History and biochemistry of Cannabinol

Cannabinol (CBN) is a non-enzymatic oxidation product of tetrahydrocannabinol (THC) and is found in large quantities in dried and aged cannabis material.1 The acid form of CBN is also found in large quantities in the cannabis plant but upon heating this acid is decarboxylated to CBN.1 CBN was first named in 1896 by Wood and colleagues in Cambridge in 1896 but the correct structure was elucidated only in 1940 by Adams et al.2 While only seven cannabinol-like derivatives were included in 2005,3 the list of CBN type-molecules has been updated to count 11 different phytocannabinoids, all of them presenting CBN’s aromatized ring.4–8 The concentration of CBN in Cannabis products depends on age and storage conditions.  It is a relatively minor constituent in fresh Cannabis because it is a product of THC oxidation. It is a weak CB1 and CB2 partial agonist, with approximately 10% of the activity of THC. It has potential therapeutic application in diseases in which cannabinoid receptors are up-regulated.9,10 Unlike other cannabinoids, CBN does not stem from cannabigerol (CBG), suggesting perhaps a different biosynthetic route for its formation. When CBN was discovered, it was believed to be an inactive component of cannabis but was instead found to have many therapeutic properties, mostly due to its activity on the cannabinoid receptors (CBs).11 It has a lower affinity for CB1 (Ki 211.2 nM) and CB2 (Ki 126.4 nM),12 and was judged inactive when tested alone in human volunteers, but produced greater sedation combined with THC.13  

Cannabinol’s receptor activity

As mentioned above, Cannabinol (CBN) like tetrahydrocannabinol (THC), acts at both CB1 and CB2 receptors but with higher affinity for CB2 than CB1 receptors.12,14,15 While it has shown agonistic activity toward CB1 receptors,16 there are instead conflicting reports about its activity at CB2 receptors. Cannabinol has shown indeed both direct as well as inverse agonistic properties depending on the concentration used in the tests.12,17 These discrepancies may not only be due to the differences in concentrations of cannabinol used between the studies, but it could also depend on the conformational state of the receptors in the tissues. Cannabinol also acts at targets outside of the endocannabinoid system. It is a potent agonist of TRPA1 cation channels, potently blocks TRPM8 cation channels, and also desensitizes TRPA1 cation channels to activation by the agonist allyl isothiocyanate.18  

Cannabinol’s biological activity

Like other phytocannabinoids, cannabinol (CBN), has shown relevant therapeutic properties toward a large amount of pharmaceutical targets. Like cannabigerol, CBN inhibits keratinocyte proliferation, independently of cannabinoid receptor effects.19 CBN demonstrated also anticonvulsant,20 anti-inflammatory and potent effects against Methicillin Resistant Staphylococcus Aureus (MRSA).21,22 Moreover, CBN is also a TRPV2 (high- threshold thermosensor) agonist of possible interest in treatment of burns.23 Furthermore, CBN stimulates the recruitment of quiescent mesenchymal stem cells in marrow, suggesting promotion of bone formation and inhibits breast cancer resistance protein, albeit at a very high concentration.24,25  

Therapeutic properties of Cannabinol

Due to the biological activities mentioned above, Cannabinol (CBN) has shown different therapeutic applications in the treatment of a diverse number of conditions:

Appetite Stimulant

Researchers found that CBN stimulated appetite in patients affected by anorexia, but also in patients whose loss of appetite is due to a primary condition like depression, cancer treatments, Alzheimer or AIDS.26


Methicillin Resistant Staphylococcus Aureus (MRSA) infections have become a very serious challenge for the researcher all over the world that are trying to find a promising alternative to those bacteria, which are antibiotic resistant. CBN, together with cannabigerol and cannabidiol was found to be effective against antibiotic resistant MRSA infections, suggesting a possible employment in the treatment of life threatening infections.22

Potential Medication for ALS Patients

In a study conducted in 2005, CBN was found to delay symptom onset in mice that were genetically designed to have a rodent version of Lou Gehrig’s Disease. Lou Gehrig’s disease is also known as Amyotrophic Lateral Sclerosis (ALS). These findings show that CBN may be effective at easing symptoms for patients with degenerative, motor neural diseases.27

