The Age of Fentanyl

Ending the Opioid Epidemic

Brodie Ramin

• Publisher: Dundurn Press
• Year: 2020
• ISBN:
  9781459746725
• Topic: Medicine
• Subtopic: Pharmacology

Ottawa Book Award 2021 — Shortlisted • The Donner Prize 2020 — Shortlisted • Speaker's Book Award 2020 — Shortlisted Is there a way to end North America's opioid epidemic? "A fascinating, wise, and humane analysis of one of the most pressing health challenges of the 21st century." — Steven Pinker, author of Enlightenment Now In The Age of Fentanyl, Brodie Ramin tells the story of the opioid crisis, showing us the disease and cure from his perspective as an addiction doctor working on the front lines. We meet his patients, hear from other addiction experts, and learn about the science and medicine of opioid addiction and its treatments. He shows us how addiction can be prevented, how knowledge can reduce stigma, and how epidemics can be beaten. Dr. Ramin brings the hopeful message that just as patients and health care workers rallied together to fight HIV one generation ago, a coalition of patients, advocates, scientists, doctors, and nurses is once again finding solutions and making plans to stem the overdose deaths, block the spread of fentanyl, and end the epidemic.

CHAPTER 1

Knocking at the Door

One week started with frantic knocking on the bathroom door at my clinic. A young woman had gone inside, but something wasn’t right; she wasn’t answering the persistent banging on the door. As the staff’s panic rose, the door was unlocked and the pale, auburn-haired girl slumped forward, a needle at her side. Everyone knew she had overdosed, and they had the antidote naloxone at hand, but they also knew it was too late. She was too cold; fumbling fingers found no pulse. In the eye of the storm, she lay still, receiving ministrations of medication, oxygen, and CPR. She was pushed and implored to return to life, but she had already gone. Opioids had taken her.

Few people grow up wanting to work in addictions. I certainly didn’t. My childhood memories of substance use involve snatches of conversations and films. My parents discussing Amsterdam’s heroin problem and the use of methadone as a treatment on a trip when I was seven. The unspooling of a man’s life owing to alcoholism in a black-and-white film I watched in grade-nine health class. I was sheltered from drugs at school and in my community; they were hidden and suppressed. I went into medicine with plans to become an infectious diseases doctor, treating tuberculosis and HIV in the slums of East Africa. But in downtown Toronto, on medicine and infectious disease wards, in the shelters and outpatient clinics, I came face to face with addiction again and again.

Three men sat at the front of our lecture hall, each looking as unremarkable as the next. “I am an alcoholic,” one of them said. Our instructor spoke to us about alcoholism while the men added the details of their lives and experiences to his broad outline of facts and diagnoses. After that day, I was awoken to the presence of addiction all around us. I learned that one in six people has a substance use disorder during their lifetime and that many of them hide it well. The mask slips when their body rebels or they overdose. I saw that hospitals were filled with untended and hidden addictions. This thin man with the long brown beard injects cocaine; that woman is in alcohol withdrawal; this man’s heart is infected with bacteria that were forced into his vein through the tip of a syringe.

Working in Toronto’s homeless shelters and downtown hospitals, I saw opioid addiction at its most raw: the oozing, swollen abscesses from dirty needles and the fevers arising from bacteria run amok in the blood. The cliché I learned from watching old episodes of ER was “treat them and street them.” I never heard anyone actually use that term during my training, but we saw the revolving door of care for the tiny percentage of patients, those with the worst addictions, who would return, either in withdrawal or after overdoses, time and again. The acute issues were treated with world-class care and the patients were discharged back to the street or the shelter. Many times we tried to get them into treatment or to a methadone clinic or into housing, and sometimes it worked. I learned of the cruel interplay between opioid addiction, homelessness, disease, and poverty.

