Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions: A systematic review and meta-analysis of controlled and observational studies

Pain

Volumn 159, Issue 10, 2018, Pages 1932-1954

  Stockings, Emily ^a   Campbell, Gabrielle ^a   Hall, Wayne D ^b,c   Nielsen, Suzanne ^a   Zagic, Dino ^a   Rahman, Rakin ^a   Murnion, Bridin ^d,e   Farrell, Michael ^a   Weier, Megan ^a   Degenhardt, Louisa ^a  

^a UNIVERSITY OF NEW SOUTH WALES   (Australia)

^b UNIVERSITY OF QUEENSLAND   (Australia)

^c KING'S COLLEGE LONDON   (United Kingdom)

^d University of Sydney   (Australia)

^e New South Wales Government   (Australia)

Author keywords

Cannabis; Chronic noncancer pain; Meta analysis; Neuropathy; Number needed to treat; Systematic review

Indexed keywords

CANNABINOID; CANNABIS; NABIXIMOLS; NONSTEROID ANTIINFLAMMATORY AGENT; OPIATE;

CHRONIC NONCANCER PAIN; CHRONIC PAIN; COGNITIVE DEFECT; CONFUSION; DEPRESSION; DISORIENTATION; DIZZINESS; EMOTION; FIBROMYALGIA; HUMAN; META ANALYSIS; MULTIPLE SCLEROSIS; NEUROPATHIC PAIN; PAIN ASSESSMENT; PAIN INTENSITY; PAIN SEVERITY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RHEUMATOID ARTHRITIS; SYSTEMATIC REVIEW; VISCERAL PAIN; VISUAL ANALOG SCALE; CLINICAL TRIAL (TOPIC); FACTUAL DATABASE; OBSERVATION; STATISTICS AND NUMERICAL DATA;

CANNABINOIDS; CANNABIS; CHRONIC PAIN; CLINICAL TRIALS AS TOPIC; DATABASES, FACTUAL; HUMANS; OBSERVATION;

EID: 85060143759     PISSN: 03043959     EISSN: 18726623     Source Type: Journal    
DOI: 10.1097/j.pain.0000000000001293     Document Type: Review

References (99)

