Cannabis and cannabinoids for symptomatic treatment for people with multiple sclerosis.

BACKGROUND: Spasticity and chronic neuropathic pain are common and serious symptoms in people with multiple sclerosis (MS). These symptoms increase with disease progression and lead to worsening disability, impaired activities of daily living and quality of life. Anti-spasticity medications and analgesics are of limited benefit or poorly tolerated. Cannabinoids may reduce spasticity and pain in people with MS. Demand for symptomatic treatment with cannabinoids is high. A thorough understanding of the current body of evidence regarding benefits and harms of these drugs is required. OBJECTIVES: To assess benefit and harms of cannabinoids, including synthetic, or herbal and plant-derived cannabinoids, for reducing symptoms for adults with MS. SEARCH METHODS: We searched the following databases from inception to December 2021: MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library), CINAHL (EBSCO host), LILACS, the Physiotherapy Evidence Database (PEDro), the World Health Organisation International Clinical Trials Registry Platform, the US National Institutes of Health clinical trial register, the European Union Clinical Trials Register, the International Association for Cannabinoid Medicines databank. We hand searched citation lists of included studies and relevant reviews. SELECTION CRITERIA: We included randomised parallel or cross-over trials (RCTs) evaluating any cannabinoid (including herbal Cannabis, Cannabis flowers, plant-based cannabinoids, or synthetic cannabinoids) irrespective of dose, route, frequency, or duration of use for adults with MS. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane Risk of bias 2 tool for parallel RCTs and crossover trials. We rated the certainty of evidence using the GRADE approach for the following outcomes: reduction of 30% in the spasticity Numeric Rating Scale, pain relief of 50% or greater in the Numeric Rating Scale-Pain Intensity, much or very much improvement in the Patient Global Impression of Change (PGIC), Health-Related Quality of Life (HRQoL), withdrawals due to adverse events (AEs) (tolerability), serious adverse events (SAEs), nervous system disorders, psychiatric disorders, physical dependence. MAIN RESULTS: We included 25 RCTs with 3763 participants of whom 2290 received cannabinoids. Age ranged from 18 to 60 years, and between 50% and 88% participants across the studies were female.  The included studies were 3 to 48 weeks long and compared nabiximols, an oromucosal spray with a plant derived equal (1:1) combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) (13 studies), synthetic cannabinoids mimicking THC (7 studies), an oral THC extract of Cannabis sativa (2 studies), inhaled herbal Cannabis (1 study) against placebo. One study compared dronabinol, THC extract of Cannabis sativa and placebo, one compared inhaled herbal Cannabis, dronabinol and placebo. We identified eight ongoing studies. Critical outcomes • Spasticity: nabiximols probably increases the number of people who report an important reduction of perceived severity of spasticity compared with placebo (odds ratio (OR) 2.51, 95% confidence interval (CI) 1.56 to 4.04; 5 RCTs, 1143 participants; I2 = 67%; moderate-certainty evidence). The absolute effect was 216 more people (95% CI 99 more to 332 more) per 1000 reporting benefit with cannabinoids than with placebo. • Chronic neuropathic pain: we found only one small trial that measured the number of participants reporting substantial pain relief with a synthetic cannabinoid compared with placebo (OR 4.23, 95% CI 1.11 to 16.17; 1 study, 48 participants; very low-certainty evidence). We are uncertain whether cannabinoids reduce chronic neuropathic pain intensity. • Treatment discontinuation due to AEs: cannabinoids may increase slightly the number of participants who discontinue treatment compared with placebo (OR 2.41, 95% CI 1.51 to 3.84; 21 studies, 3110 participants; I² = 17%; low-certainty evidence); the absolute effect is 39 more people (95% CI 15 more to 76 more) per 1000 people. Important outcomes • PGIC: cannabinoids probably increase the number of people who report 'very much' or 'much' improvement in health status compared with placebo (OR 1.80, 95% CI 1.37 to 2.36; 8 studies, 1215 participants; I² = 0%; moderate-certainty evidence). The absolute effect is 113 more people (95% CI 57 more to 175 more) per 1000 people reporting improvement. • HRQoL: cannabinoids may have little to no effect on HRQoL (SMD -0.08, 95% CI -0.17 to 0.02; 8 studies, 1942 participants; I2 = 0%; low-certainty evidence); • SAEs: cannabinoids may result in little to no difference in the number of participants who have SAEs compared with placebo (OR 1.38, 95% CI 0.96 to 1.99; 20 studies, 3124 participants; I² = 0%; low-certainty evidence); • AEs of the nervous system: cannabinoids may increase nervous system disorders compared with placebo (OR 2.61, 95% CI 1.53 to 4.44; 7 studies, 1154 participants; I² = 63%; low-certainty evidence); • Psychiatric disorders: cannabinoids may increase psychiatric disorders compared with placebo (OR 1.94, 95% CI 1.31 to 2.88; 6 studies, 1122 participants; I² = 0%; low-certainty evidence); • Drug tolerance: the evidence is very uncertain about the effect of cannabinoids on drug tolerance (OR 3.07, 95% CI 0.12 to 75.95; 2 studies, 458 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: Compared with placebo, nabiximols probably reduces the severity of spasticity in the short-term in people with MS. We are uncertain about the effect on chronic neurological pain and health-related quality of life. Cannabinoids may increase slightly treatment discontinuation due to AEs, nervous system and psychiatric disorders compared with placebo. We are uncertain about the effect on drug tolerance. The overall certainty of evidence is limited by short-term duration of the included studies.

