Synopsis: This article discusses how cannabidiol (CBD) alters brain function, despite it being non-psychoactive, and its role in protecting the brain against, and assisting it in repairing, chronic traumatic encephalopathy (CTE). With many NFL players being diagnosed with CTE, unarguably from their repeated hits to the head and subsequent concussions during football games, unveiling a preventive measure is imperative. A body of evidence is growing which suggests that using CBD for CTE can yield promising results by altering the mechanisms behind the brain’s over-excessive response to head trauma.
Imagine you’re a U.S. Marine about to travel a route known for improvised explosive devices. Maybe you’re a boxer about to enter the ring. Or maybe it’s any given Sunday and you’re facing off against the biggest defensive lineman you’ve ever seen.
Now, imagine you could take a pill that protected you from brain damage, or could help reverse it once sustained?
That’s exactly what some cannabis researchers are aiming for in studying cannabis, specifically one component: cannabidiol (CBD).
The agency lifted the ban without issuing a specific public statement, but the action was likely in recognition of the massive therapeutic potential for this non-psychoactive cannabinoid.
CBD is an anti-inflammatory, as evidenced by its growing popularity among NFL football players to help recover after games and workouts. Also promising are CBD’s neuroprotective properties. Animal studies have shown CBD to reverse the effects of chronic traumatic encephalopathy (CTE), that is, the brain damage caused by repeated blows to the head.
A company called Kannalife, founded in 2010, is currently performing clinical research on the potential neuroprotective effect of CBD for CTE, chronic concussions and similar degenerative brain diseases, and laboratories throughout the country are experimenting with CBD as a neuroprotective in a variety of different injuries and diseases.
Are people with brain injuries using CBD for CTE now?
Despite the lack of definitive clinical trials studying CBD for CTE, anecdotal evidence demonstrating its efficacy is building.
Dr. Michael Lewis is one of the pioneers in using CBD to treat chronic brain injury in veterans, athletes and accident survivors. He administers the chemical in conjunction with a regimen of healthy fats, like Omega-3 fatty acids in fish oils, that have long been known to promote brain health.
Among his many brain injury patients who have had success with CBD oil, Lewis told attendees at the 2017 annual Integrative Medicine for Mental Health Conference about a patient of his named Bobby Ghassemi.
Ghassemi sustained a serious brain injury after a car crash in 2010. Within months, Lewis had him mostly physically healed, in part with his fatty acid regimen added to more established therapies.
But Ghassemi still struggled with the aftermath of his brain injury; depression, anxiety and irritability. Lewis started his patient on CBD oil in June of 2015. Ghassemi’s anxiety disappeared almost immediately, and he stopped taking depression medication.
As of April, 2016, Ghassemi was doing stand-up comedy and participating in an active social life.
“Thanks to CBD oil, I’m feeling much more comfortable in my own skin, I’m being more social, I’m making big, noticeable changes,” he said in an email to Lewis.
What happens when you get a concussion?
Chronic concussions and their end result, CTE, present a complex problem for researchers. Studies have clearly defined only a few of the many chemical processes involved in the body’s infinitely complex response to head trauma.
One fact is apparent, however: Most of the damage from a concussion happens in the brain’s own inflammatory response. Halting and reversing this cascade of inflammation is where doctors see the biggest therapeutic potential for treating and curing CTE.
Say a defensive lineman runs you down during a failed trick play, and you lose consciousness. The immediate cause of your blackout is your brain knocking up against the inside of your skull, as illustrated in the Gif below.
The most serious damage, however, comes as your brain reacts to the insult, releasing an indiscriminate cascade of neurotransmitters and other chemicals. This upsets the ion balance inside your skull. The charged calcium and potassium ions that typically make up your brain’s electrical circuitry run smoothly being to move freely and randomly through neurons’ membranes, and the little intracellular potassium/calcium pumps that typically keep the ion balance start working overtime.
This makes the brain demand more sugar to fuel the process, but the sugar isn’t there because of decreased blood flow caused by the initial insult to the head. This energy/blood supply crisis means the pumps can’t work fast enough to restore balance, which leads to calcium backing up outside cell membranes. Calcium and other crucial neurochemicals sloshing around in the spaces between cells starts damaging the fragile filaments of the nerve connection.