1. Abrams DI, Jay C, Shade S, Vizoso H, Reda H, Press S, Kelly M, Rowbotham M, Petersen K. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology 2007;68:515-21.
2. Andreae MH, Carter GM, Shaparin N, Suslov K, Ellis RJ, Ware MA, Abrams DI, Prasad H, Wilsey B, Indyk D, Johnson M, Sacks HS. Inhaled cannabis for chronic neuropathic pain: a meta-analysis of individual patient data. J Pain 2015;16:1221-32.
3. Aviram J, Samuelly-Leichtag G. Efficacy of cannabis-based medicines for pain management: a systematic review and meta-analysis of randomized controlled trials. Pain Physician 2017;20:E755-96.
4. Ball S, Vickery J, Hobart J, Wright D, Green C, Shearer J, Nunn A, Cano MG, MacManus D, Miller D, Mallik S, Zajicek J. The Cannabinoid Use in Progressive Inflammatory brain Disease (CUPID) trial: a randomised double-blind placebo-controlled parallel-group multicentre trial and economic evaluation of cannabinoids to slow progression in multiple sclerosis. Health Technol Assess 2015;19:vii-viii, xxv-xxxi, 1-187.
5. Berman JS. A study to evaluate the effects of cannabis based medicine in patients with pain of neurological origin. 2012. NCT01606176, Vol. 2017, Clinicaltrials.gov.
6. Berman JS, Symonds C, Birch R. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. PAIN 2004;112: 299-306.
7. Bestard JA, Toth CC. An open-label comparison of nabilone and gabapentin as adjuvant therapy or monotherapy in the management of neuropathic pain in patients with peripheral neuropathy. Pain Pract 2011;11:353-68.
8. Blake DR, Robson P, Ho M, Jubb RW, McCabe CS. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology (Oxford) 2006;45:50-2.
9. Campbell G, Nielsen S, Bruno R, Lintzeris N, Cohen M, Hall W, Larance B, Mattick RP, Degenhardt L. The pain and opioids IN Treatment study: characteristics of a cohort using opioids to manage chronic non-cancer pain. PAIN 2015;156:231-42.
10. Carroll CB, Bain PG, Teare L, Liu X, Joint C, Wroath C, Parkin SG, Fox P, Wright D, Hobart J, Zajicek JP. Cannabis for dyskinesia in Parkinson disease: a randomized double-blind crossover study. Neurology 2004; 63:1245-50.
11. Cates CJ. Simpson's paradox and calculation ofnumber needed totreat from meta-analysis. BMC Med Res Methodol 2002;2:1.
12. Chung SA, Hossain NK, Blackman AS, Shapiro CM. Can the cannabinoid nabilone help with pain and sleep in fibromyalgia patients? Sleep 2009;32:A325-6.
13. Collin C, Ehler E, Waberzinek G, Alsindi Z, Davies P, Powell K, Notcutt W, O'leary C, Ratcliffe S, Nováková I. A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis. Neurol Res 2010;32:451-9.
14. Corey-Bloom J, Wolfson T, Gamst A, Jin S, Marcotte TD, Bentley H, Gouaux B. Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial. Can Med Assoc J 2012;184: 1143-50.
15. Curtin F, Elbourne D, Altman DG. Meta-analysis combining parallel and cross-over clinical trials. II: binary outcomes. Stat Med 2002;21: 2145-59.
16. Curtin F, Elbourne D, Altman DG. Meta-analysis combining parallel and cross-over clinical trials. III: the issue of carry-over. Stat Med 2002;21: 2161-73.
17. de Vries M, Van Rijckevorsel DC, Vissers KC, Wilder-Smith OH, Van Goor H. Single dose delta-9-tetrahydrocannabinol in chronic pancreatitis patients: analgesic efficacy, pharmacokinetics and tolerability. Br J Clin Pharmacol 2016;81:525-37.
18. de Vries M, van Rijckevorsel DCM, Vissers KCP, Wilder-Smith OHG, van Goor H. Tetrahydrocannabinol Does not reduce pain in patients with chronic abdominal pain in a phase 2 placebo-controlled study. Clin Gastroenterol Hepatol 2017;15:1079-86.e4.
19. Dechartres A, Trinquart L, Boutron I, Ravaud P. Influence of trial sample size on treatment effect estimates: meta-epidemiological study. BMJ 2013;346:f2304.
20. Degenhardt L, Lintzeris N, Campbell G, Bruno R, Cohen M, Farrell M, Hall WD. Experience of adjunctive cannabis use for chronic non-cancer pain: findings from the Pain and Opioids IN Treatment (POINT) study. Drug Alcohol Depend 2015;147:144-50.
