Fibromyalgia Marijuana Treatment
Today, GW Pharmaceuticals reports that Epidiolex can lower the number of drop seizures in LGS patients, too.
Earlier this year, the company reported that using Epidiolex can lower the number of convulsive seizures in Dravet syndrome patients.In that study, patients were given Epidiolex or a placebo alongside their current antiepileptic drugs. Patients receiving Epidiolex experienced 39% fewer seizures versus their baseline, while patients receiving placebo saw their number of monthly seizures fall by 11%.
These findings are especially intriguing because these patientsare among the most difficult epilepsy patients to treat. Patients in the company’s Dravet syndrome trial had previously taken and failed an average of more than four other anti-epileptic therapies, and in the LGS trial, the average patient had previously failed an average of six prior anti-epileptic drugs.
In both trials, safety appears to be OK, too.
In the Dravet syndrome trial, eight of 61 patients taking Epidiolex discontinued the trial because of adverse events, and in the LGS trial, 12 of 86 patients stopped taking Epidiolex because of adverse events. That suggests the vast majority of patients found Epidiolex to be beneficial. That thinking is reinforced by the fact that 100%of the remaining patients in the LGS trial enrolled in a follow-on study so they could continue to receive Epidiolex.
Image source: GW Pharmaceuticals.
More results are coming
In addition to the two trials that have already wrapped up, GW Pharmaceuticals expects to report results from two additional trials in the coming months.
A second trial in LGS is expected to have data available by the end of the third quarter, and results from a second trial in Dravet syndrome should be available early next year.
Assuming those studies confirm the data that’s already been released, GW Pharmaceuticals could file for FDA approval of Epidiolex in the first half of 2017. An early 2017 filing could clear the way for approval shortly thereafter, because Epidiolex is fast-tracked by the FDA for use in Dravet syndrome. If the FDA determines Epidiolex is a major treatment advance, fast-track status could result in an accelerated review by the agency, reducing the FDA approval timeline from 10 months to six months.
A win for Epidiolex in epilepsy is important for both patients and GW Pharmaceuticals. Patients need new treatment options, and a commercially approved therapy in the U.S. could go a long way toward firming up GW Pharmaceuticals’ financials. The company currentlygenerates only a few million dollars in sales per quarter, yet its marijuana research program costs it about $37 million per quarter.
There’s no guarantee the remaining trials will pan out, or that if the FDA approves Epidiolex, it will be a top seller, but these results suggest that many of the thousands of people suffering from these rare forms of epilepsy could benefit from Epidiolex. For that reason alone, it’s worth cheering for its success.
Oral Cannabis Study Grant Offers New Hope For Fibromyalgia Patients
- A history of widespread pain throughout the muscles and connective tissues (tendons and ligaments) that has lasted more than three months.
- Pain occurs throughout all four quadrants of the body (above and below the waist, on both sides).
- There are tender or “trigger” points that are especially sensitive to pressure (initially there were 18 spots, but as of 2010, diagnosis no longer requires these tender points).
- Symptoms of fibromyalgia may also include sleep disorders, bowel disturbances, fatigue, and cognitive impairment (“fibro fog”).
Fibromyalgia sufferers tend to be overwhelmingly female (80-90 percent) and of childbearing age, but men, children, and the elderly are also affected.
The condition tends to be more common among those who suffer from other rheumatic disorders, including lupus, rheumatoid arthritis. and ankylosing spondylitis (spinal arthritis).
Frustratingly for those who live with the condition, there is no known cause for fibromyalgia. It often emerges during middle age or after a traumatic injury.
New Research Grant Announced by Canadian Arthritis Society
Researchers and prevalence tracking estimates place the number of fibromyalgia patients in the United States at roughly 5 million per year, with an additional estimated 520,000 sufferers in Canada. That’s why the December 2016 announcement of a three-year grant from the Canadian Arthritis Society to study oral cannabinoids for fibromyalgia came as welcome news.
