{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T14:56:40Z","timestamp":1793717800156,"version":"4.6.1"},"reference-count":136,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T00:00:00Z","timestamp":1675036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009906","name":"Grosserer A.V. Lykfeldt og Hustrus Legat","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009906","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess the benefits and harms of cannabinoids in participants with pain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Systematic review of randomised clinical trials with meta-analysis, Trial Sequential Analysis, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Data sources<\/jats:title>\n                    <jats:p>The Cochrane Library, MEDLINE, Embase, Science Citation Index, and BIOSIS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Eligibility criteria for selecting studies<\/jats:title>\n                    <jats:p>Published and unpublished randomised clinical trials comparing cannabinoids versus placebo in participants with any type of pain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Main outcome measures<\/jats:title>\n                    <jats:p>All-cause mortality, pain, adverse events, quality of life, cannabinoid dependence, psychosis, and quality of sleep.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec006\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We included 65 randomised placebo-controlled clinical trials enrolling 7017 participants. Fifty-nine of the trials and all outcome results were at high risk of bias. Meta-analysis and Trial Sequential Analysis showed no evidence of a difference between cannabinoids versus placebo on all-cause mortality (RR 1.20; 98% CI 0.85 to 1.67; P = 0.22). Meta-analyses and Trial Sequential Analysis showed that cannabinoids neither reduced acute pain (mean difference numerical rating scale (NRS) 0.52; 98% CI -0.40 to 1.43; P = 0.19) or cancer pain (mean difference NRS -0.13; 98% CI -0.33 to 0.06; P = 0.1) nor improved quality of life (mean difference -1.38; 98% CI -11.81 to 9.04; P = 0.33). Meta-analyses and Trial Sequential Analysis showed that cannabinoids reduced chronic pain (mean difference NRS -0.43; 98% CI -0.72 to -0.15; P = 0.0004) and improved quality of sleep (mean difference -0.42; 95% CI -0.65 to -0.20; P = 0.0003). However, both effect sizes were below our predefined minimal important differences. Meta-analysis and Trial Sequential Analysis indicated that cannabinoids increased the risk of non-serious adverse events (RR 1.20; 95% CI 1.15 to 1.25; P &lt; 0.001) but not serious adverse events (RR 1.18; 98% CI 0.95 to 1.45; P = 0.07). None of the included trials reported on cannabinoid dependence or psychosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec007\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Cannabinoids reduced chronic pain and improved quality of sleep, but the effect sizes are of questionable importance. Cannabinoids had no effects on acute pain or cancer pain and increased the risks of non-serious adverse events. The harmful effects of cannabinoids for pain seem to outweigh the potential benefits.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0267420","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T14:41:24Z","timestamp":1675089684000},"page":"e0267420","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":44,"title":["Cannabinoids versus placebo for pain: A systematic review with meta-analysis and Trial Sequential Analysis"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0855-6719","authenticated-orcid":true,"given":"Jehad","family":"Barakji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven Kwasi","family":"Korang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1975-9300","authenticated-orcid":true,"given":"Joshua","family":"Feinberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Maagaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4544-0619","authenticated-orcid":true,"given":"Ole","family":"Mathiesen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Gluud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janus Christian","family":"Jakobsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,1,30]]},"reference":[{"issue":"3","key":"pone.0267420.ref001","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0304-3959(98)00117-1","article-title":"Prevalence of chronic benign pain disorder among adults: a review of the literature","volume":"77","author":"P Verhaak","year":"1998","journal-title":"PAIN"},{"issue":"1","key":"pone.0267420.ref002","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1002\/mpr.140","article-title":"Patients presenting with somatic complaints: epidemiology, psychiatric comorbidity and management","volume":"12","author":"K. Kroenke","year":"2003","journal-title":"International Journal of Methods in Psychiatric Research"},{"issue":"1","key":"pone.0267420.ref003","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1097\/00002508-198602010-00008","article-title":"Survey of pain in the United States: The nuprin pain report","volume":"2","author":"RA Sternbach","year":"1986","journal-title":"The Clinical Journal of Pain"},{"issue":"2","key":"pone.0267420.ref004","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1001\/jama.280.2.147","article-title":"Persistent pain and well-being: a World Health Organization Study in Primary Care","volume":"280","author":"O Gureje","year":"1998","journal-title":"JAMA"},{"issue":"2","key":"pone.0267420.ref005","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0885-3924(02)00465-7","article-title":"International association for the study of pain: update on WHO-IASP activities","volume":"24","author":"H. Breivik","year":"2002","journal-title":"Journal of