21. Deeks J, Higgins J, Altman D, Cochrane Statistical Methods Group. Chapter 9: analysing data and undertaking meta-analysis. In: Higgins J, Green S, editors. Cochrane handbook for systematic reviews of interventions 510 (updated March 2011). London, United Kingdom: The Cochrane Collaboration, 2011.
22. Duval S, Tweedie R. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 2000;56:455-63.
23. Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, Haythornthwaite JA, Jensen MP, Kerns RD, Ader DN, Brandenburg N, Burke LB, Cella D, Chandler J, Cowan P, Dimitrova R, Dionne R, Hertz S, Jadad AR, Katz NP, Kehlet H, Kramer LD, Manning DC, McCormick C, McDermott MP, McQuay HJ, Patel S, Porter L, Quessy S, Rappaport BA, Rauschkolb C, Revicki DA, Rothman M, Schmader KE, Stacey BR, Stauffer JW, von Stein T, White RE, Witter J, Zavisic S. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain 2008;9:105-21.
24. Elbourne DR, Altman DG, Higgins JP, Curtin F, Worthington HV, Vail A. Meta-analyses involving cross-over trials: methodological issues. Int J Epidemiol 2002;31:140-9.
25. Ellis RJ, Toperoff W, Vaida F, Van Den Brande G, Gonzales J, Gouaux B, Bentley H, Atkinson JH. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology 2009;34:672-80.
26. Els C, Jackson TD, Kunyk D, Lappi VG, Sonnenberg B, Hagtvedt R, Sharma S, Kolahdooz F, Straube S. Adverse events associated with medium-and long-term use of opioids for chronic non-cancer pain: an overview of Cochrane Reviews. Cochrane Database Syst Rev 2017;10: CD012509.
27. Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpaa M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice ASC, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M. Pharmacotherapy for neuropathic pain in adults: systematic review, meta-analysis and updated NeuPSIG recommendations. Lancet Neurol 2015;14:162-73.
28. Frank B, Serpell MG, Hughes J, Matthews JNS, Kapur D. Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study. BMJ 2008;336:199-201.
29. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017;390:1211-59.
30. Hagenbach U, Luz S, Ghafoor N, Berger J, Grotenhermen F, Brenneisen R, Mäder M. The treatment of spasticity with [Delta] 9-tetrahydrocannabinol in persons with spinal cord injury. Spinal Cord 2007;45:551.
31. Hall W, Degenhardt L. Adverse health effects of non-medical cannabis use. Lancet 2009;374:1383-91.
32. Harbord R, Harris R, Sterne J. Updated tests for small-study effects in meta-analyses. Stata J 2009;9:197-210.
33. Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual Analog Scale for Pain (VAS pain), Numeric Rating Scale for Pain (NRS pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and measure of intermittent and constant osteoarthritis pain (ICOAP). Arthritis Care Res (Hoboken) 2011;63(suppl 11):S240-52.
34. Higgins J, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0. London, United Kingdom: 2011.
35. Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions. Vol. 4. London, United Kingdom: John Wiley & Sons, 2011.
36. Hoggart B, Ratcliffe S, Ehler E, Simpson KH, Hovorka J, Lejcko J, Taylor L, Lauder H, Serpell M. A multicentre, open-label, follow-on study to assess the long-term maintenance of effect, tolerance and safety of THC/CBD oromucosal spray in the management of neuropathic pain. J Neurol 2015;262:27-40.
37. Johnston BC, Patrick DL, Thorlund K, Busse JW, da Costa BR, Schünemann HJ, Guyatt GH. Patient-reported outcomes in meta-analyses-Part 2: methods for improving interpretability for decision-makers. Health Qual Life Outcomes 2013;11:211.
38. Karst M, Salim K, Burstein S, Conrad I, Hoy L, Schneider U. Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial. J Am Med Assoc 2003;290:1757-62.
39. Langford R, Mares J, Novotna A, Vachova M, Novakova I, Notcutt W, Ratcliffe S. 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. J Neurol 2013;260:984-97.
