Journal of Clinical Toxicology

Journal of Clinical Toxicology
Open Access

ISSN: 2161-0495

+44 1478 350008


Delta-9-Tetrahydrocannabinol (THC) Protects Partly against Demyelination by Modulating the Inflammatory Response: An In Vitro Study in Aggregating Brain Cell Cultures

Antoinette Defaux, Mariano Schiffrin, Lorianne Vorlet-Fawer, Amelie Spiehlmann, Christian Giroud and Florianne Monnet-Tschudi

Delta 9-tetrahydrocannabinol (THC) has been proposed as therapeutic agent in the treatment of multiple sclerosis. In the present study, we examined whether a modulation of brain inflammation by THC may protect against demyelination. Myelinating aggregating brain cell cultures were subjected to demyelination by a repeated treatment (3x) with the two inflammatory agents interferon-γ (IFN-γ) and lipopolysaccharide (LPS). The effects of THC on an acute inflammatory response were also examined by treating the aggregates with a single application of the two inflammatory agents. THC effects on the demyelinating process and on several mediators of the inflammatory response were analyzed. THC treatment partially prevented the decreased immunoreactivity for MBP, and the decrease in MBP content measured by immunoblotting. It prevented IFN-γ + LPS-induced microglial reactivity; and decreased the IFN-γ + LPS-induced increased phosphorylation of p44/42 MAP kinase. The other inflammatory markers, i-NOS and TNF-α mRNA expression, and p38 MAP kinase phosphorylation were downregulated by THC treatment following a single application of the inflammatory agents, but not after repeated applications. THC protected partially against the IFN-γ + LPS-induced demyelination. The protective effect of THC on IFN-γ + LPS-induced demyelination may be due to a decrease of the inflammatory response. However, the anti-inflammatory effect of THC on some inflammatory markers is lost when the inflammatory response is more prominent and of longer duration, suggesting either that the anti-inflammatory effect of a molecule may depend on the properties of the inflammatory response, or that the anti-inflammatory potential of THC decreases in case of repeated exposure.