“These investments are about leading by example,” Arthritis Society president and CEO Janet Yale said in a press release. “Patients and physicians both need to be able to make informed decisions about whether cannabis has a place in the individual’s treatment plan. With these commitments, The Arthritis Society is doing its part to help fill some of the critical knowledge gaps around medical cannabis.”
She went on to call on the Canadian government to invest $25 million over the next five years in research into medical cannabis.
The lead investigator in the newly announced study, Mark Ware, M.D., said in a CNN interview in 2010, “I have patients with a range of pain syndromes who have failed all their other treatments and for whom herbal cannabis has been the only reasonable option that they have that controls their symptoms.” Dr. Ware is director of clinical research at the Alan Edwards Pain Management Unit of the McGill University Health Centre (MUHC). He has already completed the largest study to date on the long-term safety of cannabis for treatment of chronic pain.
Traditional Medical Treatment for Fibromyalgia
Traditional medical treatment requires a team approach, because every patient presents with different symptoms—sometimes at different hours of different days.
And medications that are prescribed for fibromyalgia symptoms can include a medicine cabinet full of pharmaceuticals. These include antidepressants, benzodiazepines, opioids, sleeping pills, muscle relaxants, anti-convulsants, nerve pain medications, even experimental administration of human growth hormone.
Each medication alone carries individual risk (see the following infographic for an analysis of the risks of just one pharmaceutical product vs. those of cannabis).
Taken together, however, a fistful of pharmaceutical prescriptions raise the specter of polypharmacy (taking more than four prescription medications at one time). This presents an exponentially greater risk over time.
If cannabis can provide proven relief for the widespread soft tissue pain, sleep problems, and associated symptoms, it could provide an additional arrow in the medical team’s quiver as they strive to provide care for their patients.
A small-scale 2011 pilot study has already found statistically significant effects in reduction of pain, sleep aid, and enhancement relaxation.
Beyond traditional medicine, fibromyalgia sufferers have also turned to a wide-ranging constellation of alternative therapies as they seek relief from the condition. Patients working with interdisciplinary teams of medical professionals report turning to such approaches, including:
- Trigger-point therapy
- Light therapy
- Massage therapy
- Tai Chi
- And more
Cannabis, with its 5,000-year history as a medicinal treatment, is just one more option to explore after fifty years of hysterical prohibition.
Fibromyalgia and the Clinical Endocannabinoid Deficiency Hypothesis
Dr. Ethan Russo, a pharmacologist and neurologist who has dedicated more than 15 years to researching the human body’s endocannabinoid system, first published a paper in 2003 suggesting the existence of Clinical Endocannabinoid Deficiency (CECD) as a contributing factor to fibromyalgia and a related group of disorders.
This deficiency, Russo suggested, could result in the familiar array of symptoms including sleep disorders, pain, muscle spasticity, digestive and gastrointestinal problems, and sleep disorders—the same group of symptoms that appear together in sufferers of other syndromes including fibromyalgia, irritable bowel syndrome and migraines.
In a later paper, published in 2008, Russo presented evidence that the THC in cannabis reduces hypersensitivity to pain in both fibromyalgia patients and migraine sufferers. He also pointed out that cannabis can offer anti-nausea benefits, neuroprotective antioxidant properties, and anti-insomnia properties while it acts on the body’s own endocannabinoid system. And treating the sleep problems associated with fibromyalgia is one of the fundamental keys to treating the rest of the symptoms associated with the disorder.
Furthermore, a 2014 literature review further expanded on Russo’s work, extending the hypothesis that an innate deficiency of endocannabinoids may be a common trait in the potentially related syndromes that include migraines, irritable bowel syndrome and fibromyalgia.
As the CECD hypothesis continues to receive further attention, more high-quality, randomized controlled studies are indicated. This new study should offer researchers and clinicians fruitful paths for continued exploration of a place for cannabis in treatment. And it will doubtless provide patients continued hope for a safe, natural, and effective source of relief of their symptoms.
By Ginevra Liptan, MD
Editor’s Note: Ginevra Liptan, MD is both a fibromyalgia patient and physician specialist. Her new book The FibroManual: A Complete Fibromyalgia Treatment Guide for You…And Your Doctor releases May 3, 2016.
