THC plus CBD together reduced MS-like brain inflammation in mice through changes in immune cell gene activity
A combination of THC and CBD, but not either alone, reduced paralysis and brain inflammation in a mouse model of multiple sclerosis by suppressing inflammatory immune cells and altering microRNA profiles.
Quick Facts
What This Study Found
THC+CBD combination (10 mg/kg each) attenuated experimental autoimmune encephalomyelitis in mice by reducing brain-infiltrating inflammatory T cells and pro-inflammatory molecules while increasing anti-inflammatory markers. Neither THC nor CBD alone achieved these effects. The combination also significantly altered microRNA expression in brain immune cells.
Key Numbers
THC+CBD decreased IL-17, IFN-gamma, TNF-alpha, IL-1beta, and IL-6 in the brain while increasing FoxP3, IL-4, IL-10, and TGF-beta. Seven miRNAs were downregulated (including miR-155-5p and miR-21a-5p) and two were upregulated. Effects required both CB1 and CB2 receptors.
How They Did This
Mouse model of multiple sclerosis (EAE) treated with THC+CBD combination versus individual cannabinoids. Used CB1/CB2 knockout mice to confirm receptor dependence. Performed miRNA microarray analysis on brain-derived CD4+ T cells. Included transfection studies and Mir21 knockout mice.
Why This Research Matters
THC+CBD combinations are already approved for MS-related spasticity in many countries, but how they suppress neuroinflammation was poorly understood. This study identifies specific microRNA changes as a potential mechanism, opening new avenues for understanding why the combination works better than either compound alone.
The Bigger Picture
The finding that the combination works but neither compound alone does reinforces the "entourage effect" concept in cannabinoid therapeutics. The miRNA mechanism could explain why cannabis-based medicines show different effects than isolated compounds.
What This Study Doesn't Tell Us
This is a mouse model that does not perfectly replicate human MS. The EAE model represents only certain aspects of MS pathology. Doses used in mice may not translate directly to human dosing. The miRNA findings are correlational within the treatment context.
Questions This Raises
- ?Can these miRNA changes be detected in human MS patients taking THC+CBD?
- ?Would targeting specific miRNAs directly achieve similar anti-inflammatory effects?
- ?What is the optimal THC:CBD ratio for neuroinflammation?
Trust & Context
- Key Stat:
- Combination only, not alone
- Evidence Grade:
- Rated preliminary because this is an animal study. While the mechanistic findings are detailed, translation to human MS remains unconfirmed.
- Study Age:
- Published in 2019. THC+CBD (Sativex/Nabiximols) has continued to be studied in MS since this publication.
- Original Title:
- Combination of Cannabinoids, Δ9- Tetrahydrocannabinol and Cannabidiol, Ameliorates Experimental Multiple Sclerosis by Suppressing Neuroinflammation Through Regulation of miRNA-Mediated Signaling Pathways.
- Published In:
- Frontiers in immunology, 10, 1921 (2019)
- Authors:
- Al-Ghezi, Zinah Zamil(2), Miranda, Kathryn, Nagarkatti, Mitzi(7), Nagarkatti, Prakash S
- Database ID:
- RTHC-01900
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
Why did THC+CBD work together but not separately?
The study found the combination engaged both CB1 and CB2 receptors and altered a specific set of microRNAs in brain immune cells. This pattern of changes did not occur with either compound alone.
Is this relevant to people with MS?
It provides mechanistic support for why THC+CBD combinations are used in MS treatment, but this was a mouse study. The specific miRNA findings have not yet been confirmed in humans.
What are microRNAs?
MicroRNAs are small molecules that regulate gene activity. In this study, THC+CBD changed the levels of specific microRNAs that control inflammation and cell survival in brain immune cells.
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Cite This Study
https://rethinkthc.com/research/RTHC-01900APA
Al-Ghezi, Zinah Zamil; Miranda, Kathryn; Nagarkatti, Mitzi; Nagarkatti, Prakash S. (2019). Combination of Cannabinoids, Δ9- Tetrahydrocannabinol and Cannabidiol, Ameliorates Experimental Multiple Sclerosis by Suppressing Neuroinflammation Through Regulation of miRNA-Mediated Signaling Pathways.. Frontiers in immunology, 10, 1921. https://doi.org/10.3389/fimmu.2019.01921
MLA
Al-Ghezi, Zinah Zamil, et al. "Combination of Cannabinoids, Δ9- Tetrahydrocannabinol and Cannabidiol, Ameliorates Experimental Multiple Sclerosis by Suppressing Neuroinflammation Through Regulation of miRNA-Mediated Signaling Pathways.." Frontiers in immunology, 2019. https://doi.org/10.3389/fimmu.2019.01921
RethinkTHC
RethinkTHC Research Database. "Combination of Cannabinoids, Δ9- Tetrahydrocannabinol and Ca..." RTHC-01900. Retrieved from https://rethinkthc.com/research/al-ghezi-2019-combination-of-cannabinoids-9
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.