Equity, acceptability and feasibility of using polyunsaturated fatty acids in children and adolescents with autism spectrum disorder: a rapid systematic review.

INTRODUCTION: Some recent randomized controlled trials (RCTs) assessed the efficacy and safety of polyunsaturated fatty acids (PUFAs) for the treatment of autism spectrum disorder (ASD). To optimally inform the Italian guideline for the management of ASD in children and adolescents, we reviewed the impact on equity, acceptability and feasibility for developing a pilot recommendation for PUFAs. METHODS: We performed a rapid systematic review of observational and experimental studies on PUFAs for children and adolescents with ASD, extracting data on resources required, equity, acceptability, and feasibility of PUFAs. We followed the framework provided by the grading of recommendations assessment, development and evaluation (GRADE) methodology, and we assessed risk of bias and methodological quality of included studies. Results were synthesized both narratively and quantitatively to address clinically relevant questions on equity, acceptability, and feasibility. RESULTS: We found 14 papers related to equity. PUFAs did not seem to impact equity importantly. We did not find variation in effectiveness across subgroups and in a base case scenario, the cost of a 12 weeks cycle of therapy with 1.155 g/day of PUFAs was €65.51 euro. The acceptability of PUFAs was evaluated in 17 studies, 9 of which were RCTs. PUFAs were widely used among children and adolescents with ASD (18 to 51%), and 50% of parents considered nutritional supplementation as useful. Difficulty in swallowing capsules and bad taste were identified as possible causes of poor compliance, but treatment adherence, when measured in included RCTs, was judged to be good to excellent. Discontinuation due to any cause for PUFAs could not differ from placebo (low certainty of evidence). The feasibility of using PUFAs was assessed in 12 studies. PUFAs were probably sustainable, and no particular critical issue emerged from the feasibility assessment. However, the evidence appeared scarce and indirect. CONCLUSIONS: We found the administration of PUFAs in children and adolescents with ASD to be potentially equitable, acceptable and feasible. These results are limited by the limited number and quality of retrieved documents, and need to be viewed in light of efficacy and safety data to formulate clinical recommendations.

Acupuncture vs. Pharmacological Prophylaxis of Migraine: A Systematic Review of Randomized Controlled Trials.

Introduction: Migraine is a chronic paroxymal neurological disorder characterized by attacks of moderate to severe headache and reversible neurological and systemic symptoms. Treatment of migraine includes acute therapies, that aim to reduce the intensity of pain of each attack, and preventive therapies that should decrease the frequency of headache recurrence. The objective of this systematic review was to assess the efficacy and safety of acupuncture for the prophylaxis of episodic or chronic migraine in adult patients compared to pharmacological treatment. Methods: We included randomized-controlled trials published in western languages that compared any treatment involving needle insertion (with or without manual or electrical stimulation) at acupuncture points, pain points or trigger points, with any pharmacological prophylaxis in adult (≥18 years) with chronic or episodic migraine with or without aura according to the criteria of the International Headache Society. Results: Nine randomized trials were included encompassing 1,484 patients. At the end of intervention we found a small reduction in favor of acupuncture for the number of days with migraine per month: (SMD: -0.37; 95% CI -1.64 to -0.11), and for response rate (RR: 1.46; 95% CI 1.16-1.84). We found a moderate effect in the reduction of pain intensity in favor of acupuncture (SMD: -0.36; 95% CI -0.60 to -0.13), and a large reduction in favor of acupuncture in both the dropout rate due to any reason (RR 0.39; 95% CI 0.18 to 0.84) and the dropout rate due to adverse event (RR 0.26; 95% CI 0.09 to 0.74). Quality of evidence was moderate for all these primary outcomes. Results at longest follow-up confirmed these effects. Conclusions: Based on moderate certainty of evidence, we conclude that acupuncture is mildly more effective and much safer than medication for the prophylaxis of migraine.

