# Novel approaches to understanding the role of cannabinoids and inflammation in anxiety

> **NIH NIH R01** · UNIVERSITY OF COLORADO · 2020 · $562,633

## Abstract

Project Summary
 Marijuana use is not only increasing, but gaining traction for use as an “off-label” add-on therapy for
treatment-resistant anxiety. Paradoxically, however, while data suggest that marijuana, in particular ∆9-
tetrahydrocannabinol (THC), increases anxiety acutely, cross sectional and longitudinal data suggest possible
links between chronic marijuana use and lower risk for anxiety disorders. Research is critically needed to
understand the effects of marijuana these outcomes. In light of considerable evidence that marijuana has anti-
inflammatory properties and, further evidence suggesting that inflammation plays a pivotal role in the etiology
of anxiety disorders, we propose that the anti-inflammatory properties of marijuana are linked with its anxiolytic
effects. Importantly, prior work has not considered that the psychotropic and anti-inflammatory effects of
marijuana are the compound action of different cannabinoids, which vary in their pharmacology and effects.
Specifically, cannabidiol (CBD), a non-psychotomimetic component of marijuana (doesn’t produce a “high”), is
thought to have anxiolytic properties and may mitigate some of the harmful effects of tetrahydrocannabinol
(THC). Further, preliminary data, including our own, suggest that THC and CBD render differential effects on
anxiety-related processes, such as effects on inflammatory markers and stress response. Critically, there is
huge diversity in the amounts and ratio of THC and CBD commercially available and widely used in states like
Colorado. Therefore, the ratio of CBD to THC may have a pivotal impact on the anxiolytic and anti-
inflammatory effects of various strains of marijuana, which in turn may have important implications for 1)
effects on anxiety and 2) marijuana regulation policies aimed at harm reduction.
 In order to address this gap in understanding of the effects of cannabinoids, we propose to test
the hypothesis that the anxiolytic effects and anti-inflammatory properties of marijuana vary as a
function of the ratio of CBD to THC, and that these effects may shed light on the mixed data linking
cannabis use and anxiety. We propose a unique observational study that employs real-world marijuana
strains currently available to Colorado residents that vary in their CBD to THC ratios. We test the effects of
specific strains of marijuana selected based on their differing CBD to THC ratios [i.e. a high CBD strain
(+CBD/-THC), a 1:1 (+THC/+CBD) strain, and a typical THC-based strain +THC/-CBD)] on anxiety and
inflammation, expecting that +CBD marijuana will mitigate anxiety, peripheral inflammatory responses
(including cytokine levels with and without an ex-vivo immune challenge), and behavioral and biological
responses to stress induction over the course of 4 weeks of observation. It is expected that the proposed
research will generate information about which marijuana strains produce the most harmful effects on anxiety
and inflammation and inform personal and p...

## Key facts

- **NIH application ID:** 9949688
- **Project number:** 5R01DA044131-04
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** L. Cinnamon Bidwell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $562,633
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9949688

## Citation

> US National Institutes of Health, RePORTER application 9949688, Novel approaches to understanding the role of cannabinoids and inflammation in anxiety (5R01DA044131-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9949688. Licensed CC0.

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