CBN AND SLEEP: AN INTRIGUING CASE | Bona Voluntate

 It comes from both your friends and the bartenders. CBN Isolate Bulk (cannabinol) is the cannabinoid to use if you want to use cannabis to improve your sleep!

I've spent a significant amount of time investigating the veracity of these sedative claims as a cannabis scientist and product formulator in the cannabis industry. Minor cannabinoids fascinate me, and I am always interested in reviewing the objective evidence we have for a given effect that they may produce. Despite CBN's widespread reputation for improving sleep, I was surprised to find little real data to back up those claims in the published literature.

My thoughts were echoed in a recent publication in the journal Cannabis and Cannabinoid Research, which provides a scientific summary of nearly all high-quality human CBN research.

[1] Allow me to reiterate the author's points and add some of my own in the hope that this will assist readers in making an informed decision about Bulk CBN Isolate.

FIRST AND MOST IMPORTANTLY, WHAT IS CBN?

Cannabinol was the first cannabinoid isolated from the cannabis plant in the late 1800s. CBN is now known to be a byproduct of THC degradation. This means that THC will gradually transform into CBN as cannabis ages. Older bud will typically have higher levels of Bulk CBN Isolate at the expense of higher levels of THC. Because light and heat speed up the conversion process, it's best to keep your cannabis in a cool, dark place.

According to laboratory studies, CBN interacts with our CB1 cannabinoid receptors about ten times weaker than 9-THC. Because of this CB1 affinity, CBN most likely has some minor psychoactive properties in humans (more on why I say "probably" later in this article). Because CBN binds to CB2 receptors more strongly than CB1, there is reason to believe it may have anti-inflammatory properties similar to THC.

Researchers can measure how tightly a compound binds to a receptor. This is expressed in Ki (pronounced "Kay-Eye"). A lower number indicates stronger binding, which usually indicates the potency of a drug. The binding affinity of 9-THC to the CB1 receptor is 21nM (nanomolar), which is roughly ten times greater than the binding affinity of CBN Isolate Bulk to CB1. [2,3] Bulk With a CB2 Ki = 126nM, CBN Isolate has a slightly higher affinity for CB2 receptors. [2]

WHAT DO STUDIES TELL US ABOUT CBN?

I don't want to overestimate the significance of preclinical CBN research in animals because what happens in a rodent does not always translate well to what happens in a human. The most important and relevant animal data findings are that CBN Isolate Bulk has low cannabimimetic activity (i.e., exhibits weak THC-like effects in tests that have been developed to gauge CB1 receptor activation). However, there does not appear to be a strong agreement on the effects of CBN on sleep. Some studies have found that CBN Isolate Bulk increases barbiturate-induced sleep time (in a rodent model), but other studies appear to contradict those findings[3,4]. CBN did not appear to have any effect when administered to monkeys. [5]

Similarly, I'll only talk about high-quality in-human CBN Isolate Bulk research. Not all research is done to the same high standard. Several observational or survey-based studies have concluded that Bulk CBN Isolate helps with sleep (such as here and here). These studies, however, are frequently funded by industry players with vested interests and frequently lack sufficient study design quality to place much weight in their findings or conclusions. The results are meaningless if the study is not peer-reviewed, relies solely on self-reported subjective measurements, and lacks a placebo control.

Here's why: If you give a tincture of Bulk CBN Isolate to almost any patient population and ask them to "take it daily and report how much it improved their sleep," the results will almost always be positive, even if the effects are actually neutral. If you gave those patients a cannabinoid-free tincture (aka a placebo) but told them it contained Bulk CBN Isolate, the results would almost always be positive! Simply believing that something you take will have an effect is often enough to bring about that effect.

Most people underestimate the power of placebo effects, but clinical researchers have methods for determining whether a measured effect truly outperforms a placebo effect. Because the human psyche is so powerful, proper study design is critical when evaluating evidence.

ARE YOU THE FUTURE AMBIEN?

A review of the literature turns up nine high-quality clinical research studies on the effects of CBN on human subjects. All of these studies were peer-reviewed, published in reputable scientific journals, and were either placebo-controlled or blinded appropriately.

It should be noted that the majority of these studies were not specifically focused on sleep, and it is possible that CBN Isolate Wholesale could help with some aspect of sleep that these experimental designs missed. Nonetheless, given all of the anecdotal evidence that CBN is "the next Ambien," you'd think that any of the many participants who ingested massive doses of CBN would experience some drowsiness. Despite this, almost all of these people had no effect when given THC-free CBN Isolate Wholesale preparations!

