# Analgesic and subjective effects of terpenes administered alone and in combination with THC: Potential THC- and opioid-sparing effects of myrcene and ß-caryophyllene

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $68,861

## Abstract

Project Summary (Parent Award)
Chronic pain is a significant public health burden for which there are few effective treatments;
individuals with chronic pain are a central component to the current opioid epidemic. Delta-9-
tetrahydrocannabinol (THC), the primary psychoactive chemical of cannabis, holds promise as a
therapeutic candidate to treat chronic pain. However, analgesia is accompanied by intoxication
and abuse liability, thus limiting its clinical utility. Terpenes are organic compounds that
contribute to the aromatic nature and flavor of cannabis; it has been hypothesized that these
compounds may interact synergistically with THC to enhance its therapeutic effects with
reduced adverse consequences. As such, terpenes may increase the analgesic effects of low,
minimally intoxicating, doses of THC, and/or reduce adverse consequences of higher THC
doses. Preclinical research demonstrates that the terpenes myrcene and ß-caryophyllene (BCP)
elicit antinociceptive effects and have opioid-sparing properties. These effects are, in part,
mediated by the mu-opioid receptor. It is unknown if these findings translate to humans.
Understanding if these terpenes have analgesic properties alone, or in combination with THC, is
fundamental to developing novel cannabinoid-based therapeutics to treat pain. In addition,
investigating adverse effects of these terpenes (abuse liability, intoxication) will clarify their
clinical potential. At a time when pharmacotherapeutic strategies to decrease reliance on
opioids for pain relief are desperately needed, probing the 1) analgesic effects, 2) potential
THC- and opioid-sparing properties, and 3) mechanism of these terpenes is of significant
interest. The proposed double-blind, placebo-controlled studies will be the first to rigorously
assess the dose-dependent analgesic effects of ecologically-relevant doses of myrcene and
BCP and determine their THC- and opioid-sparing effects. Study findings will be essential in
understanding the clinical potential of terpenes alone and in conjunction with THC for pain
management. The proposed double-blind, placebo-controlled, within-subject studies in
recreational cannabis smokers (N=30, 15M, 15F in each study) will first ascertain the dose-
dependent analgesic potential of vaporized myrcene and BCP alone and in combination with
sub-analgesic (5 mg) and analgesic (15 mg) doses of THC (Specific Aim 1). The myrcene/THC
and BCP/THC dose combinations that produce the greatest analgesia and minimal intoxication
and abuse liability will then be tested for their opioid sparing effects (Specific Aim 2). Opioid
modulation of combined terpene/THC analgesia will be assessed with co-administration of
naltrexone, an opioid antagonist (Specific Aim 2). Findings from these studies address a
significant public health priority by investigating terpenes as a safe, well tolerated novel
pharmacotherapeutic strategy to manage pain. This is an urgent area of research as
alternatives to opioids and s...

## Key facts

- **NIH application ID:** 11103008
- **Project number:** 3R01AT010762-04S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** ZIVA D COOPER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $68,861
- **Award type:** 3
- **Project period:** 2020-02-15 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11103008

## Citation

> US National Institutes of Health, RePORTER application 11103008, Analgesic and subjective effects of terpenes administered alone and in combination with THC: Potential THC- and opioid-sparing effects of myrcene and ß-caryophyllene (3R01AT010762-04S1). Retrieved via AI Analytics 2026-06-24 from https://api.ai-analytics.org/grant/nih/11103008. Licensed CC0.

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