Football and CTE: Using Chronic To Treat Chronic Traumatic Encephalopathy

Are You Ready For Some Football?

Chronic traumatic encephalopathy (CTE) is a neurologic condition that shares symptoms with Alzheimer’s disease (AD), but is believed to be caused by repeated blows to the head. Typical signs and symptoms include a decline of recent memory and decision-making, mood and behavioral disturbances (especially depression, impulsivity, aggressiveness, anger, irritability, suicidal behavior) and eventual progression to dementia. It can affect athletes and non-athletes alike, but it has become more well-known as a result of the NFL’s recent reversal of its denial of the condition.  First described in boxers in the 1920s (“punch drunk”), its connection to football players was reported in 2005, when neurologist Bennet Omalu performed an autopsy on former NFL player Mike Webster and reported abnormal tau proteins in the brain similar to the neurofibrillary tangles found in brains of patients with Alzheimer’s Disease.  The CTE Center at Boston University, which has partnered with the Veterans Administration to study CTE, has autopsied 94 brains of NFL players, with 90 testing positive for the disease.  Conventional treatment options for CTE are similar to Alzheimer’s disease, with medications slowing disease progression, but not preventing, delaying, or reversing the onset of symptoms.  Recently, several former NFL players have spoken publicly to promote the use of cannabinoids, specifically cannabidiol, to treat the symptoms of and delay the onset of CTE.  Cannabis is still classified as a banned substance according to NFL rules, and research specifically into the use of cannabidiol to treat CTE is just beginning.

CTE shares a similar pathological pathway as Alzheimer’s disease, but the triggering events that begin the pathway are repeated exposures to head trauma. Studies have shown increased inflammatory markers immediately after traumatic brain injury.   CTE, like Alzheimer’s disease, is believed to be caused by inflammation in the brain, which leads to the formation of tau proteins (but, in contrast to Alzheimer’s, amyloid beta proteins and plaques are not typically formed). Tau proteins are further altered by inflammation to form neurofibrillary tangles, which impair nerve cell activity.  CTE-associated neurofibrillary tangle development may begin up to 20 years before symptoms are apparent.   The tangles begin accumulating in the part of the brain responsible for memory and learning, but eventually spreading to other parts of the brain responsible for walking, talking, and eating.  Inflammation also leads to the wasting away of the cerebral cortex, responsible for impulse control and decision making.   Neurofibrillary tangles are believed to disrupt the communication between nerve cells, eventually leading to nerve cell death. Once nerve cells die, they cannot be regenerated. Death of nerve cells leads to worsening symptoms, including the loss of self-care (including basic functions such as eating, drinking, and toileting), as well as the regulation of breathing and heart rate, which slowly and eventually leads to death.

Researchers at the CTE Center at Boston University examined the brains and spinal cords (after death) of 12 individuals with suspected CTE, including 3 who had also developed amyotrophic lateral sclerosis (ALS), a progressive neurologic disease in which individuals gradually lose the ability to control muscles, resulting in progressive paralysis and eventual death.  They also examined the brains and spinal cords (after death) of 12 healthy individuals and 12 individuals with ALS not associated with CTE.  Researchers found evidence of tau-positive neurofibrillary tangles, with 80% of those studied showing inflammatory proteins.  Inflammation can be associated with alterations to tau proteins, resulting in the formation of the neurofibrillary tangles, which impair the communication between nerve cells.  When researchers examined the brains and spinal cords of the 12 healthy individuals, they found rare amounts of tau-positive proteins, but no neurofibrillary tangles and no inflammatory proteins.  In the brains and spinal cords of the patients with ALS, but not CTE, only 1 of 12 showed tau positive proteins and no neurofibrillary tangles but all had inflammatory proteins.  The inflammation associated with ALS in the absence of CTE led to progressive paralysis, but the inflammation associated with repeated head trauma resulted in the development of neurofibrillary tangles, similar to the neurofibrillary tangles associated  with inflammation in Alzheimer’s disease.

Building upon this earlier research, in an article published in the December 2012 issue of the Oxford Press journal Brain, researchers from the CTE Center at Boston University examined brains of 85 men after their deaths, all of whom had been exposed to mild, repetitive traumatic brain injury, and an additional 18 individuals without a history of traumatic brain injury.  Of these men with exposure to traumatic brain injury, 64 were athletes in a variety of sports, 21 were military veterans (including 16 who were also athletes), and 1 individual who engaged in self-injurious head banging.   The researchers found evidence of chronic traumatic encephalopathy in 80% of the brains examined that had traumatic brain injury exposure.  The extent of disease observed in these brains ranged from occasional spots of neurofibrillary tangles to widespread disease.  The extent of observed disease in the brain correlated with extent of disease symptoms reported by family and friends, as well as with the patient’s age and extent of exposure to traumatic brain injury.   As patients lived longer with the disease, more of the brain became covered with neurofibrillary tangles, and more symptoms were experienced.  And patients that had more episodes of traumatic brain injury experienced more severe disease.  Researchers found the same types of inflammation-altered tau proteins in patients with CTE, which led to the formation of the neurofibrillary tangles.

