The Woman With Knives in Her Neck

When traditional painkillers fail, is medical marijuana the answer?

By David Casarett|Thursday, August 27, 2015
woman-with-knives
woman-with-knives
Stuart Briers
There’s no such thing as a “typical” medical marijuana patient. The marijuana clinics that I’ve visited have encompassed a wide swath of society, and the people I’ve met are living proof of the diversity of this population. Nevertheless, my first thought when I meet Rachel in this particular clinic waiting room is that she doesn’t belong here.

Rachel is in her early 40s, blond and wearing a crisply tailored deep-blue suit that looks like it’s made of expensive silk. Just for comparison, the guy sitting next to her is a skinny, unshaven lad wearing baggy shorts, a tank top and flip-flops. He looks like he’s heading to the beach, while Rachel looks like she’s taking a well-earned break from a board meeting. Later I find out she’s the co-owner of a large chain of boutiques.

Rachel tells me that her experience with medical marijuana began about a year ago, when she was at the site of a new store. A piece of construction equipment fell on her, fracturing her cervical spine and initially leaving her paralyzed. After a month in the hospital, her spine was stabilized, and she was able to walk again.

But she was far from well because pieces of her spine damaged some of the nerves that emerge from the spinal cord. Those damaged nerves caused unpredictable episodes of sharp pain. Rachel tells me the pain feels like knives are stabbing her neck and shooting down her arms as far as her fingers. 

marijuana-jars
marijuana-jars
Good Meds medical cannabis center in Lakewood, Colo., lines its shelves with medical marijuana. Centers like this one are a resource for patients who need an alternative when typical pain relievers don’t work for them.
Matthew Staver/The Washington Post/Getty Images
“They hit me when I move the wrong way, but I can’t avoid them. They just . . . happen.”

Those attacks were so severe, and so unpredictable, they scared her away from regular exercise. Eventually she avoided walking her corgi, Max, or even doing the dishes because she was afraid that the wrong move would bring on another lightning strike. The drugs her doctors prescribed didn’t help much, and opioids like morphine made her feel “drugged.” So she turned to marijuana.

Rachel tells me that once she started using it, two things happened. First, as she’d hoped, the bouts of pain became less severe. Then as her pain improved a little, she became less afraid of the next episode. She began to exercise more. She took Max for long walks. And then she started seeing her trainer again for light aerobic workouts. Soon it seemed that the spells of pain became less frequent.

She uses a marijuana-based oil in a vape pen. These devices are like e-cigarettes, except that they deliver tetrahydrocannabinol (THC) and cannabidiol (CBD) instead of nicotine. Rachel tells me she uses her vape pen “all day.”

How many times in a typical day?

Rachel thinks carefully. “A dozen.”

I’m not sure what my expression reveals, but it causes her to re-evaluate her estimate — though not in the direction I expected.

“Maybe two dozen?”

I’m having trouble imagining the effects of 24 doses of THC, the ingredient in marijuana that produces the “high” feeling for which it’s so well known. I’m also wondering how that regimen might affect a daily routine that involves managing a chain of clothing stores. But Rachel seems bemused by my questions.

“Well, we opened two new stores in the last three months. I must be doing something right.”

Brain Bubble Wrap

Is she doing something right? Could the ingredients in marijuana be effective in treating pain? To find out, I track down a researcher who has thought a lot about this question.

Barth Wilsey is tall and baby-faced with short-cropped hair and the peaceful gravity of a Buddhist monk. He’s an anesthesiologist by training, and he’s done some of the most interesting research I’ve seen on marijuana and pain. As I tell him Rachel’s story, Wilsey listens patiently, nodding. He tells me it was people like Rachel who led him to study the uses of marijuana in treating pain. Wilsey recalls how, two decades ago, when he was in a pain fellowship in San Francisco, many of his patients got marijuana through a buyer’s club in Oakland. They told him it was the only treatment that worked.

pain-types
pain-types
Alila Medical Media/Shutterstock and Alison Mackey/Discover
“That,” he says, “really grabbed my attention.”

Then he says something that grabs my attention.

“Those people all had neuropathic pain, like Rachel did.”

What he means is that they had a very specific type of pain. Neuropathic pain isn’t caused by a direct injury, like arthritis or a broken bone, that stimulates normal pain nerves — that’s nociceptive pain. Instead, neuropathic pain is caused by the nerves themselves.

To understand neuropathic pain, it helps to think about the way that electronic devices like pagers and cell phones work. When I was a resident, two of us had to carry a “code pager” at all times. This was the pager that would go off if someone had a cardiac arrest anywhere in the hospital. Because these devices were so important, they were designed to withstand the apocalypse. To make them especially dependable, these pagers operated on local emergency radio channels that were bulletproof, but filled with static. So every once in a while, a pager would spring to life, emitting an unintelligible squawk and three beeps that would send a confused resident scrambling for the door, until it became apparent that it was just a false alarm.