Pain and Symptom Management"},{"issue":"3","key":"pone.0267420.ref006","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.ackd.2005.03.008","article-title":"Chronic pain in end-stage renal disease","volume":"12","author":"S. Davison","year":"2005","journal-title":"Advances in Chronic Kidney Disease"},{"issue":"3","key":"pone.0267420.ref007","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.jpainsymman.2009.08.008","article-title":"Impact of pain and symptom burden on the health-related quality of life of hemodialysis patients","volume":"39","author":"SN Davison","year":"2010","journal-title":"Journal of Pain and Symptom Management"},{"issue":"9","key":"pone.0267420.ref008","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1038\/sj.ki.5000184","article-title":"Cross-sectional validity of a modified Edmonton symptom assessment system in dialysis patients: a simple assessment of symptom burden","volume":"69","author":"SN Davison","year":"2006","journal-title":"Kidney International"},{"issue":"11","key":"pone.0267420.ref009","doi-asserted-by":"crossref","first-page":"3189","DOI":"10.1093\/ndt\/gfl380","article-title":"Longitudinal validation of a modified Edmonton symptom assessment system (ESAS) in haemodialysis patients.","volume":"21","author":"SN Davison","year":"2006","journal-title":"Nephrology, Dialysis, Transplantation: Official Publication of the European Dialysis and Transplant Association\u2014European Renal Association"},{"issue":"4","key":"pone.0267420.ref010","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/S0272-6386(03)00907-7","article-title":"ESRD patient quality of life: symptoms, spiritual beliefs, psychosocial factors, and ethnicity.","volume":"42","author":"PL Kimmel","year":"2003","journal-title":"American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation"},{"issue":"3","key":"pone.0267420.ref011","doi-asserted-by":"crossref","first-page":"572","DOI":"10.2215\/CJN.03370708","article-title":"Relationship between conditions addressed by hemodialysis guidelines and non-ESRD-specific conditions affecting quality of life.","volume":"4","author":"L Leinau","year":"2009","journal-title":"Clinical Journal of the American Society of Nephrology: CJASN"},{"issue":"7","key":"pone.0267420.ref012","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1093\/ndt\/gfg105","article-title":"Symptom burden, quality of life, advance care planning and the potential value of palliative care in severely ill haemodialysis patients.","volume":"18","author":"SD Weisbord","year":"2003","journal-title":"Nephrology, Dialysis, Transplantation: Official Publication of the European Dialysis and Transplant Association\u2014European Renal Association"},{"issue":"8","key":"pone.0267420.ref013","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1681\/ASN.2005020157","article-title":"Prevalence, severity, and importance of physical and emotional symptoms in chronic hemodialysis patients.","volume":"16","author":"SD Weisbord","year":"2005","journal-title":"Journal of the American Society of Nephrology: JASN"},{"key":"pone.0267420.ref014","first-page":"w13750","article-title":"Frequency and severity of pain and symptom distress among patients with chronic kidney disease receiving dialysis","volume":"143","author":"C Gamondi","year":"2013","journal-title":"Swiss Medical Weekly"},{"key":"pone.0267420.ref015","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.3389\/fphar.2018.01259","article-title":"Cannabinoids and Pain: New Insights From Old Molecules.","volume":"9","author":"S Vuckovic","year":"2018","journal-title":"Frontiers in Pharmacology"},{"issue":"June","key":"pone.0267420.ref016","volume":"2018","author":"D Gorelick","year":"2018","journal-title":"Cannabis use and disorder: Pathogenesis and pharmacology"},{"issue":"11","key":"pone.0267420.ref017","first-page":"539","article-title":"Cannabis and Cannabinoids: Pharmacology and tationale for clinical use","volume":"3","author":"RG Pertwee","year":"1997","journal-title":"Pharmacy and Pharmacology Communications"},{"issue":"9","key":"pone.0267420.ref018","first-page":"e10436","article-title":"Cannabinoid Receptors and Their Relationship With Chronic Pain: A Narrative Review.","volume":"12","author":"AT Anthony","year":"2020","journal-title":"Cureus"},{"issue":"2","key":"pone.0267420.ref019","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/sj.bjp.0707531","article-title":"Cannabinoid CB2 receptors: a therapeutic target for the treatment of inflammatory and neuropathic pain","volume":"153","author":"J Guindon","year":"2008","journal-title":"British Journal of Pharmacology"},{"key":"pone.0267420.ref020","author":"R Portenoy","year":"2017","journal-title":"Assessment of cancer pain"},{"issue":"6","key":"pone.0267420.ref021","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1097\/j.pain.0000000000000160","article-title":"A classification of chronic pain for ICD-11","volume":"156","author":"RD Treede","year":"2015","journal-title":"PAIN"},{"issue":"1","key":"pone.0267420.ref022","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1097\/j.pain.0000000000001363","article-title":"The IASP classification of chronic pain for ICD-11: chronic cancer-related pain","volume":"160","author":"M.I Bennett","year":"2019","journal-title":"PAIN"},{"issue":"6","key":"pone.0267420.ref023","doi-asserted-by":"crossref","first-page":"E755","DOI":"10.36076\/ppj.20.5.E755","article-title":"Efficacy of cannabis-based medicines for pain management: a systematic review and meta-Analysis of randomized controlled trials","volume":"20","author":"J Aviram","year":"2017","journal-title":"Pain Physician"},{"issue":"5","key":"pone.0267420.ref024","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1213\/ANE.0000000000002110","article-title":"Selective cannabinoids for