The history of Cannabinol

What is CBN?

Cannabinol (CBN) is the oxidized, non-enzymatic product of tetrahydrocannabinol (THC) and is found in large quantities in aged cannabis material. The acidic form of CBN is also present in the cannabis plant, but with decarboxylation (heat), the acid converts to CBN.
The concentration of cannabinol in cannabis products depends on the age and storage conditions of the product. It is a relatively minor component in fresh cannabis, as it is a product of THC oxidation. CBN is a weak CB1 and CB2 receptor agonist, with only about 10% of THC’s activity. It potentially offers therapeutic benefits for conditions where cannabinoid receptors are upregulated. Unlike other cannabinoids, CBN does not derive from cannabigerol (CBG), suggesting an alternative biosynthetic pathway.

When cannabinol was first discovered, it was thought to be an inactive cannabis component, but it was later found to have multiple therapeutic properties, primarily due to its interaction with cannabinoid receptors (CBs). Cannabinol has lower affinity for CB1 (Ki 211.2 nM) and CB2 (Ki 126.4 nM) receptors and was initially considered inactive in human tests. However, combined with THC, it has been shown to have a strong sedative effect.

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Cannabinol’s Receptor Activity

As mentioned above, cannabinol, like tetrahydrocannabinol (THC), interacts with the CB1 and CB2 receptors, with a stronger affinity for CB2 receptors. While CBN has demonstrated agonistic activity on CB1 receptors, there are conflicting reports regarding its activity on CB2 receptors.

CBN has shown both direct and indirect agonistic properties, depending on the concentration used in testing. These inconsistencies may not only be due to CBN concentration but likely also to the conformational state of the receptors in the tissue. CBN also affects biological targets outside the endocannabinoid system. It acts as a potent agonist on TRPA1 ion channels, effectively blocks TRPM8 ion channels, and desensitizes TRPA1 ion channels to activation by the agonistic allyl isothiocyanate.

Cannabinol’s Biological Activity

Like other phytocannabinoids, cannabinol demonstrates significant therapeutic properties across a wide range of pharmaceutical targets. Similar to cannabigerol, CBN promotes keratinocyte longevity, independent of cannabinoid receptor influence. Additionally, the molecule exhibits anticonvulsant, anti-inflammatory effects, and potent activity against Methicillin-Resistant Staphylococcus Aureus (MRSA). Furthermore, CBN acts as an agonist of the TRPV2 (high-threshold thermosensor), suggesting potential for burn treatment.

Moreover, CBN can stimulate the recruitment of dormant mesenchymal stem cells in bone marrow, which may contribute to bone growth and increase defenses against breast cancer, though this effect is observed only at very high concentrations.

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Therapeutic Properties of Cannabinol

Due to its biological activities mentioned above, cannabinol (CBN) has shown potential as a treatment option for a wide range of conditions.

 

Appetite Stimulant

CBN has demonstrated potential as an appetite stimulant, similar to THC, offering therapeutic applications for individuals with reduced appetite due to medical conditions.

 

Antibiotic

Methicillin-Resistant Staphylococcus Aureus (MRSA) infections have become a significant challenge for researchers worldwide, as they seek solutions against antibiotic-resistant bacteria. CBN, alongside cannabigerol and cannabidiol, has shown efficacy against antibiotic-resistant MRSA infections, indicating that it may be a viable treatment for these life-threatening infections.

 

Potential Medication for ALS Patients

A 2005 study showed that CBN alleviated symptoms in mice genetically engineered to have a rodent version of Lou Gehrig’s disease, also known as Amyotrophic Lateral Sclerosis (ALS). These findings suggest that cannabinol may be effective in reducing symptoms for patients with degenerative motor neuron diseases.

 

Pain Relief

According to a study published in 2002, CBN exhibits strong pain-relieving effects. Notably, CBN and THC are the only cannabinoids that address pain by releasing endorphins and causing blood vessels to relax, indicating a link between these effects and CB receptor activity.

 

Anti-Asthmatic

A 2003 study found that CBN could alleviate allergy-related asthma in mice, potentially due to its powerful anti-inflammatory properties. The study hypothesizes that cannabinoids achieve this by enhancing the rodents’ immune response, thereby reducing inflammation associated with asthma attacks.

 

Sedative

CBN has a centrally mediated effect similar to that of tetrahydrocannabinol, although it is much less potent. However, studies suggest that CBN may be the most sedative of all cannabinoids, making it a promising treatment option for anxiety and stress-related disorders.

 

Synergy with natural terpenoids

The activity of cannabinol has been shown to be enhanced by the simultaneous administration of natural terpenoids. 

 

For instance, CBN’s antibacterial activity is strengthened by pinene (a terpenoid found in pine resin), while its sedative effects are amplified by terpenoids like nerolidol and myrcene. 

 

Nerolidol is found not only in the cannabis plant but also in many other plants such as lemon balm, ginger, tea tree, lavender, and jasmine flowers. Myrcene naturally occurs in cannabis, cardamom, hops, thyme, parsley, and bay leaves.