Dataset Information

Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial.

ABSTRACT: BACKGROUND: Spasticity is a common and poorly controlled symptom of multiple sclerosis. Our objective was to determine the short-term effect of smoked cannabis on this symptom. METHODS: We conducted a placebo-controlled, crossover trial involving adult patients with multiple sclerosis and spasticity. We recruited participants from a regional clinic or by referral from specialists. We randomly assigned participants to either the intervention (smoked cannabis, once daily for three days) or control (identical placebo cigarettes, once daily for three days). Each participant was assessed daily before and after treatment. After a washout interval of 11 days, participants crossed over to the opposite group. Our primary outcome was change in spasticity as measured by patient score on the modified Ashworth scale. Our secondary outcomes included patients' perception of pain (as measured using a visual analogue scale), a timed walk and changes in cognitive function (as measured by patient performance on the Paced Auditory Serial Addition Test), in addition to ratings of fatigue. RESULTS: Thirty-seven participants were randomized at the start of the study, 30 of whom completed the trial. Treatment with smoked cannabis resulted in a reduction in patient scores on the modified Ashworth scale by an average of 2.74 points more than placebo (p < 0.0001). In addition, treatment reduced pain scores on a visual analogue scale by an average of 5.28 points more than placebo (p = 0.008). Scores for the timed walk did not differ significantly between treatment and placebo (p = 0.2). Scores on the Paced Auditory Serial Addition Test decreased by 8.67 points more with treatment than with placebo (p = 0.003). No serious adverse events occurred during the trial. INTERPRETATION: Smoked cannabis was superior to placebo in symptom and pain reduction in participants with treatment-resistant spasticity. Future studies should examine whether different doses can result in similar beneficial effects with less cognitive impact.

SUBMITTER: Corey-Bloom J

PROVIDER: S-EPMC3394820 | biostudies-other | 2012 Jul

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial.

Corey-Bloom Jody J Wolfson Tanya T Gamst Anthony A Jin Shelia S Marcotte Thomas D TD Bentley Heather H Gouaux Ben B

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 20120514 10

<h4>Background</h4>Spasticity is a common and poorly controlled symptom of multiple sclerosis. Our objective was to determine the short-term effect of smoked cannabis on this symptom.<h4>Methods</h4>We conducted a placebo-controlled, crossover trial involving adult patients with multiple sclerosis and spasticity. We recruited participants from a regional clinic or by referral from specialists. We randomly assigned participants to either the intervention (smoked cannabis, once daily for three day ...[more]

PMID: 22586334

Similar Datasets

Project description:BackgroundChronic neuropathic pain affects 1%-2% of the adult population and is often refractory to standard pharmacologic treatment. Patients with chronic pain have reported using smoked cannabis to relieve pain, improve sleep and improve mood.MethodsAdults with post-traumatic or postsurgical neuropathic pain were randomly assigned to receive cannabis at four potencies (0%, 2.5%, 6% and 9.4% tetrahydrocannabinol) over four 14-day periods in a crossover trial. Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle, followed by a nine-day washout period. Daily average pain intensity was measured using an 11-point numeric rating scale. We recorded effects on mood, sleep and quality of life, as well as adverse events.ResultsWe recruited 23 participants (mean age 45.4 [standard deviation 12.3] years, 12 women [52%]), of whom 21 completed the trial. The average daily pain intensity, measured on the 11-point numeric rating scale, was lower on the prespecified primary contrast of 9.4% v. 0% tetrahydrocannabinol (5.4 v. 6.1, respectively; difference = 0.7, 95% confidence interval [CI] 0.02-1.4). Preparations with intermediate potency yielded intermediate but nonsignificant degrees of relief. Participants receiving 9.4% tetrahydrocannabinol reported improved ability to fall asleep (easier, p = 0.001; faster, p < 0.001; more drowsy, p = 0.003) and improved quality of sleep (less wakefulness, p = 0.01) relative to 0% tetrahydrocannabinol. We found no differences in mood or quality of life. The most common drug-related adverse events during the period when participants received 9.4% tetrahydrocannabinol were headache, dry eyes, burning sensation in areas of neuropathic pain, dizziness, numbness and cough.ConclusionA single inhalation of 25 mg of 9.4% tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity of pain, improved sleep and was well tolerated. Further long-term safety and efficacy studies are indicated. (International Standard Randomised Controlled Trial Register no. ISRCTN68314063).

Project description:Baclofen, a racemic GABA-B (GABAB) receptor agonist, is commonly used for the management of multiple sclerosis-related spasticity but is associated with frequent dosing and poor tolerability. Arbaclofen, the active R-enantiomer of baclofen, exhibits 100- to 1000-fold greater specificity for the GABAB receptor compared with the S-enantiomer and ∼5-fold greater potency compared with racemic baclofen. Arbaclofen extended-release tablets have a dosing interval of 12 hours and have shown a favourable safety and efficacy profile in early-phase clinical development. The current Phase 3 study was designed to evaluate the efficacy and safety of arbaclofen extended-release tablets in patients with multiple sclerosis-related spasticity. In this multicentre, double-blind, placebo-controlled study, adults with multiple sclerosis-related spasticity were randomized to arbaclofen extended-release 40 mg/day, arbaclofen extended-release 80 mg/day or placebo for 12 weeks. The co-primary end-points were the change from baseline to Week 12 in the Total Numeric-transformed Modified Ashworth Scale in the Most Affected Limb score and the Clinical Global Impression of Change score. A hierarchical testing procedure was used to evaluate the co-primary end-points; analyses for the 80 mg/day group were considered inferential only if the arbaclofen extended-release 40 mg/day and placebo groups demonstrated a statistically significant difference (P ≤ 0.05) for both end-points. Five hundred thirty-six patients were included in the study. At Week 12, the least squares mean change from baseline in Total Numeric-transformed Modified Ashworth Scale in the Most Affected Limb score was -1.67 (95% confidence interval: -1.97 to -1.36) and -1.28 (95% confidence interval: -1.57 to -0.99) in the arbaclofen extended-release 40 mg/day and placebo groups, respectively (least squares mean difference: -0.39; P < 0.048). Improvements were seen in the mean Clinical Global Impression of Change scores for both the arbaclofen extended-release 40 mg/day and placebo groups; however, no statistically significant difference was observed between them (least squares mean difference: -0.10; P = 0.43). Most adverse events were of mild-moderate severity. Arbaclofen extended-release 40 mg/day for 12 weeks significantly reduced multiple sclerosis-related spasticity compared with placebo and was safe and well tolerated over the 12-week treatment period. Although arbaclofen extended-release 40 mg/day improved Clinical Global Impression of Change scores, a significant difference from placebo was not observed.

