TK Talk: Why have fentanyl deaths and seizures climbed so steeply (540%) in the last three years? Fentanyl is now the number one cause of drug overdoses in the US.

What are Fentanyls

~100 times a more potent analgesic than morphine (1) and ~40 times more so than heroin, Fentanyl is a powerful opioid used for pain treatment, first in the 1990s as a patch and now as a spray. An example of its potency, David Juurlink an opioid researcher at the University of Toronto says he'd give a hospital patient 10mg of morphine but only 0.1mg of fentanyl (2).

Widely considered too dangerous for humans, carefentanil is fentanyl's much more potent analog (similar chemical structure) and used as an elephant tranquilizer. So potent is carfentanil some countries including the US have even considered its use as a chemical weapon in war (3).

Fentanyls are so dangerous in overdoses because they can even negate Naloxone - Wikipedia, which is usually used to reverse heroin overdoses.

For example, where typically just one naloxone dose can reverse painkiller or heroin overdose, fentanyl overdose requires several naloxone doses. This is because of fentanyl's much higher affinity for the mu opioid receptor in the brain, which it accesses much more easily than morphine or heroin, given its much higher fat solubility (4).

Fentanyls can be so deadly (see photo below from 4), first responders need to be trained to protect themselves from accidental overdoses themselves (5).

Why Fentanyls have become a new front in the current US opioid crisis

Recent steep climbs in US fentanyl overdose deaths and seizures personify the Balloon effect - Wikipedia (2). How to optimally deal with drug abuse? Need strategies to deal with both supply and demand.

US history shows it tends to crack down hard on the supply side while doing little to tamp down demand. Arguably, tamping down hard on the supply side would reduce future demand but what happens to current demand if it isn't a priority of drug control policy? Just as air in a half-inflated balloon moves to another part of the balloon when it's pressed, when supply's squeezed without equivalent effort to reduce demand, users and traffickers figure out other means for getting high (2).

How opioid demand was created. Starting in the late 1990s, US doctors began handing out opioids like candy. Apparently both they and the FDA were taken in by opioid manufacturers' false claims these opioids weren't addictive. This practice both created and nurtured the growth for opioid demand. Supply wasn't a problem either for many years. However, starting in the early 2010s, people started dying in unprecedented numbers from opioid abuse overdose. Law enforcement started cracking down on prescribing doctors and pill mills, though interestingly not the pharmas making these opioids. As supply started drying up, users and traffickers diversified, first to heroin then to heroin laced with fentanyls.

Rationale for fentanyls. Given its easy access, drug traffickers started adding fentanyl to heroin to juice it up. Economic argument for fentanyl made itself. Fentanyl and carfentanil are just two of many fentanyls, all relatively easy to make in a lab, a far more simpler and cheaper approach than growing the opium poppy plant, extracting from it morphine and converting that to heroin. They also give a better and cheaper high than even heroin. Dealers can make more money from fentanyl-laced heroin (2). Dealers add fentanyl of questionable purity to the heroin they sell using scales and balances of questionable accuracy (3). Problem is users are unaware when their heroin is laced with fentanyl so injecting a usual heroin dose can lead to fentanyl overdose. The ensuing tragedy writes itself.

How opioid supply keeps creating new products to stay ahead of crackdowns. US law enforcement believes most fentanyl comes from labs in China (3), easily made there in bulk quantities without US regulatory or law enforcement supervision and then shipped into US via Latin America. On March 1, 2017, China banned manufacture and sale of fentanyl and some of its analogs including carfentanil (6), adding more analogs to the ban a couple of months later (7), making restrictions on a total of 138 compounds. However, chemists keep coming up with newer fentanyl analogs (see below from 6), making their control by regulators and law enforcement a case of Whac-A-Mole - Wikipedia.