The Minor Cannabinoids: CBN

Timothy Byars

President, Chief Education Officer

Radicle Health

Cannabinol (CBN) is a phytocannabinoid produced in cannabis in very small amounts (less than 1% of CBN is typically detected in cannabis flowers). [1] Unlike most cannabinoids, CBN is not produced by an enzyme synthesis of CBGa or CBG. Rather, CBN is the product of degradation of THCa and decarboxylation of CBNa. For example, THCa can oxidize to CBNa, which decarboxylates to CBN. Or, THCa can decarboxylate into THC which can subsequently oxidize into CBN. Consequently, higher levels of CBN can be detected in old, oxidized cannabis flowers.

Some of the first chemists to explore the chemistry of cannabinoids were Thomas Wood, W. T. Spivey, and Thomas Easterfield, who began the work of identifying CBN from an alcohol extraction of cannabis. [2] Their research was confirmed by British chemist Robert Cahn, who confirmed and published the structure of CBN in 1940.

When ingested orally, CBN undergoes a metabolism that is similar to that of THC (CBN is metabolized by CYP2C9 and CYP3A4). [3] CBN, however, contains one additional aromatic ring and is metabolized less extensively and more slowly than THC. Liver metabolism converts CBN into 11-OH-CBN and this metabolite has greater binding affinity at CB1, which suggests that CBN might contribute to the pharmacological effects of cannabis. [4]

The average bioavailability of inhaled CBN dose is approximately 40%. [5] Again, the prevalence of CBN is cannabis flower is so low that it likely fails to produce much effect.

It’s commonly repeated on the internet that high levels of CBN likely contribute to the sedating effects in many cannabis chemovars. In fact, Steep Hill Labs in Berkeley had noted on their website that 5mg of CBN is as effective as a 10mg dose of diazepam, which is a benzodiazepine that causes sedation (that statement was uncited and has been subsequently removed from Steep Hill’s website). The data that is available to support claims that CBN is a sedative is sparse. The study that seems to be most commonly cited included only five male subjects, and these volunteers reported additional drowsiness only when CBN was administered in combination with THC. Researchers stated, “With combined drug treatment, volunteers reported feeling more drugged, drunk, dizzy, and drowsy than under the THC condition alone.” [6] It should be noted that these volunteers, in combination with CBN, were given THC doses between 12.5-25mg. The sedative effects can likely be attributed to THC.

Studies do suggest, however, that CBN might be useful to help treat pain. An old study in rats suggested that CBN might be 3 times stronger than aspirin. [7] Also, CBN might provide analgesia by impacting the manner in which nerves communicate pain signals.[8]

In animal models, CBN is potent TRPA1 agonist and desensitizer. [9] TRPA1 receptors mediate environmental irritants such as pain, cold, and itch [10] and TRPA1 antagonists are effective in blocking pain behaviors induced by inflammation. However, some TRPA1 agonists can produce analgesia, as well. After prolonged agonist exposure, some receptors become desensitized to the signaling. CBN might produce analgesic and anti-inflammatory effects by TRPA1 activation and desensitization.

Also, CBN is an agonist at the TRPV2 receptor, and activation of the TRPV2 receptor produces a neurotransmitter that is important to pain relief. CBN’s analgesic effects might be related to TRPV2 activation. [11]

Patients who require mild to moderate pain relief during the day might consider formulations with CBN if they want to avoid impairment. That said, while CBN is naturally occurring in cannabis, it is rare (and that means it is expensive to produce). It seems unlikely that product manufacturers will be able to effectively extract CBN directly from cannabis in sufficient amounts. And while some product manufacturers have attempted to speed up THC degradation (through oxidation or by continuous low heating), the future success of CBN products is likely tied to biosynthesis or genetic engineering (despite Ethan Russo’s objection that the astounding plasticity of the cannabis genome obviates the need for genetic engineering). [12]

References [1] Cannabinol (CBN). Journal of Cannabinoid Medicine. Accessed July 6, 2020. [2] Wood TB, Spivey WTN, Easterfield TH. III.-Cannabinol. Part I. Journal of the Chemical Society, Transactions.!divAbstract. Published January 1, 1899. Accessed January 15, 2020.

[3] Canada H. Government of Canada. For health care professionals: Cannabis and cannabinoids - Published October 12, 2018. Accessed July 7, 2020.

[4] Yamamoto I, Watanabe K, Kuzuoka K, Narimatsu S, Yoshimura H. The pharmacological activity of cannabinol and its major metabolite, 11-hydroxycannabinol. Chem Pharm Bull (Tokyo). 1987;35(5):2144-2147. doi:10.1248/cpb.35.2144

[5] Pertwee RG, Huestis M., Smith M. Cannabinoid Pharmacokinetics and Disposition in Alternative Matrices. In: Handbook of Cannabis: Edited by Roger G. Pertwee. 1st ed. Oxford University Press; 2014.

[6] Karniol IG, Shirakawa I, Takahashi RN, Knobel E, Musty RE. Effects of delta9-tetrahydrocannabinol and cannabinol in man. Pharmacology. 1975;13(6):502-512. doi:10.1159/000136944

[7] Sofia RD, Vassar HB, Knobloch LC. Comparative analgesic activity of various naturally occurring cannabinoids in mice and rats. Psychopharmacologia. 1975;40(4):285-295. doi:10.1007/BF00421466

[8] Zygmunt PM, Andersson DA, Högestätt ED. Δ9-Tetrahydrocannabinol and Cannabinol Activate Capsaicin-Sensitive Sensory Nerves via a CB1 and CB2 Cannabinoid Receptor-Independent Mechanism. Journal of Neuroscience. Published June 1, 2002. Accessed July 7, 2020.

[9] De Petrocellis L, Vellani V, Schiano-Moriello A, et al. Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8. J Pharmacol Exp Ther. 2008;325(3):1007-1015. doi:10.1124/jpet.107.134809

[10] TRPA1. Wikipedia. Published May 31, 2020. Accessed July 7, 2020.

[11] Qin N, Neeper MP, Liu Y, Hutchinson TL, Lubin ML, Flores CM. TRPV2 Is Activated by Cannabidiol and Mediates CGRP Release in Cultured Rat Dorsal Root Ganglion Neurons. Journal of Neuroscience. Published June 11, 2008. Accessed July 16, 2020.

[12] Russo EB. The Case for the Entourage Effect and Conventional Breeding of Clinical Cannabis: No "Strain," No Gain. Front Plant Sci. 2019;9:1969. Published 2019 Jan 9. doi:10.3389/fpls.2018.01969


Radicle Health does not sell or distribute medicine.