Pain – Recent cannabis use linked to extremes of nightly sleep duration

CBD Treats Fibromyalgia Pain

Recent cannabis use is linked to extremes of nightly sleep duration–less than 6 hours or more than 9 hours–reveals a study of a large representative sample of US adults, published online in the journal Regional Anesthesia & Pain Medicine.

This pattern was even more pronounced among heavy users–those using on 20 out of the previous 30 days, the findings show.

Cannabis use in North America continues to increase, with around 45 million adults in the USA reporting this in 2019, which is double the figure reported in the early 2000s.

This change has partly been driven by widespread decriminalisation in many states over the past decade, as well as research suggesting that cannabinoids may have therapeutic value for pain relief and possibly anxiety and sleep disorders as well, say the researchers.

Cannabis has become popular as a sleep aid, particularly as the prevalence of sleep deprivation and insomnia has increased. Only two thirds of Americans get the recommended 7-9 hours of sleep every night, and almost half report daytime sleepiness every day.

But the evidence to date on the impact of cannabis on the sleep-wake cycle has been equivocal.

The researchers wanted to see if cannabis use might be linked to nightly sleep duration in a nationally representative sample of US adults (aged 20-59) who had taken part in the biennial National Health and Nutrition Examination Survey (NHANES) for the years 2005 to 2018 inclusive.  

And they wanted to know if respondents reported difficulty falling asleep, staying asleep, or slept too much in the preceding 2 weeks; whether they had ever consulted a doctor about a sleep problem; and whether they regularly experienced daytime sleepiness on at least 5 of the preceding 30 days.

Survey respondents were characterised as recent or non-users if they had or hadn’t used cannabis in the past 30 days. Sleep duration was defined as short (less than 6 hours), optimal (6–9 hours), and long (more than 9 hours). 

Information was gathered on potentially influential factors: age; race; educational attainment; weekly working hours; a history of high blood pressure, diabetes, and coronary artery disease; weight (BMI); smoking; heavy alcohol use (4 or more drinks daily); and prescriptions for opioids, benzodiazepines, ‘Z drugs’ (approved for insomnia), barbiturates, other sedatives, and stimulants.

Some 25,348 people responded to the surveys between 2005 and 2018, but the final analysis is based on 21,729 who answered all the questions, representing an estimated 146.5 million US adults. 

The average nightly sleep duration was just short of 7 hours across the entire sample.  Some 12% reported  less than 6 hours, while 4% reported more than 9 hours a night. 

A total of 3132 (14.5%) respondents said they had used cannabis in the preceding 30 days. Recent users were more likely to report not sleeping enough or sleeping too much.

They were 34% more likely to report short sleep and 56% more likely to report long sleep than those who hadn’t used cannabis in the preceding 30 days, after accounting for potentially influential factors.

And they were also 31% more likely to report difficulty falling asleep, staying asleep, or sleeping too much in the preceding 2 weeks, and 29% more likely to have discussed a sleeping problem with a doctor. But recent cannabis use wasn’t associated with frequent daytime sleepiness.

Further analysis of the frequency of cannabis use revealed that moderate users, defined as using on fewer than 20 out of the past 30 days, were 47% more likely to sleep 9 or more hours a night compared with non-users. 

Heavy users, defined as using on 20 or more out of the preceding 30 days, were 64% more likely to experience short sleep and 76% more likely to experience long sleep compared with non-users.

These findings differed little across the survey years.

This is an observational study, and as such, can’t establish cause, or reverse causality, for that matter. 

The researchers also point to several study limitations, including the reliance on self-reported data and the lack of information on cannabis dose. The historical and the historical and ongoing stigma associated with cannabis use may also have affected the responses to questions about cannabis use, they suggest.

But they say: “Increasing prevalence of both cannabis use and sleep deprivation in the population is a potential cause for concern.

“Despite the current literature demonstrating mixed effects of cannabis and various cannabinoid formulations on sleep architecture and quality, these agents are being increasingly used as both prescribed and unprescribed experimental therapies for sleep disturbances.”

They add: “Our findings highlight the need to further characterize the sleep health of regular cannabis users in the population…Sleep-wake physiology and regulation is complex and research about related endocannabinoid pathways is in its early stages.”

