{"id":4165,"date":"2022-01-13T02:31:08","date_gmt":"2022-01-13T02:31:08","guid":{"rendered":"https:\/\/ultimatehealthreport.com\/the-curious-case-of-cbn-sleep\/"},"modified":"2022-01-13T02:31:08","modified_gmt":"2022-01-13T02:31:08","slug":"the-curious-case-of-cbn-sleep","status":"publish","type":"post","link":"https:\/\/ultimatehealthreport.com\/the-curious-case-of-cbn-sleep\/","title":{"rendered":"The Curious Case of CBN & Sleep"},"content":{"rendered":"


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Dr. Matt Elmes is a cannabinoid scientist and cannabis enthusiast. His PhD and postdoctoral work focused on the biochemistry of cannabinoids and he made impactful research contributions prior to transitioning to a non-academic career in the California cannabis industry.<\/em><\/p>\n

You hear it from your buddies and your budtenders alike. If you\u2019re looking to cannabis to better your sleep, then CBN<\/span> (cannabinol) is the cannabinoid for you!\u00a0\u00a0<\/p>\n

As both a cannabis scientist and a product formulator within the cannabis industry, I\u2019ve spent a considerable amount of time looking into the validity of these soporific claims. I find the minor cannabinoids to be fascinating and I always like to review what objective evidence we have substantiating a given effect that they may produce. Despite the overwhelming reputation CBN<\/span> has for improving sleep, I was surprised to find little real data in the published literature to actually support those claims.<\/p>\n

My sentiments were echoed in a recent review article, published in the journal Cannabis and Cannabinoid Research<\/em>, which lays out a scientific summary of nearly all the high-quality human research that has been published around CBN<\/span>.[1]\u00a0Allow me to reiterate the author\u2019s points and include some additional thoughts of my own with the hope that this will help readers form an educated opinion about CBN<\/span>.<\/p>\n

First things first: What is CBN<\/span>?<\/h2>\n
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Cannabinol was the very first cannabinoid to be isolated from the cannabis plant in the late 1800s. We have since learned that CBN<\/span> is a degradant product of THC<\/span>. This means that THC<\/span> will slowly transform into CBN<\/span> over time as cannabis ages. Older bud will generally contain higher CBN<\/span> levels at the expense of its THC<\/span> content. Light and heat will accelerate this conversion process, which is part of the reason it\u2019s typically recommended to store your cannabis in a cool, dark place.<\/p>\n

Laboratory studies show that CBN<\/span> interacts with our CB1<\/span> cannabinoid receptors about 10 times weaker than \u22069<\/sup>–THC<\/span>. Due to this CB1<\/span> affinity, CBN<\/span> probably<\/em> does have some weak psychoactive properties in humans (more on why I say \u201cprobably\u201d later in this article). CBN<\/span> binds to CB2<\/span> receptors with greater affinity compared to CB1<\/span>, so there is reason to believe that it could have some beneficial anti-inflammatory effects similar to THC<\/span>.<\/p>\n

Scientists are able to determine how tightly a compound attaches to a receptor. This is expressed as a Ki<\/sub> (pronounced \u201cKay-Eye\u201d) value. A lower number indicates stronger binding, which usually means higher potency for a drug. \u22069<\/sup>–THC<\/span>\u2019s binding affinity to the CB1<\/span> receptor = 21nM (nanomolar); this is roughly 10 times stronger than CBN<\/span>\u2019s binding affinity to CB1<\/span>, which = 211nM.[2,3]\u00a0CBN<\/span>\u2019s binding affinity for CB2<\/span> receptors is comparatively a bit stronger, with CB2<\/span> Ki = 126nM.[2]<\/p>\n

What Does the Research Say About CBN<\/span> &<\/span> ZZZ<\/span>\u2019s?<\/h2>\n