This damage feeds on itself as glucose demand drops off and becomes more sluggish than even before your concussion. Other cascade effects include:
- generation of lactic acid, which can corrode tissue;
- decreased intracellular magnesium, further altering the chemical balance;
- production of free radicals, which are unstable molecules that tear off chunks of healthy cells in their quest to reach stability;
- and inflammatory responses, which can cause swelling and impair function.
What is Tau protein?
In CTE, the repeated inflammatory cascades described above cause a type of protein called Tau protein to build up in the brain.
In a healthy brain, these Tau proteins help support the fragile interconnections among the billions of neurons that make up your brain and generate your consciousness. Repeated injury stimulates a response similar to scarification; the scar tissue becomes thicker and tougher to protect the site of injury. When this happens in the brain, protein deposits sever neural connections, eventually shrinking brain tissue.
In many degenerative brain diseases, the Tau protein accumulates because it’s got too much phosphorous as part of the molecule, meaning you’re brain can’t use its normal processes to break down the Tau. Considering the protein’s normal function is to build little tubes, an excess of the protein eventually builds up into “neurofibrillary tangles,” like a mess of electrical cords. Some studies have shown CBD can help stop Tau combining with so much phosphorous, making it easier for the brain’s cleanup system to dispose of excess.
Tau proteins are also implicated in Alzheimer’s disease and other types of dementia.
Glial cells and brain trauma
Glial cells are the neural cells that help insulate neurons, facilitate transmission of neural impulses, and clean up waste products and pathogens. They’re the cells that form the brain’s immune response to trauma and pathogens, and they tend to help produce myelin which wraps around the parts of your neurons like insulation on an electrical wire.
Remember that first step in the cascade of crises that happens right after you get a concussion? Your brain starts squirting out a bunch of potassium, screwing up your polarity. With mild trauma — say, a quick left jab sustained while sparring with a buddy in the boxing ring, or knocking your head against an open kitchen cabinet — your glial cells suck up that extra potassium and you move on.
When the glial cells are overwhelmed is when you lose consciousness and the cascade of damage begins.
Researchers still aren’t sure exactly how the neuroprotective effects of cannabidiol work, but studies over the past decade have provided some clues. By activating endocannabinoid receptors in the brain, CBD seems to affect the actions of glial cells. Astrocytes and microglia seem to be two of the different types of glial cell types most affected by administering CBD for CTE.
Astrocytes are the glial cells present throughout the brain — there are more astrocytes than actual neurons in your brain. Astrocytes keep the synapses between nerve cells open, allowing impulses to propagate. They absorb excess neurotransmitters and keep the ion balance in check.
A 2017 study in the International Journal of Molecular Sciences is the latest to show CBD suppresses the activity and inflammation caused by astrocytes after injury to the nerves, whether from trauma, stroke or disease (like Alzheimer’s).
The other sort of glial cells implicated in CTE are microglia. They perform the function of brain janitor, cleaning up any waste neurochemicals or pathogens and then breaking them down for removal.
A 2017 study in Frontiers in Immunology noted that activating one of the brain’s natural types of cannabinoid receptor suppressed the microglia’s inflammatory response to brain bleeding. This inflammatory response is a central cause of secondary injury after trauma, whether from stroke or impact to the head.
Further research into CBD in rodents with Alzheimer’s showed the cannabinoid had a suppressing effect to the inflammatory response triggered by microglia. This allowed the rats to learn relatively complex spatial reasoning tasks, despite their degenerative disease.
What is the future of CBD for CTE?
Lewis’ patients’ successes still only count as case studies. Double-blind clinical trials are the gold standard for development and approval of new drugs.
The cannabis-focused pharma company Kannalife, started in 2011, has been obtaining financing, patents, licenses and partnerships over the last 6 years with the specific intention to create drugs with CBD for CTE.
The company’s current research involves administering cannabidiol in conjunction with a new chemical Kannalife scientists have developed called KLS-13109. Kannalife presented its latest findings at the 27th Annual International Cannabinoid Research Society Symposium in July, 2017.
“When we set out to design a better molecule and keep much of the pharmacological properties of CBD such as neuroprotection and reducing oxidative stress, we hoped to come up with an answer to the limitations of CBD,” said CEO of Kannalife, Dean Petkanas in a press release. “We believe we’ve answered that problem with KLS-13019.”
No information is yet available about when Kannalife’s drugs will be ready for clinical trials.
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