Explore the vast range of titles available.

Central neuropathic pain (CNP) occurs in many multiple sclerosis (MS) patients. The provision of adequate pain relief to these patients can very difficult. Here we report the first phase III placebo-controlled study of the efficacy of the endocannabinoid system modulator delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (USAN name, nabiximols; Sativex, GW Pharmaceuticals, Salisbury, Wiltshire, UK), to alleviate CNP. Patients who had failed to gain adequate analgesia from existing medication were treated with THC/CBD spray or placebo as an add-on treatment, in a double-blind manner, for 14 weeks to investigate the efficacy of the medication in MS-induced neuropathic pain. This parallel-group phase of the study was then followed by an 18-week randomized-withdrawal study (14-week open-label treatment period plus a double-blind 4-week randomized-withdrawal phase) to investigate time to treatment failure and show maintenance of efficacy. A total of 339 patients were randomized to phase A (167 received THC/CBD spray and 172 received placebo). Of those who completed phase A, 58 entered the randomized-withdrawal phase. The primary endpoint of responder analysis at the 30 % level at week 14 of phase A of the study was not met, with 50 % of patients on THC/CBD spray classed as responders at the 30 % level compared to 45 % of patients on placebo ( p  = 0.234). However, an interim analysis at week 10 showed a statistically significant treatment difference in favor of THC/CBD spray at this time point ( p  = 0.046). During the randomized-withdrawal phase, the primary endpoint of time to treatment failure was statistically significant in favor of THC/CBD spray, with 57 % of patients receiving placebo failing treatment versus 24 % of patients from the THC/CBD spray group ( p  = 0.04). The mean change from baseline in Pain Numerical Rating Scale (NRS) ( p  = 0.028) and sleep quality NRS ( p  = 0.015) scores, both secondary endpoints in phase B, were also statistically significant compared to placebo, with estimated treatment differences of −0.79 and 0.99 points, respectively, in favor of THC/CBD spray treatment. The results of the current investigation were equivocal, with conflicting findings in the two phases of the study. While there were a large proportion of responders to THC/CBD spray treatment during the phase A double-blind period, the primary endpoint was not met due to a similarly large number of placebo responders. In contrast, there was a marked effect in phase B of the study, with an increased time to treatment failure in the THC/CBD spray group compared to placebo. These findings suggest that further studies are required to explore the full potential of THC/CBD spray in these patients.

Background: Open-label studies are not ideal for providing robust evidence for long-term maintenance of efficacy of medicines, especially where medicines provide symptom relief and where long-term use of a placebo may be problematic and not ethical. Objective: To evaluate the maintenance of efficacy of Sativex in subjects who have gained long-term symptomatic relief of spasticity in multiple sclerosis (MS), and to assess the impact of sudden medicine withdrawal. Methods: An enriched enrolment randomized withdrawal study design was used. Eligible subjects with ongoing benefit from Sativex for at least 12 weeks entered this 5-week placebo-controlled, parallel-group, randomized withdrawal study. Each subjects’ previous effective and tolerated dose was continued. Results: A total of 18 subjects per group were enrolled. Demographics showed a mean duration of MS of 16.4 years, spasticity 12.7 years, mean duration of Sativex use of 3.6 years (median 3.4 years) and a mean daily dose of 8.25 sprays. Primary outcome of time to treatment failure was significantly in favour of Sativex (p = 0.013). Secondary endpoints showed significant changes in the Carer and Subject’s Global Impression of Change scales in favour of Sativex. Conclusions: Maintenance of Sativex efficacy in long-term symptomatic improvement of spasticity to a group of subjects with MS has been confirmed using this study design.

Sativex is an endocannabinoid system modulator principally containing Δ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD). During a 6-week randomised controlled trial, Sativex had a clinically relevant effect on spasticity associated with multiple sclerosis (MS). Patients self-titrated oromucosal Sativex to symptom relief or maximum tolerated dose (maximum of 130 mg THC and 120 mg CBD daily). The primary objective was to evaluate the safety and tolerability of long-term treatment by recording the incidence and severity of adverse events (AEs). Secondary outcomes were to determine evidence of developing tolerance and to assess the long-term dosing profile of Sativex. A validated 11-point Numerical Rating Scale of spasticity severity was used to assess efficacy. A total of 146 patients elected to enter this open-label follow-up safety trial. Mean treatment exposure was 334 days (standard deviation, SD = 209 days), and patients administered on average 7.3 (SD = 4.42) actuations per day. Fifty-two (36 %) patients withdrew from the study in the first year, 14 % due to AEs and 9 % due to lack of efficacy. Most AEs were mild/moderate in severity. Common (>10 %) treatment-related AEs were dizziness (24.7 %) and fatigue (12.3 %). Serious AEs occurred in five patients (3.4 %), with two psychiatric events reported by one patient. No psychoses, psychiatric AE trends, or withdrawal symptoms occurred following abrupt cessation of treatment. Baseline symptoms including spasticity did not deteriorate but were maintained to study completion in those patients who did not withdraw. No new safety concerns were identified with chronic Sativex treatment, and serious AEs were uncommon. There was no evidence of tolerance developing, and patients who remained in the study reported continued benefit.

The major developments in pain management over the last 20 years have been achieved through the application of modern scientific and medical techniques. Although some patients benefit, many do not, and all pain management services have huge reservoirs of unmet need. The understanding of pain is normally limited to western scientific descriptions. There are other perspectives. The book by Fritjof Capra, The Tao of physics, is an exploration of physical science using eastern philosophical principles. This same process can be applied to the subject of pain and provides challenging new ways of addressing the complex problems that physicians encounter every day.

Background: Open-label studies are not ideal for providing robust evidence for long-term maintenance of efficacy of medicines, especially where medicines provide symptom relief and where long-term use of a placebo may be problematic and not ethical.Objective: To evaluate the maintenance of efficacy of Sativex in subjects who have gained long-term symptomatic relief of spasticity in multiple sclerosis (MS), and to assess the impact of sudden medicine withdrawal.Methods: An enriched enrolment randomized withdrawal study design was used. Eligible subjects with ongoing benefit from Sativex for at least 12 weeks entered this 5-week placebo-controlled, parallel-group, randomized withdrawal study. Each subjects' previous effective and tolerated dose was continued.Results: A total of 18 subjects per group were enrolled. Demographics showed a mean duration of MS of 16.4 years, spasticity 12.7 years, mean duration of Sativex use of 3.6 years (median 3.4 years) and a mean daily dose of 8.25 sprays. Primary outcome of time to treatment failure was significantly in favour of Sativex (p = 0.013). Secondary endpoints showed significant changes in the Carer and Subject's Global Impression of Change scales in favour of Sativex.Conclusions: Maintenance of Sativex efficacy in long-term symptomatic improvement of spasticity to a group of subjects with MS has been confirmed using this study design.