scholarly journals Living Systematic Review on Cannabis and Other Plant-Based Treatments for Chronic Pain

2021 ◽  
Author(s):  
Marian S. McDonagh ◽  
Jesse Wagner ◽  
Azrah Y. Ahmed ◽  
Rongwei Fu ◽  
Benjamin Morasco ◽  
...  

Objectives. To evaluate the evidence on benefits and harms of cannabinoids and similar plant-based compounds to treat chronic pain. Data sources. Ovid® MEDLINE®, PsycINFO®, Embase®, the Cochrane Library, and SCOPUS® databases, reference lists of included studies, submissions received after Federal Register request were searched to July 2021. Review methods. Using dual review, we screened search results for randomized controlled trials (RCTs) and observational studies of patients with chronic pain evaluating cannabis, kratom, and similar compounds with any comparison group and at least 1 month of treatment or followup. Dual review was used to abstract study data, assess study-level risk of bias, and rate the strength of evidence. Prioritized outcomes included pain, overall function, and adverse events. We grouped studies that assessed tetrahydrocannabinol (THC) and/or cannabidiol (CBD) based on their THC to CBD ratio and categorized them as high-THC to CBD ratio, comparable THC to CBD ratio, and low-THC to CBD ratio. We also grouped studies by whether the product was a whole-plant product (cannabis), cannabinoids extracted or purified from a whole plant, or synthetic. We conducted meta-analyses using the profile likelihood random effects model and assessed between-study heterogeneity using Cochran’s Q statistic chi square and the I2 test for inconsistency. Magnitude of benefit was categorized into no effect or small, moderate, and large effects. Results. From 2,850 abstracts, 20 RCTs (N=1,776) and 7 observational studies (N=13,095) assessing different cannabinoids were included; none of kratom. Studies were primarily short term, and 75 percent enrolled patients with a variety of neuropathic pain. Comparators were primarily placebo or usual care. The strength of evidence (SOE) was low, unless otherwise noted. Compared with placebo, comparable THC to CBD ratio oral spray was associated with a small benefit in change in pain severity (7 RCTs, N=632, 0 to10 scale, mean difference [MD] −0.54, 95% confidence interval [CI] −0.95 to −0.19, I2=28%; SOE: moderate) and overall function (6 RCTs, N=616, 0 to 10 scale, MD −0.42, 95% CI −0.73 to −0.16, I2=24%). There was no effect on study withdrawals due to adverse events. There was a large increased risk of dizziness and sedation and a moderate increased risk of nausea (dizziness: 6 RCTs, N=866, 30% vs. 8%, relative risk [RR] 3.57, 95% CI 2.42 to 5.60, I2=0%; sedation: 6 RCTs, N=866, 22% vs. 16%, RR 5.04, 95% CI 2.10 to 11.89, I2=0%; and nausea: 6 RCTs, N=866, 13% vs. 7.5%, RR 1.79, 95% CI 1.20 to 2.78, I2=0%). Synthetic products with high-THC to CBD ratios were associated with a moderate improvement in pain severity, a moderate increase in sedation, and a large increase in nausea (pain: 6 RCTs, N=390 to 10 scale, MD −1.15, 95% CI −1.99 to −0.54, I2=39%; sedation: 3 RCTs, N=335, 19% vs. 10%, RR 1.73, 95% CI 1.03 to 4.63, I2=0%; nausea: 2 RCTs, N=302, 12% vs. 6%, RR 2.19, 95% CI 0.77 to 5.39; I²=0%). We found moderate SOE for a large increased risk of dizziness (2 RCTs, 32% vs. 11%, RR 2.74, 95% CI 1.47 to 6.86, I2=0%). Extracted whole-plant products with high-THC to CBD ratios (oral) were associated with a large increased risk of study withdrawal due to adverse events (1 RCT, 13.9% vs. 5.7%, RR 3.12, 95% CI 1.54 to 6.33) and dizziness (1 RCT, 62.2% vs. 7.5%, RR 8.34, 95% CI 4.53 to 15.34). We observed a moderate improvement in pain severity when combining all studies of high-THC to CBD ratio (8 RCTs, N=684, MD −1.25, 95% CI −2.09 to −0.71, I2=50%; SOE: moderate). Evidence on whole-plant cannabis, topical CBD, low-THC to CBD, other cannabinoids, comparisons with active products, and impact on use of opioids was insufficient to draw conclusions. Other important harms (psychosis, cannabis use disorder, and cognitive effects) were not reported. Conclusions. Low to moderate strength evidence suggests small to moderate improvements in pain (mostly neuropathic), and moderate to large increases in common adverse events (dizziness, sedation, nausea) and study withdrawal due to adverse events with high- and comparable THC to CBD ratio extracted cannabinoids and synthetic products in short-term treatment (1 to 6 months). Evidence for whole-plant cannabis, and other comparisons, outcomes, and PBCs were unavailable or insufficient to draw conclusions. Small sample sizes, lack of evidence for moderate and long-term use and other key outcomes, such as other adverse events and impact on use of opioids during treatment, indicate that more research is needed.

