CBN and Pain

WRITTEN BY MELANIE FLORES AND DR. SWATHI

What are cannabinoids?

As of 2022, there are over 100 cannabinoids discovered. Cannabinoids are certain types of compounds found in cannabis plant.

What are major cannabinoids?

Cannabidiol (CBD) and tetrahydrocannabinol (THC) are referred to as major cannabinoids, meaning that they make up the chemical profile of the plant in high percentages. Along with these key players, there are also hundreds of other molecules in the cannabis plant; these are known as minor cannabinoids.

What are minor cannabinoids?

While many people are familiar with the psychological and possible medicinal benefits of the major cannabinoids, scientists are now committing more research to discover the possible therapeutic effects of the minor cannabinoids. The most common molecules that are being studied for medicinal use include cannabigerol (CBG), cannabinol (CBN), and cannabichromene (CBC), among others. Although the minor cannabinoids are produced in smaller amounts in the cannabis plant, they are still vital to the molecular profile and production of specific effects.

What is the endocannabinoid system?

The human body houses an innate endocannabinoid system (ECS) where chemicals that are naturally made within the body can bind to specific receptors, known as cannabinoid receptors. These cannabinoid receptors are expressed ECS is still being researched, receptors sitting on the central nervous system are known to play a role in regulating processes such as appetite, memory, mood balance, occasional pain, perception, and cognition.

What is the ensemble effect (or entourage effect)?

This is important knowledge, as minor cannabinoids bind to the cannabinoid receptors in the human body and exert their various effects. The effects on minor cannabinoids is currently of great interest due to the proposed theory of the “entourage effect.” The entourage effect is the proposed increased effect that cannabinoids have when they are administered together. Multiple cannabinoids given to human and animal models together are thought to work in synergy.

Can CBN help with occasional pain?

Millions of adults have been reported living with some type of pain on a daily basis. For this reason, it is vital that non-addictive options are discovered–like cannabinoids. The cannabinoid that has shown the most promising effects thus far for modulating pain is cannabinol (CBN). CBN has had the greatest research for its analgesic effects in human and rat models, and has been studied in head-to-head studies against gold standards for pain. One study in rats showed that CBN was highly effective for its analgesic effect, with results showing its effectiveness was four times that of aspirin. It did note that its analgesic effect only lasted up until a dose of 50 mg/kg, and that doses beyond that did not provide a more potent effect. CBN’s analgesic effect did however show that it was only 1/10 as potent as morphine, so it should not be assumed that CBN will be used for pain in the future.The analgesic effects of the CBN minor cannabinoid was also tested on the rhesus  macaques species of monkey. In this particular 2020 experiment, the theory being tested was one that cannabinoids can enhance the effect of opioids in a synergistic mechanism. This theory is important because it could mean that smaller doses of opioids could be used to help patients. This study did find that CBN did not enhance the analgesic effects of the opioid, but authors warranted that further research must be done to detect the effect of CBN on pain stimulus alone. Given the results of the first study, it is possible that CBN did not exert additive effects with opioids because there seems to be a “ceiling effect” on the intensity of pain stimulus as CBN. A 2019 study on rat models studied the effect of cannabinol on reducing myofascial pain and showed further benefits. Fifty-four female rats were first injected with nerve growth factor (NGF) to mimic fibromyalgia pain. 1mg/ml CBN was injected intramuscularly into rats post NGF injection and mechanical muscle sensitization was measured. CBN was shown to increase the mechanical withdrawal threshold for the muscle 10 minutes after it was administered. The rats were also tested with a CBD/CBN 1:1 mg/mL, which showed an even greater improvement in pain. This result is telling of the likelihood that the “entourage effect” is in effect here. In summary, although minor cannabinoids are not as abundant in the cannabis plant they should not be overlooked for their powerful therapeutic potential in medicine.

References

1. Sofia RD, Vassar HB, Knobloch LC. Comparative analgesic activity of various naturally occurring cannabinoids in mice and rats. Psychopharmacologia. 1975;40(4):285-95. doi: 10.1007/BF00421466. PMID: 1170585.
2. Nilges MR, Bondy ZB, Grace JA, Winsauer PJ. . Opioid-Enhancing Antinociceptive Effects of Delta-9-Tetrahydrocannabinol and Amitriptyline in Rhesus Macaques. Experimental and Clinical Psychopharmacology. 2020; 28 (3): 355-364. doi: 10.1037/pha0000313.
3. Wong H, Cairns BE. Cannabidiol, cannabinol and their combinations act as peripheral analgesics in a rat model of myofascial pain. Arch Oral Biol. 2019 Aug;104:33-39. doi: 10.1016/j.archoralbio.2019.05.028. Epub 2019 May 28. \

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This article was edited by Dr. Swathi and was written by Element Apothec Scientific Communications Intern, Melanie Flores. She is a Doctor of Pharmacy (PharmD) student at Oregon State University and Oregon Health & Science University College of Pharmacy in Portland, Oregon.