chronic neuropathic pain: a systematic review and meta-analysis","volume":"125","author":"H Meng","year":"2017","journal-title":"Anesthesia and Analgesia"},{"issue":"1","key":"pone.0267420.ref025","doi-asserted-by":"crossref","first-page":"7","DOI":"10.11607\/ofph.1274","article-title":"The effectiveness of cannabinoids in the management of chronic nonmalignant neuropathic pain: a systematic review.","volume":"29","author":"DG Boychuk","year":"2015","journal-title":"Journal of Oral & Facial Pain and Headache"},{"issue":"8","key":"pone.0267420.ref026","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1111\/j.1526-4637.2009.00703.x","article-title":"Systematic review and meta-analysis of cannabis treatment for chronic pain","volume":"10","author":"E Martin-Sanchez","year":"2009","journal-title":"Pain Medicine (Malden, Mass)"},{"key":"pone.0267420.ref027","first-page":"Cd012182","article-title":"Cannabis-based medicines for chronic neuropathic pain in adults","volume":"3","author":"M Mucke","year":"2018","journal-title":"The Cochrane Database of Systematic Reviews"},{"issue":"7303","key":"pone.0267420.ref028","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1136\/bmj.323.7303.13","article-title":"Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systematic review","volume":"323","author":"FA Campbell","year":"2001","journal-title":"BMJ (Clinical research ed)"},{"issue":"8","key":"pone.0267420.ref029","first-page":"e372","article-title":"Efficacy and adverse effects of medical marijuana for chronic noncancer pain: Systematic review of randomized controlled trials","volume":"61","author":"A Deshpande","year":"2015","journal-title":"Canadian Family Physician"},{"issue":"5","key":"pone.0267420.ref030","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1111\/j.1365-2125.2011.03970.x","article-title":"Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials","volume":"72","author":"M Lynch","year":"2011","journal-title":"British Journal of Clinical Pharmacology"},{"key":"pone.0267420.ref031","first-page":"Cd011694","article-title":"Cannabinoids for fibromyalgia.","volume":"7","author":"B Walitt","year":"2016","journal-title":"The Cochrane Database of Systematic Reviews"},{"key":"pone.0267420.ref032","article-title":"CADTH rapid response reports, in medical cannabis for the treatment of chronic pain: A review of clinical effectiveness and guidelines.","author":"S. Banerjee","year":"2019","journal-title":"Canadian Agency for Drugs and Technologies in Health"},{"issue":"10","key":"pone.0267420.ref033","doi-asserted-by":"crossref","first-page":"e031574","DOI":"10.1136\/bmjopen-2019-031574","article-title":"Cannabinoids versus placebo or no intervention for pain: protocol for a systematic review with meta-analysis and trial sequential analysis","volume":"9","author":"J.A. Barakji","year":"2019","journal-title":"BMJ Open"},{"issue":"7","key":"pone.0267420.ref034","doi-asserted-by":"crossref","first-page":"e1000097","DOI":"10.1371\/journal.pmed.1000097","article-title":"Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement.","volume":"6","author":"D Moher","year":"2009","journal-title":"PLOS Medicine"},{"issue":"2","key":"pone.0267420.ref035","first-page":"231","article-title":"International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH) adopts consolidated guideline on good clinical practice in the conduct of clinical trials on medicinal products for human use.","volume":"48","year":"1997","journal-title":"International Digest of Health Legislation"},{"key":"pone.0267420.ref036","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0","author":"JP Higgins","year":"2011"},{"key":"pone.0267420.ref037","article-title":"The visual analogue scale versus numerical rating scale in measuring pain severity and predicting disability in low back pain","author":"TS Shafshak","year":"2020","journal-title":"J Clin Rheumatol"},{"issue":"11","key":"pone.0267420.ref038","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1002\/sim.1186","article-title":"Quantifying heterogeneity in a meta-analysis.","volume":"21","author":"JP Higgins","year":"2002","journal-title":"Statistics in Medicine"},{"issue":"7414","key":"pone.0267420.ref039","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","article-title":"Measuring inconsistency in meta-analyses.","volume":"327","author":"JP Higgins","year":"2003","journal-title":"BMJ (Clinical research ed)"},{"issue":"20","key":"pone.0267420.ref040","doi-asserted-by":"crossref","first-page":"3443","DOI":"10.1002\/sim.2380","article-title":"A modified test for small-study effects in meta-analyses of controlled trials with binary endpoints.","volume":"25","author":"RM Harbord","year":"2006","journal-title":"Statistics in Medicine"},{"issue":"7109","key":"pone.0267420.ref041","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1136\/bmj.315.7109.629","article-title":"Bias in meta-analysis detected by a simple, graphical test","volume":"315","author":"M Egger","year":"1997","journal-title":"BMJ (Clinical research ed)"},{"key":"pone.0267420.ref042","volume-title":"Review Manager (RevMan) [program]. 