2021 ◽  
Author(s):  
Marian S. McDonagh ◽  
Jesse Wagner ◽  
Azrah Y. Ahmed ◽  
Benjamin Morasco ◽  
Devan Kansagara ◽  
...  

Overview This is the third quarterly progress report for an ongoing living systematic review on cannabis and other plant-based treatments for chronic pain. The first progress report was published in January 2021 and the second in March 2021. The draft systematic review was available for public comment from May 19 through June 15, 2021, on the Agency for Healthcare Research and Quality (AHRQ) Effective Health Care website. The systematic review synthesizes evidence on the benefits and harms of plant-based compounds (PBCs), such as cannabinoids and kratom, used to treat chronic pain, addressing concerns about severe adverse effects, abuse, misuse, dependence, and addiction. The purpose of this progress report is to describe the cumulative literature identified thus far. This report will be periodically updated with new studies as they are published and identified, culminating in an annual systematic review that provides a synthesis of the accumulated evidence. Main Points In patients with chronic (mainly neuropathic) pain with short-term treatment (4 weeks to <6 months): • Studies of cannabis-related products were grouped based on their tetrahydrocannabinol (THC) to cannabidiol (CBD) ratio using the following categories: high THC to CBD, comparable THC to CBD, and low THC to CBD. • Comparable THC to CBD ratio oral spray is probably associated with small improvements in pain severity and may be associated with small improvements in function. There was no effect in pain interference or serious adverse events. There may be a large increased risk of dizziness and sedation, and a moderate increased risk of nausea. • Synthetic THC (high THC to CBD) may be associated with moderate improvement in pain severity and increased risk of sedation, and large increased risk of nausea. Synthetic THC is probably associated with a large increased risk of dizziness. • Extracted whole-plant high THC to CBD ratio products may be associated with large increases in risk of withdrawal due to adverse events and dizziness. • Evidence on whole-plant cannabis, low THC to CBD ratio products (topical CBD), other cannabinoids (cannabidivarin), and comparisons with other active interventions was insufficient to draw conclusions. • Other key adverse event outcomes (psychosis, cannabis use disorder, cognitive deficits) and outcomes on the impact on opioid use were not reported. • No evidence on other plant-based compounds, such as kratom, met criteria for this review.


2021 ◽  
Author(s):  
Patricia Pauline M. Remalante-Rayco ◽  
Evelyn O. Salido ◽  
Joey A. Tabula ◽  
Maria Teresa S. Tolosa

Objective. To assess the association between D-dimer and clinical outcomes in adults with COVID-19. Methods. We reviewed published articles and preprints from MEDLINE, Cochrane Library, Cornell Open Access Publication (COAP), MedRxiv, and BioRxiv databases. We included cohort studies on the association between D-dimer and the outcomes of thromboembolism, mortality, and worsening severity among hospitalized adults with COVID-19. Results. We found 25 observational studies on the association between D-dimer and the outcomes of thromboembolism, mortality, or worsening severity. There was an increased risk of thromboembolism (OR 5.61 [95% CI 3.97, 7.94]) with higher D-dimer levels across different COVID-19 severities. D-dimer levels are associated with higher in-hospital mortality (OR 5.57 [95% CI 2.74, 11.31]) and worsening severity manifesting as critical illness (OR 1.91 [95% CI 1.05, 3.48] to 2.58 [95% CI 1.57, 4.24]), disease progression (HR 2.846 [95% CI 2.10, 3.85]), or need for mechanical ventilation (HR 3.28 [95% CI 1.07, 10.10]). However, some methodological flaws, such as incomplete laboratory or follow-up data and concern on varied D-dimer cut-offs and definitions of worsening disease, raise some uncertainty in the widespread use of D-dimer as a prognostic marker. Conclusion. A higher D-dimer value is associated with worse clinical outcomes among hospitalized adults with COVID-19 and may be a useful prognostic indicator.


