Cannabinol

Cannabinol (CBN), a cannabinoid with the molecular formula C21H26O2, was the first cannabinoid identified and isolated from cannabis in 1899. Cannabinol is the non-enzymatic oxidation byproduct of tetrahydrocannabinol, but is only found in small amounts in Cannabis indica. When cannabis is exposed to air or ultraviolet light (e.g., sunlight) for an extended period of time, THCA converts to cannabinolic acid (CBNA). CBN is then formed by decarboxylation of CBNA. Degraded or oxidized cannabis products such as traditionally produced hashish contain CBN in relevant concentrations.

Cannabinoids are a collective group of compounds that act on cannabinoid receptors. They include plant phytocannabinoids, synthetic cannabinoids and endogenously formed endocannabinoids. Cannabinol binds as a partial agonist, preferentially to the cannabinoid G protein-coupled receptor CB2, which is expressed mainly on a variety of immune cells, such as T cells, B cells, macrophages and dendritic cells, but also on keratinocytes (Wilkinson JDet al. 2007). Stimulation of CB2 receptors by cannabinol can both induce apoptosis in these cells and inhibit the production of a variety of cytokines. Cannabinol binds only weakly to CB1 receptors. The substance exerts a weak psychotropic effect (Sheriff Tet al. 2020).

In animal and human studies, CBN was shown to have sedative and anticonvulsant effects. The substance has significant immunosuppressive, anti-inflammatory and antimicrobial effects. Cannabinoid (CB) receptors are present in human skin. Anandamide, an endogenous CB receptor ligand, inhibits epidermal keratinocyte differentiation. CBN inhibits the activity of a number of enzymes, including cyclooxygenase, lipoxygenase, and a number of cytochrome P450 (CYP) enzymes (e.g., CYP1A1, CYP1A2, CYP2B6, CYP2C9, CYP3A4, CYP3A5, CYP2A6, CYP2D6, CYP1B1, and CYP3A7). Furthermore, CBN may stimulate the activity of phospholipases.

CBN has the potential to be effective in topical applications. When applied topically, CBN is absorbed to a relevant extent (Stinchcomb AL et al 2004).

Inhibition of keratinocyte proliferation: The plant cannabinoids delta-9-tetrahydrocannabinol, cannabidiol, cannabinol, and cannabigerol inhibit the proliferation of a hyperproliferating human keratinocyte cell line in a concentration-dependent manner (Wilkinson J et al 2007).

CBN stimulates the recruitment of quiescent mesenchymal stem cells in bone marrow and promotes bone formation.

1. Casiraghi A et al. (2020) Topical Administration of Cannabidiol: Influence of Vehicle-Related Aspects on Skin Permeation Process. Pharmaceuticals (Basel)13: 337
2. Eagleston LRM et al (2018) Cannabinoids in dermatology: a scoping review. Dermatol Online J 24:13030/qt7pn8c0sb.
3. Kelly BF et al (2021) Cannabinoid Toxicity. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing PMID: 29489164.
4. Sheriff Tet al. (2020) The potential role of cannabinoids in dermatology. J Dermatolog Treat 31:839-845.
5. Stinchcomb AL et al (2004) Human skin permeation of Delta8-tetrahydrocannabinol, cannabidiol and cannabinol. J Pharm Pharmacol 56:291-297.
6. Wilkinson JDet al. (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.