5.3 version","year":"2014"},{"key":"pone.0267420.ref043","volume-title":"Stata: Release 14 [program]","author":"StataCorp","year":"2014"},{"issue":"3","key":"pone.0267420.ref044","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","article-title":"Meta-analysis in clinical trials.","volume":"7","author":"R DerSimonian","year":"1986","journal-title":"Controlled Clinical Trials"},{"issue":"3","key":"pone.0267420.ref045","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/sim.4780060325","article-title":"Methods for combining randomized clinical trials: strengths and limitations.","volume":"6","author":"DL DeMets","year":"1987","journal-title":"Statistics in Medicine"},{"key":"pone.0267420.ref046","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/1471-2288-14-120","article-title":"Thresholds for statistical and clinical significance in systematic reviews with meta-analytic methods.","volume":"14","author":"JC Jakobsen","year":"2014","journal-title":"BMC Medical Research Methodology"},{"issue":"1","key":"pone.0267420.ref047","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s12874-017-0315-7","article-title":"Trial Sequential Analysis in systematic reviews with meta-analysis.","volume":"17","author":"J Wetterslev","year":"2017","journal-title":"BMC Med Res Methodol"},{"key":"pone.0267420.ref048","article-title":"GRADE handbook for grading quality of evidence and strength of recommendations.","author":"H Sch\u00fcnemann","year":"2013","journal-title":"The GRADE Working Group"},{"key":"pone.0267420.ref049","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1136\/bmj.39489.470347.AD","article-title":"GRADE: an emerging consensus on rating quality of evidence and strenght of recommendations","volume":"336","author":"GH Guyatt","year":"2008","journal-title":"BMJ"},{"issue":"7","key":"pone.0267420.ref050","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1212\/01.wnl.0000253187.66183.9c","article-title":"Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial","volume":"68","author":"DI Abrams","year":"2007","journal-title":"Neurology"},{"issue":"7","key":"pone.0267420.ref051","doi-asserted-by":"crossref","first-page":"e2010874","DOI":"10.1001\/jamanetworkopen.2020.10874","article-title":"Effect of inhaled cannabis for pain in ddults with sickle cell disease: a randomized clinical trial.","volume":"3","author":"DI Abrams","year":"2020","journal-title":"JAMA network open"},{"issue":"8","key":"pone.0267420.ref052","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1002\/ejp.1605","article-title":"The pharmacokinetics, efficacy, and safety of a novel selective-dose cannabis inhaler in patients with chronic pain: a randomized, double-blinded, placebo-controlled trial.","volume":"24","author":"S Almog","year":"2020","journal-title":"European Journal of Pain (United Kingdom)"},{"key":"pone.0267420.ref053","author":"WS Aronow","year":"1974","journal-title":"Effect of marihuana and placebo-marihuana smoking on angina pectoris"},{"issue":"8","key":"pone.0267420.ref054","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1007\/BF03022793","article-title":"Effects of nabilone, a synthetic cannabinoid, on postoperative pain","volume":"53","author":"P. Beaulieu","year":"2006","journal-title":"Canadian Journal of Anaesthesia"},{"issue":"8","key":"pone.0267420.ref055","doi-asserted-by":"crossref","first-page":"370","DOI":"10.5694\/mja2.51014","article-title":"The CANBACK trial: a randomised, controlled clinical trial of oral cannabidiol for people presenting to the emergency department with acute low back pain","volume":"214","author":"B Bebee","year":"2021","journal-title":"Medical Journal of Australia"},{"issue":"3","key":"pone.0267420.ref056","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.pain.2004.09.013","article-title":"Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial","volume":"112","author":"JS Berman","year":"2004","journal-title":"Pain"},{"issue":"1","key":"pone.0267420.ref057","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1093\/rheumatology\/kei183","article-title":"Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis.","volume":"45","author":"DR Blake","year":"2006","journal-title":"Rheumatology (Oxford, England)"},{"issue":"1\u20132","key":"pone.0267420.ref058","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0304-3959(03)00331-2","article-title":"Lack of analgesic efficacy of oral delta-9-tetrahydrocannabinol in postoperative pain","volume":"106","author":"DJ Buggy","year":"2003","journal-title":"Pain"},{"issue":"5","key":"pone.0267420.ref059","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1179\/016164109X12590518685660","article-title":"A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis","volume":"32","author":"C Collin","year":"2010","journal-title":"Neurol Res"},{"issue":"6","key":"pone.0267420.ref060","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1097\/AOG.0000000000003850","article-title":"Cannabinoids for pain control during medical abortion: a randomized controlled trial","volume":"135","author":"AC Colwill","year":"2020","journal-title":"Obstetrics and Gynecology"},{"issue":"5","key":"pone.0267420.ref061","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.ejpain.2008.05.014","article-title":"Cannabinoid-induced effects on the nociceptive system: a neurophysiological study in patients with secondary progressive multiple sclerosis","volume":"13","author":"A Conte","year":"2009","journal-title":"European Journal of Pain (London, England)"},{"issue":"10","key":"pone.0267420.ref062","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1503\/cmaj.110837","article-title":"Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial. CMAJ","volume":"184","author":"J Corey-Bloom","year":"2012","journal-title":"Canadian Medical Association Journal"},{"issue":"4","key":"pone.0267420.ref063","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1177\/0003489415612801","article-title":"Improving quality of life with nabilone during radiotherapy treatments for head and neck cancers: a randomized double-blind placebo-controlled trial.","volume":"125","author":"M Cote","year":"2016","journal-title":"The Annals of OtologyRhinology, and Laryngology"},{"issue":"7","key":"pone.0267420.ref064","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.cgh.2016.09.147","article-title":"Tetrahydrocannabinol does not reduce pain in patients with chronic abdominal pain in a phase 2 placebo-controlled study.","volume":"15","author":"M de