Patients suffering from chronic pain who take medicinal cannabis to initiate and maintain sleep appear to experience short-term benefit, but long-term use may ultimately disrupt slumber, new research shows. Investigators found whole-plant medical cannabis use was associated with fewer problems with respect to waking up at night, but they also found that frequent medical cannabis use was associated with more problems initiating and maintaining sleep. "Cannabis may improve overall sleep in the short term," study investigator Sharon Sznitman, PhD, University of Haifa Faculty of Social Welfare and Health Sciences in Israel, told Medscape Medical News. "But it's also very interesting that when we looked at frequency of use in the group that used medical cannabis, individuals who had more frequent use also had poorer sleep in the long term. "This suggests that while cannabis may improve overall sleep, it's also possible that there is a tolerance that develops with either very frequent or long-term use," she added. The study was published online January 20 in BMJ Supportive and Palliative Care. A Common Problem Estimates suggest chronic pain affects up to 37% of adults in the developed world. Individuals who suffer chronic pain often experience comorbid insomnia, which includes difficulty initiating sleep, sleep disruption, and early morning wakening. For its part, medical cannabis to treat chronic pain symptoms and manage sleep problems has been widely reported as a prime motivation for medical cannabis use. Indeed, previous studies have concluded that the endocannabinoid system plays a role in sleep regulation, including sleep promotion and maintenance. In recent years, investigators have reported the beneficial effects of medical cannabis for sleep. Nevertheless, some preclinical research has also concluded that chronic administration of tetrahydrocannabinol (THC) may result in tolerance to the sleep-enhancing effects of cannabis. With that in mind, the researchers set out to examine the potential impact of whole-plant medicinal cannabis on sleep problems experienced by middle-aged patients suffering from chronic pain. "People are self-reporting that they're using cannabis for sleep and that it helps, but as we know, just because people are reporting that it works doesn't mean that it will hold up in research," Sznitman said. The study included 128 individuals (mean age 61±6 years; 51% females) with chronic neuropathic pain. Of these, 66 were medical cannabis users; the remaining 62 were not. Three indicators of insomnia were measured using the 7-point Likert scale to assess issues with sleep initiation and maintenance. In addition, investigators collected sociodemographic information, as well as data on daily consumption of tobacco, frequency of alcohol use, and pain severity. Finally, they collected patient data on the use of sleep-aid medications during the past month as well as tricyclic antidepressant use. Frequent Use, More Sleep Problems? On average, medical cannabis users were 3 years younger than their non-using counterparts (mean age 60±6 vs 63±6 years, respectively, P = .003) and more likely to be male (58% vs 40%, respectively, P = .038). Otherwise, the two groups were comparable. Medical cannabis users reported taking the drug for an average of 4 years, at an average quantity of 31 g per month. The primary mode of administration was smoking (68.6%), followed by oil extracts (21.4%) and vaporization (20%). Results showed that of the total sample, 24.1% reported always waking up early and not falling back to sleep; 20.2% reported always having difficulty falling asleep; and 27.2% reported always waking up during the night. After adjusting for patient age, sex, pain level, use of sleep medications and antidepressant use, medical cannabis use was associated with fewer problems with waking up at night compared with nonmedical cannabis use. No differences were found between groups with respect to problems falling asleep or waking up early without being able to fall back to sleep. The final analysis of a subsample of patients that only included medical cannabis users showed frequency of medical cannabis use was associated with sleep problems. Specifically, more frequent cannabis use was associated with more problems related to waking up at night, as well as problems falling asleep. Sleep problems associated with frequent medical cannabis use may signal the development of tolerance to the agent. However, frequent users of medical cannabis may also suffer pain or other comorbidities, which, in turn, may be linked to more sleep problems. Either way, Sznitman said the study might open the door to another treatment option for patients suffering from chronic pain who struggle with sleep. "If future research shows that the effect of medical cannabis on sleep is a consistent one, then we may be adding a new therapy for sleep problems, which are huge in society and especially in chronic pain patients," she said. Early Days Commenting on the findings for Medscape Medical News, Ryan G. Vandrey, PhD, who was not involved in the study, said the findings are in line with previous research. "I think the results make sense with respect to the data I've collected and from what I've seen," said Vandrey, associate professor of psychiatry and behavioral sciences at Johns Hopkins Medicine in Baltimore, Maryland. "We typically only want to use sleep medications for short periods of time," Vandrey continued. "When you think about recommended prescribing practices for any hypnotic medication, it's usually short term, 2 weeks or less. Longer-term use often leads to tolerance, dependence, and withdrawal symptoms when the medication is stopped, which leads to an exacerbation of disordered sleep," he said. Nevertheless, he urged caution when interpreting the results. "I think the study warrants caution about long-term daily use of cannabinoids with respect to sleep," he said. "But we need more detailed evaluations, as the trial wasn't testing a defined product, specific dose, or dose regimen. "In addition, this was all done in the context of people with chronic pain and not treating disordered sleep or insomnia, but the study highlights the importance of recognizing that long-term chronic use of cannabis is not likely to fully resolve sleep problems." Sznitman agreed that the research is still in its very early stages. "We're still far from saying we have the evidence to support the use of medical cannabis for sleep," she said. "For in the end it was just a cross-sectional, observational study, so we cannot say anything about cause and effect. But if these results pan out, they could be far-reaching and exciting." The study was funded by the University of Haifa and Rambam Hospital in Israel, and the Evelyn Lipper Foundation. Sznitman and Vandrey have disclosed no relevant financial relationships. BMJ Supportive and Palliative Care. Published online January 20, 2020. Full text Source
