Systematic reviews included in this broad synthesis

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Systematic review

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State of the evidence: Cannabinoids and cancer pain-A systematic review.

Autoren Tateo S
Zeitung Journal of the American Association of Nurse Practitioners
Year 2017
Links Pubmed DOI

Dieser Artikel ist in enthalten 1 Broad synthesis 7 Broad syntheses (1 reference)

Dieser Artikel enthält 7 Primary studies 7 Primary studies (7 references)

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BACKGROUND AND PURPOSE: Cannabinoids are widely used to alleviate intractable symptoms such as pain, nausea, and muscle spasticity. The purpose of this review was to ascertain the current state of the science regarding use of cannabinoids for cancer pain. METHODS: Four electronic databases were searched for randomized control trials of cannabinoids and cancer pain. Studies included examined the analgesic effects of cannabinoids for cancer pain. Methodological quality was assessed using the Jadad scale. CONCLUSIONS: Eight randomized control trials met the inclusion criteria for review. Most trials found analgesic effects from cannabinoids when compared to placebo, although not all associations reached statistical significance. The analgesic effects of cannabinoids were also limited by dose-dependent side effects. Side effects most commonly reported were changes in cognition, sedation, and dizziness. IMPLICATIONS FOR PRACTICE: There is evidence that cannabinoids are effective adjuvants for cancer pain not completely relieved by opioid therapy, but there is a dearth of high-quality studies to support a stronger conclusion. Cannabinoids appear to be safe in low and medium doses. Methodological limitations of the trials limited the ability to make sound conclusions. Further research is warranted before efficacy, safety, and utility of cannabinoids for cancer pain can be determined.

Systematic review

Unclassified

A systematic review of the analgesic efficacy of cannabinoid medications in the management of acute pain.

Autoren Stevens AJ , Higgins MD
Zeitung Acta anaesthesiologica Scandinavica
Year 2017
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Dieser Artikel ist in enthalten 2 Broad syntheses 7 Broad syntheses (2 references)

Dieser Artikel enthält 7 Primary studies 7 Primary studies (7 references)

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BACKGROUND: Cannabinergic medications have been postulated to demonstrate efficacy in the management of pain. The aim of this systematic review was to assess the analgesic efficacy and adverse effects of cannabinoids when used for the management of acute pain. METHODS: A systematic review was performed by searching the MEDLINE, EMBASE and CENTRAL databases, and the World Health Organization International Clinical Trials Registry Platform for human randomized controlled trials that assessed the analgesic efficacy of cannabinoids compared to placebo or active comparators. The reported outcomes for analgesic efficacy and adverse effects in included studies were qualitatively analysed. RESULTS: Seven studies, including 611 patients were included in the systematic review. In five studies, cannabinoids were found to provide equivalent analgesia to placebo, in one study the analgesia provided by cannabinoids was superior to placebo, and in one study cannabinoids provided analgesia that was inferior to that provided by placebo. No synergistic or additive analgesic effect was observed when cannabinoids were used in combination with opioids. In five of the seven studies, certain adverse effects were more frequent with cannabinoid treatment than with placebo or active comparator. CONCLUSION: On the basis of the available randomized controlled trial evidence, cannabinoids have no role in the management of acute pain.

Systematic review

Unclassified

[Efficacy, tolerability and safety of cannabinoids for chronic neuropathic pain : A systematic review of randomized controlled studies].

Zeitung Schmerz (Berlin, Germany)
Year 2016
Links Pubmed DOI

Dieser Artikel ist in enthalten 5 Broad syntheses 15 Broad syntheses (5 references)

Dieser Artikel enthält 15 Primary studies 15 Primary studies (15 references)