Vries","year":"2017","journal-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association"},{"issue":"3","key":"pone.0267420.ref065","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1111\/bcp.12811","article-title":"Single dose delta-9-tetrahydrocannabinol in chronic pancreatitis patients: analgesic efficacy, pharmacokinetics and tolerability","volume":"81","author":"M de Vries","year":"2016","journal-title":"British Journal of Clinical Pharmacology"},{"key":"pone.0267420.ref066","article-title":"Cannabidivarin for HIV-Associated Neuropathic Pain: a randomized, blinded, controlled clinical trial","author":"L Eibach","journal-title":"Clinical Pharmacology and Therapeutics"},{"issue":"3","key":"pone.0267420.ref067","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/npp.2008.120","article-title":"Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial.","volume":"34","author":"RJ Ellis","year":"2009","journal-title":"Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology"},{"issue":"3","key":"pone.0267420.ref068","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1177\/2049463717710042","article-title":"Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: two double-blind, randomized, placebo-controlled phase 3 studies.","volume":"11","author":"MT Fallon","year":"2017","journal-title":"Br J Pain."},{"key":"pone.0267420.ref069","doi-asserted-by":"crossref","first-page":"S26","DOI":"10.1016\/j.joca.2018.02.067","article-title":"Synthetic transdermal cannabidiol for the treatment of knee pain due to osteoarthritis","volume":"26","author":"D Hunter","year":"2018","journal-title":"Osteoarthritis and Cartilage"},{"issue":"6","key":"pone.0267420.ref070","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1097\/AJP.0000000000000022","article-title":"The subjective psychoactive effects of oral dronabinol studied in a randomized, controlled crossover clinical trial for pain","volume":"30","author":"MA Issa","year":"2014","journal-title":"The Clinical Journal of Pain"},{"issue":"S1","key":"pone.0267420.ref071","doi-asserted-by":"crossref","first-page":"320S","DOI":"10.1002\/j.1552-4604.1981.tb02610.x","article-title":"Evaluation of intramuscular levonantradol and placebo in acute postoperative pain","volume":"21","author":"AK Jain","year":"1981","journal-title":"Journal of Clinical Pharmacology"},{"issue":"2","key":"pone.0267420.ref072","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1002\/cpt1978242223","article-title":"Effect of benzopyranoperidine, a delta-9-THC congener, on pain","volume":"24","author":"PR Jochimsen","year":"1978","journal-title":"Clinical Pharmacology and Therapeutics"},{"issue":"2","key":"pone.0267420.ref073","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jpainsymman.2009.06.008","article-title":"Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain","volume":"39","author":"JR Johnson","year":"2010","journal-title":"Journal of Pain and Symptom Management"},{"issue":"1","key":"pone.0267420.ref074","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.sjpain.2012.08.004","article-title":"Evaluation of the analgesic efficacy of AZD1940, a novel cannabinoid agonist, on post-operative pain after lower third molar surgical removal","volume":"4","author":"J Kalliomaki","year":"2013","journal-title":"Scandinavian Journal of Pain"},{"issue":"Suppl. 1","key":"pone.0267420.ref075","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.1016\/0304-3959(81)90248-7","article-title":"A study of levonantradol, a cannabinol derivative, for analgesia in post operative pain","volume":"10","author":"TG Kantor","year":"1981","journal-title":"Pain"},{"issue":"13","key":"pone.0267420.ref076","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1001\/jama.290.13.1757","article-title":"Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial","volume":"290","author":"M Karst","year":"2003","journal-title":"JAMA"},{"issue":"9","key":"pone.0267420.ref077","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1212\/WNL.58.9.1404","article-title":"Safety, tolerability, and efficacy of orally administered cannabinoids in MS","volume":"58","author":"J Killestein","year":"2002","journal-title":"Neurology"},{"issue":"4","key":"pone.0267420.ref078","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1007\/s00415-012-6739-4","article-title":"A double-blind, randomized, placebo-controlled, parallel-group study of THC\/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis","volume":"260","author":"RM Langford","year":"2013","journal-title":"Journal of Neurology"},{"key":"pone.0267420.ref079","article-title":"Effect of THC-CBD oromucosal spray (Sativex) on measures of spasticity in multiple sclerosis: A doubleblind, placebo-controlled, crossover study.","author":"L Leocani","year":"2014","journal-title":"Multiple Sclerosis (Houndmills, Basingstoke, England)"},{"issue":"4","key":"pone.0267420.ref080","first-page":"385","article-title":"A randomized-controlled trial of nabilone for the prevention of acute postoperative nausea and vomiting in elective surgery","volume":"64","author":"DN Levin","year":"2017","journal-title":"Une etude randomisee controlee pour evaluer l\u2019efficacite du nabilone pour la prevention des nausees et vomissements postoperatoires aigus lors de chirurgie non urgente Can J Anaesth"},{"issue":"2","key":"pone.0267420.ref081","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.jpainsymman.2017.09.001","article-title":"Results of a double-blind, randomized, placebo-controlled study of nabiximols oromucosal spray as a adjunctive therapy in advanced cancer patients with chronic uncontrolled pain","volume":"55","author":"AH Lichtman","year":"2018","journal-title":"J Pain Symptom