Chasing the Frog: Keeping Up With Slippery Cheaters

by | 11.14.2013 | 8:25am

Illegal drugs in racing are certainly nothing new. Horsemen were brewing up miracle potions to get an edge as far back as the days of chariot racing, and over time the drugs of choice developed in pace with human pharmacology. For trainers who are inclined to cheat by using banned substances, the drugs in their arsenal come in and out of vogue like bad Top-40 songs.

The most recent substance in this parade is dermorphin, a relative of heroin that is 40 times more powerful than morphine and is commonly referred to as “frog juice.” As more cases of dermorphin use come to light, regulators are learning more about how dangerous it is, and how difficult it is to catch.

Modern drug wars

These days, advances in technology make it easier to catch horsemen using illegal drugs to get an edge. Ironically, it also makes it easier for cheaters to ply their trade.

Dr. Rick Sams, director of the HFL Sport Science Lab in Lexington, Ky., said that when news of dermorphin first broke in 2012, he ordered several samples from commercial labs around the country to see what he was dealing with.

One of the first things he found was that the form of dermorphin that is being used in horses is actually not identical to the substance naturally found in tree frogs.

The version of dermorphin produced by frogs has a bonding structure that makes it dissolve rapidly in biological fluids before the substance has a chance to have an effect. An edit is needed to the bonding structure to make it hold together long enough to do its work. Initially, this caused a lot of confusion in testing laboratories, which had trouble pinpointing the structural difference.

It caused confusion among the people using it, too.

Several of the samples Sams purchased, and the dermorphin detected in some of the first positive tests, were identical to the chemical structure of the dermorphin found in frogs. This meant that some of the first trainers who were caught using dermorphin were using a version that didn't work.

Once he learned more about the molecular structure of the synthetic, modified dermorphin, Sams became even more concerned.

Shape shifter

Dermorphin is an opiate, another member of the family of illegal drugs of days past. As such it's designed both to be a painkiller and to increase locomotor activity. It turns out that only a portion of the chemical structure of a molecule of dermorphin actually accomplishes this task—the rest is along for the ride, meaning it could be removed or altered without changing the drug's effects.

Any edits to the structure of a molecule, such as adding or removing part of it, changes its weight. The detection of substances in a urine or blood sample is done by comparing foreign substances in the sample to the known molecular weights of certain drugs.

Because dermorphin's weight is so easily changed, Sams said that there hundreds, if not thousands, of possible variations (called analogues) of dermorphin. Figuring out which one to look for would take an incredibly lucky guess.

“Unless somebody comes forward and says, 'Here's what they're using', and has a syringe full of it, we're not likely to stumble on this, because that's pretty much what it would take,” Sams said. “I could guess all day what kind of modifications somebody might choose to make in this molecule … I could do that and add thousands of compounds to that database, and unless I pick the right one, I'm still not going to see it.”

So, once he develops a test for one dermorphin analogue, someone can engineer another—to the tune of hundreds or thousands of possible combinations—and get away with it until science catches up.

To further complicate matters, it's not difficult to have dermorphin, or any other amino acid, made. After the commercial success that stemmed from mass penicillin production toward the middle of the 20th century, a dramatic expansion of laboratories and pharmaceutical research began. Today, there are numerous labs across the world that require only a chemical diagram to make a given amount of an amino acid, and will do so for as little as a few hundred dollars.

Even more disturbing for Sams is the level of veterinary, chemistry, and regulatory testing knowledge someone would have needed to correctly engineer and begin using dermorphin in horses.

“This stuff I don't think was on Wikipedia until recently,” quipped Sams. “I think the person [who started this] was trained. I don't know whether the person was a veterinarian or a biochemist or what. I suspect they know what analogues they could make or have made at relatively low investment and, if they know how we test for substances, they know that they can make those changes and use those compounds with impunity. “

An important distinction

One of the reasons dermorphin may be so popular is that it and other cousins of morphine produce a powerful effect on a horse—but it's not the one people think.

In humans, morphine and other opiates produce sedation and extreme pain-killing effects, because they deal with a specific part of the brain called the mu receptor. Recent studies have indicated that mu receptor drugs don't work the same way in the horse's brain—possibly because the horse has few mu receptors, or simply less sensitive ones.

“It is very difficult to produce any kind of sedation at all with an opiate in the horse. The horse is really unusual in that regard,” said Sams. “This has nothing to do with analgesia [pain relief]. They aren't good analgesics. You need to dissociate these substances from analgesia.”

Instead, dermorphin is excellent at creating “increased locomotor activity” in the horse—usually seen by rapid movement or pacing in the stall which is thought to convert to an increased capacity for speed on the track.

Because of this, dermorphin isn't just useful to trainers who have lame horses in need of some help to appear sound on race day—its ability to increase locomotor activity means it would manipulate any horse's performance, and the right analogue would be almost impossible to detect.

Going forward

Although Sams reports that he is looking into new testing technology for his lab that could one day make dermorphin analogue detection easier, he's quick to say that there are other substances found in animals that could be engineered similarly to dermorphin.

“There are others, fairly small molecular-weight peptides that have been found in a variety of animals that do produce effects similar to dermorphin, so there is the possibility that those substances can be used. For those substances that already exist, there's really no reason to make any modifications to the molecule until the laboratories learn how to detect it,” he said.

“I guess some of the good news is that not many modifications of dermorphin result in compounds that have opiate activity. But all you need is one. You can't just willy-nilly make modifications and still have opiate activity for whatever reason.“

All of this—the easy accessibility of amino acid production, the high level of education required to make these modifications, the limits to modern testing—makes Sams wonder: what else is out there that we don't know about yet?

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