Marijuana/cannabis has been touted for roughly 50 different medical conditions. Arguably, one of the most useful indications would be insomnia, which plagues roughly 70 million Americans. Although there are sleep aids sold OTC and by prescription, people have different reactions to them. Even Ambien, the most widely used prescription insomnia medication, either does not work or causes bad reactions in some people.
Some people become sleepy from weed, which begs the question (at least for chemists): Is there a specific cannabis chemical(s) that is responsible for sleepiness, and could it be isolated, synthesized (if necessary), and used as a novel sleep aid with a superior to profile than existing drugs. This is not a trivial job; there are 500 known chemicals in cannabis, 125 of them being cannabinoids.
CBN – an oxidized analog of delta-9-THC
One of these cannabinoids is called cannabinol (CBN), a minor cannabinoid, that has been the subject of anecdotal reports that it has sedative effects. This led Jonathon C. Arnold and colleagues from the University of Sydney to study (for the first time) the impact of CBN in rats. The group's findings, which are reported In a recent paper in the journal Nature Neuropsychopharmacology, examine the changes in the sleep architecture in rats given the drug.
Figure 1. The chemical structures of THC, CBN, and 11-Hydroxy-CBN. CBN is an oxidation product of delta-9 in which the cyclohexene ring (red circle) metabolite of delta-9-THC has been oxidized to a benzene ring (green circle). Further metabolism of the methyl group converts it to a hydroxymethyl group (blue circle) giving 11-Hydroxy-CBN (11-OH-CBN). This conversion takes place in the liver; it is not found in cannabis.
Sleep properties of CBN
The authors used a method called polysomnography (basically a sleep study) to measure the impact of CBN on several parameters of sleep in rats. Some are rather interesting.
- While CBN increased the total sleep time in the rats it also took longer to fall asleep. This is called a biphasic effect.
- CBN enhanced both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, leading to deeper sleep.
- The increase in NREM sleep was similar to that of Ambien (zolpidem), but Ambien did not affect REM sleep. (2)
11-Hydroxy-CBN - A surprising culprit shows up
As if the chemistry of cannabinoids isn't complicated enough, the Sydney group made an unexpected discovery. Analysis of the brains of rats that had been dosed with CBN showed CBN (duh) and its oxidation product 11-hydroxy-CBN – surprisingly present in equal amounts. Is this compound also sleep-inducing? Sort of.
Sleep properties of 11-Hydroxy-CBN
- 11-OH-CBN also increased total sleep time but also prolonged wakefulness in the rats. This biphasic effect was considerably less than that of CBN itself.
- 11-OH enhanced both NREM and REM sleep, but NREM periods were shorter leading to a fragmented sleep.
- 11-OH had a less robust effect than Ambien in increasing sleep time with a delayed onset and a weaker overall effect.
Chemistry complaint time!
It should also be noted that even though 11-OH-CBN is found in surprisingly high amounts in rat brains this will never be a source of the drugs. Instead, it must be synthesized. I looked up the published synthesis, which is no walk in the park, even for experienced organic chemists.
What does all this mean?
Although CBN is being touted as a potential sleep aid its utility probably depends upon individual metabolism, since its metabolite 11-OH-CBN is probably a weaker sleep aid. People who are rapid metabolizers of CBN would probably derive less benefit from the drug.
This study points out some of the complexities of cannabis-derived drugs. It's not as simple as taking a pill.
Perhaps the biggest issue is the biphasic effect. Both drugs kept the rats awake longer but also made them sleep more in total. These are not the properties anyone would want in a sleep aid – lying awake for hours and then not being able to get up in the morning. I'll take the Ambien.
NOTE:
(1) Both forms of sleep are critical for health. NREM supports physical restoration and REM focuses on emotional and cognitive functions.
Josh Bloom
Director of Chemical and Pharmaceutical Science
Dr. Josh Bloom, the Director of Chemical and Pharmaceutical Science, comes from the world of drug discovery, where he did research for more than 20 years. He holds a Ph.D. in chemistry.