Manage"},{"issue":"1","key":"pone.0267420.ref082","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.jpainsymman.2013.02.018","article-title":"A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain","volume":"47","author":"ME Lynch","year":"2014","journal-title":"Journal of Pain and Symptom Management"},{"issue":"2","key":"pone.0267420.ref083","first-page":"1","article-title":"Dronabinol increases pain threshold in patients with functional chest pain: a pilot double-blind placebo-controlled trial.","volume":"30","author":"Z Malik","year":"2017","journal-title":"Diseases of the Esophagus: Official Journal of the International Society for Diseases of the Esophagus"},{"issue":"3","key":"pone.0267420.ref084","first-page":"990","article-title":"Sativex\u00ae as Add-on therapy Vs. further optimized first-line ANTispastics (SAVANT) in resistant multiple sclerosis spasticity double blind randomized clinical trial.","volume":"23","author":"J. Markova","year":"2017","journal-title":"Multiple sclerosis Journal"},{"issue":"3","key":"pone.0267420.ref085","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.jpain.2007.10.018","article-title":"Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy.","volume":"9","author":"S Narang","year":"2008","journal-title":"The Journal of Pain: Official Journal of the American Pain Society"},{"key":"pone.0267420.ref086","unstructured":"NCT01606202. ClinicalTrials Gov, National Institutes of Health [http:\/\/wwwclinicaltrials.gov], 2012."},{"issue":"1\u20133","key":"pone.0267420.ref087","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.pain.2007.08.028","article-title":"Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial","volume":"133","author":"TJ Nurmikko","year":"2007","journal-title":"Pain"},{"issue":"8","key":"pone.0267420.ref088","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1097\/AJP.0b013e318219799a","article-title":"A randomized, controlled study to investigate the analgesic efficacy of single doses of the cannabinoid receptor-2 agonist GW842166, ibuprofen or placebo in patients with acute pain following third molar tooth extraction","volume":"27","author":"T Ostenfeld","year":"2011","journal-title":"Clinical Journal of Pain"},{"issue":"5","key":"pone.0267420.ref089","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jpain.2012.01.003","article-title":"Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial.","volume":"13","author":"RK Portenoy","year":"2012","journal-title":"Journal of Pain"},{"issue":"2","key":"pone.0267420.ref090","doi-asserted-by":"crossref","DOI":"10.1016\/S1474-4422(18)30406-X","article-title":"The CANALS study: a randomized, double-blind, placebo-controlled, multicentre study to assess the safety and efficacy on spasticity symptoms of a Cannabis Sativa extract in motor neuron disease patients","volume":"18","author":"N Riva","year":"2016","journal-title":"The Lancet Neurology"},{"issue":"6","key":"pone.0267420.ref091","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1212\/01.wnl.0000176753.45410.8b","article-title":"Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis","volume":"65","author":"DJ Rog","year":"2005","journal-title":"Neurology"},{"issue":"5\u20136","key":"pone.0267420.ref092","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1159\/000481089","article-title":"Dronabinol is a safe long-term treatment option for neuropathic pain patients","volume":"78","author":"S Schimrigk","year":"2017","journal-title":"European Neurology"},{"issue":"1","key":"pone.0267420.ref093","doi-asserted-by":"crossref","first-page":"128","DOI":"10.2337\/dc09-1029","article-title":"Randomized placebo-controlled double-blind clinical trial of cannabis-based medicinal product (Sativex) in painful diabetic neuropathy: depression is a major confounding factor.","volume":"33","author":"D Selvarajah","year":"2010","journal-title":"Diabetes Care"},{"issue":"1","key":"pone.0267420.ref094","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s00415-012-6634-z","article-title":"Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis","volume":"260","author":"MG Serpell","year":"2013","journal-title":"Journal of Neurology"},{"issue":"2","key":"pone.0267420.ref095","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jpain.2007.09.002","article-title":"Nabilone for the treatment of pain in fibromyalgia","volume":"9","author":"RQ Skrabek","year":"2008","journal-title":"Journal of Pain"},{"issue":"Suppl. 1","key":"pone.0267420.ref096","doi-asserted-by":"crossref","first-page":"S97","DOI":"10.1016\/0304-3959(81)90320-1","article-title":"Comparison of the analgesic effect of parenteral levonantradol to morphine and placebo in patients with moderate to severe pain of cancer","volume":"10","author":"JD Stambaugh","year":"1981","journal-title":"Pain"},{"issue":"4","key":"pone.0267420.ref097","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/cpt1978234397","article-title":"Effect of a nitrogen analog of tetrahydrocannabinol on cancer pain","volume":"23","author":"M Staquet","year":"1978","journal-title":"Clinical pharmacology and therapeutics"},{"issue":"7460","key":"pone.0267420.ref098","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1136\/bmj.38149.566979.AE","article-title":"Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial","volume":"329","author":"KB Svendsen","year":"2004","journal-title":"BMJ (Clinical research ed)"},{"issue":"10","key":"pone.0267420.ref099","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1016\/j.pain.2012.06.024","article-title":"An enriched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo-controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain","volume":"153","author":"C Toth","year":"2012","journal-title":"Pain"},{"issue":"9","key":"pone.0267420.ref100","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1007\/s00520-018-4154-9","article-title":"The effect of nabilone on