While I kept my interest in infectious diseases, I found it was addiction that was infecting and upending the lives of my patients with HIV and hepatitis C. And while so much had changed in the treatment of HIV since the widespread introduction of antiretrovirals in the mid-1990s, very little had changed in the treatment of addictions. HIV was no longer leading to AIDS, but addiction to opioids, alcohol, and tobacco was still taking the lives of my patients. I decided to train more in addiction medicine, and because of the depth of the need, every year I do a little more addiction medicine and a little less of everything else.

In 2006 I sat with my classmates and with dentistry and pharmacy students to learn about working together to treat pain. It was Pain Week at the University of Toronto. In a huge hall, our teachers spoke in sombre tones about the World Health Organization’s (WHO’s) pain ladder, the need to work up slowly in response to a patient’s suffering, from ibuprofen and acetaminophen to codeine, then up the ladder to morphine, hydromorphone, and fentanyl. They told us to be cautious and diligent, but in the emergency rooms and clinics, we saw our supervisors handing over handwritten prescriptions for hundreds of tablets of Percocet or for fentanyl patches that some patients admitted to misusing.

This situation was replayed in hospitals and clinics across the continent, where the seemingly unstoppable force of addiction repeatedly smashed into the fragile ramparts constructed to maintain prudent opioid prescribing. One common dilemma for physicians was separating addiction from the genuine needs of people suffering with chronic pain. A typical conversation went like this:

“I don’t have an addiction. I just have pain.”

“I see you have a lot of pain. You had a bad car accident and you’ve been on opioids for the past ten years.”

“That’s right, but my doctor wants to cut me off.”

“Do the opioids work for you?”

“Yes, but my pain is still really bad.”

“So why do you want to stay on the opioids?”

“Because they’re the only thing that works.”

“But they’re not working.”

“I don’t have enough, so sometimes I need to take extra.”

“Where do you get extra from?”

And that was when the whole story would come out: getting a few Percocets from a friend, then finding that chewing or snorting the pills made them work better, then starting to buy stronger opioids on the street. The more conversations like this I’ve had, the more I’ve been able to put the whole picture together for myself and for my patients who have resisted believing they have a problem with opioids.

These conversations have become easier in recent years because the culture of prescribing opioids has changed so dramatically. More awareness of the opioid epidemic means patients accept that they can no longer just storm out of your office and find a willing prescriber down the street; they accept that they need to work to find new and safer ways to manage their pain and their addiction.

A big reason these conversations have become easier is the work of Nora Volkow, the great-granddaughter of the Russian revolutionary leader Leon Trotsky. Volkow directs the National Institute on Drug Abuse (NIDA), a massive, multibillion-dollar addiction research and funding body. She has been called a general in the drug war — not the war on drugs, but the fight to combat and treat addiction in the brain and in society. Her life changed in 1981 when, as a newly minted physician, she read an article describing the use of positron emission tomography (PET) scanning to image the brain in real time. “It blew my mind,” she said of that eureka moment.¹ Brain imaging became her passion. She looked into brains afflicted by mental illnesses like schizophrenia and explored the effects of cocaine on the ebb and flow of dopamine in the brain.

A competitive swimmer and serious runner, she learned to change her own brain’s chemistry through exercise before she, or anyone else, understood the role of dopamine and other neurochemicals in shaping human motivation. Even as she led NIDA, she continued to build on her research into the brain and the science of addiction.

I remember one of my own eureka moments when, as a young addiction doctor, I read her paper on the neurobiology of addiction. I was sitting in a hotel room in Orlando as my children drifted to sleep, and I was transfixed by the awesome clarity and power of her science. So much of what I had been studying and attempting to explain to patients and their families came together.

