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Cannabis Use in Fibromyalgia M CHAPTER e16 Cannabis Use in Fibromyalgia M. Farré * , A. Farré ** , J. Fiz † , M. Torrens ‡ * Clinical Pharmacology Unit, Germans Trias i Pujol University Hospital—IGTP, and Human Pharmacology Unit, Hospital del Mar Medical Research Institute—IMIM, and Autonomous University of Barcelona, Barcelona, Spain ** Dual Disorder Unit, Addiction Program, Institute of Neuropsychiatry and Addiction—INAD, and Hospital del Mar Medical Research Institute—IMIM, Barcelona, Spain † CEDIR, Center for Diagnosis and Rehabilitation, San Martín Santa Fe, Argentina ‡ Addiction Program, Institute of Neuropsychiatry and Addiction—INAD, and Hospital del Mar Medical Research Institute—IMIM, Barcelona, Spain SUMMARY POINTS KEY FACTS OF FIBROMYALGIA • This chapter focuses on the cannabis and • Fibromyalgia is a chronic disorder characterized by fi bromyalgia and begins with the diagnosis and widespread pain and tenderness, often accompanied treatment of this condition. by fatigue, memory problems, and sleep disturbances. • Therapy includes nonpharmacological and • The origin of fi bromyalgia is unknown but it seems pharmacological treatments. to be related to a sensitization of the central nervous system. • Some drugs have demonstrated effi cacy in • The diagnosis of fi bromyalgia is based on clinical randomized controlled trials (pregabalin, symptoms, and routine laboratory and diagnostic tests duloxetine, milnacipran, amitriptyline, serotonin are normal. selective reuptake inhibitors, and cyclobenzaprine). • There is no specifi c treatment for fi bromyalgia. • Cannabis products are frequently used in patients Nonpharmacological and pharmacological therapies with fi bromyalgia. Different surveys showed that could help patients. most of the patients who tried medical marijuana • Some drugs are often used in the treatment of found it to be effective or very effective for the fi bromyalgia pain. Three of them have been approved therapy of symptoms of the condition. for this indication (pregabalin, duloxetine, and • Evidence of effi cacy is based on some milnacipran). noncontrolled studies and two randomized- • Cannabinoids by oral or smoked route can be useful to controlled clinical trials using oral nabilone for alleviate pain in fi bromyalgia. However, more studies the treatment of pain and sleep diffi culties in are needed in order to recommend their use. fi bromyalgia patients. • Nabilone appears to have benefi cial effect with signifi cant reduction in pain and functional LIST OF ABBREVIATIONS improvement, and it is well tolerated. Nabilone is more effective than amitriptyline in improving ACR American College of Rheumatology sleep in fi bromyalgia. AEA Anandamide • More studies are needed to evaluate the effi cacy CB1/CB2 Cannabinoid receptor 1 and 2 and safety of cannabinoids in fi bromyalgia. CEDS Clinical endocannabinoid defi ciency syndromes Handbook of Cannabis and Related Pathologies. http://dx.doi.org/10.1016/B978-0-12-800756-3.00112-5 Copyright © 2017 Elsevier Inc. All rights reserved. e158 CC0560.indd0560.indd 115858 115/12/165/12/16 11:59:59 PPMM INTRODUCTION e159 CNS Central nervous system no abnormalities in the region of the body where pain EMA European Medicines Agency is experienced. A number of factors are related with an FDA Food and Drug Administration individual’s sensitivity to pain. The neurotransmitters FIQ Fibromyalgia impact questionnaire involved in pain control are also known to control other GABA Gamma-aminobutyric acid functions such as mood, fatigue, memory, and sleep, of- LSEQ Leeds sleep evaluation questionnaire ten altered in the illness. To date, it has been suggested RCT Randomized clinical trial that endogenous opioidergic activity may be normal or SR-MA Systematic reviews with metaanalysis even increased while there is decreased activity in the SSNRI Selective serotonin and norepinephrine endogenous serotonergic and noradrenergic systems. In reuptake inhibitor addition, the glutamatergic system is also involved in SSRI Selective serotonin reuptake inhibitor the pathogenesis of fi bromyalgia. Recent fi ndings sug- TCA Tricyclic antidepressants gest an imbalance in the levels of the neurotransmitters THC Δ 9 -Tetrahydrocannabinol that affect pain and sensory transmission: high levels of neurotransmitters increase pain transmission and/or low levels of neurotransmitters decrease it. Neuroimag- INTRODUCTION ing studies have contributed to demonstrating the neu- rotransmitter hypothesis, and to fi nding the structures implicated in fi bromyalgia such as the insula. More- Fibromyalgia over, sensitivity to different stimuli such as heat, cold, Fibromyalgia is a chronic condition characterized by electrical stimuli, and auditory tones is also augmented widespread pain and tenderness. It is the second most ( Kuttikat & Shenker, 2013 ; Clauw, 2014, 2015; Rahman common rheumatologic disorder and approximately et al., 2014 ) 2–8% of the world’s population meets the 1990 and 2010 The symptoms of fi bromyalgia include musculoskel- American College of Rheumatology (ACR) diagnostic etal pain in various groups of muscles, especially in the criteria. Fibromyalgia is more common in women and proximal shoulder girdle muscles, which is poorly lo- can appear at any age with a similar worldwide preva- calized, of severe intensity, and diffi cult to ignore. It is lence. Most patients have had a previous medical his- present most of the day, appears every day, and for at tory of chronic pain throughout the body or chronic least 3 months. Another characteristic of this disorder is pain experienced in their fi rst-degree relatives. Roughly the appearance of focal, triggered point tenderness in af- 10–30% of patients with fi bromyalgia meet criteria for fected muscles. In addition, patients complain of fatigue, other chronic pain disorders such as osteoarthritis, rheu- muscular weakness, sleep disturbance, mood disorders, matoid arthritis, and lupus ( Rahman, Underwood, & and impairment of some cognitive domains such as con- Carnes, 2014 ). centration and alertness. Depending on the somatic and As in most illnesses, fi bromyalgia has a genetic compo- psychological symptoms, fi bromyalgia can cause func- nent, and some studies have focused on specifi c genetic tional disability ( Clauw, 2014; Rahman et al., 2014 ). polymorphisms associated with the risk of developing In 1999, the ACR published the classifi cation crite- this disorder. Findings related to polymorphisms involved ria for fi bromyalgia syndrome which have been used in pain neurotransmission, essentially those concerning widely used in therapeutic clinical trials. These criteria serotonin receptors and transporters, and dopamine re- had a sensitivity of 88% and a specifi city of 81% in a pa- ceptors, are, however, contradictory. In addition, environ- tient population ( Table e16.1 ). Subsequently, the ACR mental factors play a role in triggering development of published in 2010 further preliminary diagnostic crite- the illness. It is known that infections (Epstein–Barr virus ria, taking into account the relevance of somatic symp- infection, hepatitis C, parvovirus infection, and Lyme dis- toms such as fatigue and cognitive diffi culties associated ease) and psychological stress contribute to the precipita- with this syndrome. These new criteria developed for tion of this condition ( Clauw, 2014 ). clinical use have a symptom severity scale which can The pathophysiological bases for fi bromyalgia pain be useful for longitudinal monitoring. One major dif- are related to a sensitization of the central nervous ference is that they do not require a tender point count system (CNS) which amplifi es the peripheral nocicep- ( Table e16.2 ). In addition, there is a patient self-report tive inputs and maintains chronic pain. Patients with version ( Clauw, 2014, 2015 ). fi bromyalgia feel pain in conditions that nonsufferers Routine laboratory and radiographic tests are normal, perceive as touch, this signifi es that the former have focused on excluding other diagnoses and evaluating problems with augmented pain or sensory processing in pain generators and comorbid conditions. It is important the CNS. For this reason, they display diffuse hyperalge- to carry out a differential diagnosis because some symp- sia (increased pain from painful stimuli) and/or allodyn- toms can overlap with other chronic pain conditions ia (pain from nonpainful stimuli). There are, however, such as headaches, facial/jaw pain, regional myofascial VII. MEDICINAL CANNABIS USE CC0560.indd0560.indd 115959 115/12/165/12/16 11:59:59 PPMM e160 e16. CANNABIS USE IN FIBROMYALGIA TABLE e16.1 American College of Rheumatology 1990 Classifi cation Criteria for Fibromyalgia Criteria A. History of widespread pain for at least 3 months. Pain is considered widespread when it is present at all of the following sites (b): – the left side of the body – the right side of the body – above the waist – below the waist – in the axial skeletal (cervical spine or anterior chest or thoracic spine or low back) B. Pain on digital palpation in at least 11 of the 18 tender point sites; all sites bilateral (c): (a) For purposes of classifi cation, patients will be said to have FMS if both criteria A and B are satisfi ed. The presence of a second clinical disorder does not exclude the classifi cation of fi bromyalgia (b) Pain in a patient in for instance the left shoulder, right buttock, and cervical spine is generalized, according to these criteria (c) Digital palpation should be performed with an approximate force of 4 kg. For a tender point to be considered positive, the palpation
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