My last blog post examined the current legal and medical status of using marijuana as medicine. But how about specifically for treating fibromyalgia symptoms?
Many of my fibromyalgia patients report that medical marijuana/cannabis reduces their pain and improves sleep. A study of 28 fibromyalgia patients reported that two hours after use of cannabis they had a significant reduction of pain and stiffness.
The use of cannabis to relieve symptoms of fibromyalgia is not new. Around 2000 BC, the Chinese Emperor Shen-Nun described marijuana’s ability to diminish pain and inflammation and noted that it “undoes rheumatism” (an antiquated term for fibromyalgia). Fast forward to the U.S. in the early 1900s and we find medicinal cannabis extracts marketed by Merck, Bristol-Meyers, and Eli Lilly, among other pharmaceutical companies, along with medical textbooks listing numerous indications for cannabis including joint and muscle pain.
But then cannabis use was outlawed in 1936. All access for medical purposes was lost until 1996, when California became the first state in U.S. to legalize medical marijuana use. So now we find ourselves about 60 years behind in medical understanding of the cannabis plant.
We do know that the two primary active ingredients of cannabis are THC and CBD (cannabidiol). THC is a strong analgesic (pain reliever) and is also strong anti-inflammatory—in fact, it is 20 times stronger than aspirin! THC is responsible for the psychoactive effects or “high” of cannabis. CBD also has some pain-relieving and anti-inflammatory properties, along with strong anti-anxiety and muscle relaxation effects. CBD has the effect of lowering the psychoactive effects of THC, so cannabis with equal amounts of CBD to THC tend to be the most medicinally effective by providing desired pain relief with less of the undesirable “high.”
But we currently don’t have any standardized medication options beyond the two THC- only prescription medications, dronabinol and nabilone, which are expensive and tend to cause lots of side effects. Pharmaceutical companies are now racing to better find ways to produce standardized ingredients and dosing of cannabis.
In Canada and Europe, a cannabis-based medical extract is approved for use as an oral spray (Sativex). It is entirely derived from a specially grown plant with extensive quality control and balanced amounts of THC and CBD, and it has been shown to significantly lessen pain and improve sleep for rheumatoid arthritis, with few side effects. This product is currently undergoing clinical trials in the U.S. and will hopefully be available within the next few years.
But for now, patients who want to try medical cannabis for fibromyalgia—or any health condition—are at the mercy of the knowledge of the dispensary or growers that are providing them the cannabis. Here is a scenario I see quite frequently: a patient gets a medical marijuana card and goes to a dispensary. There, the employees are the only guide to strain and dose. It’s the equivalent of someone walking into a drugstore with a blank prescription and asking the cashier what medicine they should purchase. Some dispensary employees are quite knowledgeable, but often they are more recreational marijuana enthusiasts who have no idea what to recommend for a fibromyalgia patient.
One of my patients, who is 65 and had never used marijuana in her life, went to a dispensary and was directed to buy a cookie that contained a high amount of THC. An hour later she was hallucinating and so terrified that she called 911!
Is there anyone who should not try cannabis? There are some people for whom it is absolutely a bad idea, including those with uncontrolled psychiatric conditions characterized by psychosis or active substance abuse. Marijuana can also increase pulse rate, so should be used with caution in people with heart problems such as atrial fibrillation.
In general, you want to look for strains with roughly equal THC to CBD ratio. Start with very low dosages; one study found that while low-to-moderate doses lowered pain, high doses actually increased pain! Avoid smoking cannabis, as this is damaging and irritating to lung tissue. Instead, consider edibles, tinctures (liquid cannabis extracts), or topical balms or salves. My fibromyalgia patients report that cannabis balms and salves applied topically to sore muscles can be a very effective pain reliever with little to no brain “high.”