I don\u2019t want to put too much emphasis on all the preclinical CBN<\/span> research that\u2019s been done in animals because what occurs in a rodent all too frequently translates poorly to what happens in a human. The most important and relevant points from the animal data is that they generally agree that CBN<\/span> shows weak cannabimimetic activity (i.e., exhibits weak THC<\/span>-like effects in tests that have been developed to gauge CB1<\/span> receptor activation). However, there does not seem to be a strong consensus one way or the other on CBN<\/span>\u2019s effects on sleep. Some studies have found that CBN<\/span> increased barbiturate-induced sleep time (in a rodent model), but other studies seem to contradict those findings[3<\/span>,4]. CBN<\/span> did not appear to have any effect at all when given to monkeys.[5]<\/p>\n

In a similar vein, I\u2019ll only be discussing in-human CBN<\/span> research that is of high-quality. Not all research that\u2019s performed is of the same caliber. Various observational or survey-based studies have concluded efficacy of CBN<\/span> for sleep (such as here and here). However, these studies are frequently funded by industry players with vested interests and often do not have a sufficient quality of study design to put much stock in their results or conclusions. If the research is not peer-reviewed, relies solely on self-reported subjective measurements, and does not include any placebo control, then the \u2018results\u2019 don\u2019t carry much weight.<\/p>\n

Here\u2019s why: If you give almost any patient population a CBN<\/span> tincture and ask them to \u201ctake it daily and report how much it improved their sleep,\u201d the results will almost always come back positive, even if the effects are neutral in reality. If you instead gave those patients a cannabinoid-free tincture (aka a placebo) but lie and tell the participants that it contains CBN<\/span>, those results will almost always be positive too! Simply believing that something you take will exert some effect is often enough to manifest the realization of that effect.<\/p>\n

Most people tend to underestimate the strength of placebo effects, but clinical researchers have methods to determine whether an effect being measured truly outpaces that of a placebo. The human psyche is so powerful that it\u2019s difficult to overstate the importance of proper study design when assessing evidence.<\/p>\n

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The Next Ambien?<\/h2>\n

A literature search reveals there have been nine high-quality clinical research studies that probe the effects of CBN<\/span> on human subjects. All these studies underwent the peer-review process, were published in respected scientific journals, and at bare minimum were placebo-controlled or performed in an appropriately blinded fashion.<\/p>\n

It should be noted that most of these studies weren\u2019t focused on sleep per se, and I suppose it\u2019s possible that CBN<\/span> could aid in some facet of sleep in a manner that eluded these experimental designs. Still, given all the anecdotal talk about CBN<\/span> being \u201cthe next Ambien,\u201d you\u2019d think that there would at least be some drowsy effect noticed by any of the many participants that consumed massive doses of CBN<\/span>. Yet almost all these people could not even discern any effect at all when taking THC<\/span>-free preparations of CBN<\/span>!<\/p>\n

See the Appendix at the end of this article for a curated, chronological summary of what each of these nine studies entailed as well as their major conclusions. Of the nine high-quality clinical studies listed in the Appendix, only two might possibly indicate any signs of sleepy effects for CBN<\/span>. So these merit further discussion and critical analysis.<\/p>\n

Drugged, Drowsy, Drunk &<\/span> Dizzy<\/h2>\n

Performed in the early 1970s, a study (listed as #4 in the Appendix) conducted at Escola Paulista de Medicina in Brazil involved five male volunteers in their late twenties who were orally given a different cannabinoid or combination of cannabinoids \u2013 they took placebo; 50mgCBN; or 25mgTHC + either 0mg, 12.5mg, 25mg, or 50mg CBN<\/span>.<\/p>\n

The publication describes four of the five volunteers as being \u201cpsychiatric residents at Escola Paulista de Medicina.\u201d However, it is not clear to me whether this means these men were residents at the psychiatric hospital (as in, post-medical degree clinicians in-training). Or if they were residents at<\/u><\/em> the psychiatric hospital (as in, patients living in a psych ward?!). I think there\u2019s a decent chance that it\u2019s the latter.<\/p>\n

Recruiting psych ward inpatients for a study like this would probably be frowned upon by modern-day Ethics Review Boards, but this work was performed in Brazil nearly five decades ago when I suspect clinical research was performed a bit differently than it is today. If the study\u2019s participants were also resident patients, then that should raise some concerns around how representative this cohort is to the general population \u2013 and whether the results could have been confounded by the participants concurrently taking other psychotropic medications.<\/p>\n