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BACKGROUND: Recently published systematic reviews came to different conclusions with respect to the efficacy, tolerability and safety of cannabinoids for treatment of chronic neuropathic pain. MATERIAL AND METHODS: A systematic search of the literature was carried out in MEDLINE, the Cochrane central register of controlled trials (CENTRAL) and clinicaltrials.gov up until November 2015. We included double-blind randomized placebo-controlled studies (RCT) of at least 2 weeks duration and with at least 9 patients per treatment arm comparing medicinal cannabis, plant-based or synthetic cannabinoids with placebo or any other active drug treatment in patients with chronic neuropathic pain. Clinical endpoints of the analyses were efficacy (more than 30 % or 50 % reduction of pain, average pain intensity, global improvement and health-related quality of life), tolerability (drop-out rate due to side effects, central nervous system and psychiatric side effects) and safety (severe side effects). Using a random effects model absolute risk differences (RD) were calculated for categorical data and standardized mean differences (SMD) for continuous variables. The methodological quality of RCTs was rated by the Cochrane risk of bias tool. RESULTS: We included 15 RCTs with 1619 participants. Study duration ranged between 2 and 15 weeks. Of the studies 10 used a plant-derived oromucosal spray with tetrahydrocannabinol/cannabidiol, 3 studies used a synthetic cannabinoid (2  with nabilone and 1  with dronabinol) and 2 studies used medicinal cannabis. The 13 studies with parallel or cross-over design yielded the following results with 95 % confidence intervals (CI): cannabinoids were superior to placebo in the reduction of mean pain intensity with SMD - 0.10 (95 % CI - 0.20- - 0.00, p = 0.05, 13 studies with 1565 participants), in the frequency of at least a 30 % reduction in pain with an RD of 0.10 [95 % CI 0.03-0.16, p = 0.004, 9 studies with 1346 participants, number needed to treat for additional benefit (NNTB) 14, 95 % CI 8-45] and in the frequency of a large or very large global improvement with an RD of 0.09 (95 % CI 0.01-0.17, p = 0.009, 7 studies with 1092 participants). There were no statistically significant differences between cannabinoids and placebo in the frequency of at least a 50 % reduction in pain, in improvement of health-related quality of life and in the frequency of serious adverse events. Patients treated with cannabinoids dropped out more frequently due to adverse events with an RD of 0.04 [95 % CI 0.01-0.07, p = 0.009, 11 studies with 1572 participants, number needed to treat for additional harm (NNTH) 19, 95 % CI 13-37], reported central nervous system side effects more frequently with an RD of 0.38 (95 % CI 0.18-0.58, p = 0.0003, 9 studies with 1304 participants, NNTH 3, 95 % CI 2-4) and psychiatric side effects with an RD of 0.11 (95 % CI 0.06-0.16, p < 0.0001, 9 studies with 1304 participants, NNTH 8, 95 % CI 7-12). CONCLUSION: Cannabinoids were marginally superior to placebo in terms of efficacy and inferior in terms of tolerability. Cannabinoids and placebo did not differ in terms of safety during the study period. Short-term and intermediate-term therapy with cannabinoids can be considered in selected patients with chronic neuropathic pain after failure of first-line and second-line therapies.

Systematic review

Unclassified

Nabilone for the Management of Pain.

Autoren Tsang CC , Giudice MG
Zeitung Pharmacotherapy
Year 2016
Links Pubmed DOI

Dieser Artikel ist in enthalten 5 Broad syntheses 11 Broad syntheses (5 references)

Dieser Artikel enthält 11 Primary studies 11 Primary studies (11 references)

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Nabilone, a synthetic cannabinoid, is approved in many countries including, but not limited to, Canada, the United States, Mexico, and the United Kingdom for the treatment of severe nausea and vomiting associated with chemotherapy. Clinical evidence is emerging for its use in managing pain conditions with different etiologies. We review the efficacy and safety of nabilone for various types of pain as well as its abuse potential, precautions and contraindications, and drug interactions; summarize pertinent clinical practice guidelines; and provide recommendations for dosing, monitoring, and patient education. Citations involving nabilone were identified through systematic reviews evaluating cannabinoids for pain. A systematic search (updated July 23, 2015) of the Ovid MEDLINE, EMBASE, PubMed, and Cochrane Library databases was performed. Eight randomized controlled trials, two prospective cohort trials, and one retrospective chart review were retrieved. Cancer pain, chronic noncancer pain, neuropathic pain, fibromyalgia, and pain associated with spasticity were the pain conditions evaluated. Nabilone was most commonly used as adjunctive therapy and led to small but significant reductions in pain. The most common adverse drug reactions included euphoria, drowsiness, and dizziness. Nabilone was rarely associated with severe adverse drug reactions requiring drug discontinuation, and the likelihood of abuse was thought to be low. Although the optimal role of nabilone in the management of pain is yet to be determined, certain clinical practice guidelines consider nabilone as a third-line agent.

