Assessing the neurophysiological effects of cannabinoids on spasticity in Multiple Sclerosis

Background: Spasticity is a disabling symptom in Multiple Sclerosis (MS). Cannabinoids have been proven to reduce the subjective feeling of spasticity and thus have been suggested as an effective therapeutic option in MS. The neurophysiological mechanisms underlying their clinical efficacy, however, remain poorly understood. Objective: We combined neurophysiological methods to test the effect of cannabinoids on altered motor function in MS patients suffering from spasticity. We hypothesized that cannabinoids exert their beneficial effects through changes in motor cortical or spinal excitability. Methods: Eighteen cannabis-naïve secondary progressive MS patients with spasticity were included in a double-blind, placebo-controlled, crossover study. Patients were treated with either placebo or Cannabis Based Medicine Extract (CBME). They were assessed clinically, as well as using functional MRI (fMRI) and electrophysiological methods. Plasma levels of tetrahydrocannabinol (THC) and cannabidiol (CBD) were tested. Results: CBME treatment did not produce significant benefits on spasticity when compared with placebo. No change in fMRI motor-evoked brain activation was observed. There was no difference in intracortical and spinal motor excitability between CBME and placebo. No correlation was found between plasma levels of THC or CBD and electrophysiological or imaging measures. Conclusion: Cannabinoids do not exert beneficial effects on MS-related spasticity through a direct action on the motor system as assessed by fMRI and electrophysiological methods.