40. Lee JS, Hobden E, Stiell IG, Wells GA. Clinically important change in the visual analog scale after adequate pain control. Acad Emerg Med 2003; 10:1128-30.
41. Lynch ME, Cesar-Rittenberg P, Hohmann AG. A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. J Pain Symptom Manage 2014;47:166-73.
42. Maurer M, Henn V, Dittrich A, Hofmann A. Delta-9-tetrahydrocannabinol shows antispastic and analgesic effects in a single case double-blind trial. Eur Arch Psychiatry Clin Neurosci 1990;240:1-4.
43. McAlister FA. The "number needed to treat" turns 20-and continues to be used and misused. CMAJ 2008;179:549-53.
44. Moore THM, Zammit S, Lingford-Hughes A, Barnes TRE, Jones PB, Burke M, Lewis G. Cannabis use and riskof psychoticor affective mental health outcomes: a systematic review. Lancet 2007;370:319-28.
45. Mücke M, Phillips T, Radbruch L, Petzke F, Hauser W. Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database Syst Rev 2018;3:Cd012182.
46. Narang S, Gibson D, Wasan AD, Ross EL, Michna E, Nedeljkovic SS, Jamison RN. Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy. J Pain 2008;9:254-64.
47. National Academies of Sciences Engineering and Medicine. The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research. Washington, DC: The National Academies Press, 2017.
48. NCT00710424 (GW Pharmaceuticals). A study of Sativex® for pain relief due to diabetic neuropathy. 2008. NCT00710424, Vol. 2017, Clinicaltrials.gov.
49. NCT01606176 (GW Pharmaceuticals). A study to evaluate the effects of cannabis based medicine in patients with pain of neurological origin. 2012. NCT01606176, Vol. 2017, Clinicaltrials.gov.
50. NCT01606202 (GW Pharmaceuticals). A study of cannabis based medicine extracts and placebo in patients with pain due to spinal cord injury. 2012. NCT01606202, Vol. 2017, Clinicaltrials.gov.
51. Notcutt W. A study of cannabis based medicine extracts and placebo in patients with pain due to spinal cord injury. 2012. NCT01606202, Vol. 2017, Clinicaltrials.gov.
52. Notcutt W, Phillips C, Hughes J, Lacoux P, Vijayakulasingam V, Baldock L. A retrospective description of the use of nabilone in UK clinical practice-extension study (conference poster). Mult Scler 2014;468.
53. Novotna A, Mares J, Ratcliffe S, Novakova I, Vachova M, Zapletalova O, Gasperini C, Pozzilli C, Cefaro L, Comi G, Rossi P, Ambler Z, Stelmasiak Z, Erdmann A, Montalban X, Klimek A, Davies P. A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols∗ (Sativex), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur J Neurol 2011;18:1122-31.
54. Nugent SM, Morasco BJ, O'Neil ME, Freeman M, Low A, Kondo K, Elven C, Zakher B, Motu'apuaka M, Paynter R, Kanasagara D. The effects of cannabis among adults with chronic pain and an overview of general harms: a systematic review. Ann Intern Med 2017;167: 319-31.
55. Nurmikko TJ, Serpell MG, Hoggart B, Toomey PJ, Morlion BJ, Haines D. Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinicaltrial. PAIN 2007; 133:210-20.
56. Nyaga VN, Arbyn M, Aerts M. Metaprop: a stata command to perform meta-analysis of binomial data. Arch Public Health 2014;72:39.
57. Ostelo RWJG, de Vet HCW. Clinically important outcomes in low back pain. Best Pract Res Clin Rheumatol 2005;19:593-607.
58. Palmieri B, Laurino C, Vadala M. Short-term efficacy of CBD-enriched hemp oil in girls with dysautonomic syndrome after human papillomavirus vaccination. Isr Med Assoc J 2017;19:79-84.
59. Petzke F, Enax-Krumova EK, Hauser W. Efficacy, tolerability and safety of cannabinoids for chronic neuropathic pain: a systematic review of randomized controlled studies (article in German). Schmerz 2016;30: 62-88.
60. Pini LA, Guerzoni S, Cainazzo MM, Ferrari A, Sarchielli P, Tiraferri I, Ciccarese M, Zappaterra M. Nabilone for the treatment of medication overuse headache: results of a preliminary double-blind, active-controlled, randomized trial. J Headache Pain 2012;13:677-84.