That’s how neuropathic pain happens. An injury to a nerve creates static, but pain nerves don’t know how to interpret static any more than those pagers knew how to interpret it. Instead, nerves that carry pain signals interpret static just like they interpret any signal: as pain. Just as those emergency pagers interpreted static as an emergency and let loose a blood-curdling squawk, nerves that carry pain assume that static represents a painful stimulus, and that’s what they tell the brain.

Wilsey is particularly interested in Rachel’s story because he thinks that if marijuana can treat pain, it’s probably most effective against neuropathic pain. And he believes it is effective. In fact, he tells me about several studies that he and others have done, finding that people like Rachel report much better pain relief.

How does marijuana relieve pain? This is where things get interesting, because what Wilsey tells me is not what I expected.

“You’ve got your glial cells,” he says. “They’re the predominant cell type in the brain.”

I’m confused by this because glial cells are known primarily as the brain’s immune cells. They help to scavenge and clean up debris, but they aren’t involved in thinking or movement, as neurons are.

So how could glial cells be involved in treating pain? I admit somewhat sheepishly that I’ve always thought of them as sort of . . .

“Bubble wrap,” Wilsey says.

Bubble wrap?

“People used to think of glial cells as the bubble wrap of the brain. They’re cells that the important neurons are packed in. Helpful, even essential for immune function. But neurologically inert.”

CBD-THC
CBD-THC
CBD and THC, two of the main active ingredients in marijuana, are gaining the attention of researchers because of their pain-relieving potential.
Mauro Fermariello/Science Source
I love this analogy, but I learn that it’s not true. Wilsey explains that glial cells aren’t just structural, and they’re not just immune cells. They may have a big role in pain management. For instance, we know that they have receptors that bind to THC.

He’s not sure yet how those glial cells are involved in pain, or how marijuana might act on them to provide pain relief. One theory is that glial cells have some sort of modulating effect on neurons. That is, they might reduce neuronal activity, in much the same way that my fellow residents and I would turn down the volume on those code pagers as far as we could. That adjustment wouldn’t eliminate random beeps, but it did make them less startling. Perhaps those glial cells work through cytokines, which are molecules that coordinate the body’s response to inflammation, but we don’t really know. Whatever the mechanism, Wilsey is convinced that these glial cells are much more than bubble wrap.

If Wilsey is less interested in neurons than he is in glial cells, he’s also less interested in THC than he is in the lesser-known cannabinoid CBD.

THC and CBD have a fascinating relationship that’s a little like the one between Don Quixote and Sancho Panza in Cervantes’ picaresque tale. The Don was a loopy aristocrat with odd delusions of chivalry and a skewed perception of reality that led him — among other adventures — to imagine that a windmill was a giant against which he was honor-bound to battle. Sancho, on the other hand, was the humble servant and the practical, common-sense squire. He did his best to keep his master on the straight and narrow path, or at least to prevent him from doing too much harm to himself, or to windmills.

You can think of THC as the Don Quixote of marijuana’s cannabinoids. Its receptors are scattered all over the brain, in the cortex, in the cerebellum and in the reward centers, among other places. So it can make you goofy, confused, high and even paranoid. All those are the quixotic effects of THC, and it’s because of those effects that THC is the cannabinoid everyone notices, just as Don Quixote got top billing.

CBD, on the other hand, is more like Sancho Panza. Its most notable characteristic is what it doesn’t do. Specifically, it doesn’t produce any of the psychoactive effects of THC. It doesn’t make you feel high or paranoid, and it doesn’t make you hallucinate. Like Sancho, CBD does whatever it does quietly, and almost invisibly.

But just as Sancho is as important — in his own way — to the tale as his master is, it’s possible that CBD might be more valuable than we thought. And maybe THC isn’t as necessary as we’d assumed.

Indeed, Wilsey tells me that this possibility has led him and other researchers to reconsider the way they design clinical trials of medical marijuana for pain. Most trials, he says, focus on marijuana’s THC content. CBD content, in contrast, is mostly an afterthought. But Wilsey wants to do trials of marijuana that contains more CBD and less THC, at a ratio of 5-to-1 or higher. He thinks that marijuana with a lot of CBD might lead to greater pain relief and perhaps fewer psychological side effects.

Wilsey tells me that already his studies have pushed THC levels lower and lower. Initially he used marijuana with a THC concentration of 7 percent, then he reduced that to 3.5 percent, and then to as low as 1.3 percent. In each subsequent study, he found as much pain relief, but fewer psychological side effects.

Neuropathic pain is Wilsey’s specialty, but I wonder what he thinks about nociceptive pain. Remember, that’s the more common kind of pain you have with arthritis or if you pull a muscle or break a leg. It’s also the kind of pain that I often see in my patients with advanced cancer.