Systematic review

Unclassified

Efficacy, tolerability and safety of cannabinoids in chronic pain associated with rheumatic diseases (fibromyalgia syndrome, back pain, osteoarthritis, rheumatoid arthritis) : A systematic review of randomized controlled trials.

Zeitung Schmerz (Berlin, Germany)
Year 2016
Links Pubmed DOI

Dieser Artikel ist in enthalten 6 Broad syntheses 4 Broad syntheses (6 references)

Dieser Artikel enthält 4 Primary studies 4 Primary studies (4 references)

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BACKGROUND: In the absence of an ideal treatment for chronic pain associated with rheumatic diseases, there is interest in the potential effects of cannabinoid molecules, particularly in the context of global interest in the legalization of herbal cannabis for medicinal use. METHODS: A systematic search until April 2015 was conducted in Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, www.cannabis-med.org and clinicaltrials.gov for randomized controlled trials with a study duration of at least 2 weeks and at least ten patients per treatment arm with herbal cannabis or pharmaceutical cannabinoid products in fibromyalgia syndrome (FMS), osteoarthritis (OA), chronic spinal pain, and rheumatoid arthritis (RA) pain. Outcomes were reduction of pain, sleep problems, fatigue and limitations of quality of life for efficacy, dropout rates due to adverse events for tolerability, and serious adverse events for safety. The methodology quality of the randomized controlled trials (RCTs) was evaluated by the Cochrane Risk of Bias Tool. RESULTS: Two RCTs of 2 and 4 weeks duration respectively with nabilone, including 71 FMS patients, one 4-week trial with nabilone, including 30 spinal pain patients, and one 5-week study with tetrahydrocannbinol/cannabidiol, including 58 RA patients were included. One inclusion criterion was pain refractory to conventional treatment in three studies. No RCT with OA patients was found. The risk of bias was high for three studies. The findings of a superiority of cannabinoids over controls (placebo, amitriptyline) were not consistent. Cannabinoids were generally well tolerated despite some troublesome side effects and safe during the study duration. CONCLUSIONS: Currently, there is insufficient evidence for recommendation for any cannabinoid preparations for symptom management in patients with chronic pain associated with rheumatic diseases.

Systematic review

Unclassified

Cannabinoids for fibromyalgia

Zeitung Cochrane Database of Systematic Reviews
Year 2016
Links Pubmed DOI PubMed Central

Dieser Artikel ist in enthalten 8 Broad syntheses 2 Broad syntheses (8 references)

Dieser Artikel enthält 2 Primary studies 2 Primary studies (2 references)

