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CBC: A Look at the Potential Therapeutic Value of this Major Cannabinoid

By Leo Bear-McGuinness
Published: Oct 30, 2018   
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Cannabichromene (CBC) is one of the most abundant phytocannabinoids found in cannabis plants, yet it is one of the most poorly understood.

Now researchers from the universities of Macquarie and Sydney, Australia, have shown that CBC may contribute to the therapeutic effects of cannabis products.

By performing cellular assays, the researchers showed how CBC activates certain phytocannabinoid receptors along cell membranes. This activation is even more effective at hyperpolarizing cell membranes than THC.

It is thus thought that CBC may significantly contribute to the potential therapeutic effectiveness of some cannabis preparations, potentially by modulating cell inflammation.

The research was published in a pre-print article in BioRxiv and so has not gone through peer-review.

What is CBC?

First discovered in 1966, CBC is structurally similar to many other cannabinoids like THC and CBD. However, unlike those more notable chemicals, precious little research has been undertaken around the compound.

What is known is that its effect comes via its interactions with endocannabinoid receptors (the complex network of natural cannabinoid receptors within the human body). These receptors, such as CB1 and CB2, are found throughout the body and brain.

The compound is also known to interact with other receptors that activate pain and inflammation transmission signals, such as TRPA1 and TRPV1 receptors. It is these sensors which first alert the brain to pain or swelling.

And it's this ability to interact with different receptor channels which may be the key to CBC’s future in research; while peer-reviewed research into CBC is scarce, the work that has been undertaken has shown some promising results.

In one 2013 study, researchers demonstrated that CBC could be used to encourage new cell growth in mice. In another experiment, scientists from the University of Mississippi found that rat subjects treated with CBC performed better on stress-related tests, indicating that CBC may have a role in reducing anxiety.

In 2010, one group of researchers demonstrated that CBC’s anti-inflammatory properties could be boosted when used in conjunction with THC and CBD. They found that the combination of all three compounds was more effective than the combination of THC and CBD only.

CBC’s oldest known properties are actually anti-bacterial. Studies in the 1980s indicated that CBC might be directly act against deadly bacterial killers like E. coli.

And while the compound isn’t thought to have any psychoactive properties, more research is needed for this to be properly determined.

What were the Macquarie and Sydney researchers’ results?

Seeking to contribute to the little CBC research available, the researchers from the universities of Macquarie and Sydney aimed to better define CBC’s interactions with a human’s endocannabinoid receptors.

To achieve this goal, the group performed assays on a host of cells stably expressing human CB1 and CB2 receptors. The cellular membrane potentials and the loss of cell surface receptors were then recorded.

Their results showed that CBC evokes cellular hyperpolarisation via CB2 receptors but not CB1 receptors.

Within the CB2 receptor-lined cells, CBC caused a maximum hyperpolarization of 52 ± 4 percent pEC50 (a measurement of potency). In contrast, the maximum effect of THC (at 10 µM) was only 27 ± 6 percent, close to half the effects of CBC.

This rapid onset of cellular hyperpolarization in CB2 cells upon addition of CBC suggests a direct receptor activation rather than an end-point of secondary effects.

Within the CB1 receptor-lined cells, however, the maximum hyperpolarization the researchers measured was a pEC50 maximum of 7.8 ± 0.1. By the end of the experiment, the researchers concluded that CBC did not alter the onset or extent of cellular hyperpolarisation in CB1 receptor expressing cells, which suggests that CBC does not significantly interact with the CB1 receptor site at all.

These results were consistent with previous studies which also concluded that CBC does not significantly contribute to the CB1 receptor mediated psychoactive effects of cannabis.

What comes next?

The group’s results have made a substantial addition to the limited research on CBC. It's now even clearer that the phytocannabinoid is a strong agonist to CB2 receptors and thus a major trigger for its therapeutic and anti-inflammatory effects.

Nevertheless, as expected from a little-studied field, more research is needed to better understand CBC’s effects.

Within the paper, the Macquarie and Sydney researchers make a few recommendations.

For one, the G protein-coupled receptor (GPCR) kinase involved in CBC-induced CB2 activation needs to be identified. It's these GPCR kinases that are partly responsible for allowing ions to pass between cell membranes, which can in turn create a signal in the endocannabinoid system that's sent to the brain.

As of yet, the GPCR proteins that interact with CBC and CB2 receptors aren’t known.

The Macquarie and Sydney researchers’ results suggest that GRK2/3 kinases aren’t involved in the CBC/CB2 process, which narrows down the list of likely candidates.

Further research is thus sorely needed to finally determine which type of kinase protein is used, in order to better understand CBC’s actions.

Lastly, the group demonstrated that CBC produces higher levels of hyperpolarization in CB2 cells than THC. But they also showed that, combined, the two phytocannabinoids were even more powerful agonists.

This complementary effect may reflect pharmacokinetic interactions with THC, but also the pharmacodynamic effects of CBC itself on inflammatory processes.

Either way, future research into CBC’s effect on THC could shed more light on this beneficial relationship and help to formulate an optimal cannabis-based medicine, with pain-relieving and psychotropic effects.


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