Hemp and Marijuana, while legislated very differently, are actually the same plant (Cannabis Sativa). Currently any material from Cannabis Sativa that contains more than 0.3% THC by mass is considered marijuana, while everything else is considered hemp1.
Cannabis (both hemp and marijuana varieties) is famous as the natural source of cannabinoids like CBD and THC. These two compounds (and occasionally CBG as well) are considered the “major” cannabinoids, representing the dominant constituents of cannabis resin. However, other “minor” cannabinoids are present as well, although typically in much smaller amounts.
These minor cannabinoids play an indispensable role in the overall effects from cannabis of any variety. One of these “minor” cannabinoids with a particularly important role is CBN, and it is often present in significant amounts.
What is CBN Cannabinol?
Cannabinol (CBN) is the aromatized oxidation product of Tetrahydrocannabinol (THC), formed by exposure of THC to oxygen, heat and/or light17,16. CBN (or CBNA, its un-decarboxylated form) is not produced directly by cannabis, but can be found in the plant as a result of environmental exposure to air and sunlight. It is typically found in very low concentrations in fresh plant material, but can be present in high concentrations in aged or “compliance treated” cannabis.
The two compounds have very similar chemical structure and by extension biological activity. However, the small difference between THC and CBN molecules has a huge impact on how they affect the brain. As such, CBN is federally legal and completely unrestricted in hemp products while THC is a controlled substance and tightly regulated.
Cannabinol (CBN) Tetrahydrocannabinol (THC)
Like its relative THC, CBN partially activates both CB1 and CB2 cannabinoid receptors10,15,12 all over the body. As such it shares some effects with its illicit cousin, such as the ability to increase appetite5. However, CBN’s affinity for cannabinoid receptors is far less than that of THC.
CBN also shows an approximately 3:1 preference for non-intoxicating CB2 over psychoactive CB1 receptors10. Furthermore, due to the “biased signaling” that has been demonstrated in cannabinoid receptors19, it is likely that CBN activation of cannabinoid receptors is fundamentally different from that of THC14.
Altogether, these factors more or less explain why CBN is only minimally psychoactive, and why the difference between CBN and THC’s effect on the brain goes beyond a simple difference in dose and potency7. While CBN is mildly psychoactive, it does not produce the intoxication and euphoria that its close relative THC does.
CBN’s atypical activation of CB1 receptors leads to a prominent example of the “entourage effect”, showing unique properties when combined with other cannabinoids. The combination of CBN and THC for example, tends to enhance the sedative properties of THC while mitigating its stimulating effects and having seemingly little to no effect on the euphoria produced by THC4,22.
The mechanism behind this change likely comes down to altered conformation of the activated CB1 receptor, who’s new shape exhibits different binding affinity and efficacy toward THC, presumably enhancing CB1’s ability to couple with inhibitory intracellular machinery while reducing its ability to couple with excitatory intracellular machinery19. Furthermore, CBN may prolong the effects of other phytocannabinoids like THC by interfering with their metabolism6. The implications of this interaction extend to other cannabinoids as well, but the altered biochemical mechanisms in these cases have not yet been illuminated enough to allow any realistic speculation.
CB1 activation by CBN is not limited to direct interaction. Like other cannabinoids, CBN increases the levels of the body’s own version of cannabinoids (endocannabinoids)9,18. CBN weakly inhibits the enzymes that degrade anandamide (AEA) and 2-arachidonoylglycerol (2-AG), the dominant endocannabinoids found in the body.
CBN is also able to moderately inhibit the uptake of AEA specifically through an unknown transport protein, prolonging and amplifying its activity on both cannabinoid receptors and other biological targets. Cannabinoid receptor activation by endocannabinoids is also modified by CBN’s direct interaction with cannabinoid receptors, as is the case for THC based cannabinoid activity19. What this means for CBN’s overall effect is unclear, but it is no doubt an important factor in the subjective experience from this molecule.
As is the case for all phytocannabinoids, TRP channel activity plays an indispensable role in CBN’s pharmacology. TRP channels are involved in sensation and pain perception, as well as general neural activity. CBN has been found to activate and desensitize TRPA1 (horseradish/extreme temperature), as well as weakly activate and desensitize TRPV1 (capsaicin/high temperature)3 and TRPV2 (very high temperature) channels18. CBN has also been found to block TRPM8 (low temperature) channels18.
PPAR receptors are nuclear receptors involved in directing metabolism, growth and function of various tissues. Activation of the various forms (alpha, beta/delta, gamma) causes a wide range of biological effects; influencing inflammation, tissue growth and maintenance, and metabolic processes20. PPAR gamma in particular has been shown to have neuroprotective effects and sensitize the body to insulin24.
Many cannabinoids have been shown to activate PPAR gamma, including THC20. While CBN’s direct effect on PPAR receptors has not been well researched, its chemical similarity to THC indicates that CBN may also be a PPAR gamma activator. CBN’s effect on PPAR receptors is not limited to direct activation though, as 2-AG and AEA (upregulated by CBN) activate PPAR alpha and gamma respectively21.
In summary, cannabinol (CBN) exhibits similar pharmacology to its cousin THC, but with drastically reduced psychoactive effects. CBN is unlikely to “get you high” even in large doses, and possesses sedative4,22, appetite enhancing5, anti-inflammatory8, neuroprotective2, and antinociceptive13,11 pharmacological properties.
Some people report that after ingesting CBN they experience increased sensory appreciation and a sense of wellbeing, with a distinct “cannabis feel” without the outright intoxication associated with THC. Hemp products that contain significant quantities of CBN are likely to have an “authentic cannabis feeling”, without negatively impacting lifestyle or performance.
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