CBN is a cannabinoid with weak psycho-active properties and some therapeutic potential related to cancer, pain, ALS and eating disorders.

Chemical Name: 
Cannabinol
Wikipedia entry: 
Synthetic Pathways: 

CBN is synthesized from CBNA through decarboxylation.

Literature Discussion: 

Receptors and molecular mechanisms

CBD binds to CB1 and CB2 (Petitet, Jeantaud, Reibaud, Imperato, & Dubroeucq, 1998)

CBN modulates TRPA-1, TRPV-2, TRPV-3 and TRPV-4 (De Petrocellis et al., 2012; De Petrocellis et al., 2011; Qin et al., 2008)

CBN binds also to TRPA1 and TRPM8 (Morales, Hurst, & Reggio, 2017)

CBN has anti-bacterial properties against methicillin-resistant Staphylococcus aureus (MRSA) (Appendino et al., 2008)

CBN inhibits CYP1 enzymes (Yamaori, Kushihara, Yamamoto, & Watanabe, 2010)

CBN reduces plasma-luteinizing hormone (LH) and T levels and median eminence NE turnover (Steger, Murphy, Bartke, & Smith, 1990)

CBN potentiates the THC-induced suppression of luteinizing hormone (LH) secretion in rats (Murphy, Steger, Smith, & Bartke, 1990)

CBN, THC and CBD inhibit the binding of thyrotropin releasing hormone (TRH) to the amygdala (Bhargava & Gulati, 1988)

ALS

CBN delays the onset of myotrophic lateral sclerosis (ALS) in a transgenic mouse model of ALS (Weydt et al., 2005)

cancer

Some cannabinoids, including CBN, inhibit ABCC1 and ABCG2 proteins, which have a relevant role for the treatment of cancer (Holland, Lau, Allen, & Arnold, 2007; Michelle L. Holland, Allen, & Arnold, 2008)

CBN, as well as THC, modulates T cells activity, which have an important role in the immune system by controlling inflammatory processes (Herring & Kaminski, 1999; Herring, Koh, & Kaminski, 1998; Jan, Rao, & Kaminski, 2002; Rao & Kaminski, 2006). This modulation could have therapeutic potential in, for example, allergic airway diseases (Jan, Farraj, Harkema, & Kaminski, 2003). These two cannabinoids affect cell proliferation pathways which are related to the immunosuppressive and anti-tumorigenic properties of cannabinoids (Faubert & Kaminski, 2000; Faubert Kaplan & Kaminski, 2003; Herring, Faubert Kaplan, & Kaminski, 2001; Upham et al., 2003)

CBN and THC inhibits Lewis lung adenocarcinoma growth in animals in a dose-dependent manner (Munson, Harris, Friedman, Dewey, & Carchman, 1975)

epilepsy

In a mouse model of epilepsy (Maximal Electro Shock), the following cannabinoids were found to be anti-convulsive (ED50)(Devinsky et al., 2014): CBD 120 mg/kg Δ9THC 100 mg/kg 11-OH-Δ9THC 14 mg/kg 8β-OH-Δ9THC 100 mg/kg Δ9THCA 200-400 mg/kg 11-OH-Δ9-THC 80 mg/kg CBN 230 mg/kg Δ9α/β-OH-hexahydro-CBN 100 mg/kg Apart from that the doses reported above are incredibly high, it does provide a proof of principle that many cannabinoids exert anti-convulsive effects

Hypoxic-Ischemic Encephalopaty

CBN causes hypothermia in doses from 10 to 30 mg/kg (Hiltunen, Järbe, & Wängdahl, 1988).  

obesity

CBN stimulates appetite and increases feeding through CB1 receptor activation (Farrimond, Whalley, & Williams, 2012)

pain

CBN produces anti-nociceptive and analgesic properties with low or none psychoactive effects and it can increase THC anti-nociceptive and psychoactive effects (Booker, Naidu, Razdan, Mahadevan, & Lichtman, 2009; Karniol, Shirakawa, Takahashi, Knobel, & Musty, 1975; Sanders, Jackson, & Starmer, 1979; Sofia, Vassar, & Knobloch, 1975). CBN and CBD inhibit catalepsy induced by THC (Formukong, Evans, & Evans, 1988)

Psoriasis

THC, CBD, CBN and CBG were found to inhibit human keratinocyte (skin cell) proliferation suggesting therapeutic potential in Psoriasis (Wilkinson and Williamson, 2007).