If you are serious about trying cannabis as medicine, you need to first educate yourself, because your doctor or your grower/dispensary staff may not be able to give you much guidance. I highly recommend the book Cannabis Pharmacy: The Practical Guide to Medical Marijuana by Michael Backes. Another helpful resource is the website www.leafly.com, which is like the Yelp of marijuana, with user reviews on different strains.
Remember, we are just beginning to uncover exactly how to use the cannabis plant safely and most effectively.
Fibromyalgia: Big Pharma vs Medical Cannabis
The estimated five million Americans coping with fibromyalgia are not use to hearing good news. They live with chronic all-over pain, fatigue, depression, headaches, and sleeplessness, and doctors don’t know why this disease develops or how to cure it. Most fibromyalgia patients are women, and they often feel that healthcare professionals don’t take them seriously. The available medications frequently cause more problems than they solve. But there is finally a ray of sunshine for fibromyalgia sufferers: medical cannabis.
A recent survey of 1,339 fibromyalgia patients conducted by the National Pain Foundation showed that medical cannabis is far more effective than the three drugs approved to fight this disease (Cymbalta, Lyrica, and Savella). Of the patients who had tried medicinal cannabis, 62 percent rated it very effective at treating their fibromyalgia symptoms, 33 percent said it helped a little, and only 5 percent said it did not help at all. Compare that with the offerings from Big Pharma: 60 percent said Cymbalta did not help at all, 61 percent said Lyrica didn’t help at all, and 68 percent said the same about Savella.
Not only are these drugs expensive and ineffective, they often come with a nightmarish list of side effects. Here are just a few of the adverse reactions listed on a bottle of Lyrica:
- Serious, even life threatening, allergic reactions
- Suicidal thoughts or actions in about 1 in 500 people
- Swelling of your hands, legs and feet, which can be serious for people with heart problems
- Dizziness, blurry vision, weight gain, sleepiness, trouble concentrating, swelling of your hands and feet, dry mouth, and feeling “high”
Of those, the only side effect also caused by medical cannabis is feeling “high,” and strains of cannabis with lower ratios of THC to CBD (a non-psychoactive chemical) have been shown to be very effective at treating pain without affecting cognition.
Noting the surprising survey results, Dan Bennett, MD, an inter-ventional spine and pain surgical physician and chairman of the National Pain Foundation, commented, “Fibromyalgia is devastating for those who must live in its grip. There is much we do not understand. We need innovative ‘out of the box’ solutions that change the face of this disease.”
Unfortunately, one of the other things the survey showed was that only 29 percent of respondents had tried medical cannabis. Why are so few people getting access to the best medication for fibromyalgia? Because cannabis is still not legally available in most US states.
To add insult to injury, the federal government pretends cannabis is a dangerous drug with “no currently accepted medical use,” but for over a decade it has held a patent (#6630507) for cannabinoids, the chemicals that make cannabis an incredibly safe, useful medicine.
Despite what the Feds claim, and as they surely know, cannabis has many medical uses.In addition to being the only medication that truly helps with fibromyalgia, cannabis has been shown by study after study to help with glaucoma, tumors, nausea, epilepsy, multiple sclerosis, back pain, muscle spasms, arthritis, herpes, cystic fibrosis, rheumatism, insomnia, emphysema, stress, migraines, and nerve pain. Its topical extractions can have antibiotic properties and help with skin conditions, and it can increase appetite and reduce nausea in cancer and HIV patients suffering the side effects of treatment. This goes without saying, but none of the other drugs approved for treating fibromyalgia can claim all of that.
We need full legal access to medical cannabis so the five million Americans who struggle with fibromyalgia day in and day out will finally get some relief—and so the millions of our fellow citizens suffering the many other diseases that cannabis treats can get the medication they need, too.
Right now, a bill decriminalizing cannabis has been introduced in the House (HR 499—Ending Marijuana Prohibition Act of 2013) but has been put on the back-burner by cowardly politicians who don’t want to look “soft on drugs.” Your representatives need to know that they have your support! Call or write your representative (find out who that is here) and demand immediate decriminalization of cannabis for all Americans.
