Everything You Need to Know About Cannabinol (CBN)

Aug 17, 2023 | Written by Matthew Lees, PhD | Reviewed by Scott Sherr, MD and Marion Hall

someone holding a cannabis plant

Cannabis has historically been used for a wide range of purposes, such as industrial, ornamental, and pharmaceutical applications [1,2]. In the modern world, marijuana use is permitted in some jurisdictions to help address the nausea caused by chemotherapy, anorexia in patients with AIDS, and to manage pain. It is also used recreationally to treat anxiety, insomnia, to stimulate an appetite, to simply get “high,” and much more.

The biological activity of the cannabis plant (Cannabis sativa) is a consequence of its phytocannabinoid content [3]. Early research focused almost exclusively on perhaps the most well-known phytocannabinoid, tetrahydrocannabinol (THC), before subsequently expanding to cannabidiol, cannabigerol, and cannabichromene. These are known as the “big four” major cannabinoids [4].

As research on the narcotic properties of THC progressed, the endocannabinoid system was discovered [5], an important signaling network that has roles in neural function and as a major homeostatic balancing system.

Aside from the major cannabinoids, cannabis also possesses over 150 “minor cannabinoids” that include, most notably, cannabinol (CBN) [4,6,7]. Although CBN is much less studied than THC, there may be promise for CBN in treating certain ailments and conditions.

In this article, we will discuss what CBN is, where it comes from, how it works within the body, and other important information related to sleep, potential risks, and contraindications as well.

What is Cannabinol?

Several phytocannabinoids have been identified in plants and fungi, yet CBN only occurs in the cannabis plant. It is a degradation product of THC, and is present in cannabis leaves at a concentration between 0.1 and 1.6% (w/w of dry weight). This concentration increases as the plant ages and varies depending on the storage environment [8].

CBN is remarkable within the cannabinoid family not only due to its exceptional stability across time but also its direct relationship with THC [9]. The stability of CBN has been demonstrated from the recovery of plant material (seeds) dating back to 750 BC, found in a tomb in the Xinjiang-Uighur autonomous region in China [2].

The term “cannabinol” arose at the end of the 19th century to describe the red oil, a thick resin that contains both CBN and other major phytocannabinoid compounds [10].

How Does Cannabinol Work?

Similar to THC, CBN behaves as a partial agonist towards the cannabinoid receptor type 1 (CB1) receptors but has less relative activity (it is ten times less potent than THC at the CB1 receptor) [11]. The CB1 receptor is distributed in brain areas associated with motor control, emotions, motivated behavior, and energy balance. Peripherally, it is located in adipose tissue, the pancreas, skeletal muscle, the liver, gastrointestinal tract, heart, and reproductive system [12-14]. By contrast, the cannabinoid receptor type 2 (CB2) receptor is mainly located in the immune system.

Cellular studies have shown that CBN protects nerve cells from oxytosis/ferroptosis, a process linked with the mitochondrial dysfunction associated with the aging brain in a manner independent of cannabinoid receptors [15]. CBN specifically targets mitochondria and preserves key elements of their function such as redox regulation, calcium uptake, membrane potential, bioenergetics, biogenesis, and fusion/fission dynamics [16]. CBN is being studied as a potential neurotherapeutic in this regard [16].

In rodents, CBN was shown to increase feeding via cannabinoid receptor type 1. This is notable as CBN is considered to be non-psychotropic, whereas the more commonly used THC has psychotropic properties [17].

Cannabinol and Sleep

In recent years, cannabis products have been marketed as being uniquely sleep-promoting due to their CBN content [18]. Running counter to this is a systematic review of evidence published in 2021 that found no high-quality human studies exploring the impact of CBN on sleep. For example, studies that might have used validated sleep questionnaires and/or polysomnography.

To date, only old studies (from the 1970s and 1980s) with small sample sizes offer what is rather tenuous support for the sleep-promoting effects of CBN-containing products. High quality randomized clinical studies are needed to substantiate manufacturer claims in this regard.

There is only one study to date that showed the sedative effects of CBN and THC in combination on five male participants, and these effects were found to be stronger than THC alone [9].

Potential Benefits of Cannabinol

Human clinical trials of CBN are scarce, but preclinical work has shown that the peripheral application of CBN (1 mg/ml) could offer analgesic potential for chronic muscle pain disorders such as temporomandibular disorders and fibromyalgia, without any central side effects [19].

Elsewhere, CBN might offer potential in treating high-risk neuroblastoma, a highly aggressive pediatric tumor, that presently lacks any curative treatment for most patients. CBN has been shown to have a suppressive role in neuroblastoma tumor generation, partly through its inhibition of the protein kinase B pathway and by upregulating miR-34a [20]. miR-34a is a candidate neuroblastoma tumor suppressor gene [21], which likely highlights the promising therapeutic applications of CBN in humans in years to come.