61. Pinsger M, Schimetta W, Volc D, Hiermann E, Riederer F, Pölz W. Benefits of an add-on treatment with the synthetic cannabinomimetic nabilone on patients with chronic pain-a randomized controlled trial. Wiener Klinische Wochenschrift 2006;118:327-35.
62. Platt L, Reed J, Minozzi S, Vickerman P, Hagan H, French C, Jordan A, Degenhardt L, Hope V, Hutchinson S. Effectiveness of needle/syringe programmes and opiate substitution therapy in preventing HCV transmission among people who inject drugs. Cochrane Database of Systematic Reviews 2016;1:1-13. CD012021.
63. Rintala DH, Fiess RN, Tan G, Holmes SA, Bruel BM. Effect of dronabinol on central neuropathic pain after spinal cord injury: a pilot study. Am J Phys Med Rehabil 2010;89:840-8.
64. Riva N, Mora G, Soraru G, Lunetta C, Falzone Y, Marinou K, Maestri E, Fazio R, Comola M, Comi G. The canals study: a randomized, double-blind, placebo-controlled, multicentre study to assess the safety and efficacyon spasticity symptoms of a cannabis sativa extract in motor neuron disease patients. Amyotroph Lateral Scler Frontotemporal Degener 2016;17:44.
65. Rog DJ, Nurmikko TJ, Friede T, Young CA. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology 2005;65:812-19.
66. Rudich Z, Stinson J, Jeavons M, Brown SC. Treatment of chronic intractable neuropathic pain with dronabinol: case report of two adolescents. Pain Res Manag 2003;8:221-4.
67. Schimrigk S, Marziniak M, Neubauer C, Kugler EM, Werner G, Abramov-Sommariva D. Dronabinol is a safe long-term treatment option for neuropathic pain patients. Eur Neurol 2017;78:320-9.
68. Schley M, Legler A, Skopp G, Schmelz M, Konrad C, Rukwied R. Delta-9-THC based monotherapy in fibromyalgia patients on experimentally induced pain, axon reflex flare, and pain relief. Curr Med Res Opin 2006; 22:1269-76.
69. Scott KM, Lim C, Al-Hamzawi A, Alonso J, Bruffaerts R, Caldas-de-Almeida JM, Florescu S, de Girolamo G, Hu C, de Jonge P, Kawakami N, Medina-Mora ME, Moskalewicz J, Navarro-Mateu F, O'Neill S, Piazza M, Posada-Villa J, Torres Y, Kessler RC. Association of mental disorders with subsequent chronic physical conditions: world mental health surveys from 17 countries. JAMA Psychiatry 2016;73:150-8.
70. Selvarajah D, Gandhi R, Emery CJ, Tesfaye S. Randomized placebo-controlled double-blind clinical trial of cannabis-based medicinal product (Sativex) in painful diabetic neuropathy: depression is a major confounding factor. Diabetes Care 2010;33:128-30.
71. Serpell M, Ratcliffe S, Hovorka J, Schofield M, Taylor L, Lauder H, Ehler E. A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment. Eur J Pain 2014;18:999-1012.
72. Shah A, Craner J, Cunningham JL. Medical cannabis use among patients with chronic pain in an interdisciplinary pain rehabilitation program: characterization and treatment outcomes. J Subst Abuse Treat 2017;77:95-100.
73. Skrabek RQ, Galimova L, Ethans K, Perry D. Nabilone for the treatment of pain in fibromyalgia. J Pain 2008;9:164-73.
74. StataCorp. Stata Statistical Software: Release 15, Vol. 15.0. College Station: StataCorp LLC, 2017.
75. Sterne J, Higgins J, Reeves B. Extending the risk of bias tool to allow for assessment of non-randomised studies, cluster-randomised trials and cross-over trials: a Cochrane methods innovation fund project (Workshop). Proceedings of the Book Extending the Risk of Bias Tool to Allow for Assessment of Non-Randomised Studies, Cluster-Randomised Trials and Cross-Over Trials: A Cochrane Methods Innovation Fund Project (Workshop). In: Better Knowledge for Better Health | Un meilleur savoir pour une meilleure santé. Abstracts of the 21st Cochrane Colloquium; 2013 19-23 Sep; Québec City, Canada. John Wiley & Sons, 2013. p. 203-4.
76. Svendsen KB, Jensen TS, Bach FW. Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial. BMJ 2004;329:253.
77. Tesfaye SA. Study of Sativex® for pain relief due to diabetic neuropathy. 2008. NCT00710424, Vol. 2017, Clinicaltrials.gov.
78. The Nordic Cochrane Centre. Review Manager (RevMan). Copenhagen, Denmark: The Cochrane Collabration, 2014.