[Systematic review of safeness and therapeutic efficacy of cannabis in patients with multiple sclerosis, neuropathic pain, and in oncological patients treated with chemotherapy]. / Revisione sistematica sull'efficacia terapeutica e la sicurezza della cannabis per i pazienti affetti da sclerosi multipla, dolore neuropatico cronico e pazienti oncologici che assumono chemioterapie.

BACKGROUND: medical cannabis refers to the use of cannabis or cannabinoids as medical therapy to treat disease or alleviate symptoms. In the United States, 23 states and Washington DC (May 2015) have introduced laws to permit the medical use of cannabis. Within the European Union, medicinal cannabis laws and praxis vary wildly between Countries. OBJECTIVES: to provide evidence for benefits and harms of cannabis (including extracts and tinctures) treatment for adults in the following indications: control of spasticity and pain in patients with multiple sclerosis; control of pain in patients with chronic neuropathic pain; control of nausea and vomiting in adults with cancer receiving chemotherapy. METHODS: we searched the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE from inception to September 2016. We also searched for on-going studies via ClinicalTrials.gov and the World Health Organization and International Clinical Trials Registry Platform (ICTRP) search portal. All searches included also non-English language literature. All relevant randomized controlled trials (RCTs) evaluating the safety and efficacy of cannabis (including extracts and tinctures) compared with placebo or other pharmacological agents were included. Three authors independently evaluated the titles and abstracts of studies identified in the literature searches for their eligibility. For studies considered eligible, we retrieved full texts. Three investigators independently extracted data. For the assessment of the quality of evidence, we used the standard methodological procedures recommended by Cochrane and GRADE working Group. RESULTS: 41 trials (4,550 participants) were included; 15 studies considered efficacy and safety of cannabis for patients with multiple sclerosis, 12 for patients with chronic pain, and 14 for patients with cancer receiving chemotherapy. The included studies were published between 1975 and 2015, and the majority of them were conducted in Europe. We judged almost 50% of these studies to be at low risk of bias. The large majority (80%) of the comparisons were with placebo; only 8 studies included patients with cancer receiving chemotherapy comparing cannabis with other antiemetic drugs. Concerning the efficacy of cannabis (compared with placebo) in patients with multiple sclerosis, confidence in the estimate was high in favour of cannabis for spasticity (numerical rating scale and visual analogue scale, but not the Ashworth scale) and pain. For chronic and neuropathic pain (compared with placebo), there was evidence of a small effect; however, confidence in the estimate is low and these results could not be considered conclusive. There is uncertainty whether cannabis, including extracts and tinctures, compared with placebo or other antiemetic drugs reduces nausea and vomiting in patients with cancer requiring chemotherapy, although the confidence in the estimate of the effect was low or very low. In the included studies, many adverse events were reported and none of the studies assessed the development of abuse or dependence. CONCLUSIONS: there is incomplete evidence of the efficacy and safety of medical use of cannabis in the clinical contexts considered in this review. Furthermore, for many of the outcomes considered, the confidence in the estimate of the effect was again low or very low. To give conclusive answers to the efficacy and safety of cannabis used for medical purposes in the clinical contexts considered, further studies are needed, with higher quality, larger sample sizes, and possibly using the same diagnostic tools for evaluating outcomes of interest.

Exercises for adolescent idiopathic scoliosis: a Cochrane systematic review.

