Published Research - General Sleep and RLS (WED)

For everything and anything else not covered in the other RLS sections.
badnights
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Cannabinoids not shown to help sleep or pain in meta-analysis but limited studies done

Post by badnights »

Cannabinoids Do Not Reduce Cancer-Related Pain, Has No Clear Effect on Sleep Problems
By Will Boggs MD
https://www.medscape.com/viewarticle/92 ... 9432&faf=1

January 28, 2020

NEW YORK (Reuters Health) - Cannabinoids do not reduce cancer-related pain, and their effects on sleep problems in patients with chronic pain are unclear, according to a pair of new studies.

Up to 60% of patients undergoing anticancer therapy, and 90% of those with advanced disease report cancer-related pain. Surveys have found that many cancer patients resort to cannabinoids to address their pain, but reviews have found only very-low-quality evidence supporting their efficacy for reducing pain.

Dr. Jason W. Boland, who worked on one of the studies, a systematic review and meta-analysis, told Reuters Health by email, "Based on current evidence, cannabinoids (the active chemicals in medicinal cannabis) do not have a role in cancer-related pain."

Dr. Boland, of Hull York Medical School, University of Hull, in the UK, and colleagues found six randomized controlled trials relevant for evaluating the beneficial and adverse effects of cannabinoids, compared with placebo or other active agent, for the treatment of cancer-related pain in adults.

Change in pain as measured by a numeric rating scale did not differ significantly between cannabinoids and placebo overall and when only phase-3 studies were included in the meta-analysis.

Change in pain intensity, a secondary outcome in one trial, did not differ significantly between cannabinoids and placebo either, the researchers report in The BMJ Supportive & Palliative Care.

Cannabinoids generally carried a higher risk of adverse events, compared with placebo; in the meta-analysis, produced a 2.69-fold increase in the odds of somnolence (P<0.001) and 58% rise in the odds of dizziness (P=0.05), as well as nonsignificantly higher odds of nausea and vomiting.

Patients treated with cannabinoids had 33% higher odds of study dropout due to adverse events, compared with placebo, but this difference fell short of statistical significance.

In the other study, published in the same journal, Dr. Sharon R. Sznitman of the University of Haifa Faculty of Social Welfare and Health Sciences, in Israel, and colleagues examined the association between sleep problems and medical cannabis in 129 chronic-pain patients aged 50 years and older.

Compared with patients not using medical cannabis, those using medical cannabis were less likely to report waking up at night, but there were no differences between the groups in terms of sleep latency and early awakenings.

Among patients using medical cannabis, more frequent use was associated with more problems related to waking up at night and falling asleep.

"Cannabis may potentially help improve sleep, but it is also potentially true that long-term and frequent cannabis use may lessen the sleep-inducing effects of cannabis," Dr. Sznitman said. "Much more research is needed. We are only beginning to scrape the surface."

"Cannabis may be effective for treating sleep problems, but we are far away from a strong evidence base for this," she said. "Physicians may also speak to their patients who use cannabis long-term and frequently about the potential for cannabis to be related to poorer sleep."

Michelle Sexton, a naturopathic doctor at the University of California, San Diego, who recently surveyed cannabis users regarding its acute effects and withdrawal symptoms, told Reuters Health by email the Israeli study "supports what we see in our clinical practice at UCSD. I was surprised to see so many people reporting 'smoking' cannabis. Given that there are vaporizer devices, there is no need to smoke cannabis. Also, the pharmacokinetics of oral cannabis would lend itself better to maintaining sleep across the night."

"Overall, the safety profile of THC (delta-9-tetrahydrocannabinol) appears to be better than that of benzodiazepines, opioids, or other sleep medications," said Dr. Sexton, who was not involved in the new studies. "The beneficial effects of THC for sleep need further investigation."

Dr. Sexton added, "These subjects were using THC-dominant cannabis, not cannabidiol (CBD). This is important as the two molecules have no shared pharmacology and should not be expected to have similar pharmacodynamic properties. THC is an important medicinal component about which much more is known than CBD."

