The most up-to-date studies on CBN for sleep

This article about CBN and its reported originally appeared in leading cannabis industry publication mg. 

--For the past four months, I have been traveling up and down the state of California talking to dispensary owners, budtenders and the public about cannabis and sleep. My company dreamt uses cannabis and other active ingredients to help people sleep and our onboarding for new stores involves me giving an in-depth, hour-long cannabis and sleep science presentation.To learn more about dreamt and our formulas, click here. One of the biggest myths I have consistently encountered is that CBN is a strong sedative or potent sleep inducer. While this information is widespread across the cannabis industry, it just isn’t fully supported by the data. In this article, I’m going to unpack the existing scientific research into CBN and its effects and attempt to clear up some of the scientific hearsay that unfortunately still exists in cannabis. 

What is CBN?

Cannabinol (CBN) is a cannabinoid produced from the degradation of tetrahydrocannabinol (THC). This decomposition occurs when THC is exposed to air, heat, light, or acids. CBN is a much less potent cannabinoid than THC, and some researchers report CBN as having similar effects as THC but between 4 and 10 times weaker. [1,2]One of the first studies comparing the effects of CBN and d9-THC noted that THC induced sleep and sedative effects in mice at safe doses, and CBN induced these effects as well but only at high doses that were also lethal. Sleep inducing effects were occurring, but only at doses that killed the mice. [3,4]  

Is CBN just weaker or does it have no effect at all?

In another study, conducted at the Kyushu University in Japan, researchers showed that the dose of CBN needed to produce sleep effects such as analgesia (pain relief) and stupor is 8.7 times higher than the dose of d9-THC required to do the same. This means you need almost nine times more CBN than you do THC to get the same sleep effect. [5]A study on cannabis and sleep with healthy volunteers in California used oral doses of 20mg d9-THC combined with a placebo or with 40mg of CBN. The combination of THC with CBN produced no detectable changes in the quality, intensity, or duration of effects of THC alone. In other words, the addition of an entire 40mg of CBN did nothing to improve sleep in the subjects. [6,7]  Looking more closely into the effects of CBN, additional studies proved that CBN is much less active as a sedative than THC and that CBN counteracts the sedative effects of THC at doses of 10 mg/kg. This means CBN can interfere with THC's ability to produce sedative effects while adding no sedative effect of its own. [8]  Studies in clinical pharmacology showed that even at high oral doses (1200mg) of CBN, the most common effects of d9-THC like analgesia (pain relief) and catalepsy (loss of motion and sensitivity) were not induced by CBN despite their similar structures. [9] 

Why is CBN almost inactive regardless of its similar molecular structure to THC?

Let's take a look at the mechanisms CBN uses to interact with your body. CBN has been shown to bind two times weaker (less able to bind) to CB1 receptors than d9-THC and three times stronger (more able to bind) than d9-THC to CB2 receptors. So CBN has a weak bind to CB1 receptors and a strong bond to CB2 receptors. [10]  The primary function of the CB1 receptors is to inhibit neurotransmitter release. This means that CB1 can regulate body restlessness and deep sleep. The effects of exogenous cannabinoids, such as d9-THC, depend on how many cannabinoid molecules bind to the receptor as well as the type of endocannabinoid binding to the receptor. CB1 cannabinoid receptors are important for the regulation of movement, sensory learning, analgesia (pain relief), anxiety, and appetite behaviors among other effects. [12,14]CB1 receptors are among the most abundant receptors in the brain. CB1 receptors are also found throughout the body, but in much lower levels. However, CB2 receptors are very abundant within the immune system. [11]Moreover, the cannabinoid system exerts a control function over the immune system. Activation of CB2 receptors enhances migration and adhesion of immune cells, decreases the release of proinflammatory cytokines, and induces apoptosis in dendritic cells. [13] This means that molecules that bind to CB2 receptors efficiently, like CBN, may improve immune system functions and improve the body's ability to attack infections and may have a big role on your immunity in general.  

The verdict on CBN

CBN is a product of degraded THC which produces similar but much weaker effects (and possibly no psychoactive effects at all). The effects are so weak that researchers still debate whether CBN is a weaker version of THC or if it has any sleep effects at all. A reason for this lack of activity could be the fact that CBN interacts very weakly with the CB1 receptor and therefore it fails to have significant effects on sleep, pain relief, or relaxation. However, studies have also shown that CBN interacts strongly with CB2 receptors, and this indicates a possible impact on the immune system. For the benefit of consumers, it’s important to provide accurate information with scientific data about CBN and other cannabinoids. Conditions like sleeplessness are very serious and can negatively impact many areas of a person’s physical and mental health. When companies keep the public informed with correct information, those looking to use cannabis to treat their sleep-related issues can have better and more informed options. Based on the scientific research, CBN is not a strong sleep-inducing cannabinoid and companies that say it is are misleading the consumers. 

