Every component of the body is inherently related. When one organ fails or declines in health, another organ will follow. Liver failure, for instance, poses a dire health risk on it’s own. However, beyond the immediate, life-threatening aspects of toxins not being filtered out of the blood, damage to the brain is another physiological consequence. Toxins cause free radicals to build up, which leads to cell stress and eventual neuron death. This cellular damage translates into loss of memory, general confusion, and cognitive damage, which poses a serious impairment to quality of life. Unfortunately, liver issues cannot always be immediately solved, if they can be solved at all. In the meantime, this condition, called Hepatic Encephalopathy, should at least be minimized or ideally entirely prevented, to ensure patients mental health. Scientists have been searching for neuroprotective agents, or drugs that might enable cells to avoid damage caused by buildup of free radicals.

Cannabidiol (CBD) is a known neuroprotector, meaning that the application of CBD decreases the amount of cell damage and death brought on by toxins. Researchers do not currently understand exactly how these neuroprotective effects are achieved. However, we do know that the normal cannabinoid receptors, CB1 and CB2, are not involved. When receptor antagonists are applied, and those receptors are shut off, neuroprotective effects are still observed. Case closed, right? Why not use CBD as a neuroprotective medicine for serious health situations such as Hepatic Encephalopathy? This may indeed be one of the best options in present day, and anyone suffering from liver damage may be interested in researching CBD. Unfortunately, barriers exist for the use of pure CBD. Most importantly, CBD’s bioavailability (meaning the rate that it can be absorbed throughout the body) is limited. This is because CBD has an affinity for lipids rather than for water, the body’s main component. Ideally the molecule could be altered to have an affinity for water. This is exactly the train of thought an international research team from Pennsylvania and China had when attempting to modify the CBD molecule to be more potent in its role as a neuroprotector.

This job, however, is not as straightforward as one might think. Due to CBD’s similarity to other molecules in the cannabinoid family, minor variations to the molecule can give it a high affinity to cannabinoid receptors CB1 and CB2, possibly producing psychedelic effects. Psychoactivity should obviously be avoided in a molecule intended to be a therapeutic pharmaceutical with as few side effects as possible. Regardless, without getting into the nitty gritty details of the molecular chemistry involved, the researchers essentially decided to bond an additional ring to the molecule that would give it an attraction to water. They created several similar compounds with different types of bonds and tested to see which could be most effective. To do this, the researchers created slices from rodent hippocampus brain sections and immersed them in toxins, specifically either ethanol or ammonia. These toxins were both chosen as they represent the primary toxins associated with Hepatic Encephalopathy in the body. Cannabidiol and the new group of target chemicals were then variously applied to the slices bathed in toxins. Afterwards, researchers evaluated the number of living/surviving cells, giving an objective measure of how neuroprotective each chemical could be.

In the end KLS-13019 emerged as a chemical that is 50 times more potent as a neuroprotector than CBD. However, the real kicker is that it’s also 400 times safer, in the sense that up to 400 times more could theoretically be used without being toxic to the body. KLS-13019 is also not psychedelic, meaning that in the total package, it represents a molecule that could effectively guard against such a disease as Hepatic Encephalopathy or anything that causes excessive stress to the brain!

Of course, these studies have not been shown in humans. It is entirely possible, though unlikely, that these results could be specific to rodents. Additionally, moving this drug to a human market could take beyond a decade. FDA approval in the US is slow, for good reason. However, the basic concept is very important: as helpful as CBD is now, ideally the chemical structure will suggest a family of related compounds that will be even more effective. The more we learn about the endocannabinoid system in the body and the way it interacts with cell health, the more we understand how essential it is and how many cures it may hold the key to. In the meantime, CBD is the closest, most-effective non-toxic analog available and could be very immediately useful to illnesses where a neuroprotective agent is required. Additionally, whole plant CBD may prove to be even more effective than pure CBD. This represents yet another way that medical cannabis is currently helping patients with serious illness, and we are happy to provide our members with reliable, high-quality medicine.


Works Cited

William A. Kinney, Mark E. McDonnell, Hua Marlon Zhong, et al. Discovery of KLS-13019, a Cannabidiol-Derived Neuroprotective Agent, with Improved Potency, Safety, and Permeability. ACS Medical Chemistry Letters (2016) 7:424-428.