Trial probes mechanism of THC-CBD improvement of multiple sclerosis spasticity

BOSTON – A tetrahydrocannabinol and cannabidiol (THC-CBD) oromucosal spray significantly improved spasticity symptoms in a randomized, placebo-controlled study of 43 multiple sclerosis patients.

The spray, which goes by the trade name Sativex, has been shown to reduce symptoms associated with spasticity in MS, and is approved in several European countries and commercially licensed in many others, including the United States, where it received fast-track status from the Food and Drug Administration earlier this year. But little has been known about the correlates of these effects on objective measures of spasticity or corticospinal excitability, Dr. Letizia Leocani said at the joint meeting of the Americas and European Committees for Treatment and Research in Multiple Sclerosis.

The findings of the study suggest, however, that mechanisms other than corticospinal excitability and the monosynaptic component of the stretch reflex may play a role in spasticity, Dr. Leocani reported.

The treatment effect, as measured by the modified Ashworth Scale (MAS), was significantly greater in those who were randomized to receive active treatment, compared with those who received placebo (change in MAS score, –1.51 vs. 0.16, respectively). Patients in the treatment group improved by about 18%; those in the placebo group improved by less than 7%, said Dr. Leocani, clinical group leader of the experimental neurophysiology unit of San Raffaele Hospital, Milan.

A 20% or better response on the MAS occurred in 44% of patients on active treatment, compared with about 15% of those who received placebo.

Patients in the study were adults with progressive MS and clinical evidence of spasticity. They were randomized in double-blind fashion to a 2-week titration period plus 2 weeks of stable dose treatment with either Sativex or a placebo formulation. A second double-blind, crossover cycle followed after another 2-week washout.

The MAS and several other clinical neurophysiological measures – including spasticity and pain numeric rating scales (NRS) - were obtained before and after each cycle. MAS improvement and improvement in NRS spasticity were significantly correlated (r = 0.38), but other neurophysiological measures did not differ in the treatment and placebo groups, and were not correlated with clinical parameters, with the exception of a trend between percent change in the MAS and in the bilateral soleus ratio of maximum H reflex to maximum M response.

While the current findings confirm the clinical benefit of treatment for spasticity, there was a lack of corresponding changes on measures of corticospinal excitability and on the monosynaptic component of the stretch reflex; these findings point to a role for – and a need for exploration of – other spinal and supraspinal mechanisms in spasticity physiopathology, she concluded.

Dr. Leocani reported having no relevant disclosures.

BOSTON – A tetrahydrocannabinol and cannabidiol (THC-CBD) oromucosal spray significantly improved spasticity symptoms in a randomized, placebo-controlled study of 43 multiple sclerosis patients.

The spray, which goes by the trade name Sativex, has been shown to reduce symptoms associated with spasticity in MS, and is approved in several European countries and commercially licensed in many others, including the United States, where it received fast-track status from the Food and Drug Administration earlier this year. But little has been known about the correlates of these effects on objective measures of spasticity or corticospinal excitability, Dr. Letizia Leocani said at the joint meeting of the Americas and European Committees for Treatment and Research in Multiple Sclerosis.

The findings of the study suggest, however, that mechanisms other than corticospinal excitability and the monosynaptic component of the stretch reflex may play a role in spasticity, Dr. Leocani reported.

The treatment effect, as measured by the modified Ashworth Scale (MAS), was significantly greater in those who were randomized to receive active treatment, compared with those who received placebo (change in MAS score, –1.51 vs. 0.16, respectively). Patients in the treatment group improved by about 18%; those in the placebo group improved by less than 7%, said Dr. Leocani, clinical group leader of the experimental neurophysiology unit of San Raffaele Hospital, Milan.

A 20% or better response on the MAS occurred in 44% of patients on active treatment, compared with about 15% of those who received placebo.

Patients in the study were adults with progressive MS and clinical evidence of spasticity. They were randomized in double-blind fashion to a 2-week titration period plus 2 weeks of stable dose treatment with either Sativex or a placebo formulation. A second double-blind, crossover cycle followed after another 2-week washout.

The MAS and several other clinical neurophysiological measures – including spasticity and pain numeric rating scales (NRS) - were obtained before and after each cycle. MAS improvement and improvement in NRS spasticity were significantly correlated (r = 0.38), but other neurophysiological measures did not differ in the treatment and placebo groups, and were not correlated with clinical parameters, with the exception of a trend between percent change in the MAS and in the bilateral soleus ratio of maximum H reflex to maximum M response.

While the current findings confirm the clinical benefit of treatment for spasticity, there was a lack of corresponding changes on measures of corticospinal excitability and on the monosynaptic component of the stretch reflex; these findings point to a role for – and a need for exploration of – other spinal and supraspinal mechanisms in spasticity physiopathology, she concluded.

Dr. Leocani reported having no relevant disclosures.

BOSTON – A tetrahydrocannabinol and cannabidiol (THC-CBD) oromucosal spray significantly improved spasticity symptoms in a randomized, placebo-controlled study of 43 multiple sclerosis patients.

The spray, which goes by the trade name Sativex, has been shown to reduce symptoms associated with spasticity in MS, and is approved in several European countries and commercially licensed in many others, including the United States, where it received fast-track status from the Food and Drug Administration earlier this year. But little has been known about the correlates of these effects on objective measures of spasticity or corticospinal excitability, Dr. Letizia Leocani said at the joint meeting of the Americas and European Committees for Treatment and Research in Multiple Sclerosis.

The findings of the study suggest, however, that mechanisms other than corticospinal excitability and the monosynaptic component of the stretch reflex may play a role in spasticity, Dr. Leocani reported.

The treatment effect, as measured by the modified Ashworth Scale (MAS), was significantly greater in those who were randomized to receive active treatment, compared with those who received placebo (change in MAS score, –1.51 vs. 0.16, respectively). Patients in the treatment group improved by about 18%; those in the placebo group improved by less than 7%, said Dr. Leocani, clinical group leader of the experimental neurophysiology unit of San Raffaele Hospital, Milan.

A 20% or better response on the MAS occurred in 44% of patients on active treatment, compared with about 15% of those who received placebo.

Patients in the study were adults with progressive MS and clinical evidence of spasticity. They were randomized in double-blind fashion to a 2-week titration period plus 2 weeks of stable dose treatment with either Sativex or a placebo formulation. A second double-blind, crossover cycle followed after another 2-week washout.

The MAS and several other clinical neurophysiological measures – including spasticity and pain numeric rating scales (NRS) - were obtained before and after each cycle. MAS improvement and improvement in NRS spasticity were significantly correlated (r = 0.38), but other neurophysiological measures did not differ in the treatment and placebo groups, and were not correlated with clinical parameters, with the exception of a trend between percent change in the MAS and in the bilateral soleus ratio of maximum H reflex to maximum M response.

While the current findings confirm the clinical benefit of treatment for spasticity, there was a lack of corresponding changes on measures of corticospinal excitability and on the monosynaptic component of the stretch reflex; these findings point to a role for – and a need for exploration of – other spinal and supraspinal mechanisms in spasticity physiopathology, she concluded.

Dr. Leocani reported having no relevant disclosures.