Fibromyalgia Information: Fibromyalgia and Medical Marijuana Treatments
Fibromyalgia is a disorder that causes muscle pain and fatigue. People with fibromyalgia have “tender points” on the body. Tender points are specific places on the neck, shoulders, back, hips, arms, and legs. These points hurt when pressure is put on them. No one knows what causes fibromyalgia. Anyone can get it, but it is most common in middle-aged women.
Recent years have brought a wealth of new scientific understanding regarding how medical marijuana or cannabis can be beneficial for treating Fibromyalgia.
People with fibromyalgiamay also have other symptoms:
- Trouble sleeping
- Morning stiffness
- Painful menstrual periods
- Tingling or numbness in hands and feet
- Problems with thinking and memory (sometimes called “fibro fog”)
There is no cure for fibromyalgia, but medicine can help you manage your symptoms. Getting enough sleep, exercising, and eating well may also help.
The aim of this study was to describe the patterns of cannabis use and the associated benefits reported by patients with fibromyalgia (FM) who were consumers of this drug. In addition, the quality of life of FM patients who consumed cannabis was compared with FM subjects who were not cannabis users.
Information on medicinal cannabis use was recorded on a specific questionnaire as well as perceived benefits of cannabis on a range of symptoms using standard 100-mm visual analogue scales (VAS). Cannabis users and non-users completed the Fibromyalgia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index (PSQI) and the Short Form 36 Health Survey (SF-36).
Twenty-eight FM patients who were cannabis users and 28 non-users were included in the study. Demographics and clinical variables were similar in both groups. Cannabis users referred different duration of drug consumption; the route of administration was smoking (54%), oral (46%) and combined (43%). The amount and frequency of cannabis use were also different among patients. After 2 hours of cannabis use, VAS scores showed a statistically significant (p<0.001) reduction of pain and stiffness, enhancement of relaxation, and an increase in somnolence and feeling of well being. The mental health component summary score of the SF-36 was significantly higher (p<0.05) in cannabis users than in non-users. No significant differences were found in the other SF-36 domains, in the FIQ and the PSQI.
Citation: Fiz J, Durán M, Capellà D, Carbonell J, Farré M (2011) Cannabis Use in Patients with Fibromyalgia: Effect on Symptoms Relief and Health-Related Quality of Life. PLoS ONE 6(4): e18440. https://doi.org/10.1371/journal.pone.0018440
Editor: Antonio Verdejo García, University of Granada, Spain
Received: November 16, 2010; Accepted: March 7, 2011; Published: April 21, 2011
Copyright: © 2011 Fiz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The work was partially supported by grants from Ministerio de Sanidad – Plan Nacional sobre Drogas (SOC/3386/2004), Instituto de Salud Carlos III (FIS-Red de Transtornos Adictivos -RTA RD06/0001/1009) and Generalitat de Catalunya (AGAUR 2009 SGR 718). No additional external funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
The main complaint of patients with fibromyalgia (FM) is chronic generalized pain, although many patients suffer from concomitant symptoms, such as tiredness, morning stiffness, sleep and affective disturbances . The pathophysiology of the disorder is poorly understood. Several mechanisms have been suggested including central sensitization, suppression of descending inhibitory pathways, excessive activity of glial cells, and abnormalities of neurotransmitter release . In addition, blunting of the hypothalamic-pituitary-adrenal-axis (HPA-axis) and increased autonomic nervous system responsiveness have been consistently reported in FM patients. Emerging clues suggest that such dysfunction of the stress response system may be crucial in the onset of the symptoms of FM . Treatment is based on the symptomatic relief of symptoms but usually modest results are obtained. The overall patient’s satisfaction and the health-related quality of life are consistently poor.
Potential therapeutic uses of cannabis in different types of pain are currently extensively investigated. Data from clinical trials with synthetic and plant-based cannabinoids provide a promising approach for the management of chronic neuropathic pain of different origins . Additionally, a large body of evidence currently supports the presence of cannabinoid receptors and ligands, thus an endocannabinoid neuromodulatory system appears to be involved in multiple physiological functions .