STUDY DESIGN: Systematic review of interventions. OBJECTIVE: To evaluate the efficacy of scoliosis-specific exercise (SSE) in adolescent patients with adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: AIS is a 3-dimensional deformity of the spine. Although AIS can progress during growth and cause a surface deformity, it is usually not symptomatic. However, in adulthood, if the final spinal curvature surpasses a certain critical threshold, the risk of health problems and curve progression is increased. The use of SSEs to reduce progression of AIS and postpone or avoid other more invasive treatments is controversial. SEARCH METHODS: The following databases (up to March 30, 2011) were searched with no language limitations: CENTRAL (The Cochrane Library 2011, issue 2), MEDLINE (from January 1966), EMBASE (from January 1980), CINHAL (from January 1982), SPORTDiscus (from January 1975), PsycINFO (from January 1887), and PEDro (from January 1929). We screened reference lists of articles and conducted an extensive hand search of gray literature. SELECTION CRITERIA: randomized controlled trials and prospective cohort studies with a control group comparing exercises with no treatment, other treatment, surgery, and different types of exercises. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias and extracted data. RESULTS: Two studies (154 participants) were included. There is low-quality evidence from 1 randomized controlled study that exercises as an adjunctive to other conservative treatments to increase the efficacy of these treatments (thoracic curve reduced: mean difference 9.00, [95% confidence interval, 5.47-12.53]; lumbar curve reduced: mean difference 8.00, [95% confidence interval, 5.08-10.92]). There is very low-quality evidence from a prospective controlled cohort study that SSEs structured within an exercise program can reduce brace prescription (risk ratio, 0.24; [95% confidence interval, 0.06-1.04]) as compared with "usual physiotherapy" [many different kinds of general exercises according to the preferences of the single therapists within different facilities]). CONCLUSION: There is a lack of high-quality evidence to recommend the use of SSE for AIS. One very low-quality study suggested that these exercises may be more effective than electrostimulation, traction, and postural training to avoid scoliosis progression, but better quality research needs to be conducted before the use of SSE can be recommended in clinical practice. LEVEL OF EVIDENCE: 2.

Exercises for adolescent idiopathic scoliosis.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of the spine . While AIS can progress during growth and cause a surface deformity, it is usually not symptomatic. However, in adulthood, if the final spinal curvature surpasses a certain critical threshold, the risk of health problems and curve progression is increased. The use of scoliosis-specific exercises (SSE) to reduce progression of AIS and postpone or avoid other more invasive treatments is controversial. OBJECTIVES: To evaluate the efficacy of SSE in adolescent patients with AIS. SEARCH METHODS: The following databases (up to 30 March 2011) were searched with no language limitations: CENTRAL (The Cochrane Library 2011, issue 2), MEDLINE (from January 1966), EMBASE (from January 1980), CINHAL (from January 1982), SportDiscus (from January 1975), PsycInfo (from January 1887), PEDro (from January 1929). We screened reference lists of articles and also conducted an extensive handsearch of grey literature. SELECTION CRITERIA: Randomised controlled trials and prospective cohort studies with a control group comparing exercises with no treatment, other treatment, surgery, and different types of exercises. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias and extracted data. MAIN RESULTS: Two studies (154 participants) were included. There is low quality evidence from one randomised controlled study that exercises as an adjunctive to other conservative treatments increase the efficacy of these treatments (thoracic curve reduced: mean difference (MD) 9.00, (95% confidence interval (CI) 5.47 to 12.53); lumbar curve reduced:MD 8.00, (95% CI 5.08 to 10.92)). There is very low quality evidence from a prospective controlled cohort study that scoliosis-specific exercises structured within an exercise programme can reduce brace prescription (risk ratio (RR) 0.24, (95% CI 0.06 to1.04) as compared to usual physiotherapy (many different kinds of general exercises according to the preferences of the single therapists within different facilities). AUTHORS' CONCLUSIONS: There is a lack of high quality evidence to recommend the use of SSE for AIS. One very low quality study suggested that these exercises may be more effective than electrostimulation, traction and postural training to avoid scoliosis progression, but better quality research needs to be conducted before the use of SSE can be recommended in clinical practice.

[Summary of systematic revisions of the efficacy of smoking cessation therapy]. / Sintesi delle revisioni sistematiche sulla efficacia degli interventi di cessazione del fumo.

Smoking cessation can be considered the most effective strategy to reduce smoking related mortality at medium term. The aim of this study is to conduct an overview of systematic reviews of effectiveness of smoking cessation interventions in the general population. Medline, Embase and the Cochrane Library for the years 1990-march 2001 have been searched for those systematic reviews of primary studies evaluating the effectiveness of smoking cessation interventions in the general population, adult smokers. The outcome measure was abstinence from smoking at 6 months after the start of the intervention. Thirty papers were found, 15 Cochrane reviews and 15 other systematic reviews. The present overview focuses on Cochrane reviews, because they were more recent and followed a standardised methodology. The interventions which proved to be successful were: the simple medical advice, a structured intervention from nurses, individual counselling, group therapy, nicotine replacement therapy, and bupropion. There is not enough evidence yet that one strategy is better than another. Even though there is evidence that it is possible to quit smoking without any intervention, we can recommend that every physician register the smoking habits of his patients, encourage smokers to quit and offer all the available effective strategies.