Evidence map›Paper›PMID 31356922›Full record

ArticleBrain, behavior, and immunity2019

Combination of cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), mitigates experimental autoimmune encephalomyelitis (EAE) by altering the gut microbiome.

Zinah Zamil Al-Ghezi, Philip Brandon Busbee, Hasan Alghetaa, Prakash S Nagarkatti, Mitzi Nagarkatti

Open access · greenAbstract read
In one paragraph

Article in Brain, behavior, and immunity, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed, 3 pooled it
10.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

79 citing papers in PubMed, 3 syntheses or guidelines pooled it, 144 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Immunomodulatory Potential of Cannabidiol in Multiple Sclerosis: a Systematic Review.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021
    Pooled it
  4. Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Medicinal Cannabis and the Intestinal Microbiome.Pharmaceuticals (Basel, Switzerland) · 2024
    Review
  20. Article

19 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Zinah Zamil Al-GheziDepartment of Pathology, Microbiology and Immunology. University of South Carolina School of Medicine, Columbia, SC 29208, USA.
Philip Brandon BusbeeDepartment of Pathology, Microbiology and Immunology. University of South Carolina School of Medicine, Columbia, SC 29208, USA.
Hasan AlghetaaDepartment of Pathology, Microbiology and Immunology. University of South Carolina School of Medicine, Columbia, SC 29208, USA.
Prakash S NagarkattiDepartment of Pathology, Microbiology and Immunology. University of South Carolina School of Medicine, Columbia, SC 29208, USA. Electronic address: prakash@mailbox.sc.edu.
Mitzi NagarkattiDepartment of Pathology, Microbiology and Immunology. University of South Carolina School of Medicine, Columbia, SC 29208, USA.
University of South Carolina · US

Funding

Targeting early ceramide elevation in pre-symptomatic eczemaP20GM103641 · NIGMS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI ENOS, REILLY, NAGARKATTI, PRAKASH S · 2012 to 2023
$20.7M
Use of Resveratrol to treat experimental multiple sclerosisP01AT003961 · NCCIH · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI NAGARKATTI, PRAKASH S · 2007 to 2018
$14.2M
Epigenetic Mechanisms of T Cell Dysregulation in PTSDR01AI129788 · NIAID · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI NAGARKATTI, MITZI · 2017 to 2021
$2.4M
Role of natural indoles in experimental autoimmune encephalomyelitisR01AT006888 · NCCIH · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI NAGARKATTI, MITZI · 2011 to 2015
$2.0M
AhR ligands in epigenetic dysregulation of T cellsR01AI123947 · NIAID · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI NAGARKATTI, MITZI, NAGARKATTI, PRAKASH S · 2017 to 2021
$1.8M
Immunopathological basis of PTSDR01MH094755 · NIMH · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI NAGARKATTI, PRAKASH S · 2011 to 2015
$1.7M
NCCIH NIH HHS P01 AT003961NCCIH NIH HHS R01 AT006888NIAID NIH HHS R01 AI123947NIAID NIH HHS R01 AI129788NIGMS NIH HHS P20 GM103641NIMH NIH HHS R01 MH094755
6 · The paper itself

Abstract

Currently, a combination of marijuana cannabinoids including delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is used as a drug to treat muscle spasticity in patients with Multiple Sclerosis (MS). Because these cannabinoids can also suppress inflammation, it is unclear whether such patients benefit from suppression of neuroinflammation and if so, what is the mechanism through which cannabinoids act. In the currently study, we used a murine model of MS, experimental autoimmune encephalomyelitis (EAE), to study the role of gut microbiota in the attenuation of clinical signs of paralysis and inflammation caused by cannabinoids. THC + CBD treatment attenuated EAE and caused significant decrease in inflammatory cytokines such as IL-17 and IFN-γ while promoting the induction of anti-inflammatory cytokines such as IL-10 and TGF-β. Use of 16S rRNA sequencing on bacterial DNA extracted from the gut revealed that EAE mice showed high abundance of mucin degrading bacterial species, such as Akkermansia muciniphila (A. muc), which was significantly reduced after THC + CBD treatment. Fecal Material Transfer (FMT) experiments confirmed that THC + CBD-mediated changes in the microbiome play a critical role in attenuating EAE. In silico computational metabolomics revealed that LPS biosynthesis, a key component in gram-negative bacteria such as A. muc, was found to be elevated in EAE mice which was confirmed by demonstrating higher levels of LPS in the brain, while treatment with THC + CBD reversed this trend. EAE mice treated with THC + CBD also had significantly higher levels of short chain fatty acids such as butyric, isovaleric, and valeric acids compared to naïve or disease controls. Collectively, our data suggest that cannabinoids may attenuate EAE and suppress neuroinflammation by preventing microbial dysbiosis seen during EAE and promoting healthy gut microbiota.

Indexed as

AnimalsCannabidiolCannabinoidsCannabisCytokinesDisease Models, AnimalDronabinolDysbiosisEncephalomyelitis, Autoimmune, ExperimentalFemaleGastrointestinal MicrobiomeInflammationInterferon-gammaInterleukin-17MiceMice, Inbred C57BLCannabidiolCannabinoidsCytokinesDronabinolInterferon-gammaInterleukin-17RNA, Ribosomal, 16SAkkermansia muciniphilaCBDEAEGut microbiomeLPSMultiple sclerosisSCFAsTHC

Identifiers

PMID31356922
PMCPMC6866665
OpenAlexW2965488855

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.