appetite, nutritional status, and quality of life in lung cancer patients: a randomized, double-blind clinical trial.","volume":"26","author":"JG Turcott","year":"2018","journal-title":"Supportive Care in Cancer"},{"issue":"1","key":"pone.0267420.ref101","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/pme.12569","article-title":"Nabilone as an adjunctive to gabapentin for multiple sclerosis-induced neuropathic pain: a randomized controlled trial","volume":"16","author":"D Turcotte","year":"2015","journal-title":"Pain Medicine (Malden, Mass)"},{"issue":"9","key":"pone.0267420.ref102","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1016\/j.clinthera.2017.01.016","article-title":"Effects on spasticity and neuropathic pain of an oral formulation of Delta-9-tetrahydrocannabinol in patients with progressive multiple sclerosis.","volume":"40","author":"G van Amerongen","year":"2018","journal-title":"Clinical Therapeutics"},{"issue":"4","key":"pone.0267420.ref103","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1097\/j.pain.0000000000001464","article-title":"An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia","volume":"160","author":"T van de Donk","year":"2019","journal-title":"Pain"},{"key":"pone.0267420.ref104","article-title":"Cannabidiol treatment in hand osteoarthritis and psoriatic arthritis: a randomized, double-blind placebo-controlled trial","author":"J Vela","year":"2021","journal-title":"Pain"},{"issue":"1","key":"pone.0267420.ref105","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1191\/0269215503cr581oa","article-title":"A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms.","volume":"17","author":"DT Wade","year":"2003","journal-title":"Clinical Rehabilitation"},{"issue":"4","key":"pone.0267420.ref106","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1191\/1352458504ms1082oa","article-title":"Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients.","volume":"10","author":"DT Wade","year":"2004","journal-title":"Multiple Sclerosis (Houndmills, Basingstoke, England)"},{"issue":"7","key":"pone.0267420.ref107","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.jpain.2015.03.008","article-title":"Efficacy of inhaled cannabis on painful diabetic neuropathy.","volume":"16","author":"MS Wallace","year":"2015","journal-title":"The Journal of Pain: Official Journal of the American Pain Society"},{"issue":"14","key":"pone.0267420.ref108","doi-asserted-by":"crossref","first-page":"E694","DOI":"10.1503\/cmaj.091414","article-title":"Smoked cannabis for chronic neuropathic pain: a randomized controlled trial.","volume":"182","author":"MA Ware","year":"2010","journal-title":"CMAJ: Canadian Medical Association Journal"},{"issue":"6","key":"pone.0267420.ref109","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.jpain.2007.12.010","article-title":"A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain.","volume":"9","author":"B Wilsey","year":"2008","journal-title":"The journal of pain: Official Journal of the American Pain Society"},{"issue":"10","key":"pone.0267420.ref110","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1007\/s00415-006-0218-8","article-title":"Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain: a double-blind placebo-controlled cross-over trial","volume":"253","author":"J Wissel","year":"2006","journal-title":"Journal of Neurology"},{"issue":"9395","key":"pone.0267420.ref111","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1016\/S0140-6736(03)14738-1","article-title":"Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial.","volume":"362","author":"J Zajicek","year":"2003","journal-title":"Lancet (London, England)"},{"issue":"11","key":"pone.0267420.ref112","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1136\/jnnp-2012-302468","article-title":"MUltiple Sclerosis and Extract of Cannabis: results of the MUSEC trial","author":"P Zajicek John","year":"2012","journal-title":"Journal of Neurology Neurosurgery & Psychiatry"},{"key":"pone.0267420.ref113","unstructured":"European Medicines Agency. Guideline on multiplicity issues in clinical trials. In: Committee for Human Medicinal Products, ed., 2017."},{"issue":"24","key":"pone.0267420.ref114","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1001\/jama.2015.6358","article-title":"Cannabinoids for Medical Use: A Systematic Review and Meta-analysis","volume":"313","author":"PF Whiting","year":"2015","journal-title":"JAMA"},{"issue":"1","key":"pone.0267420.ref115","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1185\/030079906X158066","article-title":"Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain","volume":"23","author":"M Iskedjian","year":"2007","journal-title":"Current Medical Research and Opinion"},{"key":"pone.0267420.ref116","article-title":"International Association for the Study of Pain presidential task force on cannabis and cannabinoid analgesia position statement","volume":"162","author":"IASP Presidential Task Force on Cannabis","year":"2021","journal-title":"PAIN"},{"issue":"3","key":"pone.0267420.ref117","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/aas.12851","article-title":"A systematic review of the analgesic efficacy of cannabinoid medications in the management of acute pain","volume":"61","author":"AJ Stevens","year":"2017","journal-title":"Acta anaesthesiologica Scandinavica"},{"issue":"1","key":"pone.0267420.ref118","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1136\/bmjspcare-2019-002032","article-title":"Cannabinoids for adult cancer-related pain: systematic review and meta-analysis","volume":"10","author":"EG Boland","year":"2020","journal-title":"BMJ supportive & palliative care"},{"issue":"7","key":"pone.0267420.ref119","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1136\/rapm-2020-101340","article-title":"Analgesic