THC plus CBD together reduced MS-like brain inflammation in mice through changes in immune cell gene activity

What the researchers 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.

Why it 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 numbers in context

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 the study worked

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.

What this study cannot 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.

How to read the evidence

Rated preliminary because this is an animal study. While the mechanistic findings are detailed, translation to human MS remains unconfirmed.

When this study was published

Published in 2019. THC+CBD (Sativex/Nabiximols) has continued to be studied in MS since this publication.

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.

Questions still open

• 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?

Common questions

Read the original research

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

Citation

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

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