For the first time, an animal study has demonstrated that the cannabinoid cannabinol – CBN – increases sleep “with a comparable effect to the known sleep drug zolpidem”, according to researchers.
A number of studies have so far suggested that cannabis may contribute to improved sleep, however, minimal studies have examined the role of CBN in this context.
The cannabis plant contains hundreds of cannabinoids, and the cannabinoid CBN is created by the degradation of THC – the main psychoactive component of the cannabis plant. This process, however, takes time, with anecdotal reports suggesting that older cannabis causes a person to feel more sleepy than when consuming younger cannabis flowers.
In the U.S., CBN is often sold as a sleep aid, however, there is currently limited clinical evidence to back up these claims bar one study published in 1975.
CBN as a sleep aid
Researchers at the University of Sydney have now used objective measures to show that purified CBN increases sleep in rats in a study published in Neuropsychopharmacology.
The team, along with researchers at the Lambert Initiative for Cannabinoid Therapeutics, monitored sleep patterns in the animals such as non-rapid eye movement (NREM) and rapid eye movement (REM), finding that both were increased along with the total amount of sleep time.
The team used the sleep medication zolpidem as a positive control and comparison for the effects of CBN.
In a press statement, lead author Professor Jonathon Arnold, Director of Preclinical Research at the Lambert Initiative for Cannabinoid Therapeutics and the Sydney Pharmacy School, commented: “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.
“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.
“CBN was found to increase both NREM and REM sleep, leading to increased total sleep time, with a comparable effect to the known sleep drug zolpidem.”
Cannabinoids impact the body by binding to the CB1 or CB2 receptors of the Endocannabinoid System – which is found throughout the body including the brain – and THC’s intoxicating effects are thought to be created through its affinity to CB1 receptors.
Despite being created from the degradation of psychoactive THC cannabinoids, the research showed that CBN was non-intoxicating, having only a light affinity for CB1 receptors. However, the team discovered that a metabolite of CBN – 11-OH CBN – elicited strong effects on the CB1 receptors, impacting sleep architecture. The team suggest this may contribute to the overall effects of CBN on sleep.
The authors wrote: “CBN increased total sleep time, although there was evidence of biphasic effects with initial sleep suppression before a dramatic increase in sleep. CBN increased both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep.
“The magnitude of the effect of CBN on NREM was comparable to the sleep aid zolpidem, although, unlike CBN, zolpidem did not influence REM sleep. Following CBN dosing, 11-hydroxy-CBN, a primary metabolite of CBN surprisingly attained equivalently high brain concentrations to CBN. 11-hydroxy-CBN was active at cannabinoid CB1 receptors with comparable potency and efficacy to Δ9-THC, however, CBN had much lower activity.
“We then discovered that the metabolite 11-hydroxy-CBN also influenced sleep architecture, albeit with some subtle differences from CBN itself. This study shows CBN affects sleep using objective sleep measures and suggests an active metabolite may contribute to its hypnotic action.”
Arnold continued: “This provides the first evidence that CBN indeed increases sleep using objective sleep measures. It was a surprise that CBN metabolism in the body can yield a much greater effect on cannabinoid CB1 receptors than the parent molecule CBN, which has much more limited activity.
“At this stage our results are confined to testing in rats. Further research is needed to see if this translates to humans.”
Professor Iain McGregor, Director of Clinical Research at the Lambert Initiative, will soon be publishing a placebo-controlled clinical trial investigating CBN in insomnia patients.
Professor McGregor said in the statement: “Our research encourages further basic and clinical research on CBN as a new treatment strategy for sleep disorders, including insomnia. Our clinical study only administered CBN on a single occasion. A trial on a larger scale, that includes repeated dosing, is the logical next step.
“The team has now commenced a preclinical drug discovery program around CBN, as well as observing whether the pro-sleep effects of CBN can be further amplified by other molecules found in cannabis, or by conventional sleep aids, such as melatonin.”
