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Living FRIendly Summaries of the Body of Evidence using Epistemonikos (FRISBEE)
Medwave 2018 Ene-Feb;18(1):e7153 doi: 10.5867/medwave.2018.01.7153
Are cannabinoids effective for fibromyalgia?
Matías Rocco, Gabriel Rada
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Abstract

INTRODUCTION
Cannabinoids have been proposed as a therapeutic alternative for fibromyalgia. However, their clinical effectiveness is a matter of debate.

METHODS
To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies and generated a summary of findings table using the GRADE approach.

RESULTS AND CONCLUSIONS
We identified fifteen systematic reviews including two randomized trials overall. We concluded it is not clear whether cannabinoids have any benefit in fibromyalgia because the certainty of the evidence is very low. On the other hand, they are associated to frequent adverse effects.


 
Problem

Cannabinoids are a broad family of natural or synthetic compounds that can act as ligands in the cannabinoid receptors of the organism. It is postulated both CB1 and CB2 receptors have an influence on the nociceptive system [1]

The cause of fibromyalgia remains uncertain, and therapeutic response to pharmacological treatment is insufficient in a large number of patients. It is supposed cannabinoids would have a role in fibromyalgia since there is deficiency in the level of endocannabinoids in this condition [2]. It is also hypothesized that cannabinoids would reduce sensitivity of nociceptive pathways, altering cognitive and autonomous processing in states of chronic pain [3]. In addition, the distribution of cannabinoid receptors in the limbic-frontal system suggests cannabinoids may influence affective qualities of pain, which are believed to play an important role in fibromyalgia [4]. However, it is not clear what are the clinical effects of this intervention.

Methods

To answer the question, we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others, to identify systematic reviews and their included primary studies. We extracted data from the identified reviews and reanalyzed data from primary studies included in those reviews. With this information, we generated a structured summary denominated FRISBEE (Friendly Summary of Body of Evidence using Epistemonikos) using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), meta-analysis of the total of studies when it is possible, a summary of findings table following the GRADE approach and a table of other considerations for decision-making. 

Key messages

  • It is not clear whether cannabinoids improve symptoms in fibromyalgia because the certainty of the evidence is very low.
  • Cannabinoids are associated to frequent adverse effects in fibromyalgia.
About the body of evidence for this question

What is the evidence.
See evidence matrix  in Epistemonikos later

We found 15 systematic reviews [5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19], including three primary studies answering the question of interest [20],[21],[22]. Two studies correspond to randomized trials [20],[21]. This table and the summary in general are based on the latter, since the observational study did not increase the certainty of the existing evidence or provide relevant additional information.

What types of patients were included*

Both trials included patients diagnosed with fibromyalgia according to the ACR 1990 criteria.

Both trials included adults over 18 years. One trial restricted age to 70 years [20].

One trial included patients with continuous pain despite another oral medication [20] and the other trial included patients with self-reported chronic insomnia [21]

Patients with a history of substance abuse, psychotic disorders, unstable angina and previous use of cannabinoids for pain management were excluded in both trials.

What types of interventions were included*

Both trials used oral nabilone as intervention. 

Regarding the dose, one trial used 0,5 mg to 1 mg per day [20] and the other used 0,5 mg per day [21].

Regarding the comparison, one trial [21] compared against oral amitriptyline 10 mg daily and the other trial [20] compared against placebo.

What types of outcomes
were measured

Of the multiple outcomes measured by the randomized trials, the systematic reviews grouped them as follows:

  • Average daily pain, evaluated in VAS (Visual Analogue Scale) and McGill Pain Questionnaire
  • Anxiety assessed on the FIQ subscale (Fibromyalgia impact Questionnaire)
  • Sleep: Insomnia severity Index and Leeds Sleep Evaluation Questionnaire
  • Quality of life evaluated in the FIQ scale (Fibromyalgia impact Questionnaire)
  • Adverse effects (such as dizziness, dry mouth, ataxia, confusion) and withdrawal from the study due to adverse effects.
  • Serious adverse effects. 
One trial lasted 4 weeks [20] and the second trial 6 weeks (2 weeks in each period separated by two weeks of wash-out) [21].

 

* The information about primary studies is extracted from the systematic reviews identified, unless otherwise specified.

Summary of Findings

The information on the effects of cannabinoids for fibromyalgia is based on two randomized trials including 72 patients overall [20],[21]. Both trials reported the effect on pain and adverse effects. Only one trial measure sleep [21]

None of the reviews was able to extract the data in a way that could be incorporated into a meta-analysis, so the information presented below corresponds to a narrative synthesis of the information obtained from them.

