Cannabinoid‐induced effects on the nociceptive system: A neurophysiological study in patients with secondary progressive multiple sclerosis

Abstract

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.

Sativex® and clinical–neurophysiological measures of spasticity in progressive multiple sclerosis

“…In the present study, only ambulatory patients (EDSS \7) were included so as to minimize the negative contribution of musculoskeletal abnormalities on detection of CNS effects by active treatment. Conte and coworkers also failed to show changes in the H/M ratio following cannabinoid therapy in patients with secondary progressive MS [15]. Lack of significant effect of cannabis-based treatment on the H/M amplitude ratio was also reported in a limited sample of MS patients selected on the basis of neuropathic pain, not spasticity, without a placebo arm [14].…”

“…The Hoffmann (H) reflex is a neurophysiological measure of the efficiency of Iamotor neuron synaptic input related to spasticity [11,12]. Although the H-reflex has been reported to be reduced after baclofen treatment in MS patients [13], studies of Sativex have reported contrasting results [14,15].…”

Cannabis-based medicines in multiple sclerosis – A review of clinical studies

“…It is thought to correspond to the pain threshold and the reflex size is related to the level of pain perception perception (Willer, 1977). In a randomized, doubleblind, placebo-controlled, cross-over study in 18 patients with secondary progressive MS, after treatment with Sativex, RIII reflex threshold increased and RIII reflex area decreased (Conte et al, 2009). The pain VAS also decreased, though not significantly.…”

Plasma endocannabinoid levels in multiple sclerosis

“…Cannabinoid drugs such as delta-9-tetrahydrocannabinol (Δ 9 -THC) and cannabidiol have shown therapeutic potential in controlling MSassociated neurological disturbances including pain, spasticity, and mobility impairment [2] [3]. On the other hand, cannabis-based medications may also have a negative effect on symptoms associated with MS [4]. The effects or cannabis-based medicines are largely mediated through the activation of the cannabinoid receptors, CB 1 and CB 2 .…”