# Cannabinoid and terpene regulation of nocioception and peripheral sensitization through ionotropic receptors

> **NIH NIH R15** · CHAMINADE UNIVERSITY OF HONOLULU · 2020 · $432,795

## Abstract

Cannabis-derived therapeutics promise utility in pain management. Their low side effect profile and low
addictive potential add value to this proposition, and in addition, they have been shown to be `opioid-sparing'.
However, current medical marijuana patients are limited to native plant mixtures obtained licitly or illicitly from
an inconsistent supply chain that is subject to issues of contamination and undefined relationships between
formulations (plant chemovars) and efficacy. Popular chemovars have been selected over several decades for
ever-increasing THC levels, which is both medically undesirable due to the psychoactivity of THC and may be
medically unnecessary if THC is actually dispensable for some indications. These central safety and efficacy
problems reinforce the need for rational design of therapies that represent the minimal essential and efficacious
set of compounds needed to achieve analgesia. The overall goal of this pre-clinical proposal is to establish
efficacy and mechanism of action for cannabinoids (excluding THC), terpenes and rationally-designed
cannabinoid/terpene mixtures such that they can be rapidly translated for clinical evaluation in nocioceptive
pain and peripheral sensitization. The central premise of the proposed work is that ionotropic cannabinoid
receptors (Transient Receptor Potential (TRP) nocioceptive ion channels) are the most important targets for
therapeutic desensitization by cannabinoids and terpenes present in Cannabis. The proposal is innovative in
that it focuses on ionotropic receptors that are actual nocioceptors rather than CB1 and CB2 GPCR, it excludes
THC and focuses on other cannabinoids and terpenes, it embraces the idea of building synthetic mixtures that
improve upon the natural plant for efficacy and safety and excludes plant extracts, and it proposes an approach
to simultaneously addressing both nocioception and peripheral sensitization. The project is supported by
preliminary data that: (a) establish differential activity of CB and TP at nocioceptive TRPs, defining which
TRPs are targeted by each compound and identifying novel TRP ligands, (b) describe complex kinetics and
desensitization of TRP nocioceptors in response to CB/TP, offering the potential for therapeutic desensitization
and tuning of nocioceptive TRP responses; (c) demonstrate a Cannabis component improving upon an
established pain therapeutic targeting a TRP channel, and (d) demonstrate interactions of components of
complex CB/TP mixtures, informing rational mixture design. The proposed Specific Aims are: Aim 1. Test
cannabinoid and terpene regulation of nocioceptive TRP channels. We hypothesize that CB and TP,
singly or in mixtures, selectively ligate and desensitize TRPs to promote analgesia. Aim 2. Determine GPCR
dependencies and relationships in analgesic effects of cannabinoids and terpenes. We hypothesize
that CB and TP target multiple TRPs independently of CB1 and CB2 GPCR, and CB, TP and mixtures that target
TRPV1...

## Key facts

- **NIH application ID:** 10041763
- **Project number:** 1R15DA051749-01
- **Recipient organization:** CHAMINADE UNIVERSITY OF HONOLULU
- **Principal Investigator:** HELEN C TURNER
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $432,795
- **Award type:** 1
- **Project period:** 2020-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10041763

## Citation

> US National Institutes of Health, RePORTER application 10041763, Cannabinoid and terpene regulation of nocioception and peripheral sensitization through ionotropic receptors (1R15DA051749-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10041763. Licensed CC0.

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