# Effects of Cannabidiol and Tetrahydrocannabinol on the Microbiome, Endocannabinoids and Neuroinflammation in HIV

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $896,116

## Abstract

SUMMARY
 This project will constitute human research characterizing the microbiome and endocannabinoid system
(ECS) in people with HIV (PWH) and how they relate to neuroinflammation and blood-brain barrier (BBB)
function. Based on exciting new preliminary findings described here, we propose that alterations in the gut
microbiota (dysbiosis) and impaired gut barrier integrity (leaky gut) are mediators between the ECS and
neuroinflammation and BBB dysfunction in HIV. Our major goals are to (1) characterize the gut microbiota and
ECS in response to exogenous cannabinoid exposure in both PWH and people without HIV (PWoH); (2)
characterize patterns of HIV-associated inflammation (innate, adaptive, T-cell, B-cell) in blood and cerebrospinal
fluid (CSF) in response to controlled cannabis exposure; (3) assess effects of cannabinoid exposure on these
patterns and how they are mediated through changes in the ECS, gut microbiota and gut barrier function. We
will perform a clinical trial of 50 PWH and 50 PWoH exposed in a randomized, cross-over fashion to 14 days
each of oral THC and CBD to determine if treatment with either phytocannabinoid reduces inflammation and
improves gut function. The experimental approach will use fecal shogun metagenomic sequencing to
characterize the gut microbiome, with particular attention to aerotolerant bacteria, pro-inflammatory species,
Prevotella spp., Bifidobacterium and Bacteroides spp. and butyrate-producing bacteria. We will evaluate how
the microbiota and leaky gut relate to neuroinflammation and impaired BBB function, the latter potentially leading
to increased CNS exposure to microbially-produced pro-inflammatory ligands. The rationale for the study is that
virologic suppression on antiretroviral therapy (ART) does not normalize gut lymphoid tissue CD4+ T cell
depletion, leaky gut, dysbiosis, chronic gut inflammation, and microbial antigen translocation (MAT). These
alterations ultimately drive systemic and CNS inflammation. Compromised gut barrier function due to altered
tight junctions, apoptosis and reduced epithelial cell proliferation and repair render PWH susceptible to increased
tissue exposure to pro-inflammatory ligands produced by gut microbiota and are important in HIV
neuropathogenesis. Of particular relevance here are recent findings that the ECS in the large intestine interacts
with the gut microbiota to regulate epithelial barrier permeability. Thus constituents of cannabis, acting through
the gut EC system, may be therapeutic, and the existing literature suggests that the two principal constituents of
cannabis, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have differential effects on the ECS.

## Key facts

- **NIH application ID:** 10463371
- **Project number:** 1R01DA056058-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** RONALD J. ELLIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $896,116
- **Award type:** 1
- **Project period:** 2022-06-15 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463371

## Citation

> US National Institutes of Health, RePORTER application 10463371, Effects of Cannabidiol and Tetrahydrocannabinol on the Microbiome, Endocannabinoids and Neuroinflammation in HIV (1R01DA056058-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10463371. Licensed CC0.

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