# Using Cannabinoids to Enhance Opioid Analgesic Effects in Humans

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $657,143

## Abstract

This study will systematically evaluate whether cannabinoids can enhance the analgesic efficacy of opioids,
which will advance the use of cannabinoids for the treatment of acute and/or chronic pain. Chronic pain affects
over 100 million Americans. Opioids are unanimously recognized as the most effective drugs for the relief of
pain and suffering6, but the US is now suffering from an epidemic of abuse, addiction and accidental deaths
resulting from the increased sale and use of opioids. There is legitimate value in identifying adjuncts that might
reduce reliance on opioids while maintaining adequate pain relief. Preclinical studies report that co-
administering cannabinoids with opioid agonists significantly and reliably reduce the amount of opioids required
for analgesia but this hypothesis has not been rigorously evaluated in humans. This proposal will conduct 2
independent studies that will evaluate the effects of a different cannabinoid (Study 1: dronabinol, Study 2:
nabilone) on opioid-induced analgesia. Each study will enroll 60 healthy adults (30 men/women) to conduct a
within-subject, dose-response evaluation of cannabinoids on the analgesic effect of hydromorphone (Dilaudid).
Subjects will complete a Qualifying session and 6 experimental sessions that will occur once weekly and will
require subjects to admit themselves into the clinical research unit the night before the session to complete the
study session. Subjects will receive a dose of hydromorphone (1mg, IM) and a double-blind oral dose of study
drug or placebo the morning of each experimental session, and will undergo quantitative sensory testing (QST;
a comprehensive pain testing battery), provide self-report ratings of drug effects, and complete a
neurocognitive battery. QST testing will comprehensively and systematically measure pain sensitivity, and
provide information on the full range of analgesic effects possible across a wide variety of pain measures,
including threshold responses (thermal, pressure), temporal summation, cold pressor, conditioned pain
modulation, and capsaicin sensitization. Primary outcomes will be magnitude and duration of pain as a function
of study drug dose. Additional primary aims include proxy measures of abuse liability and neurocognitive
performance. All measures will be assessed as a function of sex, due to substantial evidence that men/women
differ with regard to pain perception, endogenous cannabinoid receptor density, and opioid response. We
hypothesize that cannabinoids will shift the analgesic curve of hydromorphone and enhance analgesia effects.
This will be the 1st human laboratory study to evaluate combinations of cannabinoids and opioids using QST,
and results will identify whether a signal for this medication combination exists that should be advanced into
randomized controlled trial evaluations with clinical pain populations. This study will also assess aspects that
would impact drug development (abuse liability, neurocognitive impairme...

## Key facts

- **NIH application ID:** 9962328
- **Project number:** 5R01DA040644-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Claudia Michelle Campbell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $657,143
- **Award type:** 5
- **Project period:** 2016-08-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962328

## Citation

> US National Institutes of Health, RePORTER application 9962328, Using Cannabinoids to Enhance Opioid Analgesic Effects in Humans (5R01DA040644-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9962328. Licensed CC0.

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