2018 ◽  
Vol 89 (7) ◽  
pp. 741-753 ◽  
Author(s):  
Emily Stockings ◽  
Dino Zagic ◽  
Gabrielle Campbell ◽  
Megan Weier ◽  
Wayne D Hall ◽  
...  

Review evidence for cannabinoids as adjunctive treatments for treatment-resistant epilepsy. Systematic search of Medline, Embase and PsycINFO was conducted in October 2017. Outcomes were: 50%+ seizure reduction, complete seizure freedom; improved quality of life (QoL). Tolerability/safety were assessed by study withdrawals, adverse events (AEs) and serious adverse events (SAEs). Analyses were conducted in Stata V.15.0. 36 studies were identified: 6 randomised controlled trials (RCTs), 30 observational studies. Mean age of participants was 16.1 years (range 0.5–55 years). Cannabidiol (CBD) 20 mg/kg/day was more effective than placebo at reducing seizure frequency by 50%+(relative risk (RR) 1.74, 95% CI 1.24 to 2.43, 2 RCTs, 291 patients, low Grades of Recommendation, Assessment, Development and Evaluation (GRADE) rating). The number needed to treat for one person using CBD to experience 50%+ seizure reduction was 8 (95% CI 6 to 17). CBD was more effective than placebo at achieving complete seizure freedom (RR 6.17, 95% CI 1.50 to 25.32, 3 RCTs, 306 patients, low GRADE rating), and improving QoL (RR 1.73, 95% CI 1.33 to 2.26), however increased risk of AEs (RR 1.24, 95% CI 1.13 to 1.36) and SAEs (RR 2.55, 95% CI 1.48 to 4.38). Pooled across 17 observational studies, 48.5% (95% CI 39.0% to 58.1%) of patients reported 50%+ reductions in seizures; in 14 observational studies 8.5% (95% CI 3.8% to 14.5%) were seizure-free. Twelve observational studies reported improved QoL (55.8%, 95% CI 40.5 to 70.6); 50.6% (95% CI 31.7 to 69.4) AEs and 2.2% (95% CI 0 to 7.9) SAEs. Pharmaceutical-grade CBD as adjuvant treatment in paediatric-onset drug-resistant epilepsy may reduce seizure frequency. Existing RCT evidence is mostly in paediatric samples with rare and severe epilepsy syndromes; RCTs examining other syndromes and cannabinoids are needed.PROSPERO registration numberCRD42017055412.


2021 ◽  
Vol 10 (20) ◽  
pp. 4710
Author(s):  
Ayman Jaaouani ◽  
Abdulrahman Ismaiel ◽  
Stefan-Lucian Popa ◽  
Dan L. Dumitrascu

(1) Background: Inflammatory bowel disease (IBD) induces a process of systemic inflammation, sharing common ground with acute coronary syndromes (ACS). Growing evidence points towards a possible association between IBD and an increased risk of ACS, yet the topic is still inconclusive. Therefore, we conducted a systematic review aiming to clarify these gaps in the evidence. (2) Methods: We conducted a systematic search on EMBASE, Cochrane Library, and PubMed, identifying observational studies published prior to November 2020. The diagnosis of IBD was confirmed via histopathology or codes. Full articles that fulfilled our criteria were included. Quality assessment was performed using the Newcastle–Ottawa scale (NOS). (3) Results: We included twenty observational studies with a total population of ~132 million subjects. Fifteen studies reported a significant association between ACS and IBD, while the remaining five studies reported no increase in ACS risk in IBD patients. (4) Conclusions: ACS risk in IBD patients is related to hospitalizations, acute active flares, periods of active disease, and complications, with a risk reduction during remission. Interestingly, a general increase in ACS risk was reported in younger IBD patients. The role of corticosteroids and oral contraceptive pills in increasing the ACS risk of IBD patients should be investigated.


2021 ◽  
Vol 12 ◽  
Author(s):  
Lene Kristine Juvet ◽  
Anna Hayman Robertson ◽  
Ida Laake ◽  
Siri Mjaaland ◽  
Lill Trogstad

