Although clinical studies show that cannabinoids improve central pain in patients with multiple sclerosis (MS) neurophysiological studies are lacking to investigate whether they also suppress these patients' electrophysiological responses to noxious stimulation. The flexion reflex (FR) in humans is a widely used technique for assessing the pain threshold and for studying spinal and supraspinal pain pathways and the neurotransmitter system involved in pain control. In a randomized, double-blind, placebo-controlled, cross-over study we investigated cannabinoid-induced changes in RIII reflex variables (threshold, latency and area) in a group of 18 patients with secondary progressive MS. To investigate whether cannabinoids act indirectly on the nociceptive reflex by modulating lower motoneuron excitability we also evaluated the H-reflex size after tibial nerve stimulation and calculated the H wave/M wave (H/M) ratio. Of the 18 patients recruited and randomized 17 completed the study. After patients used a commercial delta-9-tetrahydrocannabinol (THC) and cannabidiol mixture as an oromucosal spray the RIII reflex threshold increased and RIII reflex area decreased. The visual analogue scale score for pain also decreased, though not significantly. Conversely, the H/M ratio measured before patients received cannabinoids remained unchanged after therapy. In conclusion, the cannabinoid-induced changes in the RIII reflex threshold and area in patients with MS provide objective neurophysiological evidence that cannabinoids modulate the nociceptive system in patients with MS.
Journal»Journal of Neuroscience and Rehabilitation
Year»2014
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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.
CONCLUSIONS: 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.
: To study possible psychopathological symptoms and cognitive deficits, abuse induction, as well as general tolerability and effects on quality of life, fatigue and motor function in cannabis-naïve patients with multiple sclerosis (MS) treated with a free-dose cannabis plant extract (Sativex).
METHODS:
: In an 8-week, randomized, double-blind, placebo-controlled, parallel group crossover trial, 17 cannabis-naïve patients with MS were assessed at baseline and at the end of the cannabis and placebo phases of the trial (each of 3 weeks) by means of Symptom Checklist-90 Revised, Self-rating Anxiety Scale, Multiple Sclerosis Functional Composite (of which 1 dimension is the Paced Auditory Serial Additional Test that was used to evaluate cognition), Visual Analogue Scale on health-related quality of life, Multiple Sclerosis Impact Scale-29, and Fatigue Severity Scale.
RESULTS:
: Postplacebo versus postcannabinoid scores showed that no significant differences could be detected on all the variables under study. A significant positive correlation was found between Δ-9-tetrahydrocannabinol blood levels and scores at the General Symptomatic Index and at the "interpersonal sensitivity," "aggressive behaviour," and "paranoiac tendencies" subscales of the Symptom Checklist-90 Revised. No serious adverse events, abuse tendencies, or direct withdrawal symptoms were reported. Increased desire for Sativex with secondary depression was reported in 1 subject.