Wilsey shrugs. “We’re not really sure, but there’s reason to think there might not be much benefit.”

trichomes
trichomes
A close-up of glandular trichomes on the leaves of a cannabis plant, like the one pictured at left. Trichomes protect the plant, but they also secrete numerous compounds, including cannabinoids such as THC.
Antonio Romero/Science Source
As evidence, he tells me about studies that have used a common laboratory test of pain. You expose volunteers’ skin to a piece of metal heated to a temperature most of us would agree is uncomfortable (about 113 degrees Fahrenheit). That’s their “pain threshold.” Then you see whether a drug lets them tolerate a higher temperature without squirming. Wilsey says that marijuana doesn’t seem to increase pain thresholds as much as some other drugs, such as morphine.

Wilsey says we don’t know much about the effect of cannabinoids in regular nociceptive pain because there just haven’t been many studies. Most of the research has been on neuropathic pain because that kind of pain can be very difficult to treat. Rachel had visited multiple specialists and received countless drugs. Those drugs didn’t work, or caused unacceptable side effects, or both, so she was ready to try anything.

On the other hand, patients with more common nociceptive pain have numerous treatment options. There’s acetaminophen (Tylenol), which has been around for decades because it works, as well as non-steroidals like ibuprofen (Motrin) and opioids like morphine. They all work well, so there’s little pressure to come up with another drug to treat nociceptive pain.

As Wilsey says goodbye, I’m thinking that maybe Rachel was onto something. There’s research evidence that what she was doing works, and there’s even growing evidence about how it works. That’s as much as we can say about most drugs, and more than we can say about many.

Less Pain And Less Morphine? 

There’s one more element of Rachel’s story that I’m curious about. She wasn’t using marijuana only because it helped her. She also wanted to avoid the side effects of opioids like morphine.

Many of my patients would prefer to replace their opioids with something else if they could. Opioids can cause nausea and dizziness, especially at first. They cause constipation, too, often requiring the use of laxatives every day. And they can make you sleepy, forgetful and sometimes confused.

Could marijuana help someone to reduce the dose of opioids, or stop them altogether?

To answer that question, I seek out Jonathan Gavrin, a physician who has given more opioids to patients in a day than most doctors give in a year. Like Wilsey, he’s an anesthesiologist. But he’s also a palliative care physician who knows a lot about pain management. Gavrin is wiry and compact, with short hair and narrow rectangular glasses. He looks a little like a younger, fitter Kevin Spacey.

When I tell him about Rachel and her desire to avoid opioids, he nods energetically: “Oh, sure. I know that’s true.” Gavrin proceeds to tell me about his bad experiences with opioids and other drugs after he underwent a knee replacement a couple of years ago.

“They made me sick. Really sick. Hated it.” He pauses. “No euphoria, though. They didn’t make me feel good. Just crappy.” He laughs, “I got ripped off.”

So if marijuana could reduce the need for opioids? “That would be great. We don’t want our patients drowning in a pharmacological soup,” Gavrin says.

Yet we do inflict this on patients, all the time. We add drugs on top of drugs, and Rachel was by no means the only victim of a doctor’s prescription pad. I tell Gavrin this.

He laughs again. “Well, of course. We desperately want to make people feel better. So we do everything we can to help. That’s why we’ve developed such a drug culture. It’s hard to see people suffer, so we reach for a prescription pad. Maybe we get lucky with the first drug, but sometimes not, and we add, and add.”

marijuana-rx
marijuana-rx
CapturedNuance/iStock

I tell Gavrin about a study done in San Francisco by Donald Abrams, an oncologist and prominent medical marijuana researcher. He wanted to find out whether marijuana might complement — and perhaps reduce — opioids like morphine. He wasn’t trying to get people off opioids per se, but he knew that his patients often wanted to reduce their opioids if they could.

That study enrolled 21 patients, all of whom had pain for which they were taking scheduled opioids, such as morphine or oxycodone. Although some had neuropathic pain, many had regular nociceptive pain. Abrams found that patients who were given marijuana had less pain, but they had the same blood levels of opioids. So the cannabinoids in marijuana — primarily CBD and THC — might work together with opioids to give better pain relief, and that creates the possibility that marijuana might help patients get what Rachel wanted: comfort without the side effects of opioids.

Marijuana’s promise of pain relief is impressive in its own right, but when you add in the possibility of avoiding other drugs, and their side effects, it starts to look very appealing. Of course, marijuana has side effects of its own, ranging from a dry mouth and rapid heart rate to confusion and paranoia. But Rachel figured out a way to avoid those, through small frequent doses.

And that opportunity to tweak and customize and improve your treatment through trial and error might be the single most impressive promise of medical marijuana. Instead of taking pills that she was given, Rachel much preferred to find her own way, experimenting on herself until she found a regimen that worked for her. Although it was the end result of better pain management that she was looking for, her newfound control over her own health and the satisfaction of solving problems for herself was an unexpected but welcome bonus.

And could marijuana help other people reduce or avoid prescription medications?

“That,” Gavrin says, “would be cool.”

stoned
stoned
From Stoned by David Casarett, published July 14, 2015, by Current, an imprint of Penguin Publishing Group, a division of Penguin Random House LLC. Copyright © 2015 by David Casarett, M.D.
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