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This New, CBD-Based Compound Can Reverse CIPN—And Scientists Discovered It by Accident

Cancer treatment comes with many debilitating side effects, not the least of which is chemotherapy-induced peripheral neuropathy (CIPN). Up to 85 percent of chemo patients experience CIPN, characterized by chronic, burning pain, tingling, decreased sensation and increased sensitivity to touch.

Currently there are few treatment options for the condition. The primary one is morphine, which obviously comes with serious risks.

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But, in a few years time, the quality of life for individuals living with CIPN could vastly improve. That’s the hope of the team of scientists at biopharmaceutical company Kannalife, who created a new compound that, in highly predictive animal models, has successfully reversed CIPN.

What is KLS-13019?

The compound in question, KLS-13019, is an iteration of cannabidiol (CBD), one of the 113 identified cannabinoids in the cannabis plant. Medicinal chemist Bill Kinney, PhD, chief scientific officer at Kannalife, created it during a successful attempt to increase CBD’s water-solubility.

The goal was to boost CBD’s bioavailability and use it in a pill form. The result was a new, now-patented molecule with improved potency — and safety.

“CBD has a dark side,” Doug Brenneman, PhD, member of Kannalife’s scientific advisory board, tells Florence Health. “At concentrations that are only two times higher than its beneficial concentration, it actually produces neural damage.”

Dr. Brenneman has been studying neurodegeneration for the past 35 years and previously served as a section chief at the National Institutes of Health, where he led research into the developing nervous system. With KLS-13019, he’s especially excited that his team created a separation factor of five between efficacy and toxicity.

In addition, Dr. Brenneman says, the compound has more pharmacological specificity than CBD.

“One of the real conundrums of CBD is it interacts with many drug target molecules. There are literally dozens,” he explains. “That’s good in the sense that it broadens CBD’s pharmacological value in terms of preventing disease. But … we like to have a drug that’s highly directed to the therapeutic target and that’s exactly where we ended up.”

How does KLS-13019 work?

“When we give a chemotherapeutic agent, like Paclitaxel, which is what we’ve used for all our studies, there’s an acute toxicity … on the sensory neurons … related to oxidative stress,” Dr. Brenneman says. “Then there’s a chronic phase, which happens over weeks and months, where you get this excruciating pain in the hands and feet that can actually become permanent. That’s the unmet medical need in this field.”

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The question for the researchers then became: To what extent can you prevent this pain from occurring, both acutely and chronically?

Animal studies and cell cultures show that both CBD and KLS-13019 can prevent CIPN if administered before chemo. However, research indicates that only the latter is effective at reversing CIPN — “like morphine, but without the abuse potential,” Dr. Brenneman says. “Our compound is directed at sensory neurons and the ability to block oxidative stress, whatever the cause is.”

He adds: “We’re saying that if you treat it early enough … you may even be able to reverse [CIPN] in a timely fashion.”

The Challenges of KLS-13019

So, what’s the catch? Dr. Brenneman calls out the danger of CBD in general.

“People say CBD is safe, but have they really looked?” he says. “Our studies show that, at a high enough concentration and long enough duration, hippocampal neurons are not happy around CBD … There’s a potential problem with damage and cell death in the developing nervous system.”

For CIPN patients, there is more good news, though. Dr. Brenneman says the research indicates the drug will not affect liver enzymes, unlike the CBD-based Epidiolex, which the FDA has approved for use in children with epilepsy. There are also no indications the compound contributes to heart arrhythmia, but more research is needed.

“We still want to know if there’s any dangers to the developing nervous system, and we need to know the exact pharmaco-kinetic properties,” he continues. “The rest is just a matter of going through all the boxes you need to check. It’s still very early stages.”

What Should Clinicians Know

Based on his extensive CBD research, Dr. Brenneman says his ultimate takeaway for clinicians — aside from the unique capabilities of KLS-13109 — is that recommending CBD is ultimately advising patients to take an unregulated product (with the exception of FDA-approved Epidiolex).

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“We need more work done on the formulation CBD is in,” he explains. “We need to have a formulation that’s stable and has a reproducible effect in the patient.”

Dr. Brenneman acknowledges the desire to help refractory patients with pain and other maladies where current therapies don’t work well. But he warns providers that even if there is “a source they feel confident in, it still comes back to this formulation issue.”

He continues: “It’s all doomed until these things are in reproducible preparations. That’s square one. Until that problem is solved, you don’t know what you’re going to have.”


Discovery of KLS-13019, a Cannabidiol-Derived Neuroprotective Agent, with Improved Potency, Safety, and Permeability, ACS Medical Chemistry Letters.

Knockdown siRNA Targeting the Mitochondrial Sodium-Calcium Exchanger-1 Inhibits the Protective Effects of Two Cannabinoids Against Acute Paclitaxel Toxicity, Journal of Molecular Neuroscience.

Pharmacological Comparisons Between Cannabidiol and KLS-13019, Journal of Molecular Neuroscience.

Chemotherapy-Induced Peripheral Neuropathy, JAMA Oncology.

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