The summary of findings is the following:

  • It is not clear whether cannabinoids reduce pain, because the certainty of the evidence is very low.
  • It is not clear whether cannabinoids improve sleep because the certainty of the evidence is very low.
  • Cannabinoids are associated to frequent adverse effects in fibromyalgia. The certainty of the evidence is high.

Other considerations for decision-making

To whom this evidence does and does not apply

  • The evidence presented in this summary is applicable to any patient with fibromyalgia, who has not previously used cannabinoids and has persisting pain despite medical treatment.
  • The conclusions of this summary are applicable to nabilone, not to cannabis or other cannabinoids. However, in the absence of direct evidence it is reasonable to extrapolate it.
About the outcomes included in this summary
  • The outcomes presented in the summary of findings table are those critical for decision-making according to the opinion of the authors of this summary.
  • In general, the outcomes selected coincide with those presented in the main systematic reviews evaluated.
Balance between benefits and risks, and certainty of the evidence
  • It is not clear the intervention has benefits in the population assessed and it is associated to adverse effects.
  • It is not possible to estimate an adequate benefit/risk balance since there is uncertainty about the former.
  • On the other hand, the follow-up period for the trials is relatively short, which is not informative in this chronic condition.
Resource considerations
  • Commercial formulations of cannabinoids are generally expensive.
  • It is not possible to estimate an adequate cost/benefit balance since there is uncertainty about the former.
  • Use and marketing of cannabinoids is not authorized in many countries.
What would patients and their doctors think about this intervention
  • Faced with the evidence presented in this summary most patients and clinicians should lean against the use of this intervention, since there is uncertainty about the benefits, it is associated with frequent adverse effects and carries substantive costs.
  • However, there is currently a positive general opinion regarding cannabinoids for therapeutic purposes, both in the public and in many health professionals, so some patients and clinicians could decide to use them despite the evidence presented in this article. 

Differences between this summary and other sources

  • The conclusions of this summary agree with all of the systematic reviews identified, especially with the more rigorous reviews [10].
  • We did not identify recommendations in the main clinical guidelines about the use of cannabinoids for fibromyalgia. The conclusions of this summary do not agree with the Canadian Guidelines of Fibromyalgia [23] which recommend cannabinoid extract in people with fibromyalgia in the context of sleep disorders.
Could this evidence change in the future?
  • The probability of future evidence changing the conclusions of this summary is high, due to the uncertainty of the existing evidence.
  • We searched in the International Clinical Trials Registry Platform of the World Health Organization, but we did not identify any ongoing trial evaluating the effect of cannabinoids for fibromyalgia.
How we conducted this summary

Using automated and collaborative means, we compiled all the relevant evidence for the question of interest and we present it as a matrix of evidence.

Follow the link to access the interactive version: Cannabinoids for fibromyalgia

Notes

The upper portion of the matrix of evidence will display a warning of “new evidence” if new systematic reviews are published after the publication of this summary. Even though the project considers the periodical update of these summaries, users are invited to comment in Medwave or to contact the authors through email if they find new evidence and the summary should be updated earlier.

After creating an account in Epistemonikos, users will be able to save the matrixes and to receive automated notifications any time new evidence potentially relevant for the question appears.

This article is part of the Epistemonikos Evidence Synthesis project. It is elaborated with a pre-established methodology, following rigorous methodological standards and internal peer review process. Each of these articles corresponds to a summary, denominated FRISBEE (Friendly Summary of Body of Evidence using Epistemonikos), whose main objective is to synthesize the body of evidence for a specific question, with a friendly format to clinical professionals. Its main resources are based on the evidence matrix of Epistemonikos and analysis of results using GRADE methodology. Further details of the methods for developing this FRISBEE are described here (http://dx.doi.org/10.5867/medwave.2014.06.5997)

Epistemonikos foundation is a non-for-profit organization aiming to bring information closer to health decision-makers with technology. Its main development is Epistemonikos database (www.epistemonikos.org).

Potential conflicts of interest

The authors do not have relevant interests to declare.

Licencia Creative Commons Esta obra de Medwave está bajo una licencia Creative Commons Atribución-NoComercial 3.0 Unported. Esta licencia permite el uso, distribución y reproducción del artículo en cualquier medio, siempre y cuando se otorgue el crédito correspondiente al autor del artículo y al medio en que se publica, en este caso, Medwave.

 

INTRODUCCIÓN
Se postula que los cannabinoides pudieran tener beneficios en la fibromialgia, sin embargo, su efectividad clínica sigue siendo un tema de discusión.

MÉTODOS
Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios y preparamos una tabla de resumen de los resultados utilizando el método GRADE.