There is little clinical information on the effectiveness of cannabinoids in the amelioration of FM symptoms. Three clinical trials have suggested the possible benefit of cannabinoid in the management of FM –. Furthermore, a clinical endocannabinoid deficiency (CECD) has been hypothesized to underlie the pathophysiology of fibromyalgia, but a clear evidence to support this assumption is lacking .
The aim of this study was to describe the patterns of cannabis use and the associated benefits reported by patients with fibromyalgia (FM) who were consumers of this drug. In addition, the quality of life of FM patients who consumed cannabis was compared with FM subjects who were not cannabis users.
A cross-sectional survey was performed. Participants were identified through an advertisement from one Rheumatology Outpatients Unit, 15 associations of FM patients and 1 association of cannabis consumers, all of them located in the city of Barcelona, Spain. Recruitment began in August 2005, and the study was completed in April 2007. Patients were eligible if they were ≥18 years of age, had been diagnosed with FM according to the American College of Rheumatology criteria , had moderate to severe symptomatology, and were resistant to pharmacological treatment. Exclusion criteria were severe illness and history of abuse or dependence for cannabis or others psychoactive substances.
Study procedures and evaluation
Patients were divided according their status of therapeutic cannabis use. Eligibility and exclusion criteria were checked through an accurate telephone interview. Demographic (age, gender and employment status) and clinical variables (duration of FM, number of medical consultations in the last year, associated symptoms, current pharmacological treatment, comorbid conditions, and alternative and complementary medicines) were also collected through a structured telephone interview. Patients were informed that a specific questionnaire to collect information on medicinal cannabis use will be posted to them as well as visual analogue scales (VAS) to record perceived benefits with comprehensive instructions how to fill them out.
The following variables were recorded: duration of cannabis use, previous use, cannabis derivative used (hashish or marijuana), route of administration, amount and frequency of use, supply source, physician’s acknowledgement about cannabis use and changes of pharmacological treatment. Symptoms from which cannabis was used and perceived relief was recorded using 5-point Likert scale (strong relief, mild relief, not change, slight worsening, great worsening). Patients were further asked to record the perceived benefits of cannabis on a range of symptoms (pain, stiffness, relaxation, drowsiness, well-being) using 100-mm VAS scales (VAS) before and at 2 hours of cannabis consumptions. The occurrence and frequency of side effects were indicated based on a list of symptoms.
The 36-item Short Form Health Survey (SF-36) is a self-administered questionnaire, validated in Spanish, in which eight dimensions of health-related quality of life are assessed: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health. Each scale is scored using norm-based methods, with higher scores indicating better health. Scores are aggregated further to produce physical and mental component summary measures of health status, using norm-based methods. The subscale scores are standardized and range from 0 to 100 with higher scores reflecting better health-related quality of life in the domain being measured .
The Fibromyalgia Impact Questionnaire (FIQ) is a self-administered questionnaire, validated in Spanish to assess health-related quality of life specifically in patients with fibromyalgia over the previous week. It consists of VAS and questions regarding limitations of daily living activities. The total score ranges from 0 to 80; a higher score indicates a more negative impact .
The Pittsburg Sleep Quality Index (PSQI) is a self-administered questionnaire, validated in Spanish, to measure the quality and patterns of sleep over the last month. It consists of 7 components that sum each other and give a total score range from 0 (no difficulties) to 21 (severe difficulties) .
Data obtained from the questionnaires were analysed using the SPSS software (version 12.0.1). Comparisons were carried out using Fisher Exact tests for categorical variables and Student t test for continuous variables. The Mann-Whitney U test was used when the size of a comparison group was too small to assume normality. Statistical significance was at the 5% level and all tests were two sided.
In response to the advertisement, 70 patients contacted the researchers to inquire about the study and were screened by telephone. A total of 14 subjects, –6 cannabis users and 8 non-users–, did not meet the eligibility criteria. Therefore, 56 FM patients completed the study protocol, 28 of them were cannabis users (mainly recruited through FM association and cannabis association) and 28 were non-cannabis users (mainly recruited through FM associations and the Rheumatology Outpatients Unit of the hospital).
