We performed a systematic review of the scientific literature assessing the use of exogenous cannabinoids in the treatment of movement disorders including Huntington's disease, Parkinson's disease, Tourette's syndrome, tics, essential tremor, tremor associated with multiple sclerosis, Wilson's disease, dystonia, and myoclonus. Databases searched for articles published in English include: Pubmed, Web of Science, PsycINFO, and Clinicaltrials.gov. A total of 21 case series and clinical trials evaluating the use of cannabinoids in the treatment of movement disorders were identified. All studies either consisted of small sample sizes, or the primary outcome was not the effect of exogenous cannabinoid treatment on a specific movement. None of the studies reviewed were powered to detect a difference with the treatment of a cannabinoid agonist. Therefore, currently no conclusions can be made on the efficacy of cannabinoids in the treatment of movement disorders.
IMPORTANCE: Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear.
OBJECTIVE: To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids.
DATA SOURCES: Twenty-eight databases from inception to April 2015.
STUDY SELECTION: Randomized clinical trials of cannabinoids for the following indications: nausea and vomiting due to chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity due to multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, or Tourette syndrome.
DATA EXTRACTION AND SYNTHESIS: Study quality was assessed using the Cochrane risk of bias tool. All review stages were conducted independently by 2 reviewers. Where possible, data were pooled using random-effects meta-analysis.
MAIN OUTCOMES AND MEASURES: Patient-relevant/disease-specific outcomes, activities of daily living, quality of life, global impression of change, and AEs.
RESULTS: A total of 79 trials (6462 participants) were included; 4 were judged at low risk of bias. Most trials showed improvement in symptoms associated with cannabinoids but these associations did not reach statistical significance in all trials. Compared with placebo, cannabinoids were associated with a greater average number of patients showing a complete nausea and vomiting response (47% vs 20%; odds ratio [OR], 3.82 [95% CI, 1.55-9.42]; 3 trials), reduction in pain (37% vs 31%; OR, 1.41 [95% CI, 0.99-2.00]; 8 trials), a greater average reduction in numerical rating scale pain assessment (on a 0-10-point scale; weighted mean difference [WMD], -0.46 [95% CI, -0.80 to -0.11]; 6 trials), and average reduction in the Ashworth spasticity scale (WMD, -0.36 [95% CI, -0.69 to -0.05]; 7 trials). There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination.
CONCLUSIONS AND RELEVANCE: There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs.
OBJECTIVE: To determine the efficacy of medical marijuana in several neurologic conditions. METHODS: We performed a systematic review of medical marijuana (1948-November 2013) to address treatment of symptoms of multiple sclerosis (MS), epilepsy, and movement disorders. We graded the studies according to the American Academy of Neurology classification scheme for therapeutic articles. RESULTS: Thirty-four studies met inclusion criteria; 8 were rated as Class I. CONCLUSIONS: The following were studied in patients with MS: (1) Spasticity: oral cannabis extract (OCE) is effective, and nabiximols and tetrahydrocannabinol (THC) are probably effective, for reducing patient-centered measures; it is possible both OCE and THC are effective for reducing both patient-centered and objective measures at 1 year. (2) Central pain or painful spasms (including spasticity-related pain, excluding neuropathic pain): OCE is effective; THC and nabiximols are probably effective. (3) Urinary dysfunction: nabiximols is probably effective for reducing bladder voids/day; THC and OCE are probably ineffective for reducing bladder complaints. (4) Tremor: THC and OCE are probably ineffective; nabiximols is possibly ineffective. (5) Other neurologic conditions: OCE is probably ineffective for treating levodopa-induced dyskinesias in patients with Parkinson disease. Oral cannabinoids are of unknown efficacy in non-chorea-related symptoms of Huntington disease, Tourette syndrome, cervical dystonia, and epilepsy. The risks and benefits of medical marijuana should be weighed carefully. Risk of serious adverse psychopathologic effects was nearly 1%. Comparative effectiveness of medical marijuana vs other therapies is unknown for these indications.