Project description:ObjectiveTo assess the safety and efficacy of epigallocatechin-3-gallate (EGCG) add-on to glatiramer acetate (GA) in patients with relapsing-remitting multiple sclerosis (RRMS).MethodsWe enrolled patients with RRMS (aged 18-60 years, Expanded Disability Status Scale [EDSS] score 0-6.5), receiving stable GA treatment in a multicenter, prospective, double-blind, phase II, randomized controlled trial. Participants received up to 800 mg oral EGCG daily over a period of 18 months. The primary outcome was the proportion of patients without new hyperintense lesions on T2-weighted (T2w) brain MRI within 18 months. Secondary end points included additional MRI and clinical parameters. Immunologic effects of EGCG were investigated in exploratory experiments.ResultsA total of 122 patients on GA were randomly assigned to EGCG treatment (n = 62) or placebo (n = 60). We could not demonstrate a difference between groups after 18 months for the primary outcome or other radiologic (T2w lesion volume, T1w hypointense lesion number or volume, number of cumulative contrast-enhancing lesions, percent brain volume change), or clinical (EDSS, MS functional composite, and annualized relapse rate) parameter. EGCG treatment did not affect immune response to GA. Pharmacologic analysis revealed wide ranging EGCG plasma levels. The treatment was well tolerated with a similar incidence of mostly mild adverse events similar in both groups.ConclusionIn RRMS, oral EGCG add-on to GA was not superior to placebo in influencing MRI and clinical disease activity over 18 months. The treatment was safe at a daily dosage up to 800 mg EGCG. It did not influence immune parameters, despite indication of EGCG being bioavailable in patients.Classification of evidenceThis study provides Class II evidence that for patients with RRMS, EGCG added to GA did not significantly affect the development of new hyperintense lesions on T2-weighted brain MRI.Trial registration informationClinical trial registration number: NCT00525668.

Project description:ImportanceStudies suggest gut worms induce immune responses that can protect against multiple sclerosis (MS). To our knowledge, there are no controlled treatment trials with helminth in MS.ObjectiveTo determine whether hookworm treatment has effects on magnetic resonance imaging (MRI) activity and T regulatory cells in relapsing MS.Design, setting, and participantsThis 9-month double-blind, randomized, placebo-controlled trial was conducted between September 2012 and March 2016 in a modified intention-to-treat population (the data were analyzed June 2018) at the University of Nottingham, Queen's Medical Centre, a single tertiary referral center. Patients aged 18 to 61 years with relapsing MS without disease-modifying treatment were recruited from the MS clinic. Seventy-three patients were screened; of these, 71 were recruited (2 ineligible/declined).InterventionsPatients were randomized (1:1) to receive either 25 Necator americanus larvae transcutaneously or placebo. The MRI scans were performed monthly during months 3 to 9 and 3 months posttreatment.Main outcomes and measuresThe primary end point was the cumulative number of new/enlarging T2/new enhancing T1 lesions at month 9. The secondary end point was the percentage of cluster of differentiation (CD) 4+CD25highCD127negT regulatory cells in peripheral blood.ResultsPatients (mean [SD] age, 45 [9.5] years; 50 women [71%]) were randomized to receive hookworm (35 [49.3%]) or placebo (36 [50.7%]). Sixty-six patients (93.0%) completed the trial. The median cumulative numbers of new/enlarging/enhancing lesions were not significantly different between the groups by preplanned Mann-Whitney U tests, which lose power with tied data (high number of zeroactivity MRIs in the hookworm group, 18/35 [51.4%] vs 10/36 [27.8%] in the placebo group). The percentage of CD4+CD25highCD127negT cells increased at month 9 in the hookworm group (hookworm, 32 [4.4%]; placebo, 34 [3.9%]; P = .01). No patients withdrew because of adverse effects. There were no differences in adverse events between groups except more application-site skin discomfort in the hookworm group (82% vs 28%). There were 5 relapses (14.3%) in the hookworm group vs 11 (30.6%) receiving placebo.Conclusions and relevanceTreatment with hookworm was safe and well tolerated. The primary outcome did not reach significance, likely because of a low level of disease activity. Hookworm infection increased T regulatory cells, suggesting an immunobiological effect of hookworm. It appears that a living organism can precipitate immunoregulatory changes that may affect MS disease activity.Trial registrationClinicalTrials.gov Identifier: NCT01470521.

Dataset Information

Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial.

Publications

Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets