# Analgesic efficacy of single and combined minor cannabinoids and terpenes

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2020 · $396,250

## Abstract

The primary goal of the proposed research is to empirically and quantitatively test the hypothesis that
combinations of four biologically active components of Cannabis sativa act synergistically to protect against the
development of pain in two rodent models: chemotherapy-induced neuropathic pain and pain associated with
dental pulp exposure. In addition, effects of these Cannabis components on morphine analgesia and will also
be assessed. Cannabis contains over 100 phytocannabinoids as well as several terpene compounds which are
also biologically active. As stated in RFT-AT-19-008, while a growing body of literature suggests that Cannabis
may have analgesic properties, the psychoactive effects of the phytocannabinoid ∆9-tetrahydrocannabinol
(THC) limit its utility, calling for an investigation into the therapeutic potential of additional phytocannabinoids
and terpenes found in the plant. Our laboratory has been studying the anti-neuropathic efficacy of the non-
psychoactive phytocannabinoid cannabidiol (CBD) for over a decade. In addition to CBD, the minor
cannabinoid cannabigerol (CBG), the acid form of THC THCA, and the terpene beta-caryophyllene (β-CP), are
receiving increasing interest by clinicians as analgesics and/or anti-inflammatory agents. We have also
recently demonstrated that β-CP prevents the development of mechanical sensitivity in a rat model of dental
pain. Importantly, so-called “entourage effects” of Cannabis constituents are anecdotally discussed at length,
but empirical data are woefully lacking, including the potential for synergistic interactions outside of THC. We
determined that CBD acts synergistically with THC to attenuate mechanical allodynia associated with paclitaxel
administration, while attenuating the antinociceptive effects of morphine on thermal sensitivity. Testing for such
interactive effects requires rigorous dose response testing and analysis across single and combined agents,
and these requirements increase with the number of agents to be combined. Animal modeling to test unique
interactive effects of several Cannabis constituents provides a uniquely effective contribution to translational
medicine, as executing such studies in a clinical setting is immensely more challenging and expensive. In the
current proposal we will determine the efficacy of CBD, CBG, THCA, and β-CP alone and in combination on
tactile allodynia and other pain-related behaviors in males and females. We will also determine the interactive
effects of CBD, CBG, THCA, and β-CP with morphine on acute antinociceptive and visceral pain. At the
completion of behavioral testing, complementary cellular and molecular approaches will be utilized to also
characterize effects of single and combined agents on markers of pain and inflammation. The assembled team
has the expertise and collaborative relationship to ensure the feasibility and achievement of the proposed
project. The overall impact of the project will be to provide empirically-derived ev...

## Key facts

- **NIH application ID:** 10017870
- **Project number:** 5R01AT010778-02
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Sara J Ward
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $396,250
- **Award type:** 5
- **Project period:** 2019-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017870

## Citation

> US National Institutes of Health, RePORTER application 10017870, Analgesic efficacy of single and combined minor cannabinoids and terpenes (5R01AT010778-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10017870. Licensed CC0.

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