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BACKGROUND: This review is one of a series on drugs used to treat fibromyalgia. Fibromyalgia is a clinically well-defined chronic condition of unknown aetiology characterised by chronic widespread pain that often co-exists with sleep problems and fatigue affecting approximately 2% of the general population. People often report high disability levels and poor health-related quality of life (HRQoL). Drug therapy focuses on reducing key symptoms and disability, and improving HRQoL. Cannabis has been used for millennia to reduce pain and other somatic and psychological symptoms. OBJECTIVES: To assess the efficacy, tolerability and safety of cannabinoids for fibromyalgia symptoms in adults. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE to April 2016, together with reference lists of retrieved papers and reviews, three clinical trial registries, and contact with trial authors. SELECTION CRITERIA: We selected randomised controlled trials of at least four weeks' duration of any formulation of cannabis products used for the treatment of adults with fibromyalgia. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data of all included studies and assessed risk of bias. We resolved discrepancies by discussion. We performed analysis using three tiers of evidence. First tier evidence was derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for drop-outs; at least 200 participants in the comparison, eight to 12 weeks' duration, parallel design), second tier evidence from data that did not meet one or more of these criteria and were considered at some risk of bias but with adequate numbers (i.e. data from at least 200 participants) in the comparison, and third tier evidence from data involving small numbers of participants that were considered very likely to be biased or used outcomes of limited clinical utility, or both. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). MAIN RESULTS: We included two studies with 72 participants. Overall, the two studies were at moderate risk of bias. The evidence was derived from group mean data and completer analysis (very low quality evidence overall). We rated the quality of all outcomes according to GRADE as very low due to indirectness, imprecision and potential reporting bias.The primary outcomes in our review were participant-reported pain relief of 50% or greater, Patient Global Impression of Change (PGIC) much or very much improved, withdrawal due to adverse events (tolerability) and serious adverse events (safety). Nabilone was compared to placebo and to amitriptyline in one study each. Study sizes were 32 and 40 participants. One study used a cross-over design and one used a parallel group design; study duration was four or six weeks. Both studies used nabilone, a synthetic cannabinoid, with a bedtime dosage of 1 mg/day. No study reported the proportion of participants experiencing at least 30% or 50% pain relief or who were very much improved. No study provided first or second tier (high to moderate quality) evidence for an outcome of efficacy, tolerability and safety. Third tier (very low quality) evidence indicated greater reduction of pain and limitations of HRQoL compared to placebo in one study. There were no significant differences to placebo noted for fatigue and depression (very low quality evidence). Third tier evidence indicated better effects of nabilone on sleep than amitriptyline (very low quality evidence). There were no significant differences between the two drugs noted for pain, mood and HRQoL (very low quality evidence). More participants dropped out due to adverse events in the nabilone groups (4/52 participants) than in the control groups (1/20 in placebo and 0/32 in amitriptyline group). The most frequent adverse events were dizziness, nausea, dry mouth and drowsiness (six participants with nabilone). Neither study reported serious adverse events during the period of both studies. We planned to create a GRADE 'Summary of findings' table, but due to the scarcity of data we were unable to do this. We found no relevant study with herbal cannabis, plant-based cannabinoids or synthetic cannabinoids other than nabilone in fibromyalgia. AUTHORS' CONCLUSIONS: We found no convincing, unbiased, high quality evidence suggesting that nabilone is of value in treating people with fibromyalgia. The tolerability of nabilone was low in people with fibromyalgia.

Systematic review

Unclassified

Efficacy, Tolerability, and Safety of Cannabinoid Treatments in the Rheumatic Diseases: A Systematic Review of Randomized Controlled Trials.

Zeitung Arthritis care & research
Year 2016
Links Pubmed DOI

Dieser Artikel ist in enthalten 9 Broad syntheses 4 Broad syntheses (9 references)

Dieser Artikel enthält 4 Primary studies 4 Primary studies (4 references)

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OBJECTIVE: To assess the efficacy, tolerability, and safety of cannabinoids (phyto- and syntheto-) in the management of rheumatic diseases. METHODS: Multiple databases, including Medline, Embase, and CENTRAL, were searched. Randomized controlled trials with outcomes of pain, sleep, quality of life, tolerability (dropouts due to adverse events), and safety (serious adverse events), with comparison of cannabinoids with any type of control, were included. Study methodology quality was evaluated with the Cochrane risk of bias tool. RESULTS: In 4 short-term studies comprising 203 patients (58 with rheumatoid arthritis, 71 with fibromyalgia, and 74 with osteoarthritis [OA]), cannabinoids had a statistically significant effect on pain in 2, sleep in 2, and improved quality of life in 1, with the OA study prematurely terminated due to futility. The risk of bias was high for all 3 completed studies. Dizziness, cognitive problems, and drowsiness, as well as nausea, were reported for almost half of the patients. No serious adverse events were reported for cannabinoids during the study duration. No studies of herbal cannabis were identified. CONCLUSION: Extremely small sample sizes, short study duration, heterogeneity of rheumatic conditions and products, and absence of studies of herbal cannabis allow for only limited conclusions for the effects of cannabinoids in rheumatic conditions. Pain relief and effect on sleep may have some potential therapeutic benefit, but with considerable mild to moderate adverse events. There is currently insufficient evidence to recommend cannabinoid treatments for management of rheumatic diseases pending further study.

Systematic review

Unclassified

[Cannabinoids in palliative care : Systematic review and meta-analysis of efficacy, tolerability and safety].

