# Cannabinoid CB2 Agonists for Treatment of Breast Cancer Induced Bone Pain

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2020 · $337,106

## Abstract

Abstract:
 Breast cancer is the most frequent malignant tumor of women of all races in North America and is the
second leading cause of death among women (DHHS, CDC, & NCI; 2014) with an overall NIH estimate costs
to the U.S. over $200 billion with $88.7 billion in direct medical costs in 2011. The World Health Organization
predicts that global cases of cancer will rise to 15 million new cases by 2020. In advanced stages, skeletal
metastasis causes incapacitating pain and is prominent in 75–90% of cancer patients. First line therapy to treat
bone cancer pain includes mu opioid receptor agonists. Opioids are well known for producing unwanted side
effects in cancer patients including severe somnolence, constipation, etc. but recently have been shown
(clinical and preclinical) to enhance the risk of bone loss and fracture. In addition, sustained opioids have
demonstrated a propensity for increasing proliferation and migration of different cancers including breast
cancer.
 Data from our laboratory, and others, suggest that cannabinoid CB2 agonists may be effective in
alleviating bone cancer pain and bone loss. Selective CB2 agonists significantly inhibit bone cancer pain while
NOT resulting in the psychotropic or euphoric effects seen with CB1 agonists or narcotics. Recent reports and
data from our lab have identified CB2 agonists as significantly reducing self-administration of drugs of abuse
including cocaine and narcotics. Increasing endogenous cannabinoids (MAGL inhibition to increase 2-
arachidonylglycerol - 2AG) may regulate bone mass, decrease pro-nociceptive factors and act synergistically
with morphine to inhibit cancer-induced bone pain (CIBP) and attenuate tumor proliferation.
 Our preliminary studies using a murine bone cancer model indicate that MAGL inhibition and CB2
receptor activation inhibits proinflammatory cytokines/chemokines via regulating NF-κB. Yet, there is very little
known about the endogenous CB2 system in bone cancer pain/inflammation, and whether the activation of the
endocannabinoid (eCB) system, while administering mu opioids, will significantly aid bone cancer patients.
There are NO studies investigating the synergistic combination of MAGL inhibitor or CB2 agonists with a mu
opioid agonist on cancer pain, bone integrity, tumor proliferation, or attenuating mu opioid unwanted side
effects. Our progress in characterizing bone cancer pain has resulted in twelve direct peer-reviewed
publications and preliminary data to further support studies of MAGL inhibition, CB2 receptor activation in bone
cancer pain. Our preliminary data demonstrate; 1) a reproducible syngeneic breast-induced bone cancer
model representative of the clinical state, 2) MAGLipase inhibition resulting in increased 2AG, significantly
attenuating cancer-induced pain, 3) exogenous and endogenous CB2 agonists attenuating bone loss, 4)
sustained morphine alone increases bone degradation and cytokines, 5) CB2 agonists and MAGL inhibitors
decrease NF-kB signal...

## Key facts

- **NIH application ID:** 9853744
- **Project number:** 5R01CA142115-09
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** TODD W VANDERAH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $337,106
- **Award type:** 5
- **Project period:** 2010-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853744

## Citation

> US National Institutes of Health, RePORTER application 9853744, Cannabinoid CB2 Agonists for Treatment of Breast Cancer Induced Bone Pain (5R01CA142115-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9853744. Licensed CC0.

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