Pain reliever

According to a study published in 2002, CBN has strong pain-relieving effects. Interestingly enough, CBN and THC were the only cannabinoids that fought pain through the release of endorphins and by relaxing tense blood vessels, suggesting a link between that and CB receptor activity.28


A research from 2003 found that CBN stopped allergy-related asthma in mice, perhaps because of its strong anti-inflammatory properties. The study suggests cannabinoids to achieve this by boosting the rodents’ immune systems and by easing the inflammation associated with an asthma attack.29


CBN has a centrally acting effect like tetrahydrocannabinol but much less potent. However studies have suggested that CBN may be the most sedative of all of the cannabinoids representing a promising tool for the treatment of anxiety and stress related conditions.30,31

Potential Medication for Glaucoma

Along with tetrahydrocannabinol, CBN was found to be successful at lowering the ocular pressure, which produces blindness in glaucoma patients, perhaps by relaxing the peripheral circulatory system and by decreasing the heart- rate of the subjects.32  

Synergies with natural terpenoids

Cannabinol activity has shown to be potentiated by the concurrent administration of natural terpenoids. For example, its antibacterial activity seems to synergize with Pinene, a terpenoid found in pine resin while its sedative properties are potentiated by the terpenoids Nerolidol and Myrcene. Nerolidol is a common terpenoid found not only in Cannabis but also in many other different plants like lemon balm, ginger, tea tree, lavender or jasmine flowers. Myrcene on the other hand, is a natural component of cannabis, bay, cardamom, parsley, hops and some types of thyme. Moreover CBN’s anticancer activity seems to be enhanced by the co-administration of limonene, a terpenoid found in Lemons.33  


