Sativex(®), an equimolecular combination of Δ(9)-tetrahydrocannabinol-botanical
drug substance (Δ(9)-THC-BDS) and
cannabidiol-botanical
drug substance (CBD-BDS), is a licensed medicine that may be prescribed for alleviating specific symptoms of
multiple sclerosis (MS) such as spasticity and
pain. However, further evidence suggest that it could be also active as disease-modifying
therapy given the immunomodulatory, anti-inflammatory and cytoprotective properties of their two major components. In this study, we investigated this potential in the experimental
autoimmune encephalitis (EAE) model of MS in mice. We compared the effect of a
Sativex-like combination of Δ(9)-THC-BDS (10 mg/kg) and CBD-BDS (10 mg/kg) with Δ(9)-THC-BDS (20 mg/kg) or CBD-BDS (20 mg/kg) administered separately by intraperitoneal administration to EAE mice. Treatments were initiated at the time that symptoms appear and continued up to the first relapse of the disease. The results show that the treatment with a
Sativex-like combination significantly improved the neurological deficits typical of EAE mice, in parallel with a reduction in the number and extent of cell aggregates present in the spinal cord which derived from cell infiltration to the CNS. These effects were completely reproduced by the treatment with Δ(9)-THC-BDS alone, but not by CBD-BDS alone which only delayed the onset of the disease without improving
disease progression and reducing the cell infiltrates in the spinal cord. Next, we investigated the potential targets involved in the effects of Δ(9)-THC-BDS by selectively blocking CB(1) or
PPAR-γ receptors, and we found a complete reversion of neurological benefits and the reduction in cell aggregates only with
rimonabant, a selective CB(1) receptor antagonist. Collectively, our data support the therapeutic potential of
Sativex as a phytocannabinoid formulation capable of attenuating EAE progression, and that the active compound was Δ(9)-THC-BDS acting through CB(1) receptors.