Tuesday, November 20, 2018

The Radical New Fentanyl Trend That Could Save Lives and Screw Dealers

Mark Kinzly, a needle exchange worker in Austin, Texas, recently came across an opioid user who was doing what many thought impossible. The man claimed to be regularly taking carfentanil—a drug 10,000 times stronger than morphine and 100 times more potent than fentanyl—which is only approved for use in sedating large animals, like elephants. Carfentanil is typically found at autopsy in overdose victims, and not noted as a drug of choice.

Speaking at a session on fentanyls at the Harm Reduction Conference in New Orleans last month, Kinzly recalled that despite daily use, the guy was alive and seemingly OK. “He has figured out a way to take a certain amount of micrograms of the carfentanil, dilute it into a 50 milliliter solution of saline and basically draws it up a couple of times during the course of a day and injects it,” he said.



“Economically, for this individual, the amount of micrograms that he pays about $250 for will last him about three months,” Kinzly added. In other words, it was lemonade from lemons: making what could have been one deadly dose into a cheap, abundant supply that lasted for weeks. Typically, opioid users may spend around $100 or more per day on their drugs.

Faced with the literally poisonous level of potency of the opioids currently available on the street, most consumers have been hard-pressed to adapt. Nearly 30,000 fentanyl or fentanyl analog overdose deaths—more than any other drug and rising—last year was clear evidence of this.

But as people with addiction confront the daily risks posed by the fentanyl-tainted drug supply—mostly without access to evidence-based treatment even if they want it—they are taking new steps to protect themselves. The sheer danger associated with the potency of fentanyls and other powerful opioids is changing how people use drugs like heroin, and some of the strategies they’re working on could upend the economics of drug sales.

Dilution is one of several techniques in what might be best categorized as the testing stage. As Kinzly put it, “It’s a pretty common practice, starting to happen.” And if this and other harm-reduction approaches were replicated reliably, they could both save lives and alter the market in ways that make fentanyl and its analogs much less profitable for dealers.

The principle behind dilution is simple: putting a tiny bit of a strong drug into a large amount of water makes it much less potent. As Biology 101 students know, in solution, even without being mixed, chemicals tend to diffuse out from regions of high concentration to those that are lower. And so rather than a lethally large dose, a properly diluted solution would offer many, many effective but (at least somewhat) safer ones. This, in fact, is how FDA-approved fentanyls can be—and are widely—used safely in medicine.

If dilution could be done properly on the street—and this is a big if, given that most people don’t know how much of which kind of fentanyl is in their drugs and their potencies range widely, which makes it hard to determine how much water to add—it could have serious implications.

For starters, it might mean that one $5 or $10 fatal dose became dozens or even hundreds of nonfatal highs, depending on which type of fentanyl was in play. If users were to dilute drugs weaker than fentanyl, the result would obviously be a weaker high. But if they diluted synthetic, overdose-level opioids, as many as tens of thousands of effective doses could be present.

In this scenario, some people who now buy several times a day would, perhaps, buy weekly or less. Such market pressure might push dealers back to selling somewhat less potent (albeit still deadly) substances, like heroin. It could also compel them to cut fentanyls more effectively higher up the chain. (Or, it could lead to other unpredictable effects—like dealers doubling down on mainstays like coke.)

“I think dilution is a brilliant idea,” said Maya Doe-Simkins, a public health consultant and director of communications for the Chicago Recovery Alliance, which provides harm-reduction services. “I mean, it makes perfect sense,” she added, cautioning that supporting dilution as harm reduction would probably require supplies not currently stocked by needle exchanges. Saline solution, for example, would be needed instead of commonly used sterile water, in order to prevent bacteria from growing in solutions that might be stored for some time rather than injected immediately.

There’s also the question of how users might react to having more drugs on hand than they could immediately consume. Some might just overdose more slowly by way of many shots rather than one more potent one. Still, the potential for harm reduction is real.

“I think [dilution] is an important consideration moving forward,” Jeff Ondocsin, an ethnographer at the University of California San Francisco (UCSF) who’s studying changes in the heroin market, told me. “I believe that fentanyls could be used safely if the dosage was correct and it wasn’t a poisoning.”