BACKGROUND: Both chronic and acute pain have been cited as the most common symptoms amongst patients with multiple sclerosis (MS), with recent prevalence estimates as high as 83 %. The evidence for spasticity and trigeminal neuralgia pharmacological treatments in MS has been systematically reviewed, but no equivalent reviews have been published concerning MS pain unrelated to these two conditions. OBJECTIVE: Our objective was to systematically review pain management strategies for the reduction of non-spastic and non-trigeminal neuralgic pain in MS patients. DATA SOURCES: Experimental studies published after 1965 were chosen for review by searching electronic databases (e.g. PubMed, Cumulative Index to Nursing and Allied Health Literature, Science Citation Index Expanded, Conference Proceedings Citation Index-Science, and clinicaltrials.gov) and bibliographies/citations of previously published reviews. STUDY SELECTION: Studies were included if all participants were adults clinically diagnosed with MS, study sample was not restricted to participants with spasticity or trigeminal neuralgia, and participant-reported pain was a primary or secondary outcome measured with a validated tool. STUDY APPRAISAL AND SYNTHESIS METHODS: Records were screened and methodological qualities of included studies were assessed independently by two reviewers under the supervision of another reviewer using the principles recommended in the Cochrane Handbook for Systematic Review of Interventions and the levels of evidence espoused by the American Academy of Neurology. RESULTS: Fifteen studies met the inclusion and exclusion criteria for review; interventions included antidepressants, anticonvulsants, dextromethorphan/quinidine, cannabinoids, and opioids/opioid antagonists. The pooled effect size for anticonvulsants (4 studies, 78 participants) was -1.88 (95 % CI: -3.13 to -0.64). The pooled effect size for cannabinoids (3 studies, 565 participants) was 0.08 (95 % CI: -0.74 to 0.89). Overall, only four trials reported Class 1 evidence. For these trials, dizziness was the most commonly reported adverse event, followed by nausea and somnolence. LIMITATIONS: The relatively small number of trials in MS patients with chronic pain precludes specific recommendations for treatment strategies. The review did not reveal any studies of drug combinations. CONCLUSIONS: More trials with rigorous design and reporting are needed to determine effective treatments for specific pain types presenting in people living with MS.
BACKGROUND: The therapeutic use of cannabis and cannabis-based medicines raises safety concerns for patients, clinicians, policy-makers, insurers, researchers and regulators. Although the efficacy of cannabinoids is being increasingly demonstrated in randomized controlled trials, most safety information comes from studies of recreational use.
METHODS: We performed a systematic review of safety studies of medical cannabinoids published over the past 40 years to create an evidence base for cannabis-related adverse events and to facilitate future cannabis research initiatives. We critically evaluated the quality of published studies with a view to identifying ways to improve future studies.
RESULTS: A total of 321 articles were eligible for evaluation. After excluding those that focused on recreational cannabis use, we included 31 studies (23 randomized controlled trials and 8 observational studies) of medical cannabis use in our analysis. In the 23 randomized controlled trials, the median duration of cannabinoid exposure was 2 weeks (range 8 hours to 12 months). A total of 4779 adverse events were reported among participants assigned to the intervention. Most (4615 [96.6%]) were not serious. Of the 164 serious adverse events, the most common was relapse of multiple sclerosis (21 events [12.8%]), vomiting (16 events [9.8%]) and urinary tract infection (15 events [9.1%]). The rate of nonserious adverse events was higher among participants assigned to medical cannabinoids than among controls (rate ratio [RR] 1.86, 95% confidence interval [CI] 1.57-2.21); the rates of serious adverse events did not differ significantly between these 2 groups (RR 1.04, 95% CI 0.78-1.39). Dizziness was the most commonly reported nonserious adverse event (714 events [15.5%]) among people exposed to cannabinoids. INTERPRETATION: Short-term use of existing medical cannabinoids appeared to increase the risk of nonserious adverse events. The risks associated with long-term use were poorly characterized in published clinical trials and observational studies. High-quality trials of long-term exposure are required to further characterize safety issues related to the use of medical cannabinoids.
