New study provides first objective evidence of cannabinol’s potential to improve sleep

Cannabinol, a lesser-known compound found in the cannabis plant, might hold promise as a sleep aid, according to new research published in the journal Neuropsychopharmacology. 

Researchers found that cannabinol improved sleep quality in rats by increasing the duration of deep sleep and stabilizing overall sleep patterns.

Cannabinol, or CBN, is one of many naturally occurring chemicals in cannabis, though it is present in much smaller amounts than compounds like delta-9-tetrahydrocannabinol (THC) or cannabidiol (CBD). CBN forms as THC ages and degrades, leading to its nickname, the “sleepy cannabinoid.” Despite the growing popularity of CBN products marketed as sleep aids, scientific evidence supporting these claims has been limited.

The research team, led by Professor Jonathon Arnold, sought to test these claims rigorously. Their study aimed to objectively assess CBN’s effects on sleep by analyzing changes in sleep patterns and brain activity in rats.

“For decades, cannabis folklore has suggested that aged cannabis makes consumers sleepy via the build-up of CBN, however there was no convincing evidence for this,” said Arnold, the director of Preclinical Research at the Lambert Initiative for Cannabinoid Therapeutics and the University of Sydney Pharmacy School.

The researchers conducted a series of experiments to investigate the effects of cannabinol (CBN) on sleep patterns in rats. To ensure precise and objective measurement of sleep-related parameters, they used wireless telemetry probes surgically implanted in the animals.

These probes allowed continuous monitoring of brain activity, muscle tone, and other physiological indicators of sleep. The rats were housed in a controlled environment with a 12-hour light/dark cycle, and the experiments were conducted during their active (dark) phase to mimic conditions of reduced sleep pressure, similar to insomnia in humans.

The researchers administered different doses of purified CBN intraperitoneally to the rats, ranging from low to high concentrations. They also included a widely used sleep aid, zolpidem, as a comparison. During the experimental sessions, the rats’ sleep architecture was analyzed, focusing on non-rapid eye movement (NREM) sleep, rapid eye movement (REM) sleep, sleep onset latency, total sleep time, and wakefulness.

The team also performed pharmacokinetic analyses to measure CBN and its metabolites in the rats’ brains and bloodstreams, aiming to uncover the compound’s mechanism of action. Additionally, a repeated-dosing experiment was conducted to evaluate whether tolerance to CBN’s effects would develop over 15 days of daily administration.

The results showed that CBN significantly increased total sleep time in rats, particularly by enhancing NREM sleep. This effect, however, was delayed, appearing several hours after administration, in contrast to zolpidem, which acted almost immediately. The increase in NREM sleep was marked by longer sleep bouts and fewer interruptions, indicating that CBN stabilized sleep architecture.

However, CBN exhibited a biphasic effect on REM sleep, initially suppressing it before eventually increasing REM duration at lower doses. This delayed onset of CBN’s effects suggested a distinct mechanism compared to zolpidem, which primarily induces rapid sedation.

Pharmacokinetic analysis revealed that CBN’s primary metabolite, 11-hydroxy-cannabinol (11-OH-CBN), achieved high concentrations in the brain and exhibited significant activity at cannabinoid receptors, potentially contributing to the observed sleep effects. This metabolite was found to have stronger receptor activity than CBN itself, suggesting that CBN’s impact on sleep may be mediated by its conversion into active metabolites within the body.

In the repeated-dosing experiment, CBN continued to improve total sleep time initially, but some tolerance to its effects was observed over time. Despite this, certain benefits, such as longer uninterrupted NREM bouts, appeared to persist, indicating that the compound could maintain some of its sleep-stabilizing effects even with prolonged use.

“Our study provides the first objective evidence that CBN increases sleep, at least in rats, by modifying the architecture of sleep in a beneficial way,” Arnold said.

While these findings are promising, several limitations must be acknowledged. The researchers also noted that the doses of CBN tested were significantly higher than those typically found in consumer products or obtained through cannabis consumption. Further research is needed to determine whether lower doses are effective and safe for humans. The study also did not explore the potential withdrawal effects of discontinuing CBN after prolonged use, an important consideration given the association of cannabis withdrawal with sleep disturbances.

“This research provides the first objective evidence that CBN increases sleep and reveals that its active metabolite, 11-OH-CBN, might play a significant role,” said Arnold. “While our findings are confined to animal models for now, they open the door to more detailed studies in humans.”

The study, “A sleepy cannabis constituent: cannabinol and its active metabolite influence sleep architecture in rats,” was authored by Jonathon C. Arnold, Cassandra V. Occelli Hanbury-Brown, Lyndsey L. Anderson, Miguel A. Bedoya-Pérez, Michael Udoh, Laura A. Sharman, Joel S. Raymond, Peter T. Doohan, Adam Ametovski, and Iain S. McGregor.