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For all modern medicine can do, many mysteries remain unsolved. What is long COVID? Is there really such thing as a “cure” for cancer? And how to explain the surprisingly high prevalence of fibromyalgia, a debilitating, lifelong disorder of the central nervous system without a known cause that affects between 2 and 4 percent of adults worldwide?

In the absence of an answer — or a cure — treatment is the name of the game for fibromyalgia. No single drug yet exists to address all of the disease’s effects on the body, which can include widespread aches and pains, sleeplessness, fatigue, anxiety, and depression. Instead, patients turn to a mix of whatever individual medications, therapies, and lifestyle changes (especially exercise) help ease symptoms and improve quality of life.

On the drug front, anti-depressants, analgesics, and muscle relaxants might be prescribed. But there’s another option that can address mood, pain, and more at once, all with fewer side effects: cannabis.

It’s not a new idea. Researchers have been investigating the use of cannabis to treat fibromyalgia’s constellation of symptoms for decades, with early clinical trials in the 2000s1-4 suggesting a possible benefit of both pure THC and flower in managing the disease. Nor is it necessarily surprising, given the ability of cannabis to target the ubiquitous, homeostasis-seeking endocannabinoid system.

Recently published papers — a series of reviews, two human studies, and an animal study — only bolster the case that cannabis can help those suffering from this confounding condition. Still more may be forthcoming, including through a newly announced randomized controlled trial in the Netherlands that will compare cannabis, oxycodone, and a combination of the two for pain relief in 60 fibromyalgia patients.5

Solid Evidence Base

Over the last few months a number of reviews have helped refine our understanding of the relationship between cannabis, the endocannabinoid system (ECS), and fibromyalgia symptoms. In November 2022, a paper in the journal Pain Reports6 provided the first systematic review and meta-analysis of previous studies measuring levels of circulating endocannabinoids and other fatty acid derivatives in patients with both fibromyalgia and chronic widespread pain.

Across the eight studies they analyzed, the Australia-based authors identified increased levels of oleoylethanolamide and stearoylethanolamide (endocannabinoid-like molecules called N-Acylethanolamines that don’t bind with the cannabinoid receptors) in patients with these conditions compared to controls. There were no differences observed in levels of the endocannabinoids anandamide and 2-AG.

Still, the authors caution that “most studies did not account for variables that may influence ECS function, including cannabis use, concomitant medication, comorbidities, physical activity, stress levels, circadian rhythm, sleep quality, and dietary factors.” They call for additional study in this area and, more broadly, seek to “highlight the importance of investigating endocannabinoid activity in chronic widespread pain and fibromyalgia because it will underpin future translational research in the area.”

Other recent papers summarize the state of the science:

  • A review of clinical and preclinical research into cannabinoids, the ECS, and fibromyalgia in Pharmacology & Therapeutics7 (December 2022) agreed that “there is evidence for alterations in the endocannabinoid system in patients with fibromyalgia.”
  • A systematic review and meta-analysis of eight studies investigating the benefits of cannabinoids for chronic pain in Pain and Therapy8 (December 2022) reported that “cannabinoids might improve pain and quality of life in patients with fibromyalgia.”
  • And a narrative review also in Pain and Therapy9 (January 2023) on the efficacy, risks, and benefits of cannabinoids in the treatment of various pain subtypes concluded that “available data strongly support the use of cannabinoids in treating fibromyalgia pain” due to “overwhelmingly positive treatment results.”

Mice Respond to Cannabis Oil

Unlike some other areas of cannabinoid science, fibromyalgia research is not dominated by preclinical laboratory studies. But an October 2022 paper in Biomedicine and Pharmacotherapy10 offers an interesting parallel to previous human studies through the use of a well-established mouse model of fibromyalgia induced by reserpine, a drug that acts on the central nervous system (and is sometimes used to treat high blood pressure in humans).

The Italy- and Brazil-based authors sought to evaluate the effect of a “broad-spectrum” 11:1 CBD:THC cannabis oil in mice with reserpine-induced fibromylagia. They report that oral feeding of a single dose of cannabis oil was enough to mitigate some hallmarks of the condition in mice. Better yet, repeated administration over the course of two weeks reversed reserpine-induced mechanical and thermal sensitivity, and also reduced depressive-like behavior.

While the implications of these findings for human physiology and disease are perhaps unclear — given that we still don’t fully understand the etiology of fibromyalgia — they appear to lend yet more credibility to cannabis.

