# Behavioral Pharmacology of Cannabinoid and Terpenoid Effects and Interactions

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $677,123

## Abstract

Widespread legislative reforms allowing for the legal sale and use of cannabis for medical and non-medical
(e.g., recreational) purposes has greatly expanded access to cannabis and resulted in the proliferation of novel
cannabis products. Cannabis is being selectively bred to have targeted cannabinoid and terpenoid profiles,
which are marketed as having substantively different subjective and medicinal effects. However, these claims
are based on anecdote or marketing, rather than controlled scientific discovery. THC is the primary
psychoactive constituent of cannabis and has demonstrated therapeutic value (treatment of cachexia and
nausea/emesis), but is also associated with many adverse effects. There is a theoretical basis for believing
that some effects of THC may be modulated by terpenoids, abundant naturally occurring plant products
prevalent within a variety of cannabis strains. The terpenoids of interest in the present project, limonene,
myrcene, and pinene are common to human diets and designated Generally Recognized as Safe (GRAS) by
the FDA. However, human laboratory research testing the separate and combined effects of THC and
terpenoids is scarce to non-existent. The unique effects of limonene (anxiolytic), pinene (cognitive
enhancement), myrcene (sedative) that have been elucidated in independent studies suggest that these
substances may mitigate or enhance specific effects of THC. The aim of this project is to systematically
evaluate the effects of THC, limonene, myrcene, and pinene, alone, and in combination, to evaluate the validity
of the purported cannabis “entourage” effect (belief that whole plant provides substantively different effects
than THC alone). Three double-blind, placebo-controlled within-subjects crossover studies will be completed to
evaluate each terpenoid alone and in combination with moderate and high doses of THC. Healthy volunteers
who report past, but not current (past month) cannabis use will attend 9 outpatient laboratory sessions and
receive the following: 1) Placebo, 2) THC (15mg), 3) THC (30mg), 4) low dose terpenoid, 5) high dose
terpenoid, 6) THC (15mg) + low dose terpenoid, 7) THC (15mg) + high dose terpenoid, 8) THC (30mg) + low
dose terpenoid, and 9) THC (30mg) + high dose terpenoid. Dose order will be randomized and repeated
assessments will characterize behavioral, physiological, cognitive, and subjective effects. The use of two
doses of THC and each terpenoid allows for evaluation of THC-terpenoid interactions at different ratios and
both maximizes the likelihood of observing targeted THC effects and reduces the likelihood of Type II error.
Results will advance our understanding of the behavioral pharmacology of cannabis. Demonstrating an
attenuation of THC effects would support the cannabis “entourage” effect and provide data useful for the
development of novel cannabinoid medications that can mitigate adverse effects of THC. In contrast, the
absence of THC modulation by these terpenoids would i...

## Key facts

- **NIH application ID:** 10146320
- **Project number:** 5R01DA043475-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** RYAN G VANDREY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $677,123
- **Award type:** 5
- **Project period:** 2017-09-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146320

## Citation

> US National Institutes of Health, RePORTER application 10146320, Behavioral Pharmacology of Cannabinoid and Terpenoid Effects and Interactions (5R01DA043475-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10146320. Licensed CC0.

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