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They compared two groups of rats, one of which was fed sugar water until that group of rats was dependent. The other group was fed just straight water. Researchers injected both groups with minute doses of amphetamine. The rats not dependent on sugar showed no effect. The sugar-dependent rats, however, turned hyperactive. This suggested that when these animals grew dependent on sugar, it “primed” them to use another drug.
Dependence on one substance, in other words, prepared them for dependence on another.
At one point, eighteen of Janssen’s innovations were on the World Health Organization’s Model List of Essential Medicines. Janssen invented haloperidol—known commercially as Haldol—which calms the hallucinations of schizophrenics and allows them to be treated at home. The drug effectively ended the era of the insane asylum by convincing policymakers to release thousands of institutionalized mental patients who up to then could only be treated in a hospital.
(In 1961 Janssen sold his company to Johnson & Johnson, while retaining control over his research laboratory. For years he was Johnson & Johnson’s largest shareholder.)
One of these way stations—the mμ receptor—controls pain, our bowels, and our breathing. Mμ receptors were later called “opioid receptors” because drugs derived from the opium poppy seem to fit on them and produce extraordinary effects: constipation, slower breathing, sometimes euphoria, and reduced pain.
Janssen called his invention fentanyl.
Janssen riffed off the piperidine ring over the next two decades, finding new molecules to hit the opioid receptors no matter where they were in the body. One place they reside is our bowels, which is why opiates create constipation. (Thus diarrhea is a common symptom of opiate withdrawal, as the body rebalances without the drug.) Janssen surmised that the piperidine ring might also be the basis for an antidiarrheal medicine. Trial and error led him to discover loperamide (brand name: Imodium), an opiate that attaches to receptors in our bowels but cannot cross the blood barrier into the brain
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The drug was a narcotic when administered to humans; it doped them, slowed them, sent them into a stupor. But it threw horses into a manic rage—cats, too, for that matter. Opioids, in fact, tend to produce strange effects in mammals other than humans. Fentanyl will turn a rat stiff, to the point where you can stand him on his head. A horse on fentanyl will tear up a stall. On the track, the drug pushed the horse to extremes.
Meanwhile, a new pharma business model emerged: find a blockbuster drug and hire a legion of young sales reps to convince doctors of the miracles being invented. Nationwide, the pharma sales force ballooned from 38,000 in 1995 to more than 102,000 in 2005.
As agents busted these sites in those first years of street fentanyl, they discovered one of the reasons for this surging mortality. The amateur fentanyl mixers’ tool of choice, it turned out, was the most successful product in the history of infomercials: the Magic Bullet blender.
Blender blades spin; spinning blades create a vortex, and an effective mix, when the substance is a liquid, but none at all when the substances are dry powders. When both powders are white, it not only creates a notoriously bad mix, but also is impossible to tell how poor the mix actually is.
in August 2018, federal prosecutors in Cleveland went public with the indictment against the Zhengs. US officials shut down their websites and froze their assets; the US Treasury designated the Zhengs as drug kingpins. Nine months later, the Chinese government banned all forms of fentanyl, except that produced by companies the government licenses to manufacture it. With that, China’s role as a provider of illicit fentanyl faded.
Medical studies have found that two-thirds of patients using opioid painkillers for more than ninety days were still using them five years later.
Opiate addicts avoid old friends who might provide care, love, and healthy ballast by reminding them who they once were.
Our revolution in neuroscience research has shown that around 30 percent of people have a genetic disposition for addiction. But no matter what a person’s genetic disposition, no one gets addicted to drugs she hasn’t tried.
Dopamine tells us that something better awaits us; serotonin says we have enough.
Drugs and other addictive substances increase dopamine while reducing serotonin. Desire overwhelms moderation and contentment. This may be why addicts so often suffer from depression—they’re producing less serotonin to promote contentment. It’s why, Robert Lustig said in one lecture, “the more pleasure you seek, the more unhappy you get.”
But between 2012 and 2019, the CDC reported, cocaine-related death rates tripled, and those involving methamphetamine rose sixfold. Fentanyl was the driver of all that.
When addicts grew tolerant to fentanyl’s towering potency, simple heroin was too weak to prevent withdrawal. By the time I was finishing this book, heroin had all but disappeared from many areas of the United States—replaced by fentanyl from Seattle to New England.
By mid-2019, Chinese chemical companies stopped selling fentanyl under orders from their government. Instead, they switched to selling Mexican traffickers the chemical ingredients with which they could make the painkiller. Mexico emerged as the center of illicit fentanyl manufacturing.
Cocaine-and-fentanyl deaths rose more than tenfold during those years: from one hundred to over one thousand. Nationwide, cocaine-related deaths tripled between 2014 and 2019, driven by fentanyl, which accounted for some two-thirds of those.
Ephedrine meth was a euphoric, social drug, a party drug—the kind Eric Barrera remembered from his first years of using. P2P meth, made with toxic chemicals, was more sinister. As unprecedented amounts of it found their way to every part of the United States, so, too, did the mental derangement Dillon had seen in his customers and the violent delusions Eric Barrera had felt. This meth quickly drove users to symptoms of schizophrenia—violent paranoia, agonizing hallucinations, and fantastical conspiracy theories—as well as horrible dental infections.
This new meth itself was quickly, intensely damaging people’s brains. The symptoms were always the same—violent paranoia, hallucinations, figures always lurking in the shadows, isolation, rotted and abscessed dental work, uncontrollable limbs, massive memory loss, jumbled speech, and, almost always, homelessness.
Suboxone is the brand name for a combination of buprenorphine and naloxone. Buprenorphine is an addictive opioid, but it also blocks the worst cravings, dims the withdrawals, and lessens the chance of overdose. It is an essential tool in managing an opioid addict’s recovery, giving her time to move away from the drug world, restore family relationships, find work and housing, recover driver’s licenses, get health and dental care, pay traffic fines.
You generally don’t overdose and die on meth, you decay.
The United States is the world’s leading per capita consumer of both opioids and sugar.
Drug demand is important in all this. But it must be said: these stories begin with supply. Our opioid addiction epidemic began with a mighty supply of pain pills prescribed every year, which created widespread addiction that continues to this day.
This ought to concern anyone who believes, as I do, that greatly expanded drug treatment is part of what America needs. No matter how many treatment options we provide, recovering addicts face scary odds as long as the drugs that torment them are widely available, potent, and almost free. The now-cliché is “We can’t arrest our way out of this.” We can’t treat our way out of it, either, as long as supply is so potent and cheap.
The problem is, I don’t trust American capitalism to do drug legalization responsibly. The last fifty years are replete with examples of corporations turning addictive services and substances against us, fine-tuning their addictiveness, then marketing them aggressively.
I’m sympathetic to the idea of decriminalizing drugs, as well. Yet I believe it misunderstands the nature of addiction and ignores the unforgiving drug stream every addict must face today. One reason overdose deaths during the coronavirus pandemic skyrocketed is that police in many areas stopped arresting people for the minor crimes and outstanding warrants that are symptoms of their addictions.
