Summary: Researchers have demonstrated that cannabinol (CBN), a compound found in aged cannabis, improves sleep in rats. The study revealed that CBN increased both NREM and REM sleep, leading to more total sleep time with effects comparable to zolpidem, a common sleep medication.
Unlike THC, CBN did not intoxicate the rats, and its metabolite was shown to have stronger effects on cannabinoid receptors, potentially enhancing sleep. These findings highlight CBN's potential as a non-intoxicating sleep aid, paving the way for further research in humans to treat sleep disorders like insomnia.
Research by scientists at the University of Sydney has identified a constituent in the cannabis plant that improves sleep.
Their report is the first to use objective measures to show the component, known as cannabinol (CBN), increases sleep in rats.
The study has been published in the leading journal Neuropsychopharmacology.
"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 lead author on the study Professor Jonathon Arnold, Director of Preclinical Research, at the Lambert Initiative for Cannabinoid Therapeutics and the Sydney Pharmacy School.
"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 is an end-product of the main intoxicating constituent of cannabis, delta9-tetrahydrocannabinol (THC).
THC in cannabis is slowly converted to CBN over time, which means older cannabis contains higher levels of this compound. It has been suggested that the consumption of older cannabis is associated with a sleepier cannabis "high".
In the United States, highly purified CBN products are being sold as sleep aids, but there has been little high-quality scientific evidence to support this application.
The research team at the Lambert Initiative for Cannabinoid Therapeutics tested the effects of purified CBN on sleep in rats. Using high-tech monitoring, the experiments provided insights into the rats' sleep patterns including the amount of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep.
NREM is deep sleep that promotes physical recovery and strengthens memories, while REM sleep is associated with dreaming and processing of emotions.
Professor Arnold said: "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."
NON-INTOXICATING
Unlike its parent molecule THC, CBN did not appear to intoxicate rats. THC intoxicates by activating CB1 cannabinoid receptors, which are present in the brain. The study showed that unlike THC, CBN only weakly activates these receptors. To their surprise, the researchers found that a metabolite of CBN had significant effects on cannabinoid CB1 receptors.
A metabolite is a chemical produced via the metabolism of a larger molecule in the body.
They also found that the 11-OH CBN metabolite had some impact on sleep architecture, which might contribute to the overall effects of CBN on sleep.
"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," Professor Arnold said.
"At this stage our results are confined to testing in rats. Further research is needed to see if this translates to humans."
FURTHER STUDY
In a parallel study, yet to be published, Professor Iain McGregor, Director of Clinical Research at the Lambert Initiative, initiated a placebo-controlled randomised human clinical trial in insomnia patients.
This was led by PhD student Isobel Lavender with leading sleep researcher Dr Camilla Hoyos from the Woolcock Institute of Medical Research.
The trial has now been completed with very promising results that were recently announced at the International Cannabinoid Research Society and Sleep DownUnder scientific conferences.
"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," Professor McGregor said.
Professor Arnold said: "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."
Author: Marcus Strom
Source: University of Sydney
Contact: Marcus Strom - University of Sydney
Image: The image is credited to Neuroscience News
Original Research: Open access.
"A sleepy cannabis constituent: cannabinol and its active metabolite influence sleep architecture in rats" by Jonathon Arnold et al. Neuropsychopharmacology
Abstract
A sleepy cannabis constituent: cannabinol and its active metabolite influence sleep architecture in rats
Medicinal cannabis is being used worldwide and there is increasing use of novel cannabis products in the community.
Cannabis contains the major cannabinoids, Δ-tetrahydrocannabinol (Δ-THC) and cannabidiol (CBD), but also an array of minor cannabinoids that have undergone much less pharmacological characterization.
Cannabinol (CBN) is a minor cannabinoid used in the community in "isolate' products and is claimed to have pro-sleep effects comparable to conventional sleep medications. However, no study has yet examined whether it impacts sleep architecture using objective sleep measures.
The effects of CBN on sleep in rats using polysomnography were therefore examined. 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 CB receptors with comparable potency and efficacy to Δ-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.