BackgroundIn 2009, a new influenza A H1N1 virus emerged causing a global pandemic. A range of monovalent influenza A H1N1pdm09 vaccines with or without adjuvants were developed. After the mass vaccination campaigns safety concerns related to H1N1pdm09 vaccines were reported. More than a decade later, reported AEFIs are still under scrutiny. We performed a systematic review aiming to synthesize the evidence on the safety of the H1N1pdm09 vaccines on reported outcomes from existing systematic reviews.MethodsFour electronic databases, PubMed, EMBASE, Epistimonikos and the Cochrane Database of Systematic Reviews were searched for articles on H1N1pdm09 vaccination published from 2009 to January 2021. Systematic reviews assessing short- or long-term adverse events after H1N1pdm09 vaccination were considered for inclusion. Data was extracted from all selected reviews. Outcomes were grouped and results from each included review were presented narratively and in tables.Results16 systematic reviews met the inclusion criteria. Reported outcomes were short-term events (3 reviews), fetal/pregnancy outcomes (8 reviews), Guillain-Barré syndrome (GBS) (4 reviews), narcolepsy (2 reviews) demyelinating diseases (1 review based on one study only) and inflammatory bowel disease (IBD) (1 review). Short-term serious adverse events were rare, 3 cases amongst 16725 subjects in 18 randomized controlled trials (0.018%). No deaths were reported. The risks of local events were generally higher for adjuvanted vaccines as compared to unadjuvanted vaccines. Maternal H1N1pdm09 vaccination in any trimester was not associated with an increase in preterm birth, small for gestational age, congenital malformations or fetal death. For GBS, results were conflicting. The main systematic review on narcolepsy found a 5-14-fold increased risk in children, and a 2-7- fold increased risk in adults after vaccination with Pandemrix. The attributable risk of narcolepsy one year after vaccination was 1 case per 18 400 vaccine doses in children/adolescents, and 1 case per 181 000 vaccine doses in adults.ConclusionAdjuvanted vaccines had more local but not serious adverse events compared to unadjuvanted vaccines. Vaccination with Pandemrix was strongly associated with narcolepsy, particularly in children. No increased risks of pregnancy outcomes were seen after pandemic vaccination. The findings on GBS were inconclusive.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Wei Luo ◽  
Yao Zhou ◽  
Chenlin Gao ◽  
Pijun Yan ◽  
Ling Xu

Background and Aims. Recent epidemiological evidence indicates an association between urolithiasis and atherosclerosis; however, results are incongruous. Our aim is to summarize the association between urolithiasis and arteriosclerosis risk through a detailed meta-analysis. Methods. Relevant studies published before April 2019 were identified by searching OVID, EMBASE, PubMed, Web of Science database, and Cochrane Library. The relationship between urolithiasis and the risk of atherosclerosis was assessed by using odds ratio (OR) values and the corresponding 95% confidence intervals (CIs), and the selection of fixed- or random-effects model based on heterogeneity. Results. The meta-analysis includes 8 observational studies that contained 70,716 samples. Pooled results showed that urolithiasis was associated with an increased adjusted and unadjusted risk estimated for atherosclerosis (P=0.017 and P=0.014, respectively), especially in coronary artery and carotid atherosclerosis, which was associated with the outcome of CV disease. Interestingly, when we merged the data from the vast majority of these samples (n = 65,751/70,716) with serum uric acid levels less than 6.0 mg/dl, it still showed that urolithiasis was associated with a higher risk of atherosclerosis (P<0.001) and with no evidence of heterogeneity (I2 = 0.0%, P=0.697). Furthermore, we also found that renal calculi would increase the risk of moderate or severe atherosclerosis (P<0.001) and recurrent renal calculi were associated with the incidence of atherosclerosis (P=0.007). Conclusions. Urolithiasis is associated with an increased risk for atherosclerosis, especially in coronary artery and carotid atherosclerosis. Urolithiasis may be another potential risk factor of atherosclerosis, which is independent of serum uric acid levels.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Timo Siepmann ◽  
Annahita Sedghi ◽  
Erik Simon ◽  
Simon Winzer ◽  
Jessica Barlinn ◽  
...  

Introduction: Recent studies linked coronavirus disease 2019 (COVID-19) to thromboembolic complications likely mediated by increased blood coagulability and inflammatory endothelial impairment. Objective: We aimed to assess the risk of acute stroke in patients with COVID-19 related to clinical severity of the disease. Methods: We conducted an observational multicenter cohort study in four participating hospitals in Saxony, Germany to characterize consecutive patients with laboratory-confirmed COVID-19 who experienced acute stroke during hospitalization. Furthermore, we performed a systematic review using PubMed/MEDLINE, EMBASE, Cochrane Library and bibliographies of identified articles following PRISMA guidelines including data from observational studies of acute stroke in COVID-19 patients. Data was extracted by two independent reviewers and pooled with multicenter data to calculate risk ratios (RR) and 95% confidence intervals (95%CIs) for acute stroke related to COVID-19 severity using random effects model. Between-study heterogeneity was assessed using Cochran’s Q and I 2 -statistics. PROSPERO identifier : CRD42020187194. Results: Of 165 patients hospitalized for COVID-19 (49.1% males, median age 67 [57-79], 72.1% severe or critical) included in the multicenter study, overall stroke rate was 4.2% (95%CI: 1.9-8.7). Systematic literature search identified two observational studies involving 576 patients that were eligible for meta-analysis. Among 741 pooled COVID-19 patients overall stroke rate was 2.9% (95%CI: 1.9-4.5). Risk of acute stroke was increased for patients with severe compared to non-severe COVID-19 (RR 4.12, 95%CI 1.7-10.25; p=0.002) with no evidence of heterogeneity (I 2 =0%, p=0.82). Conclusions: Synthesized analysis of data from our multicenter study and previously published cohorts demonstrate that severity of COVID-19 is associated with an increased risk of acute stroke, underscoring the necessity of neurological monitoring in patients infected with SARS-CoV-2.