As with Alzheimer’s disease, conventional treatments for CTE remain focused on treating the symptoms of the disease or slowing its progression.  However, as my previous review article in the August issue of Vegas Cannabis Magazine showed, cannabis has a role in treating Alzheimer’s disease.  Cannabis showed reductions in the symptoms associated with Alzheimer’s, including agitation, delusions and irritability (Shelef, et al; 2016).  And cannabis also showed prevention of the progression of Alzheimer’s, through decreased beta-amyloid induced inflammation (Esposito, et al; 2011), which then decreases the formation of tau-protein associated neurofibrillary tangles.  Unfortunately, while CTE may be suspected while someone is alive, definitive diagnosis cannot occur until brains of affected individuals are examined after death.  Researchers are examining PET brain scans as a way to diagnose CTE while individuals are alive.  Finding a way to definitively diagnose this disorder will allow researchers to conduct studies focused on treating the disorder.  However, based on research conducted in the use of cannabidiol to treat other neurological disorders, proponents of cannabis use to treat CTE are optimistic that CBD can slow or even reverse the pathology of this devastating disease.  A group of former NFL players have banded together and partnered with CW Botanicals, a producer of hemp products, and the Colorado Springs non-profit group Realm of Caring, which funds research into medical uses for cannabis to bring awareness to the problem of CTE in the NFL.  The former players have produced a PSA titled “When The Bright Lights Fade,” which discusses the possible role of cannabis to treat many of the ailments from which former players suffer.  Using proceeds from the PSA, as well as their fundraising efforts, the players hope to establish a large-scale study at Johns Hopkins to investigate the use of CBD to treat suspected CTE and other traumatic brain injuries.

As researchers learn more about chronic traumatic encephalopathy, how it forms, who is affected, and how it progresses, they will be able to place a greater focus on newer and more effective ways both to treat and prevent the disease.  The National Football League has slowly began both to acknowledge the connection between football and the disease, and funding research into the disease.  As the federal prohibition continues on the use of cannabis to treat medical disorders, the NFL has shied away from publicly endorsing the use of cannabis or funding research into its use to treat the myriad of symptoms its players endure as a result of the game.  However, many former NFL players have called for further research into the safety and effectiveness of cannabis to treat chronic traumatic encephalopathy, chronic pain, and opioid addiction, among others.  As more players push for more research on cannabis, more fans, ready for football, will join those calling on our lawmakers to allow more cannabis research.

References:

1.       Chronic traumatic encephalopathy in a National Football League player. Omalu BI, DeKosky ST, Minster RL, Kamboh MI, Hamilton RL, Wecht CH. Neurosurgery. 2005;57:128–134.
2.       TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy. McKee AC, Gavett BE, Stern RA, Nowinski CJ, Cantu RC, Kowall NW, Perl DP, Hedley-Whyte ET, Price B, Sullivan C, Morin P, Lee HS, Kubilus CA, Daneshvar DH, Wulff M, Budson AE. J Neuropathol Exp Neurol. 2010;69:918–929.
3.       The spectrum of disease in chronic traumatic encephalopathy. Ann C. McKee, Thor D. Stein, Christopher J. Nowinski, Robert A. Stern, Daniel H. Daneshvar, Victor E. Alvarez, Hyo-Soon Lee, Garth Hall, Sydney M. Wojtowicz, Christine M. Baugh, David O. Riley, Caroline A. Kubilus, Kerry A. Cormier, Matthew A. Jacobs, Brett R. Martin, Carmela R. Abraham, Tsuneya Ikezu, Robert Ross Reichard, Benjamin L. Wolozin, Andrew E. Budson, Lee E. Goldstein, Neil W. Kowall, Robert C. Cantu. Brain. 201;: Restricted access136 (1): 43-64.
4.       Safety and Efficacy of Medical Cannabis Oil for Behavioral and Psychological Symptoms of Dementia: An-Open Label, Add-On, Pilot Study. Shelef A, Barak Y, Berger U, Paleacu D, Tadger S, Plopsky I, Baruch Y. J. Alzheimer’s Dis. 2016; 51(1): 15-9.
5.       Cannabidiol reduces Aβ-induced neuroinflammation and promotes hippocampal neurogenesis through PPARγ involvement. Esposito G, Scuderi C, Valenza M, Togna GI, Latina V, De Filippis D, Cipriano M, Carratù MR, Iuvone T, Steardo L. PLoS One. 2011; 6(12): e28668.
6.       In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging. Barrio JR, Small GW, Wong KP, Huang SC, Liu J, Merrill DA, Giza CC, Fitzsimmons RP, Omalu B, Bailes J, Kepe V. Proc Natl Acad Sci U S A. 2015 Apr 21;112(16):E2039-47