# Mechanisms of cannabidiol in persons with MS: the role of sleep and pain phenotype

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $693,674

## Abstract

Abstract
Chronic pain affects 35-40% of people with chronic neurological conditions, including persons with multiple
sclerosis (MS) - an autoimmune disease of the central nervous system affecting approximately 1 million
Americans. Unfortunately, the analgesic effects of conventional treatments for pain in neurological conditions is
limited. Cannabidiol (CBD, derived from cannabis sativa) is a safe, promising complimentary therapy that is
frequently used in combination with Δ-9-tetrahydrocannabinol (THC) to treat pain in persons with MS (PwMS).
However, the distinct analgesic mechanisms of CBD - relative to better-studied cannabinoid formulations such
as THC or THC/CBD combinations (which carry abuse potential) - are not well understood, galvanizing the
need for mechanistic research focused on CBD monotherapy. Preliminary data from a nationwide study of
PwMS conducted by the investigators suggest that CBD could independently exert analgesic effects through
improved sleep, particularly among PwMS with nociplastic (centralized) pain. Investigations that now build
upon these early findings could provide novel insight into mechanisms by which CBD induces analgesic
effects, and identify pain phenotypes that are most likely to be responsive to CBD for chronic pain. This
innovative, mechanistic study proposes to apply novel polysomnographic sleep stage analyses that extend
beyond conventional polysomnography (PSG) measures, and new features of sleep macrostructure derived
from in-home actigraphy, to assess aspects of sleep that could play key mechanistic roles in the analgesic
effects of CBD. Our overarching goal is to apply these novel sleep assessment methods, coupled with
validated pain phenotyping techniques, to uncover unique mechanistic associations between CBD, sleep, and
analgesia in PwMS, compared to THC monotherapy, THC/CBD combination therapy, or placebo. Persons with
MS who experience chronic pain will undergo pain phenotyping with validated survey measures of nociplastic
and neuropathic pain, and randomized to CBD (Epidiolex®), THC (dronabinol), THC/CBD combination, or
placebo for 12 weeks. In-lab PSG and 14-day wrist-worn actigraphy will be collected at baseline and 12 weeks’
post-treatment. Changes in sleep microstructure (Aim 1; including sleep stage bout length, sleep stage
transition probability, and entropy) and macrostructure (Aim 2; including sleep regularity, rhythmicity, timing
and duration) will be compared between cannabinoid and placebo groups, and pain phenotype will be
assessed as a predictor of CBD-related changes in sleep. Aim 3 will assess the measures of sleep
microstructure and macrostructure as mediators of analgesic response to CBD. Data generated from this study
will to inform CBD research, across a spectrum of neurological and other chronic conditions, that can be
applied to the development of precision-medicine approaches for chronic pain.

## Key facts

- **NIH application ID:** 10468081
- **Project number:** 5R01AT011341-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Tiffany Joy Braley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $693,674
- **Award type:** 5
- **Project period:** 2021-08-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468081

## Citation

> US National Institutes of Health, RePORTER application 10468081, Mechanisms of cannabidiol in persons with MS: the role of sleep and pain phenotype (5R01AT011341-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10468081. Licensed CC0.

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