# Effect of Cannabidiol on Microglial Activation and Central Pain-Sensitization

> **NIH NIH R21** · YALE UNIVERSITY · 2020 · $221,251

## Abstract

Background: Converging lines of evidence from preclinical studies, treatment studies in animals, 
and anecdotal reports suggest that cannabidiol (CBD) may have a therapeutic role in 
chronic pain disorders. Emerging neurobiological evidence suggests that the transition from 
acute to chronic pain is mediated by a) the biological mechanism of increased brain microglial 
activation and b) the physiological mechanism of increased central pain-sensitization. However, 
whether CBD modulates brain microglial activation and central pain-sensitization in humans has not 
been examined to-date. Intradermal capsaicin-induced secondary hyperalgesia (ICSH) is a validated 
measure of central pain-sensitization related to activation of specific brain regions. 
We have demonstrated, in pilot data, that ICSH is sensitive to the effects of cannabinoids (such 
as THC) in a laboratory paradigm. Low-dose lipopolysaccharide (LPS) has been shown to 
increase brain microglial activation. The combination of LPS and intradermal capsaicin 
provides a unique experimental paradigm to examine the relationship between brain microglial 
activation and central pain-sensitization. Harnessing the high sensitivity and molecular 
specificity of positron emission tomography (PET) imaging, we have demonstrated in vivo 
evidence of increased brain microglial activation following LPS, using [11C]PBR28. Additionally, 
LPS has been shown to result in a 2-fold increase in capsaicin-induced secondary hyperalgesia 
(ICSH). The combination of LPS with intradermal capsaicin (pLPS-IC) thus provides a validated and 
reliable model to examine the effects of CBD on a) the biological mechanism of increased brain 
microglial activation and b) the physiological mechanism of increased central pain-sensitization.

Hypothesis #1: CBD pretreatment will result in lower brain microglial activation (specifically in 
the thalamus) compared to placebo in healthy individuals. Aim#1: To examine the effect 
of CBD pretreatment on brain microglial activation in vivo in humans using a 
LPS-challenge paradigm and [11C]PBR28 PET imaging. Hypothesis #2: The degree of reduction in 
brain microglial activation with CBD pretreatment will correlate with the degree of reduction in 
central pain-sensitization. Aim#2: To examine the relationship between microglial activation and 
central pain-sensitization with CBD pretreatment, measured using [11C]PRB28 and ICSH in a pLPS-IC 
paradigm.

## Key facts

- **NIH application ID:** 10074663
- **Project number:** 3R21AT010763-01S1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** MOHINI RANGANATHAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $221,251
- **Award type:** 3
- **Project period:** 2019-09-27 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074663

## Citation

> US National Institutes of Health, RePORTER application 10074663, Effect of Cannabidiol on Microglial Activation and Central Pain-Sensitization (3R21AT010763-01S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10074663. Licensed CC0.

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