References

Appendino, G., Gibbons, S., Giana, A., Pagani, A., Grassi, G., Stavri, M., … Rahman, M. M. (2008). Antibacterial cannabinoids from Cannabis sativa: a structure-activity study. Journal of Natural Products, 71(8), 1427-1430. https://doi.org/10.1021/np8002673

Bhargava, H. N., & Gulati, A. (1988). Selective inhibition of the binding of 3H-(3-MeHis2) thyrotropin releasing hormone to rat amygdala membranes by some naturally occurring cannabinoids. Peptides, 9(4), 771-775.

Booker, L., Naidu, P. S., Razdan, R. K., Mahadevan, A., & Lichtman, A. H. (2009). Evaluation of prevalent phytocannabinoids in the acetic acid model of visceral nociception. Drug and Alcohol Dependence, 105(1-2), 42-47. https://doi.org/10.1016/j.drugalcdep.2009.06.009

De Petrocellis, L., Orlando, P., Moriello, A. S., Aviello, G., Stott, C., Izzo, A. A., & Di Marzo, V. (2012). cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation. Acta Physiologica (Oxford, England), 204(2), 255-266. https://doi.org/10.1111/j.1748-1716.2011.02338.x

De Petrocellis, Luciano, Ligresti, A., Moriello, A. S., Allarà, M., Bisogno, T., Petrosino, S., … Di Marzo, V. (2011). Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. British Journal of Pharmacology, 163(7), 1479-1494. https://doi.org/10.1111/j.1476-5381.2010.01166.x

Devinsky, O., Cilio, M.R., Cross, H., Fernandez-Ruiz, J., French, J., Hill, C., Katz, R., Di Marzo, V., Jutras-Aswad, D., Notcutt, W.G., et al. (2014). Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia 55, 791–802.

Farrimond, J. A., Whalley, B. J., & Williams, C. M. (2012). Cannabinol and cannabidiol exert opposing effects on rat feeding patterns. Psychopharmacology, 223(1), 117-129. https://doi.org/10.1007/s00213-012-2697-x

Faubert, B. L., & Kaminski, N. E. (2000). AP-1 activity is negatively regulated by cannabinol through inhibition of its protein components, c-fos and c-jun. Journal of Leukocyte Biology, 67(2), 259-266.

Faubert Kaplan, B. L., & Kaminski, N. E. (2003). cannabinoids inhibit the activation of ERK MAPK in PMA/Io-stimulated mouse splenocytes. International Immunopharmacology, 3(10-11), 1503-1510. https://doi.org/10.1016/S1567-5769(03)00163-2

Formukong, E. A., Evans, A. T., & Evans, F. J. (1988). Inhibition of the cataleptic effect of tetrahydrocannabinol by other constituents of Cannabis sativa L. The Journal of Pharmacy and Pharmacology, 40(2), 132-134.

Herring, A. C., Faubert Kaplan, B. L., & Kaminski, N. E. (2001). Modulation of CREB and NF-kappaB signal transduction by cannabinol in activated thymocytes. Cellular Signalling, 13(4), 241-250.

Herring, A. C., & Kaminski, N. E. (1999). Cannabinol-mediated inhibition of nuclear factor-kappaB, cAMP response element-binding protein, and interleukin-2 secretion by activated thymocytes. The Journal of Pharmacology and Experimental Therapeutics, 291(3), 1156-1163.

Herring, A. C., Koh, W. S., & Kaminski, N. E. (1998). Inhibition of the cyclic AMP signaling cascade and nuclear factor binding to CRE and kappaB elements by cannabinol, a minimally CNS-active cannabinoid. Biochemical Pharmacology, 55(7), 1013-1023.

Hiltunen, A. J., Järbe, T. U., & Wängdahl, K. (1988). Cannabinol and cannabidiol in combination: temperature, open-field activity, and vocalization. Pharmacology, Biochemistry, and Behavior, 30(3), 675-678.

Holland, M L, Lau, D. T. T., Allen, J. D., & Arnold, J. C. (2007). The multidrug transporter ABCG2 (BCRP) is inhibited by plant-derived cannabinoids. British Journal of Pharmacology, 152(5), 815-824. https://doi.org/10.1038/sj.bjp.0707467

Holland, Michelle L., Allen, J. D., & Arnold, J. C. (2008). Interaction of plant cannabinoids with the multidrug transporter ABCC1 (MRP1). European Journal of Pharmacology, 591(1-3), 128-131. https://doi.org/10.1016/j.ejphar.2008.06.079

Jan, T.-R., Farraj, A. K., Harkema, J. R., & Kaminski, N. E. (2003). Attenuation of the ovalbumin-induced allergic airway response by cannabinoid treatment in A/J mice. Toxicology and Applied Pharmacology, 188(1), 24-35.