BACKGROUND: Disabling tremor or ataxia is common in multiple sclerosis (MS) and up to 80% of patients experience tremor or ataxia at some point during their disease. A variety of treatments are available, ranging from pharmacotherapy or stereotactic neurosurgery to neurorehabilitation.
OBJECTIVES: To assess the efficacy and tolerability of both pharmacological and non-pharmacologic treatments of ataxia in patients with MS.
SEARCH METHODS: The following electronic resources were searched: Cochrane MS Group trials register (June 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2006), MEDLINE (January 1966 to June 2006), EMBASE (Jan 1988 to June 2006) and the National Health Service National Research Register (NRR) including the Medical Research Council Clinical Trials Directory (Issue 2, 2006). Manual searches of bibliographies of relevant articles, pertinent medical and neurology journals and abstract books of major neurology and MS conferences (2001-2006) were also performed. Direct communication with experts and drug companies was sought.
SELECTION CRITERIA: Blinded, randomised trials which were either placebo-controlled or which compared two or more treatments were included. Trials testing pharmacological agents must have had both participant and assessor blinding. Trials testing surgical interventions or effects of physiotherapy, where participants could not have been blinded to the treatment, must have had independent assessors who were blinded to the treatment. Cross-over trials were included.
DATA COLLECTION AND ANALYSIS: Three independent reviewers extracted data and the findings of the trials were summarised. A meta-analysis was not performed due to the inadequacy of outcome measures and methodological problems with the studies reviewed.
MAIN RESULTS: Ten randomised controlled trials met the inclusion criteria. Six placebo-controlled studies (pharmacotherapy) and four comparative studies (one stereotactic neurosurgery and three neurorehabilitation) were reviewed. No standardised outcome measures were used across the studies. In general, pharmacotherapies were unrewarding and data on neurosurgery or rehabilitation is insufficient to lead to a change in practice.
AUTHORS' CONCLUSIONS: The absolute and comparative efficacy and tolerability of pharmacotherapies to treat ataxia in MS are poorly documented and no recommendations can be made to guide prescribing. Although studies on neurosurgery and neurorehabilitation showed promising results, the absolute indications for treating with those methods cannot be developed. Standardised, well validated measures of ataxia and tremor need to be developed and employed in larger randomised controlled trials with careful blinding.
In order to assess the current knowledge on the therapeutic potential of cannabinoids, a meta-analysis was performed through Medline and PubMed up to July 1, 2005. The key words used were cannabis, marijuana, marihuana, hashish, hashich, haschich, cannabinoids, tetrahydrocannabinol, THC, dronabinol, nabilone, levonantradol, randomised, randomized, double-blind, simple blind, placebo-controlled, and human. The research also included the reports and reviews published in English, French and Spanish. For the final selection, only properly controlled clinical trials were retained, thus open-label studies were excluded. Seventy-two controlled studies evaluating the therapeutic effects of cannabinoids were identified. For each clinical trial, the country where the project was held, the number of patients assessed, the type of study and comparisons done, the products and the dosages used, their efficacy and their adverse effects are described. Cannabinoids present an interesting therapeutic potential as antiemetics, appetite stimulants in debilitating diseases (cancer and AIDS), analgesics, and in the treatment of multiple sclerosis, spinal cord injuries, Tourette's syndrome, epilepsy and glaucoma.
We performed a systematic review of the scientific literature assessing the use of exogenous cannabinoids in the treatment of movement disorders including Huntington's disease, Parkinson's disease, Tourette's syndrome, tics, essential tremor, tremor associated with multiple sclerosis, Wilson's disease, dystonia, and myoclonus. Databases searched for articles published in English include: Pubmed, Web of Science, PsycINFO, and Clinicaltrials.gov. A total of 21 case series and clinical trials evaluating the use of cannabinoids in the treatment of movement disorders were identified. All studies either consisted of small sample sizes, or the primary outcome was not the effect of exogenous cannabinoid treatment on a specific movement. None of the studies reviewed were powered to detect a difference with the treatment of a cannabinoid agonist. Therefore, currently no conclusions can be made on the efficacy of cannabinoids in the treatment of movement disorders.