SOURCE: https://bit.ly/3aD47vp and https://bit.ly/38DHq8J BMJ Supportive & Palliative Care, online January 20, 2020.
Beth - Wishing you a restful sleep tonight
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QyX
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Re: Published Research - General Sleep and RLS (WED)

Post by QyX »

Thank for you posting this. This was an interested read.

A few comments from me:

a) it is not that surprising that Cannabis is not as effective for cancer related pain. For cancer related pain, opioids are and will most likely always be the way to go. But Cannabis is absolutely awesome for nausea and appetite loss due to cancer and chemotherapy. Unfortunately it doesn't appear that it was investigated if Cannabis would boost the effects of opioids in cancer related pain. A few words about this topic in the study would have been nice given all the evidence that THC can boost the effects of opioids.

b) I am also not surprised that chronic long-term use of THC only strains is not that effective for sleeping problems. Without the use of additional oral CBD it would not work for me. I wish they would design more complex studies where they have a group of patients who is also using CBD and not just strains rich in THC. But at least this also seems an effect experts seem aware of. I was told from the very beginning that THC is for inducing sleep and CBD to maintain sleep.

stjohnh
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Re: Published Research - General Sleep and RLS (WED)

Post by stjohnh »

One other comment: Sleep is VERY complicated, in spite of our tendency to think difficulty sleeping is just one group. LOTS of different reasons for poor sleep, so it is only somewhat helpful to categorize interventions as helpful vs not helpful, when the causes are so varied.
Blessings,
Holland

badnights
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Re: Published Research - General Sleep and RLS (WED)

Post by badnights »

Nice comments, both of you.
Beth - Wishing you a restful sleep tonight
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ViewsAskew
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Gut, levadopa, and Parkinson's

Post by ViewsAskew »

https://parkinsonsnewstoday.com/2019/01 ... udy-shows/

"Levodopa, one of the main medicines used to treat Parkinson’s symptoms, can be converted into dopamine by gut bacteria, researchers report. The findings might explain why levodopa treatment is less effective in some patients. The study, “Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson’s disease,” was published in Nature Communications."

I wonder how this will play out with any medications...and those we take. So many questions...
Ann - Take what you need, leave the rest

Managing Your RLS

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badnights
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Willis-Ekbom in the abdomen?

Post by badnights »

https://assets.researchsquare.com/files ... 896883.pdf

A description of "restless abdomen" in patients with and without leg symptoms. Some of these patients meet all the criteria for WED/RLS except the location of their symptoms is the abdomen, not the legs, so it does not qualify as WED/RLS. Others have symptoms in both the legs and the abdomen. None of these patients is thought to have been experiencing augmentation.

The authors (who include William Ondo) conclude that neurologists should be aware that RLS symptoms can occur in the abdomen in the absence of worsening or augmentation, that the main symptom will be severe insomnia, and that the patient may seek a gastroenterologist rather than a sleep specialist or neurologist. I would think they would want gastroenterologists and GPs and sleep specialists to be aware of this, too...
Beth - Wishing you a restful sleep tonight
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Rustsmith
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Hepcidin may be better indicator than Ferritin

Post by Rustsmith »

The association between restless legs syndrome (RLS) and iron homeostasis remains unclear. We compared serum hepcidin and ferritin levels in patients with RLS and controls, and assessed their relationships with RLS phenotype, drug intake, and history of augmentation syndrome. 102 drug-free RLS patients (age 58.9 [24.5–77.2], 63 females) and 73 controls (age 56.8 [23.46–76.6], 45 females) underwent a polysomnography recording. Hepcidin levels were quantified by ELISA. 34 RLS patients had a second assessment after starting dopaminergic drugs. Ferritin level was low (< 50 µg/l) in 14.7% of patients and 25% of controls, with no between-group differences in the mean values. Hepcidin levels were higher in patients even after adjustment for confounding factors, and excluding participants with low ferritin levels. Ferritin and hepcidin levels were comparable before and after treatment, and between patients with (n = 17) and without history of augmentation. Ferritin and hepcidin levels correlated with age, body mass index, and periodic leg movements. Higher hepcidin levels were associated with older age, older age at RLS onset, less daytime sleepiness and familial RLS. In conclusion, serum hepcidin levels but not ferritin were higher in RLS patients regardless of treatment and history of augmentation. Serum hepcidin may be a more relevant biomarker of RLS than ferritin.
https://www.nature.com/articles/s41598-020-68851-0
Steve

