杏吧原创

ANDREW KOLODNY first noticed something was amiss in 2004, when his job as a medical director at New York City鈥檚 health department was to reduce drug overdose deaths. An expert in addiction treatment, he opened an evening and weekend clinic with the expectation that his patients would come from New York鈥檚 rougher neighbourhoods, where overdose deaths had been concentrated for decades.

But many of those who turned up came from wealthy areas like Long Island and Westchester. The majority of patients were in their聽20s and 30s. All were using prescription opioids, whether prescribed by their doctor or bought on the black market. 鈥淭hat鈥檚 when I recognised we had something awful going on,鈥� he says.

By this time tomorrow, from an accidental overdose of opioids. The opioid epidemic has . Many of these people defy the old stereotypes: they became addicted only after their pain prompted their doctor to prescribe painkillers derived from the opium poppy 鈥� the source of heroin.

If Kolodny had had his way, perhaps the catastrophe unfolding in slow motion across the US could have been averted. He has arguably fought harder than anyone to reduce the country鈥檚 opioid prescriptions, a campaign that has made him a hero to many. Others have dubbed him 鈥淜iller Kolodny鈥� and even 鈥渢he devil鈥�. Ranged against him is a pharmaceutical industry that has spent about a billion dollars in lobbying. Kolodny is regularly attacked by the very people he is trying to save: patients who are scared of losing legal access to drugs they believe are essential to ease their pain.

Within a few years of opening his clinic, there was growing evidence of an addiction epidemic. Kolodny thought, perhaps naively, that policy-makers would curtail opioid use for long-term pain treatment. But researchers who blamed the epidemic on the rise in prescription opioids found their work 鈥渞ipped apart鈥� in the pages of academic journals and at medical conferences by well-respected pain doctors. Many critics were later revealed to have been paid handsomely by the firms making these drugs. 鈥淚 realised we were going to have a harder time than I thought,鈥� says Kolodny.

Pharma firms were marketing to physicians in a big effort to destigmatise opioids. And it was working like a dream: opioid prescriptions quadrupled from 1999 to 2010. Overdose deaths involving opioids also rose sharply.

Before the late 1990s, opioids were prescribed only for severe, acute pain, and to palliative and cancer patients. Physicians were extremely careful with the drugs, due to valid concerns about their addictiveness. But there were millions of people with poorly treated chronic pain, and opioid makers saw an opportunity. Based on scant evidence, these firms, , convinced doctors that addiction was very rare, thanks to the development of sophisticated, time-release formulas. It was unfair, the argument went, to withhold these new opioids from people with back injuries, arthritis and other sources of chronic pain. Wanting to help their patients, doctors agreed. In 2007, Purdue agreed to pay $600 million in fines after pleading guilty to misleading the public about the addictive nature of opioids.

It isn鈥檛 clear exactly how opioids relieve pain. They create a surge of the feel-good chemical dopamine in the brain, and one idea is that the resulting euphoria masks pain. For short-term pain, such as in post-surgical situations, opioids can be very effective. But the dopamine release also 鈥渞einforces鈥� the drug-taking behaviour, as it does for eating or sex.

But the real driver of addiction, says Kolodny, is that 鈥減eople feel really bad without the opioid鈥�. Opioids inhibit the locus coeruleus system in the brain, which regulates fight-or-flight hormones. That鈥檚 why opioids are relaxing. But as the drug levels drop, the locus coeruleus begins to wake up, until it鈥檚 operating on overdrive. 鈥淵our brain is responding as if there鈥檚 a lion in the jungle ready to tear you to pieces,鈥� says Kolodny. The sense of impending doom, combined with other withdrawal symptoms 鈥� pain comes back with a vengeance too 鈥� makes people desperate for relief, and for that next dose. , according to a study by the US Centers for Disease Control and Prevention.

In 2010, outraged by what he saw as the failure of the US Food and Drug Administration (FDA) to tighten restrictions on opioids, Kolodny co-founded an advocacy group, . It created guidelines pointing out that the benefits of long-term opioids for chronic pain were not established and that physical dependence and tolerance can develop within days. In other words, patients need ever greater doses to achieve the same painkilling effect.

Pain doctors painted Kolodny and his peers as the 鈥渓unatic anti-opioid fringe鈥�, and PROP鈥檚 guidelines were largely ignored. But if anything, this made Kolodny more resolute. The way he describes it, it was as if he and the other nine initial PROP members were witnessing a disaster that no one in authority seemed to see. Convincing others of the reality he saw in his clinic and in national overdose statistics became an obsession.

He spent his spare time filing Freedom of Information Act requests for details of the pharmaceutical industry鈥檚 influence on FDA committees and major medical foundations. He shared his findings with journalists and created a series of educational videos. In one, he interviews Russell Portenoy, a pain-management specialist who benefited from substantial payments from opioid manufacturers. In a surprisingly candid moment, : 鈥淏ecause the primary goal was to destigmatise [opioids], we often left evidence behind.鈥�

In 2013, Kolodny finally got what he wanted: a key opportunity to make his case to the FDA. He was given 20 minutes to argue that a certain class of opioid drugs be put in a more restrictive category. The heavily lobbied FDA had resisted the move for years, but in 2013, law-makers pushed it to consult experts on the issue. The drugs in question, including Vicodin, combine the opioid hydrocodone with acetaminophen (paracetamol). The 鈥渧ast majority鈥� of addicted people got there through these combination drugs, says Kolodny, because all other opioids were in stricter categories and harder to obtain.