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. Only two of the nine high-quality clinical studies listed in the Appendix indicate that CBN Isolate Wholesale may cause sleepiness. As a result, these merit further discussion and scrutiny.

DRUGGED OUT, DREAMY, DRUNK, AND DIZZY

In the early 1970s, five male volunteers in their late twenties participated in a study at Escola Paulista de Medicina in Brazil, where they were orally given a different cannabinoid or combination of cannabinoids - they took placebo; 50mgCBN; or 25mgTHC + either 0mg, 12.5mg, 25mg, or 50mg CBN.

Four of the five volunteers, according to the publication, are "psychiatric residents at Escola Paulista de Medicina." However, I'm not sure if this means these men were psychiatric patients (as in, post-medical degree clinicians in-training). Or if they were patients in a psychiatric hospital (as in, patients living in a psych ward?!). The latter, I believe, is more likely.

Recruiting psych ward inpatients for a study like this would almost certainly be frowned upon by today's Ethics Review Boards, but this work was done nearly five decades ago in Brazil, when clinical research was probably done a little differently than it is today. If the participants in the study were also resident patients, this should raise some concerns about how representative this cohort is of the general population - and whether the results were influenced by the participants taking other psychotropic medications concurrently.

Regardless, participants were asked to rate 66 subjective pairs, such as "happy-sad," "drowsy-alert," "hot-cold," and "drunk-sober," and indicate which they felt and how strongly they felt it on a scale of 1 to 4. Taking 50mg of CBN alone was found to be no different than taking a placebo in terms of subjective effects or heart rate. Only four of the sixty-six subjective effects studied showed significant differences, including "drowsiness," and only when CBN Isolate Wholesale was combined with THC. [10] The four statistically significant effects were "drugged, drowsy, drunk, and dizzy."

To say the least, the significant differences discovered appear uninspiring. For those who are interested, the findings of the published study are shown in Figure 1. The THC+CBN doses that were significant appear haphazard, with little resemblance to a dose-response relationship. Sometimes the lowest and highest Bulk CBN Isolate doses had an effect but not the middle dose, and other times only the lowest dose did. These findings are puzzling from the standpoint of pharmacology.

My main issue with this study is that, with 66 items on four different CBN Isolate Wholesale groups (for a total of 264 comparisons), some of them are bound to be statistically significant by chance. This is known as a 'Type I Error' in statistics, and I believe it is at work here. Basically, the more things you test independently against each other, the more likely you are to have some false positives in your dataset. Furthermore, the extremely small sample size (only five people took part in the entire study!) raises the possibility that these Wholesale CBN Isolate findings on 'drugged, drowsy, drunk, and dizzy' are nothing more than statistical noise.

CANNABINOID-BASED MEDICINE ADVANCES AND INSOMNIA

Then, despite the fact that the experimental design, conduct, and analysis were all performed independently by the University of Western Australia's Center for Sleep Science, we look at a recent Phase 1a/2b clinical trial (study #9 in the Appendix) conducted by the pharmaceutical start-up Therapeutics. ZTL-101 is a cannabis extract in sunflower oil that contains three purified cannabinoids (THC+CBN+CBD). It is intended for sublingual administration. It is intended to have a THC:CBN:CBD ratio of 20:2:1.

For two weeks, 24 chronic insomniacs were given either a placebo or 0.5mL ZTL-101 (=10mgTHC+1mgCBN+0.5mgCBD) each night one hour before their desired bedtime. After the fourth night, participants had the option of increasing their dose to 1mL (=20mgTHC+2mgCBN+1mgCBD).

The study employed a cross-over design, which meant that after two weeks, all patients who had previously received placebo were switched to ZTL-101, and vice versa. Participation in both the placebo and drug groups at various points during the study helps to control for inter-person variance and greatly improves the strength of a study like this.

The researchers used three methods to assess sleep quality: self-reported sleep diaries, actigraphy (wearing a watch that tracks nighttime movement), and a single night of polysomnography measurements (a comprehensive analysis of brain waves, heart rate, blood O2 levels, leg, and eye movement).

There were no statistically significant differences between the placebo and ZTL-101 groups after one night of polysomnography measurements. Sleep diaries and actigraphy measurements, on the other hand, revealed that ZTL-101 significantly improved insomnia severity scores, time to fall asleep, nighttime wakefulness, total sleep time, and patients reported feeling more rested when they awoke.

Overall, the findings appear convincing enough to conclude that ZTL-101 decreased the severity of insomnia and improved sleep quality in these patients. This is amazing! It adds to the body of evidence supporting the efficacy of cannabinoid-based sleep therapies. THC, rather than the relatively minor amounts of Wholesale CBN Isolate or CBD, appears to be responsible for these effects. Numerous other studies have found that THC-only preparations provide self-reported sleep benefits (albeit with some seeming contradictions in the research around this).

