex pharmacology that includes the stimulation of cannabinoid receptors and the inhibition of pro-
inflammatory pathways in glial cells. These preclinical studies, and our observations linking neuroinflammation
to pain and comorbid depressive symptoms in cLBP, indicate that CBD may reduce both pain- and depression-
related neuroinflammation in cLBP patients. In addition to exerting possible anti-neuroinflammatory effects,
studies in psychiatric patients suggest that CBD might normalize striatal hypofunction, an alteration that our
group has also recently linked to depression in cLBP patients using functional magnetic resonance imaging
(fMRI). Because of its purported effects as striatal physiology, we thus hypothesize that a secondary
mechanism of action of CBD may be to reduce striatal dysfunction.
 We will conduct a randomized, double-blind, 2-arm mechanistic trial to assess the effects of CBD (n =
40) and placebo (n = 40) in patients with cLBP with mild-to-moderate depression, using integrated positron
emission tomography / magnetic resonance imaging (PET/MRI) scans. The use of integrated PET/MRI will
allow us to simultaneously evaluate neuroinflammation (using [11C]PBR28, a second-generation radioligand for
TSPO) and striatal function (using the Monetary Incentive Delay task, a validated fMRI task that probes
behavioral and neural responses to rewards and losses). In our mechanistic trial, we will use EPIDIOLEX®, an
FDA-approved product that contains a known and constant dose of purified CBD. We already hold an active
IND to test the effects of EPIDIOLEX® in cLBP with [11C]PBR28 PET/MRI, and preliminary data support our
hypotheses. By studying the neural and neuroimmune responses to CBD, this study will advance our
knowledge about the mechanisms of action of this drug, and help us understand which conditions might benefit
the most from its use. More broadly, our study will test whether modulating neuroinflammation is fea...

## Key facts

- **NIH application ID:** 10413981
- **Project number:** 5R01DA053316-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Jodi Gilman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $753,349
- **Award type:** 5
- **Project period:** 2021-06-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10413981

## Citation

> US National Institutes of Health, RePORTER application 10413981, Evaluation of Cannabidiol for Reduction of Brain Neuroinflammation (5R01DA053316-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10413981. Licensed CC0.

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