Synthetic organic chemistry is an incredibly powerful tool. It has been used for much good, but also for evil. The latter has resulted in the proliferation of so-called designer drugs, which are making the narcotic addiction problem—already responsible for 50,000 deaths per year— even worse.
It is ironic that analoging — the process of modifying chemical compounds or drugs by synthesizing analogs (close chemical "cousins" that are similar in structure to the original compound), and then testing them to see the effect of the change — has been the cornerstone of drug discovery research since its inception.
In the world of pharmaceutical research, this work is done by medicinal chemists. Having been one for 27 years, I can assure you that it works. Most drugs have been discovered in this manner, for example the antiviral therapies that tamed AIDS, and cured hepatitis C.
When used for good, analoging is the primary tool for what we call "early discovery lead optimization," —the process of modifying compounds that show promise against a particular disease or infection but are not suitable as drugs. This is because they early discovery leads almost always have one or more properties that prevent them from being successful drugs. Some of these include:
- Insufficient potency (thus, the need for a very high dose of the drug)
- Poor solubility
- Lack of absorption from the gut
- Rapid metabolism (the drug breaks down before it can do its job)
- Unacceptably low blood levels
But, it is much easier to use this process for evil, since the 10+ years typically required to show safety and efficacy in order to gain FDA approval, are out of the picture. The safety testing is done on the people who try the designer drugs.
Analoging is exactly what is going on in labs in China and Mexico. The method is being used to make different versions of illegal drugs, which makes them legal. The most recent case of this is a recent report about furanyl fentanyl — an analog of fentanyl is so similar that any medicinal chemist in his sleep could tell you it will act like fentanyl itself. Or maybe worse.
And it is legal. At least for the moment.
I spoke with Rusty Payne, a spokesman for the DEA, about why this new "fentanyl" is legal. Theoretically, it shouldn't be, since there is legislation in place (the Federal Analogue Act of 1986) that allows designer drugs that are "substantially similar" to Schedule I drugs (high abuse potential, no approved medical use in humans) to be classified the same as the actual Schedule I drug that it was based on. In this case, furanyl fentanyl could be placed in the "ridiculously similar" class, if such a thing existed. So, what is going on?
Mr. Payne explained that the issue of defining what designer drugs are illegal is not black and white. It is open to legal interpretation.
If the DEA wants to place a previously-unknown drug on the Schedule I list (making it illegal, just like the parent drug), the burden of proof lies with the government. This means that prosecution must occur on a case by case basis every time a new drug appears. In order to be able to claim that a designer drug is illegal, the DEA must prove that:
- The designer drug is chemically similar to the corresponding Schedule I drug
- The designer drug is pharmacologically similar to the corresponding Schedule I drug
- It is intended for human consumption.
According to Mr. Payne, perhaps the biggest problem that faces the DEA is "expert vs. expert." The trials are held in front of a juries of non-scientists, which hear "these two drugs are very similar chemically" from one side and "these two drugs are not chemically similar " from the other.
Although the DEA has won every case, it is an enormous effort just to keep up with the sheer number of new designer drugs that keep appearing, courtesy of Chinese organic chemists (some of whom we have almost certainly been trained as post-docs in the U.S.). This increase can best be illustrated by the number of court cases. Between 1986 and 2007, about 30 cases were prosecuted. During the time from 2008 through 2014 that number was more than 400.
It may be possible for law enforcement to get a tenuous grip on this unrelenting surge of new drugs, but it cannot be stopped. The number of possible analogs is limited only by the imagination of the organic chemist. Next year's "furanyl fentanyl" may not even exist yet. But it is all but certain that someone will think of it and then run to the lab and synthesize it. Yes, it's that easy.
For a little background, as well as the summary of a very dark story about the first famous designer drug case, you might want to read "Breaking Really Bad, 25 Years Before Walter White." It does not end well.