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Gut bacteria associated with chronic pain

People with fibromyalgia show variations in microbiome composition

Bacterial Species Composition

Bacterial species which were found in greater quantities in individuals with fibromyalgia (left) versus species which were found in greater quantities in healthy individuals (right).CREDIT Dr. Amir Minerbi

Scientists have found a correlation between a disease involving chronic pain and alterations in the gut microbiome.

Fibromyalgia affects 2-4 percent of the population and has no known cure. Symptoms include fatigue, impaired sleep and cognitive difficulties, but the disease is most clearly characterized by widespread chronic pain. In a paper published today in the journal Pain, a Montreal-based research team has shown, for the first time, that there are alterations in the bacteria in the gastrointestinal tracts of people with fibromyalgia. Approximately 20 different species of bacteria were found in either greater or are lesser quantities in the microbiomes of participants suffering from the disease than in the healthy control group.

Greater presence or absence of certain species of bacteria

Human Gut Microbiome Composition

Human gut microbiome composition shows an enormous richness. Each circle represents a bacterial species, while the different colours mark different bacterial phyla. CREDIT Dr. Amir Minerbi

“We used a range of techniques, including Artificial Intelligence, to confirm that the changes we saw in the microbiomes of fibromyalgia patients were not caused by factors such as diet, medication, physical activity, age, and so on, which are known to affect the microbiome,” says Dr. Amir Minerbi, from the Alan Edwards Pain Management Unit at the McGill University Health Centre (MUHC), and first author on the paper. The team also included researchers from McGill University and Université de Montréal as well as others from the Research Institute of the MUHC.

Dr. Minerbi adds, “We found that fibromyalgia and the symptoms of fibromyalgia – pain, fatigue and cognitive difficulties – contribute more than any of the other factors to the variations we see in the microbiomes of those with the disease. We also saw that the severity of a patient’s symptoms was directly correlated with an increased presence or a more pronounced absence of certain bacteria – something which has never been reported before.”

Are bacteria simply the markers of the disease?

At this point, it’s not clear whether the changes in gut bacteria seen in patients with fibromyalgia are simply markers of the disease or whether they play a role in causing it. Because the disease involves a cluster of symptoms, and not simply pain, the next step in the research will be to investigate whether there are similar changes in the gut microbiome in other conditions involving chronic pain, such as lower back pain, headaches and neuropathic pain.

The researchers are also interested in exploring whether bacteria play a causal role in the development of pain and fibromyalgia. And whether their presence could, eventually, help in finding a cure, as well as speed up the process of diagnosis.

Confirming a diagnosis and next steps towards finding a cure

Fibromyalgia is a disease that has proved difficult to diagnose. Patients can wait as long as 4 to 5 years to get a final diagnosis. But this may be about to change.

“We sorted through large amounts of data, identifying 19 species that were either increased or decreased in individuals with fibromyalgia,” says Emmanuel Gonzalez, from the Canadian Center for Computational Genomics and the Department of Human Genetics at McGill University. “By using machine learning, our computer was able to make a diagnosis of fibromyalgia, based only on the composition of the microbiome, with an accuracy of 87 per cent. As we build on this first discovery with more research, we hope to improve upon this accuracy, potentially creating a step-change in diagnosis.”

Amir Minerbi

Dr. Amir Minerbi, first author on the paper, along with his colleagues, have found a correlation between a disease involving chronic pain and alterations in the gut microbiome. CREDIT McGill University Health Centre

“People with fibromyalgia suffer not only from the symptoms of their disease but also from the difficulty of family, friends and medical teams to comprehend their symptoms,” says Yoram Shir, the senior author on the paper who is the Director of the Alan Edwards Pain Management Unit at the MUHC and an Associate Investigator from the BRaiN Program of the RI-MUHC. “As pain physicians, we are frustrated by our inability to help, and this frustration is a good fuel for research. This is the first evidence, at least in humans, that the microbiome could have an effect on diffuse pain, and we really need new ways to look at chronic pain.”

How the research was done

The research was based on a cohort of 156 individuals in the Montreal area, 77 of whom suffer from fibromyalgia. Participants in the study were interviewed and gave stool, blood, saliva and urine samples, which were then compared with those of healthy control subjects, some of whom lived in the same house as the fibromyalgia patients or were their parents, offspring or siblings.

The researchers’ next steps will be to see whether they get similar results in another cohort, perhaps in a different part of the world, and to do studies in animals to discover whether changes in bacteria play a role in the development of the disease.