Waking up to cannabis research: council funding more than doubles over the last year

Robert Laprairie, PhD, an assistant professor at the University of Saskatchewan, has funding for the next five years to explore the brains and behaviour of mice treated with cannabinoids to better understand how these drugs interact with body’s natural neurotransmitters to regulate wakefulness and appetite.

“We generally have a poor understanding of sleep, how it works and why it’s important,” Laprairie tells The GrowthOP. “Sleep disturbances and appetite problems are a feature of many diseases and conditions, ranging from cancer and chronic pain to insomnia and PTSD (post traumatic stress disorder),” notes the GlaxoSmithKline chair in drug discovery and development at the university’s College of Pharmacy and Nutrition.

The five-year working grant of $175,000 is part of the latest funding package through the Natural Sciences and Engineering Research Council (NSERC), which in late May announced more than a half-billion dollars in long-term grants to 588 Canadian researchers. Among these, $2.6 million has been allocated to cannabis-related research, up significantly from $1.1 million in 2017-2018 and $0.8 million in 2016-2017.

Valérie Levert-Gagnon, a public affairs officer for NSERC, says the funded cannabis-related research falls into three main categories: the impact of cannabis on human health or in veterinary medicine; the chemistry of cannabis, including its detection (for example, the development of a biosensor for drug testing); and improved growing techniques for the production of cannabis.

Research on cannabis and sleep offers some promising leads

A recent review of the scientific literature, published in Current Psychiatry Reports and conducted by U.S. Veterans Affairs and Palo Alto University, found that the available research on cannabis and sleep is “in its infancy and has yielded mixed results.” However, the preliminary studies have suggested some promising leads:

cannabidiol (CBD) may have therapeutic potential for the treatment of insomnia;

THC may decrease sleep latency, although it could impair sleep quality long-term;

synthetic cannabinoids, such as nabilone and dronabinol, may offer short-term benefits for sleep apnea;

CBD may hold promise for REM (rapid eye movement) sleep behaviour disorder and excessive daytime sleepiness; and

nabilone may reduce nightmares associated with post traumatic stress disorder (PTSD) and may improve sleep among patients with chronic pain.

A paper published earlier this year in the journal, Expert Opinion on Pharmacotherapy, looked at pharmaceutical alternatives to treat the insomnia that many sufferers of PTSD experience. The authors from StrongTower Behavioral Healthcare in Georgia and the University of New York at Buffalo concluded that “newer pharmaceutical agents with novel mechanisms of action” that act on orexin or endocannabinoid receptors may benefit PTSD patients who otherwise fail (or decline) cognitive behavioural therapy.

Both the cannabinoids and the human neurotransmitters orexin-1 and -2 exert “a critical involvement in appetite and sleep,” Laprairie explains. “Orexin stimulates both appetite and wakefulness, while cannabinoids make you hungry, but also tend to make you sleepy. The two systems interact, but we don’t know how they do so or the effects those interactions produce.”

THC and CBD also behave in different ways

The two major (and likely most well-known) cannabinoids—THC and CBD—also appear to behave “in very different fashions,” Laprairie says. THC is a partial agonist, a drug that binds to and activates cannabinoid receptors in the body, boosting the activity of the body’s own endocannabinoid system to affect mood, pain perception and appetite. On the other hand, CBD may bind with a wider array or receptors, including serotonin receptors that regulate mood and appetite.

A study published recently in the journal, Experimental and Clinical Psychopharmacology, suggested that cannabinoids could improve sleep quality, decrease sleep disturbances and decrease sleep onset latency. It noted, however, that additional research is needed on the differing effects of THC and CBD, as well as any long-term adverse effects of the medicinal use of cannabinoids.

The authors from the departments of medicine, psychiatry and behavioural neurosciences at McMaster University in Hamilton, Ont. said much of the work conducted to date has been hampered by small sample sizes, a lack of objective measurements and examining sleep only as a secondary outcome in the context of another illness.

Understanding how endocannabinoid and orexin systems work together

The NSERC grant will fund five years of preclinical research work by Laprairie and his team of graduate students using cell cultures and lab mice. “The short-term goal of the planned program is to better understand the different functions of the endocannabinoid and the orexin systems and how they work together,” he says. “The long-term goal is to help people.”

Researchers will report their results to NSERC on an annual basis, as well as share their findings at conferences and through scientific literature.

Laprairie first developed his scientific interest in cannabinoids nine years ago, while working on his master’s degree in pharmacology and neuroscience at Dalhousie University in Halifax. “We found that patients diagnosed with Huntington’s disease (HD) had lost approximately 50 percent of their cannabinoid [CB1] receptors, and this occurred before any of the other disease symptoms had appeared,” he says.

Work with cell models showed that increases in CB1 levels could reduce the severity of some of the molecular pathologies observed in HD. This early work sparked his keen, ongoing interest on how cannabinoids react with other receptors in the brain.

“There was some preliminary work published eight or nine years ago that began our understanding of the molecular biology of cannabinoids and orexin, but there’s been little since then,” says Laprairie. “There is no end of questions that need answering. The NSERC grant will help us build the body of research that shows how cannabinoids and orexin interact to affect sleep and appetite,” he says.

“Hopefully, five or six years down the road, this preclinical work will lay the groundwork for human studies,” says Laprairie. In the meantime, “people are going to use cannabis anyway. Our findings will help inform cannabis policies by expanding our understanding of the possible benefits and adverse effects,” he adds.

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