Cannabinol – A New Therapeutic Cannabinoid on the Block

Dr Elisabeth Philipps | PhD BSc (Hons) BSc Nutr Med

The Cannabis sativa plant yields many different compounds that have been shown to have a wide range of different activities in the body. Many of these compounds are cannabinoids, with CBD (cannabidiol) and THC (tetrahydrocannabinol) being the major forms used for therapeutic benefits for many decades. But as the cannabis plant progresses through its life cycle, other rare cannabinoids can be produced at different stages. Some of these rare cannabinoids, so called because they account for less than 1% of cannabinoids present in cannabis plant biomass, are now coming under research scrutiny for their standalone therapeutic properties.

Cannabinol (CBN) is one of the minor cannabinoid just coming to light. It occurs naturally in cannabis as a degradant of tetrahydrocannabinol (THC): As the plant is cut, stored and dried, THC is exposed to light and heat, causing its oxidation into CBN. This means the presence of CBN in cannabis is usually associated with ageing of the plant: as THC disappears, the concentration of CBN increases. However, as opposed to THC, CBN is generally accepted as non-psychoactive. 

Therapeutic Properties of CBN

Each cannabinoid has a specific structure that confers unique physiological properties in humans. Evidence demonstrates that even a slight difference in the structure of these compounds can result in profound differences in biological activity, safety and potential therapeutic effect in the human body. 

CBN has distinct affinity and specificity for CB2 receptors in the human endocannabinoid system (ECS), making this a cannabinoid that has immune modulating properties.

As with other cannabinoids, CBN also has affinity for receptors sites outside of the ECS including orphan receptors such as GPR55 found predominantly within the bones, brain and intestinal tract. Research into CBN’s biological activity has shown a number of therapeutic qualities including a number of promising physiological properties:

Glaucoma | In preclinical studies, CBN in eye-drop formulation has been demonstrated to provide neuroprotection within the retina and to reduce intraocular pressure of the eye as presented in glaucoma. 

Epidermolysis Bullosa | Preclinical studies using CBN as the active ingredient of a topical cream demonstrated activity in reducing markers of inflammation and pain healing chronic wounds caused by prolonged inflammation. CBN also upregulates expression of a type of keratin (keratin 15, or K15), which might lead to skin strengthening and reduction of blister formation in epidermolysis bullosa simplex (EBS), an inherited disorder in which the skin, mainly on the palms of the hands and soles of the feet, is fragile and blisters at sites of friction. 

Neuroprotection | A study conducted on rodents has shown that CBN delays the onset of amyotrophic lateral sclerosis (ALS; also known as Motor Neurone Disease) by ameliorating symptoms, suggesting a potential neuroprotective role for CBN.

ADHD | A recent study suggests that CBN, along with other cannabinoids, may help to reduce the symptoms of Attention Deficit Hyperactivity Disorder (ADHD). The small-scale study investigated adult ADHD patients taking licensed medicinal cannabis. Participants used self-reported questionnaires to rate their ADHD, sleep and anxiety patterns with those on higher doses requiring lower levels of ADHD medication.

Sleep | One study, which requires further rigorous investigation, suggests that older cannabis plants have the potential to make people feel sleepier, with this effect ascribed to presence of greater levels of CBN from oxidation of THC after harvest. 

Appetite Stimulant | One rodent study demonstrated that CBN could help to stimulate appetite suggesting the use of non-psychoactive cannabinoids like CBN for supporting patients struggling with appetite, including those with HIV and on cancer medication, removing the use of intoxicating cannabinoids such as THC.

Anti-bacterial | Studies have shown that CBN could match the anti-bacterial properties of CBD and Cannabigerol (CBG) having been tested against strains of MRSA bacteria that are antibiotic-resistant.

CBN Safety | Safety of cannabinoid use in humans is currently a hot scientific and clinical topic. Several preclinical safety pharmacology and toxicology studies using CBN at very high doses (achieving systemic exposure (i.e. blood levels) hundreds of times higher than what would occur with topical dosing in humans) demonstrated no adverse events in a rigorous and extensive evaluation of central nervous system assessment including behavior posture, gait, and movement.

No adverse effects have also been observed even at the highest doses in preclinical studies where the drug was applied either as a cream (for local effects) or injected under the skin (for systemic effects) daily for 28 days. While these data are very encouraging, more research is required to understand the full safety profile of CBN in humans.

CBN Extraction | Due to its particular chemical structure, CBN maintains its structural integrity/stability under external stresses (e.g. heat, light) for a longer period of time. This unique feature of CBN may provide for longer shelf-life, which is an important commercial pharmaceutical parameter.

However, since CBN is naturally found in such small quantities, it is currently not economically feasible to extract CBN directly from the plant for large-scale pharmaceutical use. Therefore, a major goal of some cannabinoid pharmaceutical manufacturers is to produce nature-identical cannabinoids. Biosynthesis or chemical synthesis of CBN may provide a reliable, consistent, scalable and compliant process compared to the variability and complexity associated with the extraction and purification of pure CBN from the cannabis plant. In addition, the costs associated with the large carbon footprint of greenhouses or exterior fields in combination with the security requirements, use of pesticides, fertilisers and variability in growth and expression of the target compound at a highly consistent level in the plant may make the biosynthetic approach of rare cannabinoids a more economically sound and socially responsible strategy. 

Final thoughts

There are a vast array of rare (minor) cannabinoids including CBN that are increasingly demonstrating their therapeutic and clinical importance both synergistically within medicinal cannabis products and as standalone treatments, as demonstrated by the CBN eye drops and topical creams. By progressing cannabinoid research into clinically translatable models, we have the potential through pharmaceutical technologies and specialist scientists and clinicians to unlock a whole raft of novel and natural therapeutic cannabis-based options in treating a wide range of diseases.