“We’ve tried it all” AN EMPTY FEELING. With saliva leaking from his mouth, Preston experiences an absent seizure, which looks and feels like it sounds: He stops interacting and stares into Keppra And CBD Oil Interaction Self-determined tendencies to use cannabis (SDTC) monotherapy may occur in some patients. Two cases of SDTC monotherapy had associated mortality. The decision
“We’ve tried it all”
AN EMPTY FEELING. With saliva leaking from his mouth, Preston experiences an absent seizure, which looks and feels like it sounds: He stops interacting and stares into nothing.
Inside Children’s Hospital Colorado, Ana Watson stares across the small exam room at the woman in a white lab coat quizzing her. Banzel? “Tried it,” Ana says. Keppra? “Is that the one that causes the rash?” Ana asks. “Keppra often causes behavioral issues,” the doctor responds. “Yes, that’s what we got with that,” Ana says. The doctor continues down the list of anti-epilepsy medications, collecting the medical history of Ana’s 12-year-old son, Preston, whose seizures cause such unrelenting brain damage that he functions at the level of a 2-year-old. The doctor ticks through 13 medicines, but Preston already has tried each one, to little effect.
That’s why Ana moved her family across the country to Colorado, where Preston could try a treatment that’s not on the doctor’s list. Three days before the doctor’s appointment in mid-July, Ana gave Preston his first dose of an unregulated medical marijuana extract that is high in a compound called CBD. Hundreds of families like Ana’s have moved to Colorado for the treatment, hoping it will calm their children’s seizures.
A desperate hope and well-publicized stories about kids who have responded to the drug drive the families here, despite scant research on CBD’s overall efficacy. Scientists know so little about the treatment that it’s not even clear what CBD might do in the brain to impact seizures.
So, the entire day after that first dose, Ana watched Preston like a poker player looking for a tell.
Preston yawned. Did that mean the marijuana made him sleepy? Preston ate. Did the extract make him hungry? Preston didn’t seem to seize as often.
Then the next day, Preston suffered a grand mal seizure that left him writhing violently. He had another one the day after that. Getting him to eat or drink had become nearly impossible, and that meant he wasn’t getting consistent doses of either the CBD treatment or his traditional medications, both of which Ana tried to hide in Preston’s food or sweet tea.
So now Ana is sitting in the hospital whose doctors have been the most outspoken in Colorado in urging parents not to use marijuana to control seizures — it’s too risky, they say; there are too many unknowns — and she is hoping for advice on what to do.
Ketogenic diet, the doctor asks?
“Basically, we’ve tried it all,” Ana says. “That’s why we moved here for CBD. His doctors said we can’t go up in his meds anymore, and we were at a stopping point.”
The doctor looks at her list. She looks sympathetically at Ana.
“Have you tried Stiripentol?”
“Yes,” Ana sighs, “we’ve tried everything.”
The CBD rush to Colorado is a movement that divides patients from doctors.
Even as families flock to the state, few doctors here condone the use of marijuana to treat seizures. And that means the very people on whom families depend for medical advice are often silent when it comes to critical questions about the new treatment.
The state health department, which manages the patient registry that all children using medical marijuana must join, offers almost no guidance.
“What I always tell people is you have to be really careful,” said Dr. Larry Wolk, the executive director of the Colorado Department of Public Health and Environment. “They have to know that it’s outside of the regulatory process, outside of the (Food and Drug Administration), and it’s very much ‘Buyer beware.’ “
Many of the families arriving in the state for medical marijuana — as well as those already living here — seek out the care of specialists at Children’s Hospital Colorado. About 100 kids who see doctors at the hospital have tried a CBD treatment.
But no doctor at Children’s recommends using cannabis or gives more than cautious advice about it.
“We don’t make recommendations about the marijuana therapy because we don’t have the information to do that,” said Dr. Amy Brooks-Kayal, the head of pediatric neurology at Children’s. “We feel very strongly that we need to act on good medical and scientific evidence, and that doesn’t exist.”