RESULTADOS Y CONCLUSIONES
Identificamos quince revisiones sistemáticas que en conjunto incluyen dos ensayos aleatorizados pertinentes. Concluimos que no está claro si los cannabinoides tienen beneficios en la fibromialgia porque la certeza de la evidencia es muy baja. Por otra parte, están asociados a efectos adversos frecuentes.

RESULTADOS Y CONCLUSIONES
Identificamos quince revisiones sistemáticas que en conjunto incluyen dos ensayos aleatorizados pertinentes. Concluimos que no está claro si los cannabinoides tienen beneficios en la fibromialgia porque la certeza de la evidencia es muy baja. Por otra parte, están asociados a efectos adversos frecuentes.

Authors: Matías Rocco[1,2], Gabriel Rada[2,3,4,5,6]

Affiliation:
[1] Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
[2] Proyecto Epistemonikos, Santiago, Chile
[3] Departamento de Medicina Interna, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
[4] Centro de Evidencia UC, Pontificia Universidad Católica de Chile, Santiago, Chile
[5] The Cochrane Collaboration
[6] GRADE working group

E-mail: radagabriel@epistemonikos.org

Author address:
[1] Centro Evidencia UC
Pontificia Universidad Católica de Chile
Centro de Innovación UC Anacleto Angelini
Avda.Vicuña Mackenna 4860
Macul
Santiago
Chile

Citation: Rocco M, Rada G. Are cannabinoids effective for fibromyalgia?. Medwave 2018 Ene-Feb;18(1):e7153 doi: 10.5867/medwave.2018.01.7153

Submission date: 26/12/2017

Acceptance date: 29/12/2017

Publication date: 14/2/2018

Origin: This article is a product of the Evidence Synthesis Project of Epistemonikos Fundation, in collaboration with Medwave for its publication.

Type of review: Non-blinded peer review by members of the methodological team of Epistemonikos Evidence Synthesis Project.