Zeitung Schmerz (Berlin, Germany)
Year 2016
Links Pubmed DOI

Dieser Artikel ist in enthalten 7 Broad syntheses 9 Broad syntheses (7 references)

Dieser Artikel enthält 9 Primary studies 9 Primary studies (9 references)

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BACKGROUND: Cannabinoids have multiple medical indications in palliative care, such as relief of pain or nausea or increase of appetite and weight stabilisation. The value of cannabinoids for these indications is not resolved sufficiently for palliative patients. A systematic review with meta-analysis of the efficacy, tolerability and safety on the basis of randomised controlled studies (RCT) or randomised open label or crossover studies has not yet been conducted. MATERIALS AND METHODS: An extensive search for RCTs, randomised open label or crossover studies dealing with the underlying question was performed in the databases of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, PubMed, Scopus and Clinicaltrials.gov up to April 2015. Studies with a duration of ≥ 2 weeks and ≥ 10 participants per treatment group were included into analysis. Using a random effects model, pooled estimates of event rates for categorical data and standardized mean differences (SMD) for continuous variables and risk differences (RD) for dichotomous variables were calculated. RESULTS: Out of initially 108 studies 9, with a total of 1561 participants suffering from advanced or end stage diseases, were included. The median study duration of the cancer research was 8 weeks (16 days-11 weeks), of the HIV research 6 weeks (3-12 weeks) and of the study concentrating on Alzheimer's 2 × 6 weeks. The outcome results for cannabis/cannabinoids vs. placebo in patients with cancer were not significant for the 30 % decrease in pain (RD: 0.07; 95 % confidence interval (CI): - 0.01 to 0.16; p = 0.07), caloric intake (SMD 0.2; 95 % CI: - 0.66 to 1.06; p = 0.65) or sleep problems (SMD - 0.09; 95 % CI: - 0.62 to 0.43; p = 0.72). In the treatment of HIV cannabinoids were superior to placebo for the outcome of weight change (SMD 0.57; 95 % CI: 0.22-0.92; p = 0.001). Change in appetite was significant for the treatment of HIV (SMD 0.57; 95 % CI: 0.11-1.03; p = 0.02), but not for treatment of cancer (SMD 0.81; 95 % CI: - 1.14 to 2.75; p = 0.42). Nausea/vomiting (SMD 0.20; 95 % CI: - 0.03 to 0.44; p = 0.09) and health-related quality of life (HRQoL; SMD 0.00; 95 % CI: - 0.19 to 0.18; p = 0.98) did not show significant differences in the therapy of the two diseases. For the outcomes of tolerability the results were not significant for occurrence of dizziness (RD: 0.03; 95 % CI: - 0.02 to 0.08; p = 0.23) or psychiatric diseases, such as hallucinations or psychosis (RD: - 0.01; 95 % CI: - 0.04 to 0.03; p = 0.69) in the therapy of cancer. The outcome of psychiatric diseases in the treatment of HIV was significant (RD: 0.05; 95 % CI: 0.00-0.11; p = 0.05). The number of withdrawals due to adverse events, as a marker for tolerability, and the reports of serious adverse events as a measure of safety was not significantly different (RD: 1.20; 95 % CI: 0.85-1.71; p = 0.30 and RD: 1.15; 95 % CI: 0.88-1.49; p = 0.30, respectively). Dronabinol vs. megestrol acetate showed a superiority of megestrol in the therapy of cancer-associated anorexia for the endpoints change of appetite (49 vs. 75 %; p = 0.0001), weight gain (3 vs. 11 %; p = 0.02), HRQoL (p = 0.003) and tolerability (p = 0.03). There was no difference in the safety of the therapies (p = 0.12). In the treatment of HIV-associated wasting syndrome megestrol acetate was better than dronabinol for the endpoint of weight gain (p = 0.0001), whereas tolerability and safety did not differ. In the therapy of Alzheimer's dronabinol was better than placebo in the endpoint of weight gain according to one study (n = 15). A difference between herbal cannabis and synthetic cannabinoids, analysed by one study (n = 62) could not be found. CONCLUSION: Cannabinoids can lead to an increase in appetite in patients with HIV wasting syndrome but the therapy with megestrol acetate is superior to treatment with cannabinoids. The included studies were not of sufficient duration to answer questions concerning the long-term efficacy, tolerability and safety of therapy with cannabis or cannabinoids. Due to the sparse amount of data it is not possible to recommend a favoured use of cannabis or cannabinoids at this point.

Publication Thread

Andreae et al (Systematic review: Cannabis for chronic neuropathy)

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Publication Thread

Lynch et al (Systematic review: Cannabinoids for Chronic Non-Cancer Pain)

This thread includes 2 references