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Clinical Challenges: Cannabis Gains Ground as Sleep Aid

— But efficacy of CBD, THC products to treat sleep disorders remains largely untested

MedpageToday

Cannabis products are having a moment -- according to one recent market projection, the U.S. cannabidiol (CBD) market could up from $238 million in 2018.

In addition, sales of CBD and legal tetrahydrocannabinol (THC) products combined are projected to reach $45 billion by 2024.

Celebrities are on board with CBD, with Kim Kardashian West having a , while Whoopi Goldberg, Willie Nelson, and, of course, Snoop Dogg of CBD or THC products.

CBD and THC in the form of commercial oils, creams, lotions, and edibles are marketed for a wide range of ailments, from anxiety to chronic pain to post-traumatic stress disorder (PTSD).

They are also widely touted for improving sleep and for treating sleep disorders like obstructive sleep apnea (OSA), although their efficacy remains largely untested.

In a , the American Academy of Sleep Medicine (AASM) concluded that, "based on the available evidence" medical cannabis should not be used for the treatment of OSA, and the statement advised regulators and policymakers not to include OSA in their list of indicated conditions for medical cannabis programs.

OSA Tx 'Overreach'

The AASM position statement was published after became the first and, so far, only state in the U.S. to approve medical cannabis for the treatment of OSA.

"Further research is needed to better understand the mechanistic actions of medical cannabis and its synthetic extracts, the long-term role of these synthetic extracts on OSA treatment, and the harms and benefits," the AASM position statement read.

Bhanu Prakash Kolla, MD, of the Mayo Clinic Center for Sleep Medicine in Rochester, Minnesota, told ľֱ that the Minnesota Health Department based its OSA approval on minimal scientific evidence: two animal studies, a proof of concept study involving just 17 adults, and a phase II study of the THC cannabinoid drug dronabinol (Marinol, Syndros) that enrolled 73 adults.

Dronabinol is approved by the FDA for the treatment of nausea symptoms in patients on chemotherapy and anorexia associated with HIV and AIDS.

"I believe it is a significant overreach to say that these studies show that [THC products] are useful in the treatment of OSA," he told ľֱ.

Kolla said increased daytime sleepiness may be a potential downside to THC as OSA treatment because daytime sleepiness is already a common symptom of the sleep disorder.

In a , the combined use of THC and CBD was found to increase daytime sleepiness in healthy young adults.

Cannabis use is also associated with increased calorie intake, and this could also represent a potential pitfall for OSA patients, Kolla said.

"We know that THC increases appetite and that sleep apnea gets worse with weight gain," he said.

"From a sleep apnea standpoint, the evidence for the efficacy of THC products is very tenuous. There are the potential downsides, and there are much better treatment options. So go with treatments that are evidence-based, " Kolla added.

"As for CBD products, there just isn't much evidence one way or another, but people may be spending a lot of money on something that may not work," he pointed out. "These are substances that are not regulated by the FDA. They are sold as supplements, and it is hard to tell what you are really getting."

Available Data

A compared the effect of 300 mg of CBD to placebo on sleep in healthy adults.

The study showed little evidence of an impact on several variables of sleep, including total sleep time, sleep efficiency, and stages of sleep, reported Ila Linares, PhD, of the University of Sao Paulo, and colleagues. They concluded that CBD did not appear to change normal sleep architecture.

"Different from anxiolytic and antidepressant drugs such as benzodiazepines and selective serotonin reuptake inhibitors, acute administration of an anxiolytic dose of CBD did not seem to interfere with the sleep cycle of healthy volunteers," they wrote.

A by Scott Shannon, MD, of the University of Colorado Denver, and colleagues was conducted at a large psychiatric outpatient clinic, and examined the impact of CBD at doses of 25 mg/day to 175 mg/day on anxiety and sleep problems when given as an adjunct to usual treatment.

The study included 72 adult patients complaining of anxiety, sleep problems, or both. Anxiety scores decreased within the first month of the study, and remained decreased during the 3-month study duration. Sleep scores improved within the first month in 48 patients (66.7%), but they fluctuated during the course of the study.

More research has been done on THC and sleep, but the findings are far from conclusive.

A evaluating the use of cannabis products for sleep concluded that while many studies showed CBD and THC to have a positive impact on sleep, study limitations included small sample sizes, the evaluation of sleep as a secondary study outcome, and a the lack of validated measures of sleep quality and quantity.

Nirushi Kuhathasan of McMaster University in Montreal, and colleagues, identified 18 clinical trials evaluating sleep and THC derivatives (dronabinol and nabilone [Cesamet]). Sleep was a secondary outcome in most of the trials, but the majority showed subjective evidence of improvements in sleep. Seven of the 18 studies reported subjective decreases in sleep disturbances and nightmare frequency.

The researchers concluded that while the available evidence suggests a benefit for THC and THC-derivatives, alone or in combination with CBD, in terms of improved sleep, additional studies to confirm this are "urgently needed."

"Although 'sleep' remains one of the main reasons people seek medicinal marijuana, to date there is a surprising lack of placebo-controlled trials examining the use of cannabinoids specifically for treatment of sleep disorders," they wrote. "In addition, many available studies used nonstandardized, non-validated questionnaires and the use of validated objective and subjective sleep measures is strongly encouraged in future research."

'Minimal Impact'

Timothy Roehrs, PhD, directs the Sleep Disorders Research Center at Henry Ford Health System in Detroit. His own, unpublished research suggests that controlled delivery of THC may increase nighttime wakefulness among regular marijuana users.

When Roehrs and colleagues studied the among patients with insomnia, they found that while alcohol improved sleep during the first few nights, greater alcohol doses were needed to maintain the effect over the course of the week-long study.

"Our study showed an almost immediate risk for dose escalation among people with insomnia using alcohol as a sleep aid, and I suspect the same thing may be true in people using cannabis products for insomnia," he told ľֱ. "My guess is that these products have minimal impact on sleep. And we don't yet know to what extent tolerance develops."

Disclosures

The study by Linares' group was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico of Brazil (CNPq). Linares and co-authors disclosed CNPq fellowships. STI-Pharm provided CBD for the study group.

Kolla disclosed no relevant relationships with industry. Co-authors disclosed relationships with ResMed, AASM, UpToDate, Axovant, the NIH, the Michael J. Fox Foundation, and Wiley Blackwell.

CV Sciences provided cannabidiol products for the study by Shannon's group. Shannon disclosed support from the Multidisciplinary Association for Psychedelic Studies, and serving as principal investigator for a phase III study of MDMA-assisted psychotherapy for severe posttraumatic stress disorder.

Kuhathasan and a co-authors disclosed support from the Michael G. DeGroote Centre for Medicinal Cannabis Research Master's Studentship.