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)
CBN delays the onset of myotrophic lateral sclerosis (ALS) in a transgenic mouse model of ALS (Weydt et al., 2005)
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)
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 Δ8THC 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
CBN causes hypothermia in doses from 10 to 30 mg/kg (Hiltunen, Järbe, & Wängdahl, 1988).
CBN stimulates appetite and increases feeding through CB1 receptor activation (Farrimond, Whalley, & Williams, 2012)
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)
THC, CBD, CBN and CBG were found to inhibit human keratinocyte (skin cell) proliferation suggesting therapeutic potential in Psoriasis (Wilkinson and Williamson, 2007).
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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
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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.
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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.
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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
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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
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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.