A randomized controlled trial found a CBD-terpene formulation increased restorative sleep in insomnia patients, providing novel insights into the effects of cannabidiol on sleep physiology. 

Interview by Alyx Arnett

Cannabidiol, or CBD for short—the non-intoxicating compound derived from the cannabis plant—has gained significant attention over the last several years for its potential therapeutic properties, including improving sleep, but little scientific evidence has existed to support such benefits. 

Paul J. Muchowski, PhD

A recent clinical trial has shed new light on the potential of CBD in addressing insomnia and improving sleep quality. The double-blind, placebo-controlled, randomized, crossover investigational study examined the effects of specific CBD-terpene ratios on sleep physiology by outfitting six insomnia patients who took the formulation once daily for 28 days with wrist-worn sleep-tracking devices. Terpenes are small molecules found in plants that have been studied for their effects on sleep in animals. 

Paul J. Muchowski, PhD, and co-investigators found the formulation significantly increased both the absolute time and relative percentage of time that people with insomnia spent in slow wave and rapid eye movement (REM) sleep without influencing other sleep metrics, including total sleep time.

“The findings are significant because these sleep stages are widely thought to be critical for the immune system, tissue regeneration, cognition, and memory. In contrast, many commonly prescribed sleep medications are sedatives/hypnotics that actually decrease slow wave sleep and REM sleep,” says Muchowski.

Muchowski, CEO and chief scientific officer of Defined Research Inc, a company created to commercialize the formulation, discussed the study with Sleep Review over email. 

[Editor’s Note: Read a preprint of the full study, A cannabidiol/terpene formulation that increases restorative sleep in insomniacs: A double-blind, placebo-controlled, randomized, crossover pilot study, online on medRxiv.]

What is the significance of your findings? 

Approximately 33% of the US population has tried CBD, and a high percentage of users list “improving sleep” as the top reason why they take CBD. Practicing physicians are increasingly asked by their patients regarding the merits of using CBD for insomnia and other ailments but lack any rigorous results to support recommending its use. The current study, if confirmed in larger clinical trials, suggests that select CBD-terpene ratios might offer a promising alternative to other sleep medications. 

How does your study stand apart from others? 

All clinical studies on the effects of CBD on sleep physiology to date have some fundamental limitations that prevent any strong scientific conclusions from being drawn from the data. First, these studies have typically used ill-defined hemp extracts that contain hundreds of other molecules, so it is hard to deduce if any sleep-promoting effects are due to CBD or these other unidentified molecules. In our study, we studied the effects of highly purified CBD (>99.9% purity) and terpenes (>98% purity), so we know that the sleep-promoting benefits we observed are not due to other molecules. 

Second, sleep studies to date have relied solely on subjective readouts. In other words, after each treatment period, study participants would provide subjective feedback on whether the treatment helped them. Because we know that there is a big placebo effect in these types of studies, we believe studies that collect objective data are far more compelling. In our study, the primary outcome measure was the percentage of time study participants spent in deep and REM sleep as measured by a wrist-worn sleep-tracking device.

Finally, most other studies that have examined the effects of CBD on sleep are confounded by the fact that the CBD treatment also may contain high levels of THC (sometimes 10 milligrams or more). We know that high levels of THC are intoxicating, which essentially leads to an unblinding of the data. In other words, if you are high from the THC, but not high on the placebo, then it is impossible to have a true placebo control group. When you couple this with only using subjective readouts, it is impossible to draw any strong scientific conclusions from these types of studies.  

Are there any unanswered questions that arose from this study?

As with most interesting research, it often raises more questions than answers. We are extremely interested in determining the precise mechanism for how the CBD-terpenes formula increases deep and REM sleep. If you look closely at the individual data from our study, for many participants, the CBD-terpenes formula seemed to normalize the deep and REM sleep time such that it was similar night after night, in contrast to when they were on the placebo control, and the data varied widely. 

These results might suggest that the CBD-terpenes ratio we tested might somehow be regulating the machinery that controls the cycling of sleep stages. We will also be launching a clinical trial later in 2023 to address if the CBD-terpenes formula can increase deep and REM sleep in adolescents with autism and whether this might influence other features of autism.     

How might your findings be translated into practical recommendations for those seeking natural sleep aids?

Our research findings indicate that a highly defined mixture of CBD and terpenes can significantly increase the absolute and relative percentage of time people with insomnia spend in deep and REM sleep. We believe these results are exciting, and initial feedback from sleep physicians has been highly encouraging. 

Broadly speaking, our recommendation is that consumers seeking benefit from natural sleep aids need to look carefully at what they are taking, ask if the product was made in a good manufacturing practice-rated facility, and determine if there is any research that actually backs the medical claims that each product is making. Moreover, many CBD sleep aids that are currently sold contain high levels of THC. We would highly recommend avoiding such products.

Photo caption: Defined Research’s CBD-terpene formulation