CBN can also have an effect on neurotransmitters, particularly monoamine neurotransmitters (dopamine, serotonin, and norepinephrine) as well as GABA, by blocking the synaptosomal uptake of them [22,23].

There is some evidence in rodent trials that CBN can reduce the inflammation caused by arthritis, however these findings are yet to be fully substantiated in humans [24].

Risks and Contraindications of Cannabinol

Despite the fact that there is a limited amount of published research on CBN in humans, there is some evidence that CBN could increase the risk of getting a positive drug test. One study showed that CBN can have a “boosting” effect on THC concentrations, effectively increasing the appearance of THC and biasing its level higher [25].

Other preclinical and human research has shown that CBN potentiates the action of THC in reducing the concentrations of luteinizing hormone secretion and dysregulating reproductive hormones in general [26,27]. The luteinizing hormone is important for the regulation of the ovulatory cycle and the hormonal processes necessary to support pregnancy.

Summary

This article has discussed the origins of CBN, our understanding of how it works in the body, as well as the risks and contraindications that might present themselves upon usage. If you’d like to learn more about the cannabis plant and its other cannabinoids, or perhaps the effects of cannabinoids on the GABA system, you can check out our previously linked blog articles.

If you’re interested in trying out cannabinol for better sleep, check out Tro Zzz, our buccal troche for sleep that contains cannabinol and cannabidiol, both of which modulate the endocannabinoid system and the GABA system indirectly.

 

References

[1]          M.R. de Souza, A.T. Henriques, R.P. Limberger, Medical cannabis regulation: an overview of models around the world with emphasis on the Brazilian scenario, J Cannabis Res. 4 (2022) 33. https://doi.org/10.1186/s42238-022-00142-z.

[2]          C. Maioli, D. Mattoteia, H.I.M. Amin, A. Minassi, D. Caprioglio, Cannabinol: History, Syntheses, and Biological Profile of the Greatest “Minor” Cannabinoid, Plants (Basel). 11 (2022) 2896. https://doi.org/10.3390/plants11212896.

[3]          G.N. Nguyen, E.N. Jordan, O. Kayser, Synthetic Strategies for Rare Cannabinoids Derived from Cannabis sativa, J Nat Prod. 85 (2022) 1555–1568. https://doi.org/10.1021/acs.jnatprod.2c00155.

[4]          Z. Atakan, Cannabis, a complex plant: different compounds and different effects on individuals, Ther Adv Psychopharmacol. 2 (2012) 241–254. https://doi.org/10.1177/2045125312457586.

[5]          V. Di Marzo, New approaches and challenges to targeting the endocannabinoid system, Nat Rev Drug Discov. 17 (2018) 623–639. https://doi.org/10.1038/nrd.2018.115.

[6]          W. Jaidee, I. Siridechakorn, S. Nessopa, V. Wisuitiprot, N. Chaiwangrach, K. Ingkaninan, N. Waranuch, Kinetics of CBD, Δ9-THC Degradation and Cannabinol Formation in Cannabis Resin at Various Temperature and pH Conditions, Cannabis Cannabinoid Res. 7 (2022) 537–547. https://doi.org/10.1089/can.2021.0004.

[7]          A.J. Hiltunen, T.U. Järbe, K. Wängdahl, Cannabinol and cannabidiol in combination: temperature, open-field activity, and vocalization, Pharmacol Biochem Behav. 30 (1988) 675–678. https://doi.org/10.1016/0091-3057(88)90082-2.

[8]          I. Chousidis, T. Chatzimitakos, D. Leonardos, M.D. Filiou, C.D. Stalikas, I.D. Leonardos, Cannabinol in the spotlight: Toxicometabolomic study and behavioral analysis of zebrafish embryos exposed to the unknown cannabinoid, Chemosphere. 252 (2020) 126417. https://doi.org/10.1016/j.chemosphere.2020.126417.

[9]          I.G. Karniol, I. Shirakawa, R.N. Takahashi, E. Knobel, R.E. Musty, Effects of delta9-tetrahydrocannabinol and cannabinol in man, Pharmacology. 13 (1975) 502–512. https://doi.org/10.1159/000136944.

[10]        T.B. Wood, W.T.N. Spivey, T.H. Easterfield, XL.—Charas. The resin of Indian hemp., J. Chem. Soc., Trans. 69 (1896) 539–546. https://doi.org/10.1039/CT8966900539.

[11]        M.A. Huestis, Pharmacokinetics and metabolism of the plant cannabinoids, delta9-tetrahydrocannabinol, cannabidiol and cannabinol, Handb Exp Pharmacol. (2005) 657–690. https://doi.org/10.1007/3-540-26573-2_23.

[12]        Z. Mouslech, V. Valla, Endocannabinoid system: An overview of its potential in current medical practice, Neuro Endocrinol Lett. 30 (2009) 153–179.

