# Comparative Pharmacology of Cannabinoids in Rodent Models

> **NIH NIH R01** · RESEARCH TRIANGLE INSTITUTE · 2021 · $424,908

## Abstract

PROJECT SUMMARY
Cannabis sativa/indica (marijuana plant) is the most commonly abused substance in the United States, but is
still classified as illegal to possess under federal law. Psychoactive phytocannabinoids such as Δ9-
tetrahydrocannabinol (THC) produce their effects on physiology and behavior through activation of CB1 and CB2
receptors. These receptors are part of the endocannabinoid system, one of several lipid signaling systems in the
brain/body. Discovery of these mechanisms underlying cannabinoid action and characterization of their effects
on physiology and behavior were due, in part, to research conducted in animals, and specifically, in rodent
models. Future progress in this area also will involve findings derived from work with these models. Hence,
fundamental knowledge of the advantages and limits of the models are crucial. Recently, we discovered an
intriguing species X sex interaction in the effects of THC in rats and mice. Briefly, rats exhibited pronounced sex
differences in physiological and behavioral responses following THC injection whereas female and male mice
showed similar responses. The overall goals of the proposed project are to investigate mechanisms that may
underlie these differences and to determine the extent to which a similar profile characterizes THC’s effects on
physiology and behavior. Side-by-side comparisons of the physiological (temperature and cardiac and
pulmonary function) and behavioral (discriminative stimulus) effects of THC and cannabis extracts will be made
in female and male rats and mice. Differences in pharmacokinetics and receptor mechanisms will be
characterized following parenteral injection routes of administration for rodent studies and after administration
via more translationally relevant inhalational and oral routes of administration. The results of these studies will
provide an empirical basis for choice of rodent model with which to investigate mechanisms underlying cannabis
use.

## Key facts

- **NIH application ID:** 10074552
- **Project number:** 5R01DA045003-04
- **Recipient organization:** RESEARCH TRIANGLE INSTITUTE
- **Principal Investigator:** JENNY L. WILEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $424,908
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074552

## Citation

> US National Institutes of Health, RePORTER application 10074552, Comparative Pharmacology of Cannabinoids in Rodent Models (5R01DA045003-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10074552. Licensed CC0.

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