Understanding that addiction is a chronic brain disease allows us to move past the counterproductive, blame-based explanations for it and the stigmatization of those who suffer from it. As the writer Lorna Crozier put it, “Those who know little about substance abuse see it as something unsavoury and shameful. Why don’t the drunks, the junkies, the smokers, the bulimics just smarten up? Pull themselves up by the bootstraps. Get some willpower. Stop.”²

As I sat in that Orlando hotel room, I read that a “more comprehensive understanding of the brain disease model of addiction may help to moderate some of the moral judgment attached to addictive behaviours and foster more scientific and public health–oriented approaches to prevention and treatment.”³ It can help remove stigma and foster compassion toward people with addictions.

Science can also explain why certain substances are addictive and others are not. Opioids are addictive because they release a cascade of pleasure-inducing molecules in the brain. We have opioid receptors scattered throughout our brain, our nerves, our lungs, and our intestines. When opioids enter the brain, our pain is numbed and we feel euphoric. But the brain is also where our respiration and alertness is controlled, and when opioids lock on to receptors in the brain stem, they reduce the drive to breathe. This manipulation in the centre of our brain is what makes opioids so alluring and so deadly. Someone who takes opioids will appear drunk, nod off, and speak in slurred confusion as the opioids turn down their level of consciousness.

Addiction is about dopamine. Addictive substances push dopamine to high, often massively elevated, levels in the nucleus accumbens, the reward centre of the brain. This is the high of the street vernacular. You get high, then you come down. You get dope, then you get dope sickness. You use. You need a fix, a drink, a toke. Stimulating the opioid receptors leads to a cascade in the brain that ends with increased dopamine.⁴ The writer William S. Burroughs described the experience of using opioids vividly in Naked Lunch: “Morphine hits the backs of the legs first, then the back of the neck, a spreading wave of relaxation slackening the muscles away from the bones so that you seem to float without outlines, like lying in warm salt water.”

Floating on a cloud is a common description of the first high.

Opioids constrict the pupils. Tiny pinpoint pupils are a sign of an opioid overdose, although other drugs, such as benzodiazepines and antipsychotics, can also constrict the pupils. When opioids hit smooth muscles in the bronchi of the lungs, they block the cough reflex, which is why heroin was originally marketed as a cough medicine and used to treat tuberculosis. When opioids hit the smooth muscles in the intestines, they paralyze the bowel, which leads to constipation, a near universal experience among opioid users.

A long-term effect of opioids is their impact on hormones. Opioids get into the hypothalamus and inhibit the release of two master hormones that control the production of sex hormones, including testosterone. Women will often stop having their periods after prolonged opioid use and men will notice reduced libido and increasing problems with erectile dysfunction.⁵

Many opioids are consumed in one form but are transformed — or metabolized — to become something different in the body. These metabolites may or may not be active. An older opioid that was widely misused was Demerol. It was pernicious because of the toxic accumulation of active metabolites, one of which caused seizures. Heroin is metabolized to morphine and to 6-monoacetylmorphine, both of which are active in the brain. Heroin is particularly reinforcing because it can pass quickly through the blood–brain barrier and work at high levels in the brain.⁶

Opioids affect the brain’s response to stimuli and impair decision-making. We are all creatures of habit, and addiction is a deeply ingrained habit. Think about an activity or food you love; then think about all the context that makes the experience so great. I love to run. So when I get out my running clothes and put on my running shoes, my brain knows that I’m about to experience the rush of neurochemicals associated with exercise. When you smell your favourite food, you start salivating before a morsel has passed your lips. So it is with drugs. Entering a room where you have used drugs or taking out the equipment to smoke or inject a drug leads your dopamine-producing cells to start firing in anticipation of the rush to come. Repetition turns opioid use into an automatic and compulsive behaviour. These changes in the brain endure; they last years after drug use stops, which is why addiction is a chronic disease.⁷

A few years ago, I was at a meeting about opioid addiction. To try to get us to understand the effect of the drug, one of the doctors in the room told a story from his youth about hiking through a rural area in Thailand with a companion.

“My friend was really starting to get on my nerves,” he said. “We’d been arguing about where we were going to travel next, and we were worried about running out of money. Then one evening, a group of men invited us to sit with them while they smoked opium. We both tried it, and when I inhaled on the pipe, I felt all my worries disappear and I felt so much love for my friend.”