efficacy of cannabinoids for acute pain management after surgery: a systematic review and meta-analysis","volume":"45","author":"FW Abdallah","year":"2020","journal-title":"Reg Anesth Pain Med"},{"issue":"1","key":"pone.0267420.ref120","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s12916-016-0775-3","article-title":"Pain relief that matters to patients: systematic review of empirical studies assessing the minimum clinically important difference in acute pain","volume":"15","author":"MF Olsen","year":"2017","journal-title":"BMC Medicine"},{"key":"pone.0267420.ref121","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jclinepi.2018.05.007","article-title":"Minimum clinically important differences in chronic pain vary considerably by baseline pain and methodological factors: systematic review of empirical studies","volume":"101","author":"MF Olsen","year":"2018","journal-title":"Journal of Clinical Epidemiology"},{"issue":"35","key":"pone.0267420.ref122","first-page":"1","article-title":"Influence of reported study design characteristics on intervention effect estimates from randomised controlled trials: combined analysis of meta-epidemiological studies.","volume":"16","author":"J Savovic","year":"2012","journal-title":"Health Technology Assessment (Winchester, England)"},{"issue":"5","key":"pone.0267420.ref123","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1001\/jama.1995.03520290060030","article-title":"Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials","volume":"273","author":"KF Schulz","year":"1995","journal-title":"JAMA"},{"issue":"9193","key":"pone.0267420.ref124","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1016\/S0140-6736(99)04149-5","article-title":"Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses","volume":"354","author":"D Moher","year":"1999","journal-title":"Lancet (London, England)"},{"issue":"11","key":"pone.0267420.ref125","doi-asserted-by":"crossref","first-page":"982","DOI":"10.7326\/0003-4819-135-11-200112040-00010","article-title":"Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses","volume":"135","author":"LL Kjaergard","year":"2001","journal-title":"Annals of Internal Medicine"},{"issue":"3","key":"pone.0267420.ref126","doi-asserted-by":"crossref","first-page":"219","DOI":"10.7326\/0003-4819-149-3-200808050-00023","article-title":"Correction: reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses","volume":"149","author":"LL Gluud","year":"2008","journal-title":"Annals of Internal Medicine"},{"issue":"7644","key":"pone.0267420.ref127","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1136\/bmj.39465.451748.AD","article-title":"Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study","volume":"336","author":"L Wood","year":"2008","journal-title":"BMJ (Clinical research ed)"},{"key":"pone.0267420.ref128","first-page":"Mr000033","article-title":"Industry sponsorship and research outcome","volume":"12","author":"A Lundh","year":"2012","journal-title":"The Cochrane Database of Systematic Reviews"},{"issue":"6","key":"pone.0267420.ref129","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/j.jpainsymman.2010.08.016","article-title":"Studies comparing Numerical Rating Scales, Verbal Rating Scales, and Visual Analogue Scales for assessment of pain intensity in adults: a systematic literature review","volume":"41","author":"MJ Hjermstad","year":"2011","journal-title":"Journal of Pain and Symptom Management"},{"issue":"1","key":"pone.0267420.ref130","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s00586-002-0464-0","article-title":"The clinical importance of changes in outcome scores after treatment for chronic low back pain","volume":"12","author":"O Hagg","year":"2003","journal-title":"European Spine Journal: Official Publication of the European Spine Societythe European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society"},{"issue":"4","key":"pone.0267420.ref131","first-page":"407","article-title":"Measurement of health status. Ascertaining the minimal clinically important difference.","volume":"10","author":"R Jaeschke","year":"1989","journal-title":"Controlled Clinical Trials"},{"issue":"5","key":"pone.0267420.ref132","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/S0895-4356(03)00044-1","article-title":"Defining clinically meaningful change in health-related quality of life","volume":"56","author":"RD Crosby","year":"2003","journal-title":"Journal of Clinical Epidemiology"},{"key":"pone.0267420.ref133","volume-title":"Medical use of cannabis and cannabinoids.","author":"The European Monitoring Centre for Drugs and Drug Addiction","year":"2018"},{"issue":"4","key":"pone.0267420.ref134","first-page":"719","article-title":"Medicinal cannabis law reform: lessons from canadian litigation.","volume":"22","author":"I. Freckelton","year":"2015","journal-title":"J Law Med"},{"issue":"1","key":"pone.0267420.ref135","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00482-015-0083-4","article-title":"Medical use of cannabis products: Lessons to be learned from Israel and Canada.","volume":"30","author":"J Ablin","year":"2016","journal-title":"Schmerz"},{"key":"pone.0267420.ref136","volume-title":"The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research","author":"National Academies of Sciences E, and Medicine","year":"2017"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0267420","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T14:43:05Z","timestamp":1675089785000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0267420"}},"subtitle":[],"editor":[{"given":"Tariq Jamal","family":"Siddiqi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,1,30]]},"references-count":136,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0267420","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,30]]}}}