As shown in Table 1, there were no statistically significant differences between the cannabis users and non-users groups in any demographic or clinical variables. The most frequent comorbid diseases were also balanced between the study groups. No significant differences were observed for the percentage of patients with irritable bowel syndrome, chronic fatigue syndrome, restless legs syndrome, osteoarthritis, Sjögren’s syndrome, and hypothyroidism (data not shown in Table 1). With regard to treatment based on complementary and alternative medicines, there were no significant differences between groups, neither in number (cannabis group 64%; non-users group, 75%) or modalities chosen (data not shown in Table 1).
Patterns of cannabis use
Of the 28 FM patients using cannabis, 11 (40%) reported a duration of cannabis use of less than one year, 9 (32%) between 1 and 3 years, and 8 (29%) more than 3 years. Only 8 patients in the cannabis group have used cannabis recreationally before the medicinal use. Cannabis derivate used in every case was marijuana. The usual methods of administration were smoking and eating, and some patients use to combine both methods. Only smokers were 11%, only eaters were 46% and those using both methods were 43%. The amount and frequency of cannabis use were diverse among patients. The most frequent doses were between 1 and 2 cigarettes each time when patients smoked and 1 spoonful each time when eating. Most of the patients (n = 12) used cannabis daily, while 5 used it 2–4 days per week, 3 used it less than twice a week and 8 patients used it only occasionally. Related amount of cannabis used in one day, 12 reported once a day, 11 reported 2–3 times a day and 3 reported more than 3 times a day. Source of supply of cannabis were from family and friends (n = 14), illicit market (n = 7), growing (n = 5) and associations (n = 2). A total of 19 patients have informed their doctor about cannabis use, and reduction of pharmacological treatment was accomplished in 19 (68%) patients as well when they started using cannabis.
Perceived effects of cannabis use
Main symptoms leading to cannabis use and perceived benefits is shown in Figure 1. Patients used cannabis not only to alleviate pain but for almost all the symptoms associated to FM, and no one reported worsening of symptoms following cannabis use. The proportion of patients who reported strong relief ranged from 81% for sleep disorders to 14% for headache.
Note: Perceived relief was recorded using 5-point Likert scale (strong relief, mild relief, not change, slight worsening, great worsening). Black bars: strong relief; grey bars: mild relief; white bars: not change.
All symptoms assessed by VAS showed statistically significant improvement following 2 hours of cannabis self-administration (Figure 2). The mean reduction of pain was 37.1 mm (p<0.001, t-Test) and of stiffness 40.7 mm (p<0.001). The change from baseline in VAS relaxation and somnolence scores also significantly increased (27.6 mm, p<0.05 and 20.0 mm, p<0.05 respectively). In addition, perception of well-being was significantly higher as compared with baseline (40.0 mm, p<0.001).
Perceived side effects of cannabis use
At least one side effect was reported by 96% (n = 27) of patients. The most frequent were somnolence (n = 18), dry mouth (n = 17), sedation (n = 12), dizziness (n = 10), high (n = 9), tachycardia (n = 8), conjunctival irritation (n = 7) and hypotension (n = 6). The frequency most commonly reported were ‘sometimes’ for somnolence, sedation, dizziness, high, tachycardia and conjunctival irritation, and ‘always’ for dry mouth, sedation and hypotension. No serious adverse events occurred.
Quality of life
The mental health component summary score of the SF-36 questionnaire was slightly but significantly higher in the cannabis group (mean (M) = 29.6±standard deviation (SD) = 8.2) than in the non-users group (M = 24.9±SD = 8.9), p<0,05, t-Test. In the physical component summary score the differences were non significant between groups (cannabis group: M = 26.29±SD = 6.7; non-users group: M = 27.34±SD = 5.8; p = 0,53, t-Test).