Cannabis Helps “Treatment-Resistant” Patients

Two new prospective cohort studies build upon this work with additional real-world data that may well wind up in future reviews. A November 2022 article in the journal Pain Practice11 covers a clinical trial in which 30 women suffering from fibromyalgia symptoms resistant to traditional pharmacological treatments were provided medicinal cannabis. That seemed to make all the difference. Comparing the women’s scores on the World Health Organization Quality of Life questionnaire before and after a month of cannabis use revealed “a marked improvement in general quality of life, general health, physical health, and psychological domain.”

And a similar, earlier study by researchers in Canada — with 323 fibromyalgia patients followed for 12 months — also found through quarterly physician assessments that initiating cannabis use was associated with improvements on a variety of fronts. As the authors report in the journal Arthritis Care & Research,12 observed reductions in pain intensity appeared to be partly explained by concurrent benefits to both sleep and mood.

“With suboptimal response to current medications, many patients with fibromyalgia seek … cannabis,” the authors conclude. “Medical cannabis may present a useful treatment strategy for patients with fibromyalgia in light of an effect on the triad of symptoms of pain, negative affect, and sleep disturbances.”


Nate Seltenrich, Project CBD contributing writer, is the author of the column Bridging the Gap. An independent science journalist based in the San Francisco Bay Area, he covers a wide range of subjects, including environmental health, neuroscience, and pharmacology. © Copyright, Project CBD. May not be reprinted without permission.


Footnotes

  1. Schley, Marcus et al. “Delta-9-THC based monotherapy in fibromyalgia patients on experimentally induced pain, axon reflex flare, and pain relief.” Current medical research and opinion vol. 22,7 (2006): 1269-76. doi:10.1185/030079906×112651
  2. Skrabek, Ryan Quinlan et al. “Nabilone for the treatment of pain in fibromyalgia.” The journal of pain vol. 9,2 (2008): 164-73. doi:10.1016/j.jpain.2007.09.002
  3. Ware, Mark A et al. “The effects of nabilone on sleep in fibromyalgia: results of a randomized controlled trial.” Anesthesia and analgesia vol. 110,2 (2010): 604-10. doi:10.1213/ANE.0b013e3181c76f70
  4. Fiz, Jimena et al. “Cannabis use in patients with fibromyalgia: effect on symptoms relief and health-related quality of life.” PloS one vol. 6,4 e18440. 21 Apr. 2011, doi:10.1371/journal.pone.0018440
  5. van Dam, Cornelis Jan et al. “Cannabis-opioid interaction in the treatment of fibromyalgia pain: an open-label, proof of concept study with randomization between treatment groups: cannabis, oxycodone or cannabis/oxycodone combination-the SPIRAL study.” Trials vol. 24,1 64. 27 Jan. 2023, doi:10.1186/s13063-023-07078-6
  6. Kurlyandchik, Inna et al. “Plasma and interstitial levels of endocannabinoids and N-acylethanolamines in patients with chronic widespread pain and fibromyalgia: a systematic review and meta-analysis.” Pain reports vol. 7,6 e1045. 7 Nov. 2022, doi:10.1097/PR9.0000000000001045
  7. Bourke, Stephanie L et al. “Cannabinoids and the endocannabinoid system in fibromyalgia: A review of preclinical and clinical research.” Pharmacology & therapeutics vol. 240 (2022): 108216. doi:10.1016/j.pharmthera.2022.108216
  8. Giossi, Riccardo et al. “Systematic Review and Meta-analysis Seem to Indicate that Cannabinoids for Chronic Primary Pain Treatment Have Limited Benefit.” Pain and therapy vol. 11,4 (2022): 1341-1358. doi:10.1007/s40122-022-00434-5
  9. Ang, Samuel P et al. “Cannabinoids as a Potential Alternative to Opioids in the Management of Various Pain Subtypes: Benefits, Limitations, and Risks.” Pain and therapy, 10.1007/s40122-022-00465-y. 13 Jan. 2023, doi:10.1007/s40122-022-00465-y
  10. Ferrarini, Eduarda Gomes et al. “Broad-spectrum cannabis oil ameliorates reserpine-induced fibromyalgia model in mice.” Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie vol. 154 (2022): 113552. doi:10.1016/j.biopha.2022.113552
  11. Hershkovich, Oded et al. “The role of cannabis in treatment-resistant fibromyalgia women.” Pain practice : the official journal of World Institute of Pain vol. 23,2 (2023): 180-184. doi:10.1111/papr.13179
  12. Sotoodeh, Romina et al. “Predictors of Pain Reduction Among Fibromyalgia Patients Using Medical Cannabis: A Long-Term Prospective Cohort Study.” Arthritis care & research, 10.1002/acr.24985. 25 Jul. 2022, doi:10.1002/acr.24985



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