79. Toth C, Mawani S, Brady S, Chan C, Liu C, Mehina E, Garven A, Bestard J, Korngut L. 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. PAIN 2012;153:2073-82.
80. Turcotte D, Doupe M, Torabi M, Gomori A, Ethans K, Esfahani F, Galloway K, Namaka M. Nabilone as an adjunctive to gabapentin for multiple sclerosis-induced neuropathic pain: a randomized controlled trial. Pain Med 2015;16:149-59.
81. Turk DC, Dworkin RH, Allen RR, Bellamy N, Brandenburg N, Carr DB, Cleeland C, Dionne R, Farrar JT, Galer BS. Core outcome domains for chronic pain clinical trials: IMMPACT recommendations. PAIN 2003; 106:337-45.
82. van Amerongen G, Kanhai K, Baakman AC, Heuberger J, Klaassen E, Beumer TL, Strijers RLM, Killestein J, van Gerven J, Cohen A, Groeneveld GJ. Effects on spasticity and neuropathic pain of an oral formulation of delta9-tetrahydrocannabinol in patients with progressive multiple sclerosis. Clin Ther 2017 Feb 9. pii: S0149-2918(17)30054-1. doi: 10.1016/j.clinthera.2017.01.016 [epub ahead of print].
83. Veritas Health Innovation. Covidence systematic review software. Melbourne. Available at: www.covidence.org. Accessed 2 July 2018.
84. Vermersch P, Trojano M. Tetrahydrocannabinol: cannabidiol oromucosal spray for multiple sclerosis-related resistant spasticity in daily practice. Eur Neurol 2016;76:216-26.
85. Wade DT, Makela P, Robson P, House H, Bateman C. 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. Mult Scler J 2004;10:434-41.
86. Wade DT, Robson P, House H, Makela P, Aram J. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms-cross over study. Clin Rehabil 2003;17:21-9.
87. Walitt B, Klose P, Fitzcharles MA, Phillips T, Hauser W. Cannabinoids for fibromyalgia. Cochrane Database Syst Rev 2016;7:Cd011694.
88. Wallace MS, Marcotte TD, Umlauf A, Gouaux B, Atkinson JH. Efficacy of inhaled cannabis on painful diabetic neuropathy. J Pain 2015;16: 616-27.
89. Ware MA, Fitzcharles M-A, Joseph L, Shir Y. The effects of nabilone on sleep in fibromyalgia: results of a randomized controlled trial. Anesth Analg 2010;110:604-10.
90. Ware MA, Wang T, Shapiro S, Collet JP; Team Cs. Cannabis for the management of pain: assessment of safety study (COMPASS). J Am Pain Soc 2015;16:1233-42.
91. Ware MA, Wang T, Shapiro S, Robinson A, Ducruet T, Huynh T, Gamsa A, Bennett GJ, Collet JP. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. Can Med Assoc J 2010;182: E694-701.
92. Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, Keurentjes JC, Lang S, Misso K, Ryder S, Schmidlkofer S, Westwood M, Kleijnen J. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA 2015;313:2456-73.
93. Wilsey B, Marcotte T, Deutsch R, Gouaux B, Sakai S, Donaghe H. Low-dose vaporized cannabis significantly improves neuropathic pain. J Pain 2013;14:136-48.
94. Wilsey B, Marcotte T, Tsodikov A, Millman J, Bentley H, Gouaux B, Fishman S. A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J Pain 2008;9:506-21.
95. Wilsey B, Marcotte TD, Deutsch R, Zhao H, Prasad H, Phan A. An exploratory human laboratory experiment evaluating vaporized cannabis in the treatment of neuropathic pain from spinal cord injury and disease. J Pain 2016;17:982-1000.
96. Wissel J, Haydn T, Müller J, Brenneis C, Berger T, Poewe W, Schelosky LD. Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain. J Neurol 2006;253:1337-41.
97. Wong BS, Camilleri M, Busciglio I, Carlson P, Szarka LA, Burton D, Zinsmeister AR. Pharmacogenetic trial of a cannabinoid agonist shows reduced fasting colonic motility in patients with nonconstipated irritable bowel syndrome. Gastroenterology 2011;141:1638-47. e1637.
98. Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A, Thompson A; UK MS Research Group. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet 2003;362:1517-26.
99. Zajicek JP, Hobart JC, Slade A, Barnes D, Mattison PG, Group MR. Multiple sclerosis and extract of cannabis: results of the MUSEC trial. J Neurol Neurosurg Psychiatry 2012;83:1125-32.