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History and biochemistry of Cannabinol

What is CBN?

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

hemp plant close-up

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

cbd oil extract

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

laboratory products

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

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

Antibiotic

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

Anti-Asthmatic

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

Sedative

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

cbd oil in nature

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

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