No differences were found either in the Fibromyalgia Impact Questionnaire (M = 65.5±SD = 11.9; M = 65.5±SD = 12.8; p = 0.36, t-Test) or in the Pittsburg Sleep Quality Index (M = 14.1±SD = 3.2; M = 14.4±SD = 3.3; p = 0.73, t-Test).
This observational study provides information on the patterns of cannabis use for therapeutic purposes among a group of patients with FM. Most of them were middle-aged women that did not respond to current treatment and self-administered marijuana, devoid of medical advice. Patients referred cannabis use in order to alleviate pain as well as other manifestations of FM. Significant relief of pain, stiffness, relaxation, somnolence and perception of well-being, evaluated by VAS before and 2 hours after cannabis self-administration was observed.
Although the mental health component summary score of the SF-36 questionnaire was slightly but significantly higher in the cannabis group than in the non-users group, whether these findings are clinically significant remains unclear.
The external validity of this study can be limited for some factors. The main limitation is the self-selection bias, mainly related to the fact that the majority of patients in the cannabis group were recruited from a cannabis association. It is not known how these patients are different from the ones recruited from FM associations or from the rheumatology unit. In addition the patients included in the study were all responders to cannabis self-administration. Consequently, characteristics of the patients that have used cannabis and have not obtained symptoms relief are unidentified. Others limitations were the small size of the sample and, the variability of patterns of cannabis use among FM patients.
A previous observational study of patients with chronic pain of different origins using cannabis has revealed similar results regarding symptoms relief . Furthermore, significant reductions in VAS score for pain, FIQ global score and FIQ anxiety score were also seen in the first randomized controlled trial of 40 FM patients with continued pain despite the use of other medications treated with nabilone (synthetic cannabinoid agonist) during 4 weeks . In a recent randomized, equivalency and crossover trial, nabilone was found to have a greater effect on sleep than amitriptyline on the ISI (Insomnia Severity Index), and was marginally better on the restfulness based on the LSEQ (Leeds Sleep Evaluation Questionnaire) . These results seem to indicate a possible role of cannabinoids on the treatment of FM, although it should be confirmed in further clinical trials.
Moreover, according to hypothetical and experimental evidence, a Clinical Endocannabinoid Deficiency has been proposed to be involved on the pathophysiology of FM and other functional conditions alleviated by cannabis . The participation of the endocannabinoid system in multiple physiological functions such as pain modulation, stress response system, neuroendocrine regulation and cognitive functions among others, is well known . Additionally, the innovative psychoneuro-endocrinology-inmunology (PNEI) studies have shown that chronic pain may be strongly influenced by dysfunctions of the stress system and, particularly, the HPA-axis . Studies have shown that the HPA- axis and the autonomic nervous system is disturbed in patients with fibromyalgia  and, polymorphisms of genes in the serotoninergic, dopaminergic and catecholaminergic systems may also play a role in the pathogenesis of FM . Notably, these polymorphisms all affect the metabolism or transport of monoamines, compounds that have a critical role in both sensory processing and the human stress response . Endocannabinoids and cannabinoid receptors are involved in the responses of animals to acute, repeated and variable stress  and there is good evidence that the cannabinoid receptors play a major role in modulating neurotransmitter release such as serotonin and dopamine among others . However, the endocannabinoid system and its implication in stress response in humans have not been so far investigated. Because of many methodological pitfalls in life stress research, high quality studies of the role of stress in the etiopathogenesis of unexplained chronic pain syndromes, such as fibromyalgia, are scarce.
We observe significant improvement of symptoms of FM in patients using cannabis in this study although there was a variability of patterns. This information, together with evidence of clinical trials and emerging knowledge of the endocannabinoid system and the role of the stress system in the pathopysiology of FM suggest a new approach to the suffering of these patients.
The present results together with previous evidence seem to confirm the beneficial effects of cannabinoids on FM symptoms. Further studies regarding efficacy of cannabinoids in FM as well as cannabinoid and stress response system involvement in their pathophysiology are warranted.
Conceived and designed the experiments: JF DC MF. Performed the experiments: JF. Analyzed the data: JF MF. Wrote the paper: JF MD DC JC MF.
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