PubMed record

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  1. Pacher P, Bátkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev. 2006 Sep;58(3):389-462. | PubMed | PMC |
  2. Russo EB. Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro Endocrinol Lett. 2008 Apr;29(2):192-200. | PubMed |
  3. Guindon J, Hohmann AG. The endocannabinoid system and pain. CNS Neurol Discord Drug Targets. 2009 Dec;8(6):403-21. | PubMed | PMC |
  4. Lee MC, Ploner M, Wiech K, Bingel U, Wanigasekera V, Brooks J, Menon DK, Tracey I. Amygdala activity contributes to the dissociative effect of cannabis on pain perception. Pain. 2013 Jan;154(1):124-34. | CrossRef | PubMed | PMC |
  5. Whiting PF, Wolff R, Westwood M, Duffy S, Misso K, Keurentjes C, Lang S, Harker J, Despande S, Ryder S, Di Nisio M, Hernández AV, Schmidlkofer S, Kleijnen J. Systematic review of cannabis for medical use. Kleijnen Systematic Reviews Ltd. 2014. | Link |
  6. 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 Jun 23-30;313(24):2456-73. Erratum in: JAMA. 2016 Apr 12;315(14):1522. JAMA. 2015 Dec 1;314(21):2308. JAMA. 2015 Aug 4;314(5):520. JAMA. 2015 Aug 25;314(8):837. | CrossRef | PubMed |
  7. Fitzcharles MA, Ste-Marie PA, Häuser W, Clauw DJ, Jamal S, Karsh J, Landry T, Leclercq S, Mcdougall JJ, Shir Y, Shojania K, Walsh Z. Efficacy, Tolerability, and Safety of Cannabinoid Treatments in the Rheumatic Diseases: A Systematic Review of Randomized Controlled Trials. Arthritis Care Res (Hoboken). 2016 May;68(5):681-8. | CrossRef | PubMed |
  8. de Souza Nascimento S, Desantana JM, Nampo FK, Ribeiro EA, da Silva DL, Araújo-Júnior JX, da Silva Almeida JR, Bonjardim LR, de Souza Araújo AA, Quintans-Júnior LJ. Efficacy and safety of medicinal plants or related natural products for fibromyalgia: a systematic review. Evid Based Complement Alternat Med. 2013;2013:149468. | CrossRef | PubMed | PMC |
  9. Fitzcharles MA, Baerwald C, Ablin J, Häuser W. Efficacy, tolerability and safety of cannabinoids in chronic pain associated with rheumatic diseases (fibromyalgia syndrome, back pain, osteoarthritis, rheumatoid arthritis): A systematic review of randomized controlled trials. Schmerz. 2016 Feb;30(1):47-61. | CrossRef | PubMed |
  10. Walitt B, Klose P, Fitzcharles MA, Phillips T, Häuser W. Cannabinoids for fibromyalgia. Cochrane Database Syst Rev. 2016 Jul 18;7:CD011694. | CrossRef | PubMed |
  11. Tsang CC, Giudice MG. Nabilone for the Management of Pain. Pharmacotherapy. 2016 Mar;36(3):273-86. | CrossRef | PubMed |
  12. Hazekamp A, Grotenhermen F. Review on clinical studies with cannabis and cannabinoids 2005-2009. Cannabinoids. 2010;5(special issue):1-21. | Link |
  13. Lynch ME, Campbell F. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. Br J Clin Pharmacol. 2011 Nov;72(5):735-44. | CrossRef | PubMed | PMC |
  14. Choy E, Marshall D, Gabriel ZL, Mitchell SA, Gylee E, Dakin HA. A systematic review and mixed treatment comparison of the efficacy of pharmacological treatments for fibromyalgia. Semin Arthritis Rheum. 2011 Dec;41(3):335-45.e6. | CrossRef | PubMed |
  15. Martín-Sánchez E, Furukawa TA, Taylor J, Martin JL. Systematic review and meta-analysis of cannabis treatment for chronic pain. Pain Med. 2009 Nov;10(8):1353-68. | CrossRef | PubMed |
  16. Lynch ME, Ware MA. Cannabinoids for the Treatment of Chronic Non-Cancer Pain: An Updated Systematic Review of Randomized Controlled Trials. J Neuroimmune Pharmacol. 2015 Jun;10(2):293-301. | CrossRef | PubMed |
  17. Landry T, Fitzcharles MA, Ste-Marie P, Shir Y. Efficacy and safety of cannabinoid treatments in the rheumatic diseases: A systematic review of randomized controlled trials. Journal of Rheumatology. 2015;1320. | Link |
  18. Nugent SM, Morasco BJ, O'Neil ME, Freeman M, Low A, Kondo K, Elven C, Zakher B, Motu'apuaka M, Paynter R, Kansagara D. The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. Ann Intern Med. 2017 Sep 5;167(5):319-331. | CrossRef | PubMed |
  19. 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 Sep;20(6):E755-E796. | PubMed |
  20. Skrabek RQ, Galimova L, Ethans K, Perry D. Nabilone for the treatment of pain in fibromyalgia. J Pain. 2008 Feb;9(2):164-73. Epub 2007 Nov 5. | PubMed |
  21. Ware MA, Fitzcharles MA, Joseph L, Shir Y. The effects of nabilone on sleep in fibromyalgia: results of a randomized controlled trial. Anesth Analg. 2010 Feb 1;110(2):604-10. | CrossRef | PubMed |
  22. Fiz J, Durán M, Capellà D, Carbonell J, Farré M. Cannabis use in patients with fibromyalgia: effect on symptoms relief and health-related quality of life. PloS one. 2011;6(4):e18440.
  23. Fitzcharles MA, Ste-Marie PA, Goldenberg DL, Pereira JX, Abbey S, Choinière M, Ko G, Moulin DE, Panopalis P, Proulx J, Shir Y; National Fibromyalgia Guideline Advisory Panel. 2012 Canadian Guidelines for the diagnosis and management of fibromyalgia syndrome: executive summary. Pain Res Manag. 2013 May-Jun;18(3):119-26. | PubMed | PMC |
Pacher P, Bátkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev. 2006 Sep;58(3):389-462. | PubMed | PMC |

Russo EB. Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro Endocrinol Lett. 2008 Apr;29(2):192-200. | PubMed |

Guindon J, Hohmann AG. The endocannabinoid system and pain. CNS Neurol Discord Drug Targets. 2009 Dec;8(6):403-21. | PubMed | PMC |

Lee MC, Ploner M, Wiech K, Bingel U, Wanigasekera V, Brooks J, Menon DK, Tracey I. Amygdala activity contributes to the dissociative effect of cannabis on pain perception. Pain. 2013 Jan;154(1):124-34. | CrossRef | PubMed | PMC |

Whiting PF, Wolff R, Westwood M, Duffy S, Misso K, Keurentjes C, Lang S, Harker J, Despande S, Ryder S, Di Nisio M, Hernández AV, Schmidlkofer S, Kleijnen J. Systematic review of cannabis for medical use. Kleijnen Systematic Reviews Ltd. 2014. | Link |

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 Jun 23-30;313(24):2456-73. Erratum in: JAMA. 2016 Apr 12;315(14):1522. JAMA. 2015 Dec 1;314(21):2308. JAMA. 2015 Aug 4;314(5):520. JAMA. 2015 Aug 25;314(8):837. | CrossRef | PubMed |

