How cannabis is helping one company research treatment of CTE
“Imagine if you said to Paul Tagliabue, back in 2003, that Ricky Williams might one day be able to save Junior Seau’s life…”— Thoma Kikis, co-founder of Kannalife Sciences
Imagine that it’s the year 2025. In locker rooms across the NFL, as ankles are taped and braces strapped on, trainers hand out gel capsules for players to ingest minutes before they take the field. The capsules are scientifically designed to protect against the deleterious effect of concussive blows to the head and traumatic brain injury—and, as a result, they have helped to sustain the viability of the sport of football. Oh, and yeah, they are derived from marijuana.
That’s the bet those at Kannalife Sciences are making about our future reality. Kannalife is an independent pharmaceutical company that has entered into a burgeoning, and lucrative, new industry: the study of the cannabis plant and its chemical constituents for therapeutic value. They believe they have found something, something still relatively unknown and very much in its nascent stages, yet something they say has shown great promise as a neuroprotectant. Something that could change the landscape of how brain injuries of all varieties—from chronic traumatic encephalopathy (CTE) to Alzheimer’s and Parkinson’s—will eventually be treated.
“We’re pushing the boundaries on this whole industry,” Kikis says. “We think this is going to be the new wave of medicine.”
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In March 2009, Kikis, a film producer and self-described entrepreneur, approached Dean Petkanas, a former investment banker and fellow entrepreneur, with an unexpected idea. Kikis wanted to get into the medical marijuana space. After his cousin developed a brain tumor, Kikis took it upon himself to research treatment options, and that’s when he discovered the potential therapeutic use of cannabis. Although his cousin was not responsive to trying medical marijuana and soon died, the idea of entering this emerging market still intrigued Kikis. Petkanas, however, wanted nothing to do with it.
But Kikis relentlessly persisted, and the two went back and forth, late night phone calls extending into early morning discussions.
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“I took off my entrepreneur hat and put on my bankers hat,” Petkanas says. “And I wondered: How can we raise money in this business? Especially with the 800 pound gorilla, which is the controlled substance act.”
Petkanas eventually decided that if they were to do this, they shouldn't get into the medical marijuana side of the industry, but rather look into the pharmaceutical side—in which he had some prior experience. (He had worked for a biotech company, assisting them with the commercialization of a phyto-phamaceutical compound that treated Sickle Cell disease.) It was there, Petkanas maintained, where they could make real medicine.
So in early 2010 Petkanas spent about four months researching the therapeutic benefits of cannabis, and in April he woke up Kikis in the middle of the night with a phone call.
“I found something,” Petkanas said. “I found our disease. But I bet you won’t be able to pronounce it. It’s called hepatic encephalopathy (HE).”
The phone went silent.
“What, you’re not going to say anything?” Petkanas joked. “Cat caught your tongue?”
“My dad has that disease,” Kikis responded. “I was just in the hospital with him last week.”
What was once mainly a monetary pursuit turned into a personal one. And so Kannalife was born.
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The cannabis plant is made up of over 400 chemicals. Of those, approximately 70 to 120 are unique to the plant and are known as cannabinoids. The two main cannabinoids in cannabis are tetrahydrocannabinol (THC), which is the psychotropic ingredient responsible for the “high” feeling, and cannabidiol (CBD), which has no psychoactive effects.
It is CBD that Kannalife has focused its research on.
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CBD actually works to balance out the negative effects of THC, a sort of ying and yang, as it’s been proven in animal studies to have antipsychotic, anticonvulsant, anti-oxidant, and anti-inflammatory properties, among others.
“CBD has an amazing amount of potential,” says Dr. Bill Kinney, the chief scientific officer of Kannalife. “Think about this: What if a football player could just take a pill that is non-psychoactive before the game and now have a greater level of protection against brain injury? What could be better than that?”
Seem a little far-fetched? Maybe. But the U.S. government issued a patent (#6,630,507) for the use of cannabinoids as antioxidants and neuroprotectants way back in October of 2003. That patent was backed by the research of Nobel Prize winning biochemist Julius Axelrod. So this is not exactly a novel idea, nor is it a radical concept.
Kannalife’s initial research was in regards to the treatment of HE, a liver disease that results in toxins (ammonia) being released into the brain and causing neuro-degeneration. It soon realized that this disease is not dissimilar from the cognitive impairments that one exhibits after they experience repeated blows to the head, or traumatic brain injury. By 2014 it was conducting studies for the treatment of CTE and had obtained patents to treat both diseases with CBD.
“We know that CBD is neuroprotective,” Kinney says. “We have seen effects in both protecting against cell death and increasing cell viability… We think CBD could protect the neurons from future injury and also help them repair.”
