North America’s unregulated drug supply has grown ever more unpredictable, which often means deadly. Since the arrival of fentanyl, the likes of benzodiazepines, other tranquilizers and nitazenes have all become more prevalent in the mix. I’ve overdosed on “benzo dope” myself.
In Canada, there have been more recent reports of drugs showing up that will be unfamiliar to most. The media default is to try to scare people about any “new” substance. Risks shouldn’t be minimized, but at the same time, harm reductionists know that people aren’t just going to stop using based on these reports.
A legal, regulated, safe supply of drugs—so people know what they’re getting and how much of it—would be the best answer. In the absence of that, we should learn as much as we can about what’s out there, to try to keep ourselves and others aware and safe.
Two substances that have made news lately are protonitazepyne, found in Quebec City, and medetomidine (and/or dexmedetomidine), found in Toronto.
Protonitazepyne is a synthetic opioid from a class called benzimidazole-opioids, AKA nitazenes. These range in potency, but some sources estimate protonitazepyne (N-pyrrolidino protonitazene) to be roughly 25 times more potent than fentanyl—meaning you’d need one 25th of the quantity to get an equivalent effect.
Medetomidine is a tranquilizer which is approved only for veterinary use (like xylazine, which by now is more familiar in the supply). Its close relative dexmedetomidine is also approved for anesthesia or pain relief in humans; the two are so structurally similar that Toronto’s Drug Checking Service can’t distinguish between them, and classifies them together. It notes that the drugs “are considered to be more potent than xylazine (longer acting and produce greater sedation).”
These are just a couple of examples of substances showing up, including in counterfeit pharmaceuticals. There’s no way of knowing everything that’s out there, when chemical structures can easily be tweaked by those in the know, incentivized by profits and the need to avoid detection under prohibition.
McDonald described how her service initially found protonitazepyne in a sample of pills sold as oxy 80s.
Reaching out to people to interview for this article, I was made aware of a national Canadian drug checking working group. I was invited to join one of the meetings, co-hosted by the Canadian Centre for Substance Use and Addiction and the Canadian Community Epidemiology Network on Drug Use.
The meeting’s structured format covered updates from various drug checking programs coast-to-coast. When it opened up for questions, I was able to interview some of the members, adding to comments two of them had previously given.
Karen McDonald is the lead at Toronto’s Drug Checking Service at St. Michael’s Hospital, a site of Unity Health Toronto, and has been instrumental in advancing drug checking services in Canada. She described how her service initially found protonitazepyne on March 6, in a sample of pills sold as oxy 80s.
“The unregulated opioid supply is increasingly more contaminated and less predictable,” she told Filter. “This can largely be attributed to the Iron Law of Prohibition: As enforcement of substances intensifies, the strength of prohibited substances increases. Furthermore, as more substances are scheduled, novel substances take their place.”
She suggested an additional factor behind the emergence of more unfamiliar opioids: “‘New’ high-potency opioids may also be introduced to the unregulated supply to meet the needs (increased tolerances) of people who use drugs.”
It’s important to remember that not everyone who uses emerging drugs does so unwillingly or unknowingly. Fentanyl was once portrayed solely as an unwelcome adulterant, but some people—including me, not so long ago—have come to prefer it. Some of us also just like to experiment.
“We know little about its dose response curve, duration, side effects and interactions. Claims for protonitazepyne’s potency must be taken with nuance.”
Antoine Marcheterre is the drug checking lead at Interior Health, based out of British Columbia, and he stressed what we don’t yet know about protonitazepyne.
“Anytime a new substance appears on the market, it brings a new set of unknowns with it,” he told Filter. “In this case, we know very little about its dose response curve, duration of action, side effects and interactions.”
He also pointed out: “The claims for protonitazepyne’s potency are based on in vitro data, so must be taken with nuance.”
Doris Payer, senior knowledge broker at the Canadian Centre on Substance Use and Addiction, based in Ottawa, Ontario, also referenced the inevitable effects of prohibition in driving the emergence of drugs like protonitazepyne.
“It’s probably in part because more potent drugs are easier to move and more cost-effective, in part because drug busts and crackdowns limit the supply of what people actually want, and in part because [the drugs in question] might produce effects that some people want,” she told Filter.
“Medetomidine may put those who use it in a deep state of unconsciousness, much like xylazine and benzodiazepine-related drugs.”
Turning to medetomidine/dexmedetomidine, McDonald said she believes drugs of this type are occurring in the supply principally due to their relative accessibility and their potential effects: They may give fentanyl more “legs,” making the effects of that short-acting drug last longer; they also carry risks.