Fitzcharles MA, Ste-Marie PA, Häuser W, Clauw DJ, Jamal S, Karsh J, Landry T, Leclercq S, Mcdougall JJ, Shir Y, Shojania K, Walsh Z. Efficacy, Tolerability, and Safety of Cannabinoid Treatments in the Rheumatic Diseases: A Systematic Review of Randomized Controlled Trials. Arthritis Care Res (Hoboken). 2016 May;68(5):681-8. | CrossRef | PubMed |

de Souza Nascimento S, Desantana JM, Nampo FK, Ribeiro EA, da Silva DL, Araújo-Júnior JX, da Silva Almeida JR, Bonjardim LR, de Souza Araújo AA, Quintans-Júnior LJ. Efficacy and safety of medicinal plants or related natural products for fibromyalgia: a systematic review. Evid Based Complement Alternat Med. 2013;2013:149468. | CrossRef | PubMed | PMC |

Fitzcharles MA, Baerwald C, Ablin J, Häuser W. Efficacy, tolerability and safety of cannabinoids in chronic pain associated with rheumatic diseases (fibromyalgia syndrome, back pain, osteoarthritis, rheumatoid arthritis): A systematic review of randomized controlled trials. Schmerz. 2016 Feb;30(1):47-61. | CrossRef | PubMed |

Walitt B, Klose P, Fitzcharles MA, Phillips T, Häuser W. Cannabinoids for fibromyalgia. Cochrane Database Syst Rev. 2016 Jul 18;7:CD011694. | CrossRef | PubMed |

Tsang CC, Giudice MG. Nabilone for the Management of Pain. Pharmacotherapy. 2016 Mar;36(3):273-86. | CrossRef | PubMed |

Hazekamp A, Grotenhermen F. Review on clinical studies with cannabis and cannabinoids 2005-2009. Cannabinoids. 2010;5(special issue):1-21. | Link |

Lynch ME, Campbell F. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. Br J Clin Pharmacol. 2011 Nov;72(5):735-44. | CrossRef | PubMed | PMC |

Choy E, Marshall D, Gabriel ZL, Mitchell SA, Gylee E, Dakin HA. A systematic review and mixed treatment comparison of the efficacy of pharmacological treatments for fibromyalgia. Semin Arthritis Rheum. 2011 Dec;41(3):335-45.e6. | CrossRef | PubMed |

Martín-Sánchez E, Furukawa TA, Taylor J, Martin JL. Systematic review and meta-analysis of cannabis treatment for chronic pain. Pain Med. 2009 Nov;10(8):1353-68. | CrossRef | PubMed |

Lynch ME, Ware MA. Cannabinoids for the Treatment of Chronic Non-Cancer Pain: An Updated Systematic Review of Randomized Controlled Trials. J Neuroimmune Pharmacol. 2015 Jun;10(2):293-301. | CrossRef | PubMed |

Landry T, Fitzcharles MA, Ste-Marie P, Shir Y. Efficacy and safety of cannabinoid treatments in the rheumatic diseases: A systematic review of randomized controlled trials. Journal of Rheumatology. 2015;1320. | Link |

Nugent SM, Morasco BJ, O'Neil ME, Freeman M, Low A, Kondo K, Elven C, Zakher B, Motu'apuaka M, Paynter R, Kansagara D. The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. Ann Intern Med. 2017 Sep 5;167(5):319-331. | CrossRef | PubMed |

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 Sep;20(6):E755-E796. | PubMed |

Skrabek RQ, Galimova L, Ethans K, Perry D. Nabilone for the treatment of pain in fibromyalgia. J Pain. 2008 Feb;9(2):164-73. Epub 2007 Nov 5. | PubMed |

Ware MA, Fitzcharles MA, Joseph L, Shir Y. The effects of nabilone on sleep in fibromyalgia: results of a randomized controlled trial. Anesth Analg. 2010 Feb 1;110(2):604-10. | CrossRef | PubMed |

Fiz J, Durán M, Capellà D, Carbonell J, Farré M. Cannabis use in patients with fibromyalgia: effect on symptoms relief and health-related quality of life. PloS one. 2011;6(4):e18440.

Fitzcharles MA, Ste-Marie PA, Goldenberg DL, Pereira JX, Abbey S, Choinière M, Ko G, Moulin DE, Panopalis P, Proulx J, Shir Y; National Fibromyalgia Guideline Advisory Panel. 2012 Canadian Guidelines for the diagnosis and management of fibromyalgia syndrome: executive summary. Pain Res Manag. 2013 May-Jun;18(3):119-26. | PubMed | PMC |