For at least the first few dozen times a person uses an opioid, even a small amount, they feel euphoric; they feel no pain; they get sedated. But with extended opioid use — and this is a reason opioids do not actually work very well for chronic pain in the long term — people develop a tolerance. The brain is modified if exposed on a recurrent basis to a drug — any drug — and becomes less sensitive to that drug. The release of dopamine is diminished and so the euphoric effect of opioids is muted with recurrent use. One patient told me that he sometimes felt like every time he used heroin, he was actually chasing his “very first high.” The first high is the best, and for someone predisposed to becoming addicted, nothing else in life compares with the calm and warmth they experience the first few times they use a drug.

Ann Marlowe, a Harvard-educated writer, described this experience in her addiction memoir, How to Stop Time: Heroin from A to Z: “The nearest I can come to explaining to someone who doesn’t take illegal drugs the unrecapturable specialness of your first heroin high is to invoke the deep satisfaction of your first cup of coffee in the morning. Your subsequent coffees may be pleasant enough, but they’re all marred by not being the first. And heroin use is one of the indisputable cases where the good old days really were the good old days. The initial highs did feel better than the drug will ever make you feel again.”⁸

The tragedy for nearly all people who use drugs is that they never return to that initial state of bliss. With repeated use, smaller and smaller amounts of dopamine are released. People need to increase the quantity and frequency of opioid use. Even worse, they become less sensitive to the stimulation for non-drug-related rewards, and they lose motivation to do quotidian and necessary activities such as show up at work and maintain their relationships. The joys of drug use plateau and then decline, but so do the joys of life. Food doesn’t taste as good, careers become a barrier to using drugs, and love feels less like love.

It gets worse. Not only does the brain’s reward system flatline, but there is a concurrent rise of the brain’s anti-reward system, the network of brain pathways involved in stress and negative emotions. Chronic drug use makes the anti-reward system overactive. That is why people who use opioids chronically are more likely to develop depression and to stop caring about every aspect of life other than drugs. People who use opioids are pulled to the rewards of drugs while also being pushed to avoid withdrawal, depression, and pain. Over a short period of time, a person transitions from taking drugs in order to get high to using them to get a brief respite from depression.⁹ Rather than using to get the feeling of floating on a cloud, people begin to seek opioids to make the pain stop.

As Kevin put it one morning, as snow fell on the streets outside, “I’ve been taking everything I can get my hands on to kill the fucking pain.” It wasn’t pain from an injury or arthritis he was describing; it was the deeper and more pervasive pain of withdrawal and the anti-reward system.

He needed to vent. “The government says don’t use drugs because you might overdose, but they don’t say your life will also be shit for twenty years.”

It doesn’t have to be shit, I tried to tell him. He kept refusing to get on to an effective dose of methadone or buprenorphine, always agreeing to take a starting dose for a few days but then missing his appointment and showing up in bad withdrawal a few weeks later. I tried to explain that this pain, this depression, gets better with treatment involving a steady dose of an opioid substitute. But I knew he had to make his own decision about treatment. Although he would show flashes of anger against me, against the government, against the bullshit, he kept coming back, and I felt that was, at the le...

Table of contents

• Cover
• Half Title
• Copyright
• Dedication
• Contents
• Introduction
• 1 Knocking at the Door
• 2 The Story of Opium
• 3 The Engine of the Epidemic
• 4 Fentanyl Arrives
• 5 Explaining the Epidemic
• 6 Treating Addiction
• 7 Rethinking Our Relationship with Opioids and Big Pharma
• 8 Searching for Solutions
• 9 Expanding the Treatment Tool Kit
• 10 Treating the Whole Person
• 11 Breaking the Cycle
• Conclusion: Ten Steps Toward a Better Future
• Acknowledgements
• Notes
• Bibliography