  1. Harvey, D. J. Journal of Ethnopharmacology,. J. Ethnopharmacol. 28, 117–128 (1990).
  2. Adams, R., Baker, B. R. & Wearn, R. B. Structure of Cannabinol. III. Synthesis of Cannabinol, 1-Hydroxy-3-n-amyl-6,6,9-trimethyl-6-dibenzopyran. JACS 62, 2204–2207 (1940).
  3. ElSohly, M. A. & Slade, D. Chemical constituents of marijuana: The complex mixture of natural cannabinoids. Life Sci. 78, 539–548 (2005).
  4. Elsohly, M. A., Radwan, M. M., Gul, W., Chandra, S. & Galal, A. Phytocannabinoids. 103, (2017).
  5. Ahmed, S. A. et al. Cannabinoid Ester Constituents from High-Potency Cannabis sativa. J. Nat. Prod. 71, 536–542 (2008).
  6. Zulfiqar, F. et al. Cannabisol, a novel delta- 9-THC dimer possessing a unique methylene bridge, isolated from Cannabis sativa. Tetrahedron Lett. 53, 3560–3562 (2012).
  7. Radwan, M. M. et al. Isolation and Pharmacological Evaluation of Minor Cannabinoids from High-Potency Cannabis sativa. J. Nat. Prod. 78, 1271–1276 (2015).
  8. Ahmed, S. A. et al. Minor oxygenated cannabinoids from high potency Cannabis sativa L. Phytochemistry 117, 194–199 (2015).
  9. Pertwee, R. G. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br. J. Pharmacol. 153, 199–215 (2008).
  10. Izzo, A. A., Borrelli, F., Capasso, R., Di Marzo, V. & Mechoulam, R. Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol. Sci. 30, 515–527 (2009).
  11. Loewe, S. Marjiuana Activity of Cannabinol. Science (80-. ). 102, 615–616 (1945).
  12. Rhee, M.-H. et al. Cannabinol Derivatives : Binding to Cannabinoid Receptors and Inhibition of Adenylylcyclase. J . Med. Chem. 40, 3228–3233 (1997).
  13. Karniol, I. G., Shirakawa, I., Takahashi, R. N., Knobel, E. . & Musty, R. E. ·. Effects of delta-9-Tetrahydrocannabinol and Cannabinol in Man. Pharmacology 13, 502–512 (1975).
  14. Showalter, V. M., Compton, D. R., Martin, B. R. & Abood, M. E. 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, 989–999 (1996).
  15. Felder, C. C. et al. Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors. Mol. Pharmacol. 48, 443–450 (1995).
  16. Pertwee, R. Pharmacology of cannabinoid receptor ligands. Curr Med Chem 6, 635–637 (1999).
  17. MacLennan, S. J., Reynen, P. H., Kwan, J. & Bonhaus, D. W. Evidence for inverse agonism of SR141716A at human recombinant cannabinoid CB1 and CB2 receptors. Br. J. Pharmacol. 124, 619–22 (1998).
  18. De Petrocellis, L. et al. Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br. J. Pharmacol. 163, 1479–1494 (2011).
  19. Wilkinson, J. D. & Williamson, E. M. Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis. J. Dermatol. Sci. 45, 87–92 (2007).
  20. Siemens, A. J. & Turner, C. E. Marijuana research findings: 1980. NIDA Res. Monogr. Ser. 31 31, 167–198 (1980).
  21. Kargmanss, S., Prasitn, P. & Evans, J. F. Translocation of HL-60 Cell 5-Lipoxygenase. J. Biol. Chem. 266, 23745–23752 (1991).
  22. Appendino, G. et al. Antibacterial Cannabinoids from Cannabis sativa : A Structure - Activity Study. J. Nat. Prod. 71, 1427–1430 (2008).
  23. Qin, N. et al. TRPV2 is activated by cannabidiol and mediates CGRP release in cultured rat dorsal root ganglion neurons. J. Neurosci. 28, 6231–6238 (2008).
  24. Scutt, A. & Williamson, E. M. Cannabinoids stimulate fibroblastic colony formation by bone marrow cells indirectly via CB2 receptors. Calcif. Tissue Int. 80, 50–59 (2007).
  25. Lee, S. Y., Oh, S. M. & Chung, K. H. Estrogenic effects of marijuana smoke condensate and cannabinoid compounds. Toxicol. Appl. Pharmacol. 214, 270–278 (2006).
  26. Osei-Hyiaman, D. Endocannabinoid system in cancer cachexia. Curr. Opin. Clin. Nutr. Metab. Care 10, 443–448 (2007).
  27. Weydt, P. et al. Cannabinol delays symptom onset in SOD1 (G93A) transgenic mice without affecting survival. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 6, 182–184 (2005).
  28. Zygmunt, P. M., Andersson, D. A. & Hogestatt, E. D. Delta 9-Tetrahydrocannabinol and Cannabinol Activate Capsaicin-Sensitive Sensory Nerves via a CB1 and CB2 Cannabinoid Receptor-Independent Mechanism. J. Neurosci. 22, 4720–4727 (2002).
  29. Jan, T. R., Farraj, A. K., Harkema, J. R. & Kaminski, N. E. Attenuation of the ovalbumin-induced allergic airway response by cannabinoid treatment in A/J mice. Toxicol. Appl. Pharmacol. 188, 24–35 (2003).
  30. Kalant, H. Smoked marijuana as medicine: not much future. Clin Pharmacol Ther. 83, 517–519 (2008).
  31. Gregg, J. M., Campbell, R. L., Levin, K. J., Ghia, J. & Elliott, R. A. Cardiovascular effects of cannabinol during oral surgery. Anesth. Analg. 55, 203–213 (1976).
  32. ELSOHLY, HARLAND, E., MURPHY, J. C., WIRTH, P. & WALLER, C. W. Cannabinoids in Glaucoma : A PrimaryScreening Procedure. Cournal Clin. Pharmacol. 21, 472S–478S (1981).
  33. Russo, E. B. Taming THC: Potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br. J. Pharmacol. 163, 1344–1364 (2011).

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* Cannabidiol (CBD) is a natural constituent of hemp oil

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