Augmentation Evaluation http://bb.rls.org/viewtopic.php?f=4&t=9005

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stjohnh
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Re: Published Research - General Sleep and RLS (WED)

Post by stjohnh »

Interesting, mostly as an addition to our understanding of the disease. Their results do not show hepcidin to be a useful diagnostic test for RLS.

"The best cut off hepcidin value to discriminate patients with RLS from controls was 18.1 µg/L, with a sensitivity of 52% and a specificity of 75%, and with significant between-group differences (p = 0.0004)."

Still seems to me that a useful drug would be an hepcidin blocker, might make IV Iron unneccessary (for those that respond to IV iron).
Blessings,
Holland

badnights
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Re: Published Research - General Sleep and RLS (WED)

Post by badnights »

I admire Winkelman for trying to make the medical community aware of augmentation in this way. He has looked at 670,000 WED/RLS patients: 400,000 take a DA, and about 80,000 of those are prescribed more than the FDA-recommended maximum, which - an aside, here - is way more than the "new" maximums recommended by WED/RLS specialists like Buchfuhrer (see his 2012 paper in my signature link). The article is worth a read.

https://www.sleepreviewmag.com/sleep-tr ... 1598468832

My favorite quote follows a description of how DAs are so effective initially, but then they make the symptoms worse, so the doctors raise the dose. They quote: "Doctors and their RLS patients fall into this pattern because dopamine agonists are seductive medications for RLS. They work almost immediately, and almost in everybody, and that’s very seductive for doctors. Who doesn’t want to help their patients quickly and effectively?” Seductive for patients, too. Seductive is the perfect word, here.
Beth - Wishing you a restful sleep tonight
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badnights
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WED/RLS is associated with SAT3

Post by badnights »

Here's a weird one that I feel like sharing -

I didn't know what SAT3 was. I had to look it up: it's "a condition characterized by progressive problems with movement. People with this condition initially experience problems with coordination and balance" and go on to develop uncontrolled muscle tensing, rigidity, tremors, double vision, loss of sensation and weakness in the limbs (peripheral neuropathy), muscle cramps, muscle twitches, and swallowing difficulties. "People with SCA3 eventually require wheelchair assistance. They usually survive 10 to 20 years after symptoms first appear." People with SCA3 commonly have RLS/WED or REM sleep behavior disorder.

The authors show that RLS/WED is way more common in SCA3 patients than in controls, and that it's associated with being female, being over 30, having peripheral neuropathy, and iron deficiency in those SCA3 patients.

From the abstract (https://link.springer.com/article/10.10 ... 20-01170-2)
Which Factors in Spinocerebellar Ataxia Type 3 Patients Are Associated with Restless Legs Syndrome/Willis-Ekbom Disease?
There is evidence of a higher prevalence of restless legs syndrome/Willis-Ekbom disease (RLS/WED) in individuals with spinocerebellar ataxia type 3 (SCA3), although the factors underlying this association remain unknown. The present study aimed to determine the prevalence of RLS/WED in SCA3 patients and to investigate which factors of SCA3 patients are associated with presence of RLS/WED.

From February to August of 2006, we carried out clinical interviews in 40 controls and 40 SCA3 patients, diagnosed and followed up at Faculty of Medicine of Ribeirão Preto, University of São Paulo. .... RLS/WED was found in 27.5% of SCA3 patients and 2.5% of normal controls (p = 0.003).