[13]        D. Jesudason, G. Wittert, Endocannabinoid system in food intake and metabolic regulation, Curr Opin Lipidol. 19 (2008) 344–348. https://doi.org/10.1097/MOL.0b013e328304b62b.

[14]        F. Rodríguez de Fonseca, I. Del Arco, F.J. Bermudez-Silva, A. Bilbao, A. Cippitelli, M. Navarro, The endocannabinoid system: physiology and pharmacology, Alcohol Alcohol. 40 (2005) 2–14. https://doi.org/10.1093/alcalc/agh110.

[15]        J. Lewerenz, G. Ates, A. Methner, M. Conrad, P. Maher, Oxytosis/Ferroptosis-(Re-) Emerging Roles for Oxidative Stress-Dependent Non-apoptotic Cell Death in Diseases of the Central Nervous System, Front Neurosci. 12 (2018) 214. https://doi.org/10.3389/fnins.2018.00214.

[16]        Z. Liang, D. Soriano-Castell, D. Kepchia, B.M. Duggan, A. Currais, D. Schubert, P. Maher, Cannabinol inhibits oxytosis/ferroptosis by directly targeting mitochondria independently of cannabinoid receptors, Free Radic Biol Med. 180 (2022) 33–51. https://doi.org/10.1016/j.freeradbiomed.2022.01.001.

[17]        J.A. Farrimond, B.J. Whalley, C.M. Williams, Cannabinol and cannabidiol exert opposing effects on rat feeding patterns, Psychopharmacology (Berl). 223 (2012) 117–129. https://doi.org/10.1007/s00213-012-2697-x.

[18]        J. Corroon, Cannabinol and Sleep: Separating Fact from Fiction, Cannabis Cannabinoid Res. 6 (2021) 366–371. https://doi.org/10.1089/can.2021.0006.

[19]        H. Wong, B.E. Cairns, Cannabidiol, cannabinol and their combinations act as peripheral analgesics in a rat model of myofascial pain, Arch Oral Biol. 104 (2019) 33–39. https://doi.org/10.1016/j.archoralbio.2019.05.028.

[20]        B. Wang, D. Li, V. Cherkasova, M. Gerasymchuk, A. Narendran, I. Kovalchuk, O. Kovalchuk, Cannabinol Inhibits Cellular Proliferation, Invasion, and Angiogenesis of Neuroblastoma via Novel miR-34a/tRiMetF31/PFKFB3 Axis, Cancers (Basel). 14 (2022) 1908. https://doi.org/10.3390/cancers14081908.

[21]        K.A. Cole, E.F. Attiyeh, Y.P. Mosse, M.J. Laquaglia, S.J. Diskin, G.M. Brodeur, J.M. Maris, A functional screen identifies miR-34a as a candidate neuroblastoma tumor suppressor gene, Mol Cancer Res. 6 (2008) 735–742. https://doi.org/10.1158/1541-7786.MCR-07-2102.

[22]        J. Wallach, Medicinal Cannabis: an overview for health-care providers, in: Remington, Elsevier, 2021: pp. 75–101. https://doi.org/10.1016/B978-0-12-820007-0.00005-2.

[23]        R.G. Pertwee, M.G. Cascio, Known Pharmacological Actions of Delta-9-Tetrahydrocannabinol and of Four Other Chemical Constituents of Cannabis that Activate Cannabinoid Receptors, in: R. Pertwee (Ed.), Handbook of Cannabis, Oxford University Press, 2014: pp. 115–136. https://doi.org/10.1093/acprof:oso/9780199662685.003.0006.

[24]        R.B. Zurier, S.H. Burstein, Cannabinoids, inflammation, and fibrosis, FASEB j. 30 (2016) 3682–3689. https://doi.org/10.1096/fj.201600646R.

[25]        G.M. Kroner, K.L. Johnson-Davis, K. Doyle, G.A. McMillin, Cannabinol (CBN) Cross-Reacts with Two Urine Immunoassays Designed to Detect Tetrahydrocannabinol (THC) Metabolite, J Appl Lab Med. 5 (2020) 569–574. https://doi.org/10.1093/jalm/jfaa020.

[26]        L.L. Murphy, R.W. Steger, M.S. Smith, A. Bartke, Effects of delta-9-tetrahydrocannabinol, cannabinol and cannabidiol, alone and in combinations, on luteinizing hormone and prolactin release and on hypothalamic neurotransmitters in the male rat, Neuroendocrinology. 52 (1990) 316–321. https://doi.org/10.1159/000125604.

[27]        P.P. Vescovi, M. Pedrazzoni, M. Michelini, L. Maninetti, F. Bernardelli, M. Passeri, Chronic effects of marihuana smoking on luteinizing hormone, follicle-stimulating hormone and prolactin levels in human males, Drug Alcohol Depend. 30 (1992) 59–63. https://doi.org/10.1016/0376-8716(92)90036-c.

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