# Mechanism and Optimization of CBD-mediated analgesic effects

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2021 · $264,303

## Abstract

Abstract
Substantial evidence indicates that cannabis is effective for the treatment of chronic pain in adults, but medical
use of cannabis is restricted by its main psychoactive component tetrahydrocannabinol (THC). Minor
cannabinoids, such as cannabidiol (CBD), do not have psychotropic activity. However, their analgesic effects
are not as potent as THC and the neural mechanisms by which minor cannabinoids-mediated analgesia may be
optimized remain largely unknown. Accordingly, the overall objective of this project is to identify neural
mechanisms involved in minor cannabinoids signaling in order to optimize their analgesic effects. In light of
compelling evidence that CBD acts on a1 and a3-glycine receptors (GlyRs), which are only a part of molecular
players in neuropathic pain, we will investigate the effects and mechanisms of the combination of CBD or other
minor cannabinoids with manipulations based on KCC2, a neuron-specific chloride extruder expressed in most
neurons. Our test hypothesis is that CBD's mechanistic effects may be modulated by KCC2 dose-dependently
and increasing KCC2 activity in spinal cord and/or cortex may enhance CBD analgesia. Specifically, we will
determine whether modulating KCC2 activity will alter CBD analgesia in a dose-dependent manner, and define
circuit mechanisms by which KCC2 modulates CBD analgesia. In addition to CBD, we will also examine whether
KCC2 activity will regulate the analgesic effects of a family of CBD-related minor cannabinoids. Identifying the
novel circuit targets and mechanisms of minor cannabinoids-mediated analgesia will not only help optimize non-
psychoactive cannabinoid-based therapies but also provide routes to develop effective new treatments with
minimal side-effects.

## Key facts

- **NIH application ID:** 10468403
- **Project number:** 3R01AT010779-03S1
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** ZHIGANG HE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $264,303
- **Award type:** 3
- **Project period:** 2019-09-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468403

## Citation

> US National Institutes of Health, RePORTER application 10468403, Mechanism and Optimization of CBD-mediated analgesic effects (3R01AT010779-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10468403. Licensed CC0.

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