A national survey of doctors by the American Epilepsy Society found that while 94 percent said they have been asked by a patient about using cannabis to control seizures, fewer than a third would actually recommend that patients try it. Another 13 percent said they would support its use but would rather have another doctor provide the recommendation needed to obtain it.
“For the doctor to know what they need to know about an illegal drug is a very high expectation,” said Dr. Jacqueline French, an epilepsy specialist at New York University’s Langone Medical Center. She said CBD is “driving the conversation” many doctors now have with their patients.
The result of that one-sided conversation, though, is that parents who give CBD to their children must turn to one another and their medical marijuana providers for help. Facebook has become a crowd-sourced doctor’s office. Colorado’s sometimes ragtag community of medical marijuana growers acts as a de facto human services agency.
By not engaging more with providers, doctors often lack an understanding of the types of marijuana products their patients are using and are unaware of the sometimes contradictory advice their patients receive.
For instance, CBD providers commonly tell newly arrived parents that they should reduce the level of an anti-seizure drug called Onfi before starting CBD because the two could have a dangerous interaction. Parents often reduce the medicine without consulting their doctors. Doctors at Children’s, though, say they haven’t seen conclusive evidence that CBD has an impact on Onfi levels. Meager research makes it impossible to know who is right.
Some physicians are now stepping forward to work with providers on clinical trials for CBD, and doctors at Children’s have begun recording more specific details of the CBD products their patients are using — who is providing the medical marijuana and how much the child is taking, for instance. But the broader dynamic still hinders the study of CBD’s effectiveness. And that only increases the uncertainty that hangs over families such as Ana’s in their Colorado exile.
Leaving Children’s after the first visit, Ana still has questions about CBD. But doctors there have set up several new appointments to address other aspects of Preston’s care. He soon will have a feeding tube inserted into his stomach, allowing Ana to give him food and medicine consistently. She’ll take him to get fitted for a new helmet to protect him in falls.
A plan is taking shape.
“I thought it went really well,” she says.
Parents hope to see progress
Two days later, they’re back again. A blue line squiggles furiously up and down on a computer screen.
Preston is talking.
“Silly mommy,” he says to Ana, as she snuggles into a single hospital bed with him.
“Silly Preston,” she says back.
He leans in to give her a kiss on the cheek. A maroon line on the computer screen jumps to life.
A bundle of 21 multicolored electrical wires poke from the top of a wrapping on Preston’s head, running off the bed and to the computer. Every gesture, every word, every eye blink shows up as activity on the screen, where blue, maroon and green lines measure Preston’s brain activity. It is one answer to the question that has vexed Ana for the past 12 years: What is happening inside her son’s head?
But, even now, the seizures from a rare form of epilepsy known as Dravet syndrome remain a mystery. Some little eye-flutter seizures cause leaping spikes on the screen. Some seem to skip by without a change in the pattern. So chaotic is Preston’s brain that, looking later at the electroencephalogram, or EEG, doctors will have a hard time telling from the readings when he was awake and when he was asleep, when he was seizing and when he was still.
At the end of their first visit, Dr. Kelly Knupp, Preston’s new neurologist at Children’s, suggested the EEG so that the hospital could have some starting record of Preston’s brain activity. The timing worked; Preston was already in the hospital, after the feeding tube surgery the day before.
But, to get a true starting level, the EEG meant Ana would need to take Preston off CBD temporarily. She had spent seven months planning how to get to Colorado for the treatment. She was pausing it after five days.
“The point of this is to get a baseline,” Knupp had told Ana, “so that after you’re on CBD, you can have a baseline to look at.”
While doctors at Children’s don’t exactly want their patients on CBD, they are eager to find out what it’s doing. Knupp told Ana that doctors at the hospital now recommend all patients have both an EEG and a bloodwork exam prior to starting CBD. They would like to run follow-up tests every three or four months.
