Pubdate: Mon, 08 Dec 2014
Source: Denver Post (CO)
Copyright: 2014 The Denver Post Corp
Author: John Ingold


The Migration to Colorado by Families of Sick Children Seeking 
Medical Marijuana Is Fueled by Hope, Not Science. Little Is Known 
About the Treatment's Effects, and Researchers Suggest That Some 
Parents See Progress Because They're Desperate to See It.

Inside Children's Hospital Colorado, Ana Watson stares across the 
small exam room at the woman in a white lab coat quizzing her.


"Tried it," Ana says.


"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 different 
medicines, but Preston has already tried each one, to little effect.

August 20 Ana Watson gets a firsthand view of the trimming and drying 
process that goes into making the CBD oil she is using to treat her 
son, Preston.

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.

Was it working?

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."

No recommendations

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 
with 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 will soon 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 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 different types 
of CBD-rich marijuana therapies are represented in the studies.

The results swing wildly. The studies show anywhere from 30 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 out 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."

"An uncontrolled experiment"

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 up 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 
also 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.

"No. Not yet."

"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.
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MAP posted-by: Jay Bergstrom