Deadly Euphoria

For opioid addicts, it’s all too tempting to give the drug one more try. A heroin euphoria—temporary warmth, dulled senses, painlessness—slips away after 10 or 15 minutes, abandoning the addict to several days of withdrawal symptoms that could fade with the easy pleasure of one more dose.

It’s no surprise, then, that the odds of relapse for those with opioid addiction are grim: according to a 2010 study, nine out of ten patients relapse. Over half of those relapses occur within the first week. Nationally, opioid addiction is on the rise— the National Institute on Drug Abuse found in 2012 that nearly 670,000 people had used heroin, the most commonly abused opioid, within the past year, with over 150,000 new heroin users that same year alone.

Art by Annalisa Leinbach.
Art by Annalisa Leinbach.

To prevent death—and in the long-term, to help patients recover from persistent opioid use disorders—scientists are exploring treatments that may ease opioid withdrawal symptoms, including a medication called buprenorphine. The research raises a host of questions from policymakers, whose decisions impact the medication’s availability, and insurance companies, who decide when to help patients pay for it. How freely should drugs like buprenorphine be available? To what extent should they merit reimbursement? How can abuse of these drugs be prevented?

In a recent review, a team of researchers set out to give clinicians and policymakers the facts on buprenorphine. With Wayne State University professor Mark Greenwald and Yale professor David Fiellin, this team aimed to address concerns about the safety and necessity of larger doses of buprenorphine for clinicians and policymakers, and to defend the availability of buprenorphine.

The Challenges of Fighting Addiction

In order to understand how buprenorphine can help patients recover from opioid addiction, one needs to understand why this addiction is so difficult to manage. When a patient develops an opioid addiction, nerve receptors in the brain and other areas of the body get used to receiving opioid molecules. The body tries to adjust itself to the presence of these molecules, and in turn, it becomes physically dependent on the opioid to maintain an internal status quo. As the body adapts to the opioid, it craves more, and more, and more.

“You’re resetting the thermostat on your neurobiology,” said Mark Greenwald, a professor at Wayne State University who has done extensive research on substance abuse. “Those adaptations have a price when all of a sudden you stop using it.”

So what happens to the body when the opioid supply is cut off? A host of withdrawal symptoms hit: anxiety, insomnia, or muscle aches, followed by dilated pupils or vomiting. To ease the transition between addiction and abstinence, patients are tapered gradually off of medications to treat withdrawal symptoms and receive therapy and assistance from physicians—but recovery still isn’t easy. It’s all too tempting for addicted patients to put a stop to these symptoms by returning to the illicit drugs.

The solution? Help the body stop those withdrawal symptoms so that the patient can recover without the temptation of returning to illegal drugs. “To give the old analogy, it’s sort of a lock and key,” Greenwald said. The buprenorphine drug binds to the same receptors that were previously filled by the opioid particles. In doing so, buprenorphine performs similarly to how an illegal opioid would in the body. This reduces the severity of the withdrawal symptoms that the patient experiences. The more opioid-hungry receptors the buprenorphine occupies, the less craving the recovering addict has for the illegal drugs.

“What we try and do with [buprenorphine] is to reduce the availability of those receptors,” Greenwald said. “It will provide a safer replacement that helps start the person on the right track.”

A Scientific Call to Action

Greenwald and his team found that in order to be effective against withdrawal symptoms, buprenorphine had to be able to occupy at least half of the receptors that would otherwise be craving opioids. “Higher doses are generally demonstrated to produce greater reductions in illegal opioid use,” Greenwald said.

But here’s the problem: the question of how much buprenorphine each patient ought to receive doesn’t have a one-size- fits-all answer. Individual patients may require different amounts of buprenorphine to block enough receptors in order to adequately ease their withdrawal symptoms. And buprenorphine is often used as just one component of a multi-faceted treatment approach, which may also include therapy or treatment for other psychiatric problems. Even patients’ environments—whether their peers are using or encouraging them to return to opioid use—can impact their odds of successful recovery.

Clinicians have to toe a fine line in deciding how much buprenorphine to provide to patients. Recovering addicts need enough buprenorphine to ease withdrawal symptoms as they detoxify their bodies, or to prevent opioid cravings and highs during maintenance—but since buprenorphine provides a sensation similar to other opioids, it could become a source of recreational abuse.

Safety is an issue. Since buprenorphine is designed to make the body feel like it is under the influence of opioids, there is a risk that people might abuse it recreationally. Richard Schottenfeld, professor of psychiatry at the Yale School of Medicine, has worked with opioid addiction and buprenorphine. He’s watched the debate over the availability of the buprenorphine. Like other medications used to treat opioid addiction, buprenorphine “does have some abuse potential on the street,” he said. “If it’s not used as prescribed, it can cause some problems.”

Policymakers and insurance companies are wary of the costs and safety quandaries of buprenorphine. Many insurance companies are reluctant to cover an unlimited amount of the medication, and policymakers are concerned about making it too widely available or endorsing high dosages. They’re wondering where the limits ought to be drawn on how much buprenorphine can be provided and reimbursed.

Weighing the Risks

When Greenwald and his team put together their review of recent buprenorphine research, they did so with the intention of injecting scientific data into the controversy. “It had come to our attention that some policymakers were limiting the reimbursement for higher doses of buprenorphine,” Greenwald said, referring to Medicaid and some third-party insurance companies. “If you’re paying for somebody to receive treatments, your eye is on the bottom line… [but] that should not be the driving factor in our scientific decisions.”

“The impetus for doing this re-analysis was to try to come to a clearer overall understanding of what the data were telling us,” he said. But that research was hard to gather. The researchers faced an ethical obstacle: although they wanted to work with as large a sample size as possible, they couldn’t research the behavior of patients trying to recover from opioid addiction at the risk of harming these patients’ recoveries. Instead, Greenwald and his fellow researchers could only study the behavior of participants who were not currently seeking treatment for opioid addiction. Their study had to exclude patients for other reasons as well—such as those dealing with other psychiatric disorders that might affect their receptor abilities and therefore distort the research findings. Although there has been substantial research to prove the usefulness and relative safety of buprenorphine, there’s still much left to discover.

So, how should policymakers and clinicians weigh the risks of buprenorphine abuse and the cost of its administration against its potential benefits? Schottenfeld realizes that buprenorphine needs to be widely available enough that patients who need it can access it. Weighing the potential benefits of the medication as a means of decreasing opioid addiction against the chance of abuse, Schottenfeld believes that insurance coverage ought to be considered separately from how much buprenorphine a patient can receive. “I wouldn’t personally come up and say, ‘well, here’s a blanket way of giving it so we can avoid abuse possibilities,’” he said. Greenwald’s paper adopts a “use it or lose it” attitude: either the patient uses the drug appropriately to work toward opioid abstinence, or clinicians might consider cutting back on the amount of the drug that should be made available to the patient.

But perhaps the best way to evaluate the availability of buprenorphine is by weighing the gravity of the consequences if it’s not used.

“Opioid disorders are often chronic and lifetime disorders,” Schottenfeld said. As he puts it, if patients with hypertension, diabetes, or other lasting medical problems may need lifelong medication, then patients struggling with opioid addiction ought to be able to receive extended medications as well if necessary. Over a 30-year period, Schottenfeld said that half of patients with untreated opioid use disorders ultimately die from causes related to addiction.

“It’s important to keep that in mind,” he said. “This really is a lethal disease that we’re treating.”