The results from the first batch of CBD kids tested made their way into a study that Knupp and two other doctors will present this week at the American Epilepsy Society conference in Seattle. Of the 58 children tested, 31 percent saw their seizures reduce by half, the study found. About 50 percent of the patients saw at least some seizure reduction.
But the results were ultimately even less conclusive.
The doctors relied on parents to report how much CBD reduced seizures. And that opened the door for the study’s two most intriguing findings.
The hospital didn’t see any improvement in the before-and-after EEGs of four kids whose seizures appeared to lessen significantly. That may have been due to something called “electroclinical dissociation,” where the seizure still occurs but its outward indicators disappear. It also might be that parents can pick up on smaller improvements than an EEG can, said Dr. Kevin Chapman, a pediatric neurologist at Children’s who was a co-author on the study.
But the study also calls into question parents’ ability to be objective. The doctors found that parents who had moved to Colorado for medical marijuana were much more likely to report that it had helped their children significantly than those who were already living in Colorado — 52 percent compared with 17 percent. In other words, the greater the leap of hope it took to try CBD, the more likely a parent was to see progress.
“We worry about all the stresses that families had to go through to start the treatment,” Chapman said. “That desire for it to be effective may cloud their recognition of seizures.”
Supporters of the CBD treatment say Children’s sample was skewed because the hospital might not be seeing the kids doing best on medical marijuana. State health officials have recommended that Children’s receive nearly $1 million in grants for further research.
Even if the treatment is successful, though, no one knows what will happen if kids who have seized their whole lives suddenly stop. Do they develop normally? Or does their underlying condition continue to inhibit their growth?
Including the new Children’s study, the nine studies or surveys looking at whether CBD controls seizures in humans form a scientific crazy quilt.
They look at different forms of epilepsy, different kinds of seizures and different measurements of success. At least five types of CBD-rich marijuana therapies are represented in the studies.
The results swing wildly: The studies show 30 percent to 80 percent of children seeing a significant seizure reduction while on CBD. And now even some doctors involved in the research question the findings.
Dr. Edward Maa, an epilepsy specialist at Denver Health Medical Center, worked with the most famous CBD provider in Colorado, the Realm of Caring, and a Colorado Springs medical marijuana doctor on a patient survey — one of the earliest studies on the efficacy of CBD in the state. The study found that nine of the 11 families surveyed saw at least a 75 percent reduction in seizures. It was an overwhelming success rate.
But now Maa wonders whether families who tried CBD with little success quit using the treatment before they could be included in the study. The Realm of Caring says only one patient had stopped using CBD at the time the survey was conducted. Maa is working on a genetic study trying to determine why some kids respond to CBD and some don’t.
“The vast majority of people, if they were going to respond, had a dramatic reduction of seizures,” Maa said. “That doesn’t represent the larger, global number of people who had exposure to it. We don’t know those true numbers yet.”
A faint smell of cow manure wafts in the breeze as Ana pulls her minivan up to a house in eastern Boulder County.
In the five weeks since Preston left the hospital, Ana has restarted him on CBD — now shooting it efficiently into his feeding tube. Preston went the first two weeks without suffering a grand mal, but his blinky seizures remained.
“But they don’t seem to me to be as long,” Ana said.
The CBD oil she was using then was a roughly 35:1 mixture of CBD to THC. But Ana, concerned that she wasn’t using the best formulation, sought out the opinion of a Denver doctor who specializes in making medical marijuana recommendations. The doctor, Alan Shackelford, suggested Ana try a mix with more THC.
“In a way,” he told Ana, “it’s an uncontrolled experiment. Which I don’t necessarily like. But we are pressed into this circumstance.”
So Ana visited her CBD provider, who gave her oil at a 10:1 ratio of CBD to THC, and the next day she watched as her son ate better than he had in months: a plate of fried okra, a plate of potato chips smothered in barbecue sauce, a stick of string cheese, a Frosty and, most surprising of all, tuna salad with crackers.
