Tag: Sleep

Posted on by — Leave a comment

THC & CBD-Rich Cannabis for Fibromyalgia

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.

“Available data strongly support the use of cannabinoids in treating fibromyalgia pain” due to “overwhelmingly positive treatment results.”

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, an independent science journalist based in the San Francisco Bay Area, 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

The post THC & CBD-Rich Cannabis for Fibromyalgia appeared first on Project CBD.

Original Article

Posted on by — Leave a comment

Cannabinoids for Tinnitus?

Recently my wife returned from a night out with a ringing in one ear and significantly diminished hearing. It was a sure sign of injury caused by standing too close to a speaker. She was upset with herself for being so careless and concerned that the condition would persist. For the next couple days, she got extra sleep to aid recovery, and for good measure took an extra dose or two of CBD.

For many other people of all ages, tinnitus is indeed a chronic condition that has nothing to do with loud ‘80s cover bands in small clubs. Risk factors span a wide range of physical and psychological conditions including concussion, smoking, certain medications, ear infection, high blood pressure, anxiety, depression, and, most commonly, age-related hearing loss.

And it’s not just ringing. Technically, tinnitus (pronounced tih-NITE-us or TIN-ih-tus) is the perception of sound originating from within the nervous system that’s unrelated to external stimulation. Tinnitus can also be experienced as buzzing, whirring, humming, whooshing, clicking, and hissing. Whatever the precise nature of the phantom sound, it often comes with a constellation of symptoms related to the disruption such a condition can bring: sleep problems, difficulty concentrating, low mood, etc. Estimates vary, but tens of millions of people in the United States alone likely suffer from chronic tinnitus.

My wife’s ringing tinnitus did fade, and her hearing gradually improved over the course of a few days. The CBD she took may or may not have helped, but according to a recent survey of tinnitus patients, she wasn’t alone in trying — or at least in being interested in cannabis as a potential remedy.

Auditory & Other Symptoms

The survey, whose findings were published in February 2023 in the Journal of Otolaryngology – Head & Neck Surgery1evaluated cannabis perceptions and consumption among 45 adult tinnitus patients randomly selected and recruited from an outpatient ear, nose, and throat clinic in Ontario, Canada.

Among the 45 respondents, median age 55, only 10 said they were current cannabis users (19 had never used, and 16 had used in the past). But of the 10 current users, eight reported that cannabis did help with some of their tinnitus-related symptoms — if not necessarily the sound itself. Seven of the eight found it helpful for sleep disturbances, seven for pain, six for emotional complaints, four for functional difficulties, and three for dizziness symptoms. Only three of the ten found cannabis helpful for the actual auditory symptoms characterizing tinnitus.

But many more patients were willing to try, perhaps as an indication of the intractability of chronic tinnitus. All but two of the 45 respondents said they’d consider cannabis as a treatment, with 29 seeking help for sleep disturbances, 27 for emotional complaints, 25 for functional disturbances, and nine for pain. Of note, however, 41 of the 45 said they’d turn to cannabis for auditory symptoms — the primary concern for most tinnitus patients yet the least improved by cannabis according to the survey’s 10 current users.

Interestingly, and perhaps unfortunately for patients, previous reviews in 2020 and 20192 also concluded there was insufficient evidence that cannabis can diminish chronic tinnitus.

Mixed Findings

A December 2020 review in the journal Laryngoscope Investigative Otolaryngology3 by researchers at Yale University and nearby University of Connecticut tackles the question head-on. Its title: “Does cannabis alleviate tinnitus? A review of the current literature.”

And its conclusion? “While animal studies have revealed that cannabinoid receptors likely have a role in modulating auditory signaling, there is no compelling data either from animal or human studies for the use of cannabinoids to alleviate tinnitus.”

There could be a role for cannabinoids in the management of tinnitus through their anticonvulsant effects.

In fact, there’s some evidence from animal research that cannabinoid administration may actually induce or exacerbate tinnitus. That’s what appeared to happen in rats injected with the synthetic CB1 agonists WIN55,212‐2 and CP55,940 in a 2010 study4 and THC and CBD in a 1:1 ratio in a 2011 follow-up study.5

As far as human studies, the review authors also summarize two previous surveys in 2010 and 2019, a 1975 clinical trial and a 2006 case study — whose cumulative findings are, at best, entirely unclear.

Despite all this, there is a potential biological rationale for the treatment of tinnitus with cannabinoids, the authors explain. Other animal studies have suggested that cannabinoid receptor expression in the cochlear nucleus may vary with tinnitus symptomatology. And since the most widely accepted hypothesis for the pathophysiology of tinnitus relates to something called “neuronal hyperexcitability” — a mechanism that has also been observed in epilepsy, they note — “there is a potential role of cannabinoids in the management of tinnitus through its anticonvulsant effects.”

Cannabinoid Receptors Influence Hearing

Finally, a November 2020 review in Frontiers in Neurology6 adds more complexity and subtlety to the issue. The article wisely notes that animal studies showing cannabinoids to potentially worsen tinnitus have focused on CB1 agonists. This excludes compounds that target, among others:

  • CB2 receptors, which influence immune function and are “increasingly recognized as essential in understanding nervous system pathological responses”
  • and “non-classical” cannabinoid targets like TRP (“trip”) channels, which mediate processes including vision, taste, olfaction, touch and hearing.

While the collective evidence to date is mixed and inconclusive, it’s also incomplete. The potential is huge for new animal studies using cannabinoids other than CB1 agonists, and for more robust human studies (indeed any clinical trial at all) to contribute fresh insights to this burning, buzzing question.

Nate Seltenrich, an independent science journalist based in the San Francisco Bay Area, covers a wide range of subjects including environmental health, neuroscience, and pharmacology. Copyright, Project CBD. May not be reprinted without permission.

Footnotes

  1. Mavedatnia, Dorsa et al. “Cannabis use amongst tinnitus patients: consumption patterns and attitudes.” Journal of otolaryngology – head & neck surgery vol. 52,1 19. 24 Feb. 2023, doi:10.1186/s40463-022-00603-8
  2. Zheng, Yiwen, and Paul F Smith. “Cannabinoid drugs: will they relieve or exacerbate tinnitus?.” Current opinion in neurology vol. 32,1 (2019): 131-136. doi:10.1097/WCO.0000000000000631
  3. Narwani, Vishal et al. “Does cannabis alleviate tinnitus? A review of the current literature.” Laryngoscope investigative otolaryngology vol. 5,6 1147-1155. 30 Oct. 2020, doi:10.1002/lio2.479
  4. Zheng, Yiwen et al. “The effects of the synthetic cannabinoid receptor agonists, WIN55,212-2 and CP55,940, on salicylate-induced tinnitus in rats.” Hearing research vol. 268,1-2 (2010): 145-50. doi:10.1016/j.heares.2010.05.015
  5. Zheng, Y et al. “Acoustic trauma that can cause tinnitus impairs impulsive control but not performance accuracy in the 5-choice serial reaction time task in rats.” Neuroscience vol. 180 (2011): 75-84. doi:10.1016/j.neuroscience.2011.02.040
  6. Perin, Paola et al. “Cannabinoids, Inner Ear, Hearing, and Tinnitus: A Neuroimmunological Perspective.” Frontiers in neurology vol. 11 505995. 23 Nov. 2020, doi:10.3389/fneur.2020.505995

The post Cannabinoids for Tinnitus? appeared first on Project CBD.

Original Article