# Cannabinoid Effects on Sleep and Pain Mechanisms in Osteoarthritis of the Knee

> **NIH NIH K01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $142,475

## Abstract

Abstract
Chronic pain due to knee osteoarthritis (OA) is a large contributor to disability, affecting millions of Americans.
Sleep disturbances contribute to worsened pain symptoms in knee OA. However, treatment outcomes for knee
OA remain poor. This is because pain is not monolithic, and differences in underlying pain mechanisms affect
treatment response. While knee OA pain can be due to tissue and joint damage (nociceptive pain), it can also
be augmented and maintained by central nervous system (CNS) dysfunction - i.e., nociplastic pain. Different
underlying mechanisms may explain inconsistent clinical trial results with cannabinoids - the active compounds
in Cannabis sativa. While clinical trials suggest that cannabinoids may be useful analgesics and sleep-aids,
these trials were done with Δ⁹-tetrahydrocannabinol (THC) and THC analogs, which have abuse potential.
However, a recent study showed that cannabidiol (CBD) reduced pain and increased function in men with knee
OA. CBD is non-intoxicating, exerts analgesic and anti-inflammatory effects, and also shows promise for
improving sleep. The proposed studies will examine how CBD and/or THC affect sleep in knee OA, and the
degree to which associated changes in sleep affect pain. Our overarching hypothesis is that CBD+THC will
improve sleep the most, followed by THC, and then CBD, and that improvements in sleep will partially mediate
improvements in pain. To test this hypothesis, we propose three aims that will provide me with the additional
training necessary to unify chronic pain, sleep, and cannabinoid mechanisms as an independent researcher: 1)
Acquire training in clinical trial conduct and cutting edge pain-phenotyping methods by helping lead a
randomized, double-blinded, 2x2 factorial design study that assesses whether pain centralization predicts
differential analgesic responsiveness to CBD and THC in knee OA (parent study R01AT010381); 2) In an
ancillary trial within Aim 1, investigate cannabinoid effects on sleep through self-report and objective measures;
3) Assess if cannabinoid sleep effects mediate changes in pain and explore interactions between sleep and
pain phenotype. Given that pain centralization occurs in many chronic pain conditions, our approach in knee
OA may have broad implications for developing non-opioid analgesics. This award will take place at the
University of Michigan (UM) under Drs. Daniel Clauw, Richard Harris, Steven Harte, Alexander Tsodikov,
Helen Burgess, and David Williams, who are world-renowned experts in chronic pain, neuroimaging,
psychophysics, clinical trial analyses, sleep, and pain psychometrics, respectively. UM is an ideal environment
for this award because of the available resources, including faculty who are committed to clinical pain research
and mentoring, research-devoted magnetic resonance imaging (MRI) scanners and state-of-the-art pain testing
equipment, and ample laboratory and office space at the Chronic Pain and Fatigue Research Center. U...

## Key facts

- **NIH application ID:** 10436239
- **Project number:** 5K01DA049219-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Kevin Foxman Boehnke
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $142,475
- **Award type:** 5
- **Project period:** 2020-07-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436239

## Citation

> US National Institutes of Health, RePORTER application 10436239, Cannabinoid Effects on Sleep and Pain Mechanisms in Osteoarthritis of the Knee (5K01DA049219-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10436239. Licensed CC0.

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