Jan, T.-R., Rao, G. K., & Kaminski, N. E. (2002). Cannabinol enhancement of interleukin-2 (IL-2) expression by T cells is associated with an increase in IL-2 distal nuclear factor of activated T cell activity. Molecular Pharmacology, 61(2), 446-454.

Karniol, I. G., Shirakawa, I., Takahashi, R. N., Knobel, E., & Musty, R. E. (1975). Effects of Δ9-Tetrahydrocannabinol and Cannabinol in Man. Pharmacology, 13(6), 502-512. https://doi.org/10.1159/000136944

Morales, P., Hurst, D. P., & Reggio, P. H. (2017). Molecular Targets of the Phytocannabinoids-A Complex Picture. Progress in the chemistry of organic natural products, 103, 103-131. https://doi.org/10.1007/978-3-319-45541-9_4

Munson, A. E., Harris, L. S., Friedman, M. A., Dewey, W. L., & Carchman, R. A. (1975). Antineoplastic activity of cannabinoids. Journal of the National cancer Institute, 55(3), 597-602.

Murphy, L. L., Steger, R. W., Smith, M. S., & Bartke, A. (1990). 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(4), 316-321.

Petitet, F., Jeantaud, B., Reibaud, M., Imperato, A., & Dubroeucq, M.-C. (1998). Complex pharmacology of natural cannabivoids: Evidence for partial agonist activity of Δ9-tetrahydrocannabinol and antagonist activity of cannabidiol on rat brain cannabinoid receptors. Life Sciences, 63(1), PL1-PL6. https://doi.org/10.1016/S0024-3205(98)00238-0

Qin, N., Neeper, M. P., Liu, Y., Hutchinson, T. L., Lubin, M. L., & Flores, C. M. (2008). TRPV2 Is Activated by Cannabidiol and Mediates CGRP Release in Cultured Rat Dorsal Root Ganglion Neurons. The Journal of Neuroscience, 28(24), 6231-6238. https://doi.org/10.1523/JNEUROSCI.0504-08.2008

Rao, G. K., & Kaminski, N. E. (2006). cannabinoid-mediated elevation of intracellular calcium: a structure-activity relationship. The Journal of Pharmacology and Experimental Therapeutics, 317(2), 820-829. https://doi.org/10.1124/jpet.105.100503

Sanders, J., Jackson, D. M., & Starmer, G. A. (1979). Interactions among the cannabinoids in the antagonism of the abdominal constriction response in the mouse. Psychopharmacology, 61(3), 281-285.

Sofia, R. D., Vassar, H. B., & Knobloch, L. C. (1975). Comparative analgesic activity of various naturally occurring cannabinoids in mice and rats. Psychopharmacologia, 40(4), 285-295.

Steger, R. W., Murphy, L. L., Bartke, A., & Smith, M. S. (1990). Effects of psychoactive and nonpsychoactive cannabinoids on the hypothalamic-pituitary axis of the adult male rat. Pharmacology, Biochemistry, and Behavior, 37(2), 299-302.

Upham, B. L., Rummel, A. M., Carbone, J. M., Trosko, J. E., Ouyang, Y., Crawford, R. B., & Kaminski, N. E. (2003). cannabinoids inhibit gap junctional intercellular communication and activate ERK in a rat liver epithelial cell line. International Journal of cancer, 104(1), 12-18. https://doi.org/10.1002/ijc.10899

Weydt, P., Hong, S., Witting, A., Möller, T., Stella, N., & Kliot, M. (2005). Cannabinol delays symptom onset in SOD1 (G93A) transgenic mice without affecting survival. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders: Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases, 6(3), 182-184. https://doi.org/10.1080/14660820510030149

Yamaori, S., Kushihara, M., Yamamoto, I., & Watanabe, K. (2010). Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective and potent inhibitors of human CYP1 enzymes. Biochemical Pharmacology, 79(11), 1691-1698. https://doi.org/10.1016/j.bcp.2010.01.028

Wilkinson, J.D., and Williamson, E.M. (2007). 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.