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References

1. Huestis, M. A. (2005). Pharmacokinetics and Metabolism of the Plant Cannabinoids, Δ9-Tetrahydrocannabinol, Cannabidiol and Cannabinol. Cannabinoids, 657–690. https://pubmed.ncbi.nlm.nih.gov/16596792/

2. Trofin, Irenne & Dabija, Gabriel & Vaireanu, Danut-Ionel & Laurentiu, Filipescu. (2012). The Influence of Long-term Storage Conditions on the Stability of Cannabinoids derived from Cannabis Resin. Revista de Chimie. 63. 422-427. https://www.revistadechimie.ro/pdf/TROFIN%20I%204%2012.pdf

3. Loewe S. Studies on the pharmacology and acute toxicity of compounds with marihuana activity. J Pharmacol Exp Ther. 1946 Oct;88(2):154-61. http://jpet.aspetjournals.org/content/88/2/154.short

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5. Yamamoto, I., Watanabe, K., Kuzuoka, K., Narimatsu, S., & Yoshimura, H. (1987). The pharmacological activity of cannabinol and its major metabolite 11-hydroxycannabinol. Chemical & pharmaceutical bulletin. 35(5), 2144–2147. https://www.jstage.jst.go.jp/article/cpb1958/35/5/35_5_2144/_article/-char/ja/

6. Leo E. Hollister, M.D., and Hampton Gillespie,(1985). Interactions in man of delta-9-tetrahydrocannabinol. Palo Alto, Calif. Veterans Administration Hospital and Stanford University School of Medicine. https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1002/cpt197518180

7. Linares, I. M. P., Crippa, J. A. S., & Chagas, M. H. N. (2017). Beneficial Effects of Cannabis and Related Compounds on Sleep. Handbook of Cannabis and Related Pathologies, 877–882. https://www.sciencedirect.com/science/article/pii/B978012800756300106X

8. Domino, E. F. (1976). Effects of Δ9-Tetrahydrocannabinol and Cannabinol on Rat Brain Acetylcholine. Marihuana, 407–413. https://link.springer.com/chapter/10.1007/978-3-642-51624-5_33

9. Gong, H., Tashkin, D. P., Simmons, M. S., Calvarese, B., & Shapiro, B. J. (1984). Acute and subacute bronchial effects of oral cannabinoids. Clinical Pharmacology and Therapeutics, 35(1), 26–32. https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1038/clpt.1984.4

10. Showalter VM1, Compton DR, Martin BR, Abood ME.(1996) Evaluation of binding in a transfected cell line expressing a peripheral cannabinoid receptor (CB2): identification of cannabinoid receptor subtype selective ligands. J Pharmacol Exp Ther. 278(3), 989-999. http://www.demeter.org.es/pdf/investi_a/Evaluation_of_Binding_in_a_Transfected_Cell_Line_Expressing_a_Peripheral_Cannabinoid_Receptor_-CB2-_Identification_of_Cannabinoid_Receptor_Subtype_Selective_Ligands1.pdf

11. Howlett AC, Abood ME. (2007) CB1 and CB2 Receptor Pharmacology. Adv Pharmacol. 2017;80:169–206. https://www.sciencedirect.com/science/article/abs/pii/S1054358917300340

12. Mackie, K. et. al, (2006) Mechanisms of CB1 receptor signaling: endocannabinoid modulation of synaptic strength. Int J Obes 30, S19–S23. https://www.nature.com/articles/0803273

13. Albayram, O., Alferink, J., Pitsch, J., Piyanova, A., Neitzert, K., Poppensieker, K. Bilkei-Gorzo, A. (2011). Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging. Proceedings of the National Academy of Sciences, 108(27), 11256–11261. https://www.pnas.org/content/108/27/11256.short

14. Arévalo, C., de Miguel, R., & Hernández-Tristán, R. (2001). Cannabinoid effects on anxiety-related behaviours and hypothalamic neurotransmitters. Pharmacology Biochemistry and Behavior, 70(1), 123–131. https://www.sciencedirect.com/science/article/pii/S0091305701005780