Can a Pill Replace Pot for Treating Concussions?

In 2012, the former Pittsburg Steelers lineman Ralph Wenzel died from early-onset dementia. It was brought on by his severe chronic traumatic encephalopathy (CTE), a progressive brain disease triggered by repeated concussions. Earlier this year, the former NFL fullback Kevin Turner was diagnosed with CTE, too, after dying from the disease at age 46. Doctors thought Turner had ALS until they performed the autopsy.

In a 2015 study, researchers with the Department of Veterans Affairs and Boston University examined the brains of 91 former NFL players. They found 96 percent showed signs of CTE. Many players suffering the debilitating mental effects of CTE have committed suicide—Steelers offensive lineman Terry Long, Chargers safety Paul Oliver, and Eagles safety Andre Waters, to name a few.

Some former NFL players, like Eugene Monroe, argue that marijuana could combat the debilitating long-term health effects of repeated concussions. But while NFL team owners are beginning to talk about the need to reform their policy, smoking weed continues to be a punishable offense.

Now, a team of researchers at the University of Miami may be on to a less contentious solution—a treatment with the medicinal benefits of marijuana but none of the psychoactive kick.

The researchers recently began a five-year study aimed at creating a pill that athletes could take after a concussion to avert brain damage. They plan to develop this pill using cannabidiol and dexanabinol. Cannabidiol, also known as CBD, is one of the-113 plus chemical compounds found in cannabis known as cannabinoids. Dexanabinol is a synthetic cannabinoid. Current evidence suggests these two particular cannabinoids have the capability to disrupt the series of chemical reactions that follow a concussion and lead to brain-cell death. CBD activates receptors that trigger a cellular repair mechanism in the brain, while dexanabinol prevents calcium from accumulating in the cells and draining their energy.

“What that pill would do is stabilize the brain, so that when you get a head injury, there may only be a few brain cells that are injured to the point of no return,” says Michael Hoffer, a professor of otolaryngology at the University of Miami Miller School of Medicine who will conduct trials for the study. “There are a lot of brain cells at risk right around those cells. If we can stabilize those, we can prevent the dominos from falling.”

There is some evidence that this effect could be achieved simply by smoking marijuana, but the major benefit to working with isolated cannabinoids is that researchers can choose which compounds to use and which to exclude. With the cannabinoid THC absent, the concussion pill, which could be taken up to 24 hours after an injury, won’t get anyone high and presumably won’t inspire the institutional backlash of its leafy progenitor.

Stripped down to its cannabinoid components, marijuana has already made a powerful foray into the mainstream medical world. “We’re starting to learn more and more [about marijuana],” says Gillian Hotz, another researcher at the University of Miami Miller School of Medicine who is working on the study. “It’s not [just] the guy who sits in the basement smoking a joint and playing video games anymore. We’re way past that.” Research suggests CBD may be effective for treating epilepsy and cancer. A few cannabinoid-based drugs, including nabilone and dronabinol, are commercially available for treating cancer side effects.

If the Miami team’s pill succeeds, the compound could become a neurological game changer. The Centers for Disease Control reports that about 1.28 million people suffer a concussion or other form of mild traumatic brain injury each year. And while professional football has grown notorious for its high concussion risk, the epidemic isn’t limited to the pros. From 2001 to 2005, 135,000 children ages 5 to 18 reported to the emergency room for concussions sustained while playing sports. While they are prevalent in football and boxing, concussions are common in sports ranging from basketball to hockey, with research suggesting female athletes actually experience them at a higher rate than males. Concussions are also widespread in the military, with 300,000 service members diagnosed between 2000 and 2015.

There is no prescription for concussions; the standard treatment is simply to rest until the symptoms fade. But the unseen damage from repeated concussions doesn’t really fade—and it can change the brain in ways that may take years to surface. For those unlucky enough to develop CTE, the brain gradually descends into a state of progressive degeneration associated with memory loss, impaired judgment, loss of impulse control, aggression, depression, suicidal thoughts, and—ultimately—dementia.

Despite the apparent need for research like theirs, the Miami research team has a challenging road ahead—starting with the legal hoops they must jump through to get the compounds they need. Marijuana, a schedule 1 drug, is notoriously difficult for researchers to obtain, and CBD is no easier. “As far as the DEA is concerned, they’re the same,” says Hoffer. “While almost all doctors have class 2 through 5 licenses, getting a class 1 addition to your license requires a lot of paperwork.”

When they begin clinical trials in about a year, the team will be stepping into relatively uncharted territory. Not only will this be the first large-scale study in the U.S. to look at cannabinoids as a treatment for concussions, it will be one of just a handful of concussion treatment studies currently underway.

“Designing treatments has not really taken off because, despite the fact that millions and millions of people are having concussions every year, we’ve just been behind the game,” says David Wright, a neurologist at the Emory University School of Medicine. Wright also studies traumatic brain injuries, although his work focuses on moderate to severe head trauma rather than concussions. In 2014, he led a study investigating the hormone progesterone’s effect on traumatic brain injuries. It proved unsuccessful despite promising preclinical trials.

“Right now, we’re all trying to better define the disease and figure out what in the world is going on,” he says.

One reason concussions are tricky to study is that they are difficult to define. There is no one characteristic doctors can use to diagnose a concussion beyond doubt. “It’s a clinical system, almost like a psychiatric disorder,” says Wright. “So there’s not currently a good marker.”

To deal with this, the Hoffer and his colleagues at the University of Miami will use I-Portal goggles, a device that measures eye movements to diagnose concussions with 95 percent specificity. The team tested the device with a 2014 grant from the NFL. Hoffer also says that each individual patient’s criteria will be clearly recorded, so that later on the researchers can see if all the patients with headaches, for example, respond differently from those with dizziness.

Another challenge will be figuring out how to measure whether patients’ brains are truly healing. “We don’t know what’s going on microscopically within their brain, but at least functionally their memory and things like that return back to normal [without treatment],” says Wright. The team plans to draw from peer-reviewed research to find measures that have proven successful in other studies.

Whatever the end result, Hotz believes the team’s quest for a concussion pill will be a meaningful step in traumatic brain-injury research, not to mention an imperative plunge into the medicinal components of one of the most hotly debated drugs in America. “Because cannabinoids and marijuana are getting such big press and usage now, I think somebody has to step out and start really doing the hard work, to really start looking at therapeutic windows, dosing, safety, and timing to make sure this is efficacious,” she says.