“Medetomidine may put those who use it in a deep state of unconsciousness, much like xylazine and benzodiazepine-related drugs,” McDonald said. “The risk of extreme drowsiness and sedation is increased when medetomidine is used in combination with high-potency opioids, benzodiazepine-related drugs and xylazine.”
“This is noteworthy,” she continued, “because 100 percent of the samples checked by Toronto’s Drug Checking Service that contained medetomidine [also] contained at least one high-potency opioid. Many of these samples also contained a benzodiazepine-related drug or xylazine.”
Marcheterre agreed that one of the main reasons we’re seeing these drugs is because they’re fairly easy to acquire. They can be purchased on the regular internet, he noted, by people who search the chemical identification numbers and look up various vendors. If shipments are seized, vendors will often resend them, reducing the risks and hassle of online shopping.
“I can only speak to what we observe locally. We have seen nitazenes in pills that are sold as opioids, replacing oxycodone or hydromorphone for example.”
Kathryn Balind, who works at GRIP (Groupe de Recherche et d’Intervention Psychosociale) in Montréal, Quebec, described what she and her colleagues have been seeing. “I can only speak to what we observe locally,” she told Filter. “We have seen nitazenes in pills that are sold as opioids, replacing oxycodone or hydromorphone for example, or alone, as the desired substance.”
As for why it’s happening, she broadly agreed with the other experts: “I think the nitazenes are showing up in the supply as replacements for other desired substances, because perhaps they are easier to acquire and they are more potent, so less is needed in a pill.”
So how worried should we be? Clearly, there are serious potential risks associated with high-potency drugs. That doesn’t mean there aren’t potential benefits for some. But knowledge is everything.
“What is most worrisome about these drugs is that their presence is unexpected by people using them,” McDonald said. “How can someone attempt to use safely when they don’t even know they are using something?”
“Because protonitazepyne is so strong, the risk of overdose is increased,” she continued. “Even if folks were aware protonitazepyne was present in their drugs, it is highly unlikely they would know how much of it is present—a luxury we have with essentially anything [other than unregulated drugs] we put in our bodies.”
Payer agreed, noting how hard not knowing makes it for people “to prepare or protect themselves.”
But there are some important things we can do, as all the experts emphasized.
“Starting with a tiny amount first to test the waters could be the difference between waking up or not.”
These include carrying naloxone, the opioid-overdose reversal drug; never using alone if you can possibly avoid it; and doing a “tester” when you use a new batch—”Start low and go slow,” as the harm reduction saying has it.
“Starting with a tiny amount first to test the waters could be the difference between waking up or not,” Marcheterre said.
And of course, checking your drugs before you use them—if you have any chance to do that—is a crucial way to increase your safety.
“Drug checking services can help you determine what is in your drug before you choose to use it,” Marcheterre said. “This can be lifesaving in cases where you end up with a substance that was not expected.”
“The dosage in tablets may vary from one tablet to another,” he warned. So don’t just assume that because one was ok, the other will be too.
In terms of dealing with an emergency, the experts also recommended utilizing oxygen for overdoses that leave people extremely sedated, including in cases when naloxone has been administered first.
But none of these critical resources is a cure-all.
“The unregulated drug supply is unpredictable; we never know what could be in our drug, and we need to keep in mind that drug checking technologies have limits,” Balind said. “There are synthetic opioids circulating that are super-potent and hard to detect. There are adulterants circulating that are not meant for use in humans, and the side effects of repeated use are not well known.”
Regulation is the only way to truly transform this picture.
New or unfamiliar drugs are not going to stop appearing in our supply; without radical policy change, it will just keep happening.
“For nitazenes, this is the continuation of a trend where we see stronger and stronger analogues and families of substances entering the unregulated market,” Balind said. “The possibilities are almost infinite in terms of small modifications that can be made on known molecules, turning them into something else, which could be more potent and hard to identify with our current drug checking technologies.”
These experts are dedicated to spreading knowledge to keep people who use drugs safer, and we’re lucky to have them. But the mechanisms of prohibition ensure that the supply will keep shifting faster than anyone can keep up with, and that will continue to cost lives.
Regulation is the only way to truly transform this picture. People don’t want to die—and if they know the ingredients and dosage of what they’re using, they’ll overwhelmingly stay alive. When will we have governments that recognize this—rather than the futile goal of eliminating drug use—as the priority?
Image by Caroline Davis2010 via Flickr/Creative Commons 2.0