Spasticity is frequently experienced by people with Multiple Sclerosis (MS), negatively
impacting on patient's motor functional outcome, including walking. Currently, none of the
available MS disease-modifying medications has been shown to stop or reverse gait disability.
Recently the nabiximols has been tested for the treatment of spasticity and walking
impairment in MS. Nabiximols (trade name Sativex®) is an oromucosal spray formulation
containing 1:1 fixed ratio of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)
derived from cloned Cannabis sativa L. plant. The main active substance, THC, acts as a
partial agonist at human cannabinoid receptors (CB1 and CB2), and may modulate the effects of
excitatory (glutamate-GLU-) and inhibitory (gamma-aminobutyric acid -GABA-)
neurotransmitters, leading to muscle relaxation, which in turn is responsible for spasticity
improvement. Cannabinoid receptors may modulate both excitatory and inhibitory transmission
at central synapses, and have been heavily implicated, in animal models, in multiple forms of
synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD).
Indeed, in a previous study implying transcranial magnetic stimulation (TMS) technique, it
has been hypothesized that the activation of cannabinoid receptors by Sativex® could modulate
the balance between LTP and LTD like plasticity by changing the state of cortical
excitability. In a recently study it has been proposed that Sativex may modulate the cortical
excitability changing the activity of inhibitory GABAergic cortico-cortical synapses. Aim of
our study is to clarify the role of Sativex coupled to a robotic neurehabilitation training
in MS patients in improving the motor outcome, by means of clinical, kinematic, beside some
neurophysiological and measures.