When the day came, Kolodny was so nervous he forgot to shave. 鈥淚 got there looking like a total mess, but I knew this was it,鈥� he tells me. He told the FDA: 鈥淎ll of us should be pretty lucky that we were born at a time when our environment wasn鈥檛 flooded with pain pills, because if we weren鈥檛, some of us might not be here today. We have a responsibility to protect this generation, and we鈥檙e failing. We鈥檙e losing a generation.鈥�

It was a powerful speech. Judy Rummler remembers it well. 鈥淗e was just so eloquent and so knowledgeable,鈥� she recalls. Rummler was there because her son, Steve, became addicted to opioids after taking them medically for five years. In 2011, days after he successfully completed rehab, Steve walked into a pharmacy and walked out with hydrocodone combination drugs. He had an old prescription on file that permitted refills. It was all too easy to start using again, and his addiction once again consumed him. He moved on to illegal heroin, and died of an overdose that same year.

On the afternoon of his speech, while Kolodny was still fired up, the FDA鈥檚 advisory committee voted 19-10 in favour of making the rules more restrictive. This meant people would no longer be able to get their prescription refilled without consulting their doctor. 鈥淭hat was probably the happiest moment of my life,鈥� says Kolodny. 鈥淚 was so high 鈥� like on-a-drug high 鈥� and it lasted for a couple of days.鈥� The tightening resulted in 1.1 billion fewer hydrocodone combination-product tablets dispensed compared with the previous year, a 22 per cent drop. But his success has come at a price. Advocacy groups for chronic pain patients, many at least partially funded by opioid manufacturers and distributors, claim Kolodny is responsible for making their drugs more difficult to access. Every week, he is the target of a barrage of angry messages on social media. A package of nails was once mailed to his house. The note it came with read: 鈥淚magine what it would feel like to have these stuck in your body.鈥�

In online forums, people on pain medication are claiming he owns stock in a chain of rehabs, or that he is bankrolled by the makers of Suboxone, an opioid replacement given for addiction. Kolodny maintains he has never taken money from the pharmaceutical industry, but he is generous in his reading of such reactions. Many patients genuinely believe their opioids are life-saving. 鈥淚f they go without a dose, they start feeling agonising pain,鈥� Kolodny says. 鈥淪o they鈥檙e convinced the opioid is treating the underlying pain problem, when it鈥檚 probably treating the withdrawal pain.鈥� A smaller group, he thinks, is worried about being cut off from the legal supply of the drugs they know they are hooked on. 鈥淭hey鈥檙e wondering, are they going to wind up going to a methadone clinic every day, or buying heroin. They鈥檙e petrified, and with good reason: we don鈥檛 have adequate addiction treatment.鈥�

鈥淵our brain is responding as if there鈥檚 a lion in the jungle ready to tear you to pieces鈥�

Do the personal attacks bother him? 鈥淚鈥檇 like to say they don鈥檛, but it does get to me.鈥� He quickly changes the topic. He prefers to talk about the evidence, the numbers, and has been doing it so long it is hard to get him to reflect on how that has affected him.

What Kolodny wants to talk about is why overdose deaths have rocketed in the past five years, despite opioid prescriptions falling by a fifth from 2010 to 2015. Some argue that crackdowns on prescribing have sent patients to the black market, something Kolodny disputes. People have been turning to it from the beginning, he says, as their addiction outgrew their prescriptions, or as doctors suspected addiction and stopped prescribing. Overdose deaths have risen sharply because the illegal supply has become more dangerous, Kolodny says: the synthetic opioid fentanyl is a big seller on the black market, and 50 times more powerful than morphine. It鈥檚 all too easy to take a fatal overdose (see Graph).

A heroin overdose killed Madelyne Lawry鈥檚 son, aged 33, in 2016 after he鈥檇 been off prescription drugs for nine months. He had struggled with addiction since being prescribed opioids for a year, due to a back injury at the age of 17. Two days before his death he called her, saying, 鈥淚t鈥檚 too hard, I can鈥檛 do it any more.鈥�

Lawry hasn鈥檛 met Kolodny, but has followed his work for years. She cried as she talked to me about him. 鈥淲hen we鈥檝e had all kinds of problems in history, there鈥檚 someone who will say: 鈥榳ait a minute鈥�. He鈥檚 that person,鈥� she says. Lawry recently called Kolodny鈥檚 employer to pass on her appreciation. She was surprised when he called back to thank her personally. 鈥淗e said, 鈥業 don鈥檛 get a lot of positive feedback.'鈥�

This article appeared in print under the headline 鈥淎gainst the tide in an ocean of opioids鈥