2010 ◽  
Vol 27 (1) ◽  
pp. 22-26
Author(s):  
Santhana Gunasekaran

AbstractObjective: This study aims to identify and review available evidence in the literature to determine the strength of association between antipsychotic medications and thromboembolism as an adverse effect.Method: Electronic databases were searched for evidence.Results: A total of 15 case reports, 14 case series, two observational studies and three case-control studies were found in the literature. Two case control studies found significantly increased risk of venous thromboembolism (OR 13.3 and 7.1 respectively). The risk was high for low potency antipsychotics. Studies were critically appraised to determine the strength of evidence.Conclusion: The studies reviewed indicate a significant association between antipsychotics and venous thromboembolism. Patients using the antipsychotics and those who prescribe them should be aware of this association.


Cephalalgia ◽  
2014 ◽  
Vol 35 (2) ◽  
pp. 118-131 ◽  
Author(s):  
G Roberto ◽  
E Raschi ◽  
C Piccinni ◽  
V Conti ◽  
L Vignatelli ◽  
...  

Background Apart from the underlying cardiovascular (CV) risk associated with migraine, both triptans and ergotamines can induce vasoconstriction and potentially increase the risk of serious ischemic events. Because of the low frequency of such events in eligible patients, randomized controlled trials are not exhaustive to assess the drug-related CV risk. Observational studies are, therefore, an essential source of information to clarify this matter of concern. Aim The aim of this study was to systematically review the available published observational studies investigating the risk of serious CV events in triptan or ergotamine users, as compared to unexposed migraineur controls. Methods We systematically searched MEDLINE and EMBASE electronic databases for cohort or case-control studies up to December 1, 2013. Studies retrieved from CDSR, DARE and HTA databases of the Cochrane Library were used for snowballing. Studies investigating the risk of any CV outcome in patients with a migraine diagnosis and exposed to triptans or ergotamines were considered for inclusion. Selection of studies, data extraction, and risk of bias assessment were conducted independently by two reviewers. Pooled odds ratios (ORs) with 95% confidence interval (95% CI) were computed using a random-effects model for studies and outcomes judged eligible for quantitative data synthesis. Results From a total of 3370 citations retrieved, after duplicate removal and screening, only four studies met the inclusion criteria (three nested case-control analyses and one retrospective cohort study). These studies investigated the risk of different CV outcomes associated with either the recency or the intensity of exposure to the studied drugs. As for the intensity of use, the pooled OR of serious ischemic events was 2.28 (95% CI 1.18–4.41; I2 = 0%) for ergotamine use (two studies), whereas for triptans (three studies) it was 0.86 (95% CI 0.52–1.43; I2 = 24.5%). Recent use of ergotamines was not significantly associated with any CV outcome (only one available study). Two studies investigated the risk of stroke related to recent triptan use: the first study reported an OR of 0.90 (0.64–1.26), and the second one suggested an increased risk of 2.51 (1.10–5.71). In this case, because of the high degree of heterogeneity, results were not pooled. Conclusions To date, few comparative observational studies have investigated the CV safety of migraine-specific drugs in clinical practice. Evidence gathered here suggests that intense consumption of ergotamines may be associated with an increased risk of serious ischemic complications. As for triptans, available studies do not suggest strong CV safety issues, although no firm conclusions can be drawn. In particular, evidence on stroke risk is conflicting. However, if an increase of the absolute stroke risk in recently exposed patients does actually exist, it must be small. Overall, residual uncontrolled confounding factors reduce the confidence in the risk estimates collected from the included studies. Further investigations are needed to better define the risk for rare but serious CV events related to triptan and ergotamine use for treatment of migraine.


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