Preston’s grandmother, Milly, thought he had the munchies.
“But you have to be careful that you’re not making things in your brain,” she said. “We’re all watching him and his behavior.”
While Preston played later in the backyard August sunshine, his eyes seemed to roar.
The toy was a Slip ‘N Slide, on which he and his sister, Sydney, were supposed to be shooting across the tarp and under an inflatable shark’s mouth that held a spraying hose. Instead, Preston grabbed the hose and became the shark.
His hunting spared no one. He drenched Milly. Sydney escaped back inside, water dripping down her hair. And Preston laughed with such big gulps of air that it sounded as if his own joy might strangle him. Until, suddenly, his laughter stopped.
Preston’s legs folded under him, and he crashed hard to the ground. Milly burst from her chair and ran over to him, reaching him in time to see his eyes roll toward his brows. And then, lying there in the grass he had soaked, Preston began to shake violently.
“It’s OK,” Milly whispered into his ear, trying to talk him out of the seizure. “It’s OK.”
Milly gathered Preston and sat him on her lap in a chair. He breathed heavily, wheezing in and huffing out. His eyes were shut.
“It’s OK,” Milly whispered again. “It’s OK.”
The shaking calmed.
“We pushed that too far, didn’t we?”
Preston’s breaths grew quieter.
“You were being a big, mean shark. It’s OK.”
His muscles relaxed.
“It was fun, though, wasn’t it, Preston?”
A roller coaster
The seizure — the second grand mal in a week — flustered Ana. And that’s why she finds herself back at the house in eastern Boulder County. Jason Cranford meets her on the porch.
Although he owns a medical marijuana store and several licensed cultivation warehouses, Cranford provides CBD to young patients out of his home under the state’s less-stringent regulations for medical marijuana caregivers. He says it keeps the cost down for patients and creates a more personal atmosphere.
After he harvests his marijuana plants, he hangs them over the arms of a weight bench in his front room, ready to be trimmed. He extracts the oil in a lab he assembled in his garage. When families arrive, his German shepherd is there to greet them.
Soon, Jason hands Ana new bottles of cannabis oil. This time, he’s giving her one bottle of high-CBD oil and another bottle containing high-THC.
Now she can make any ratio she wants, Jason says. It’s the third formulation change since Preston started the oil six weeks ago.
She asks about the amount she’s giving. “Should I up it?”
“Are you seeing any results?” Jason asks.
Ana’s reply is quiet.
“Then you need to up it,” Jason says.
In the next week, blinky seizures will overwhelm Preston each afternoon. A week after that, Ana will write on Facebook, “Preston started a new ratio oil yesterday higher THC, today only being on it for the second day we saw 70-80 percent seizure reduction. BAM. Bite that seizures. ” And then a week after that, Preston will have three grand mals in a day. A roller coaster, Ana will call it.
But for now, she walks back to her minivan and returns home to try again.
She’s learning that when it comes to Preston’s treatment, traditional medicine and marijuana have at least this much in common: There are still far more questions than answers.
John Ingold: 303-954-1068, [email protected] or twitter.com/johningold
Keppra And CBD Oil Interaction
Self-determined tendencies to use cannabis (SDTC) monotherapy may occur in some patients.
Two cases of SDTC monotherapy had associated mortality.
The decision to use cannabis monotherapy may not be a benign substitute for traditional anti-seizure drugs.
Mortality associated with cannabis used for treatment of epilepsy is not well documented. We discuss two fatalities in the setting of epilepsy and self-determined therapy with cannabis (SDTC). One patient had probable sudden unexpected death in epilepsy, the second death was due to seizure-associated drowning. Both directed SDTC over conventional anti-seizure medications. Where recreational cannabis is legal, decisions to use cannabis are often self-directed and independent of physician advice of cannabis risks, in part because physicians may not be aware of the risk of SDTC. Further study of morbidity and mortality of SDTC in patients with epilepsy is needed.