In simpler terms, they maintain that CBD has been proven efficacious as a protector of brain cells—albeit it only in animal studies, not yet in clinical trials with humans, and that does not guarantee that it will effectively treat CTE. Even Kannalife admits that their research is in the earliest stages.
“There are some unknowns present right now, and we are trying to understand why it works,” says Dr. Doug Brenneman, a developmental neurobiologist for Kannalife who previously had 22 years of experience at the National Institute of Health studying neuroprotection. “But we are convinced, after several years, that it does work.”
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Kannalife’s laboratories are located in the Pennsylvania Biotechnology Center in Doylestown, Pa., a co-op space where several different scientific research groups share a sterile, labyrinth-like building that unfolds in interminable twists and turns. About an hour south of their Doylestown facility is the Lewis Katz School of Medicine at Temple University.
Kannalife has partnered with doctors and researchers at Temple in order to further their research. Dr. Ron Tuma and Dr. Sara Jane Ward are professors at the university who have been studying the therapeutic potential of cannabinoid-based compounds for years. Their work centers around another potential way that CBD helps to prevent and treat brain injury.
“With CTE, and other injuries to the central nervous system, inflammation plays a very important role in exacerbating the injury,” Tuma says. “So it’s the interaction of cannabinoids with the inflammatory process that gives us the hope that it will have therapeutic benefit.”
When a head injury occurs, the brain becomes inflamed as a natural response. This then creates a positive feedback cycle, where the inflammation begins to feed on itself, making the injury progressively worse— hence the continual degeneration of cognitive function that comes as a result of CTE.
The research being done at the Temple facilities is working to prove that CBD, and their synthetically produced ‘super-CBD’ (more on that in a second) will help to stem inflammation in the brain as a result of injury.
“It seems to be able to do many things,” Ward says, “[but] there is a strong belief that one of the most effective properties of these cannabinoids is treating inflammation.”
It’s here where the animal trials for brain injuries will take place they hope, pending funding, later this year. They will test three sources of brain injury—pressure when the head gets hit, deformation when the brain moves inside the skull as a result of acceleration, and contusion or direct contact—to see if rodents who are pretreated with CBD show better cognitive results after the stimulated brain injury.
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The group has applied for grants with the Department of Defense and to the National Institute of Health, in hopes to get the funds necessary to continue their animal trials and eventually begin clinical trials. They emphasize repeatedly that CBD is in no way similar to THC and should not be a Schedule 1 drug—meaning that the U.S. Government classifies it as a substance with a high potential for abuse without any medical purpose. They say that classification has hindered their potential to get funding, and that CBD is merely guilty by association.
“It’s Schedule 1 only because it looks like THC on paper,” Ward says. “That’s as sophisticated as the Drug Enforcement Administration (DEA) is thinking.”
Kikis and Petkanas say that they approached the NFL a few years back with an information packet about the potential benefits of cannabinoid treatment. They maintain that they tried to explain to the league that it is a compound with its own dynamic, with therapeutic value, and that owners wouldn't have to worry about players failing a drug test or the potential of abuse. It doesn’t get you high, and it has no performance-altering qualities. Petkanas says he has no idea if the NFL even looked at his packet because he never heard back.
“What will it take for us to work with the NFL?” Petkanas asks. “A phone call. That’s it.”
The issue Kannalife has found with CBD is that it is not conducive to being used as a medicine, since it is toxic in very large doses and is not very orally bioavailable (meaning it doesn't readily get into the bloodstream if you take it in pill form). So Kinney synthetically produced several different versions of CBD based off its natural chemical composition but with slight variations, in order to create a ‘super-CBD.’
Kannalife believes it has found just that in a compound that they call “KLS-13019,” which, they say, is 50 times more potent, 500-fold safer, and 10 times more bioavailable than naturally produced CBD.
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“We have no illusions, since we in neuroscience have been trying to find ways to protect the brain for many years,” Brenneman says, “and it’s turned out to be a very elusive thing. But the fact is, at this stage, we just look for promising molecules. And we have found one.”
The next step is to test KLS-13019 in animal studies, to ensure that it has the same neuroprotecting qualities that CBD has been proven to have. After that comes the human studies. Kannalife is also working with two groups Catalent and Noramco, a subsidiary of Johnson and Johnson, to figure out the best way to encapsulate the molecule.
“Imagine if you had a molecule that is structurally different than CBD, so it’s not a controlled substance, but still has that same benefit of neuroprotection,” Kinney says. “That is something the NFL could wrap its arms around.”