The factors related to RLS/WED in SCA3 patients were:
  • female gender,
  • age at start of the symptoms of ataxia after 30 years,
  • presence of peripheral neuropathy, and
  • documented iron deficiency.
...There is a relation between RLS/WED and SCA3, which seems to be resultant of different factors whose identification could improve the quality of assistance to those patients as well as to promote a better comprehension of the pathophysiology of both RLS/WED and SCA3.
Beth - Wishing you a restful sleep tonight
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Oozz
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Re: Published Research - General Sleep and RLS (WED)

Post by Oozz »

This was recently posted in the blog. A new drug to help stop augmentation. I’m not a fan of drugs to prevent side effects of other drugs, but at least it is something.

https://rlsfoundation.blogspot.com/2020 ... 797352&m=1

Anyone have any additional information about this?

Rustsmith
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Re: Published Research - General Sleep and RLS (WED)

Post by Rustsmith »

I know that my former doctor in Houston was part of a clinical trial evaluating this or something very like it. Everything else that I know was included in his blog in the form of the comment about normal DAs eventually causing issues with the D1 receptors when augmentation occurs and that this approach helps clear the D1 receptors and hopefully blocks augmentation. But it looks like there is still a huge amount to do before we will know for sure.
Steve

Augmentation Evaluation http://bb.rls.org/viewtopic.php?f=4&t=9005

Opinions presented by Discussion Board Moderators are personal in nature and do not, in any way, represent the opinion of the RLS Foundation, and are not medical advice.

badnights
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Gut Microbes and Sleep

Post by badnights »

Gut microbes: a key to normal sleep
(from Nov 20 at https://www.sciencedaily.com/releases/2 ... ceDaily%29)

With fall and winter holidays coming up, many will be pondering the relationship between food and sleep. Researchers led by Professor Masashi Yanagisawa at the University of Tsukuba in Japan hope they can focus people on the important middlemen in the equation: bacterial microbes in the gut. Their detailed study in mice revealed the extent to which bacteria can change the environment and contents of the intestines, which ultimately impacts behaviors like sleep.

The experiment itself was fairly simple. The researchers gave a group of mice a powerful cocktail of antibiotics for four weeks, which depleted them of intestinal microorganisms. Then, they compared intestinal contents between these mice and control mice who had the same diet. Digestion breaks food down into bits and pieces called metabolites. The research team found significant differences between metabolites in the microbiota-depleted mice and the control mice. As Professor Yanagisawa explains, "we found more than 200 metabolite differences between mouse groups. About 60 normal metabolites were missing in the microbiota-depleted mice, and the others differed in the amount, some more and some less than in the control mice."

The team next set out to determine what these metabolites normally do. Using metabolome set enrichment analysis, they found that the biological pathways most affected by the antibiotic treatment were those involved in making neurotransmitters, the molecules that cells in the brain use to communicate with each other. For example, the tryptophan-serotonin pathway was almost totally shut down; the microbiota-depleted mice had more tryptophan than controls, but almost zero serotonin. This shows that without important gut microbes, the mice could not make any serotonin from the tryptophan they were eating. The team also found that the mice were deficient in vitamin B6 metabolites, which accelerate production of the neurotransmitters serotonin and dopamine.

The team also analyzed how the mice slept by looking at brain activity in EEGs. They found that compared with the control mice, the microbiota-depleted mice had more REM and non-REM sleep at night -- when mice are supposed to be active -- and less non-REM sleep during the day -- when mice should be mostly sleeping. The number of REM sleep episodes was higher both during the day and at night, whereas the number of non-REM episodes was higher during the day. In other words, the microbiota-depleted mice switched between sleep/wake stages more frequently than the controls.

Professor Yanagisawa speculates that the lack of serotonin was responsible for the sleep abnormalities; however, the exact mechanism still needs to be worked out. "We found that microbe depletion eliminated serotonin in the gut, and we know that serotonin levels in the brain can affect sleep/wake cycles," he says. "Thus, changing which microbes are in the gut by altering diet has the potential to help those who have trouble sleeping."

So, this holiday season, when you're feeling sleepy after eating tryptophan-stuffed turkey, please don't forget to thank your gut microbes!
Beth - Wishing you a restful sleep tonight
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I am a volunteer moderator. My posts are not medical advice. My posts do not reflect RLS Foundation opinion.

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