There is no way to know until additional comparative studies are conducted because this study only tested CBN in conjunction with THC and CBD. If more than 1000mgCBN/day had no discernible sleepy effects, it's doubtful that the 1-2mgCBN used in this study did much.

THC CHANGES THE ARCHITECTURE OF SLEEP

The endocannabinoid system (ECS) is intricately linked to our sleep and dreams in ways we are still learning about. We know that marijuana users have fewer dreams (or at least, do not remember their dreams very well). They frequently have difficulty falling asleep when they stop using cannabis, and when they do fall asleep, they have very vivid dreams. The ECS is known to help regulate circadian sleep-wake cycles, and these findings point to cannabis's ability to change our sleep architecture.

In high-quality sleep studies, CBD was not found to alter sleep architecture, and I am not aware of any reported dream rebound effects after discontinuing chronic CBD use.

[7] The primary cause of cannabis's sleep-related effects appears to be THC. THC's effect on sleep is unclear, but it is thought to reduce sleep onset latency (the time it takes to fall asleep), increase slow wave sleep, and shorten the REM stages of sleep [6].

Consuming CBN isolate may cause a weak stimulation of your ECS, which may aid in some aspects of sleep. However, from a mechanical standpoint, this should be no different than taking a very low dose of THC. Furthermore, because high-CBN cannabis will almost always contain some contaminating THC, almost no one has ever tried Wholesale CBN Isolate. Because THC out-competes CBN for CB1 receptor binding if CBN works by tickling the CB1 receptor, there won't be much real synergy between THC and CBN. In other words, combining CBN with THC (as most CBN products do) should not make it sleepier.

So, if CBN does not induce sleep, where did this myth originate? Historically, older cannabis has been associated with sedative effects. When it became widely known that Wholesale CBN Isolate is the major degradation product of THC, people began attributing these effects to the relatively higher CBN content found in old flower.

TERPENES AND TERPENODIES

While it is true that older cannabis has more sedative effects, I doubt this is due to CBN. THC is not the only compound that changes over time in cannabis, which is a complex mixture of thousands of chemical constituents. Plant phytochemicals degrade or change in a variety of ways over time. Cannabinoids that are acidic decarboxylate into neutral cannabinoids or oxidise into a variety of minor cannabinoids. Terpenes can absorb oxygen atoms from the air and convert them into terpenoids with sedative properties (such as linalool).

Terpene and terpenoid are terms that are frequently used interchangeably; however, terpenes are exclusively hydrocarbons (that is, they only contain carbons and hydrogens), whereas terpenoids contain additional functional groups, usually an incorporated oxygen atom.

Furthermore, because monoterpenes ('light terps'; such as limonene) are relatively more volatile and thus evaporate away from plant matter more readily, aged cannabis may have a higher ratio of sesquiterpenes (aka 'heavy terps'; such as beta-caryophyllene). Terpene profiles in aged cannabis may change, resulting in more sedating or sleepy effects.

Terpene pharmacology research in humans is deplorably lacking, but many terpenes have been shown in animal models to produce adequate analgesic and sedative effects.

[8,9] Interestingly, many of these effects can be reversed by administering naloxone (aka Narcan) to the rodent, implying that some terpenes act via our endogenous opioid system.

Terpenes, by themselves, are not opioids because they do not activate opioid receptors. Some terpenes, on the other hand, may boost our bodies' natural opioid production and/or act as positive allosteric modulators of opioid receptors. A positive allosteric modulator interacts with receptors to make them more receptive to other compounds' activation (known as "agonists" by scientists).

CBN CONCLUSIONS

The cannabis market has recently seen a significant increase in CBN, and manufacturers have taken advantage of the opportunity to widely publicise its anecdotal reputation as a sleep aid. According to previous research, this minor cannabinoid does not appear to have any special sleepy properties. Although there is a lot of anecdotal evidence supporting CBN as a sleep aid, I am sceptical of these widely held beliefs.

Clinical research on Wholesale CBN Isolate is still insufficient to develop a thorough understanding of its pharmacology. While it's possible that CBN hasn't yet discovered mechanisms of action that could aid in sleep, I haven't seen any solid evidence to support this theory. CBN's alleged sleep-aid property is most likely an unfounded rumour that can be attributed to two factors. The first is that in the past, people noticed that older cannabis had more sedative effects and incorrectly associated them with degraded THC. The second point to mention is that a placebo can be an extremely effective drug!