During the panel discussion, Ondocsin, and his colleagues Dan Ciccarone, professor of family and community medicine at UCSF and Sarah Mars, project director for their research, presented initial findings on geographic “hotspots” marked by swift changes in heroin markets. This “Heroin in Transition” project includes San Francisco, Chicago, Baltimore and Lawrence and Lowell in Massachusetts, and in-depth interviews had so far been conducted with 111 people who were taking heroin—or what was being sold as such—in those places, they said.

A number of strategies have emerged to contain street fentanyl’s capacity to kill. The first and most effective was for people to never use alone—while keeping the antidote, naloxone, on hand in case of an overdose. Perhaps most obviously, it is better to avoid overdose than to have to reverse it.

But Ondocsin described several other techniques in use among research participants, whom he kept anonymous for ethical reasons but quoted during his talk. A man he called Riley from San Francisco, for example, discussed smoking a bit of his black tar heroin to see how strong it was before injecting. “I’ll smoke it just to see how I feel from taking a couple of hits,” Riley told researchers, adding that if he got “spooked” by how strong it seemed, he would inject much less than usual.

Other tactics that came up in the research included trying a very small “tester” injection first or snorting a small amount of the powder and getting a sense of how it tasted when it hit the back of the throat. One Chicago man told the researchers, “When you toot it’s supposed to go down your nose and go down smooth with no burn and none of that, and once you get that drain, it’s the taste. It tastes like dope.” Rather than using a small initial shot, other people instead injected their dose extremely slowly, the research suggested, at least theoretically giving them time to pull out if the dose was too high.

The incredible variability of the heroin and fentanyls market loomed large. “I know a lot has been said about how potent fentanyl is,” Ciccarone said at the panel. “But a bigger concern from a pharmacological point of view, if you will, is the changes in it… We gather these stories about how the substance itself changes on a daily basis.”

This irregularity—in and of itself—may also be increasing overdose death risk via an effect it has on tolerance. After all, tolerance to a dose is produced by repeated exposure, which over time means that more of the same drug is needed to get the same effect.

But what causes tolerance to kick in is a process of learning: the response is elicited by cues associated with the drug, such as the place where you use it, the smell of the substance, its taste, and the sequence of the ritual connected with use. In a highly variable market where the drug’s composition is constantly shifting, these cues may not be present. Blue heroin may not cause tolerance to occur as reliably as in a person who has only previously used white, for example.

The risk isn’t just theoretical: One study found that if rats were given an opioid dose they were tolerant to in an unfamiliar cage, 50 percent would die even though they were taking exactly the same amount they’d survived in the past. Research on humans with alcohol—dubbed the "Four-Loko Effect"—has suggested people will get more drunk— in other words, have lower tolerance—if their beverages are extremely oddly colored and flavored in contrast with typical drinks.

This speaks to another harm-reduction tactic for the age of fentanyls: People are best off using with the same friends in the same place in the same way at the same time whenever possible, in order to maximize tolerance, by giving their bodies as many familiar cues as they can. (This is one way safe-injection facilities could help; another is providing test strips and other supplies that could bolster safer injection outside designated spaces.)

Ciccarone noted a telling phenomenon in fentanyl world: even now, these drugs often have no real street name. While the apt “null” and “nil” are heard in some regions, several years after heroin markets in the Eastern US were flooded with the stuff, fentanyls are mostly nameless or sold as heroin, he said. This may speak to both the rapidity and the variability through which the substances have changed the opioid crisis.

For his part, Ciccarone saw this as evidence of their unpopularity and the fact that they were introduced not because of new demand, but because they were cheaper to produce. “A drug that’s popular, that people want, slang gets developed around it,” he said. “There’s not a lot of slang for fentanyl. Even the dealers were surprised.” Though reports have begun to surface of people who actively seek it, many consumers do the opposite and avoid it: between 50 and 75 percent, according to Ondocsin's sample.

While it would obviously be better if fentanyls were not in the street opioid supply at all, if dilution made them safer and cheaper, it really might help ease the opioid crisis. Perhaps the dealers benefiting from opioid addiction at the street level would have to change up their strategy. We don't know exactly what that might look like, but almost anything would be better than what’s going on now.

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