Designer Drug Detective Work.

Abstract

On an unseasonably warm spring morning in his office in Baltimore, neurochemist Michael H. Baumann eagerly flipped through a spreadsheet. It listed hundreds of chemical names of suspected drugs seized by local, state, and federal law enforcement agencies over the past three years. “When police bust people with some white powder or a baggie full of pot-looking material, it gets sent to forensic laboratories, and they test what’s in it”, he says. All that data gets dumped into a database catalogued by the Drug Enforcement Administration (DEA), and Baumann asks for a rundown of what’s been found. That rundown provides Baumann, head of the Designer Drug Research Unit at the National Institute on Drug Abuse (NIDA), with a guide to the ever-changing world of designer drugs. As of December 2014, 541 new psychoactive substances—the preferred term for synthetic designer drugs—had been reported. And it’s reasonable to think that the number is higher now. Many synthetic designer drugs are sold semilegally online with a wide array of names and labels. Credit: B. Christopher/Alamy Stock Photo. The drugs, often sold in stores and on the internet as innocuous-sounding “spice” or “bath salts”, are designed to mimic the physiological actions of well-characterized drugs such as marijuana, cocaine, ecstasy, LSD, and heroin. “They are psychoactive drugs sold under false pretenses, often as household products”, Baumann says. “This is purely to skirt regulation”. Because these synthetic drugs are chemically distinct from controlled substances, they can be bought and sold in a quasilegal market existing largely on the internet. Baumann, along with four other scientists in the unit, examines the neurochemistry of these emerging psychoactive substances. The scientists focus mainly on compounds being sold in large volumes or linked to deaths. They try to determine what these molecules do in the brain to get users high. His team’s findings provide valuable information to forensic toxicologists and policymakers involved with the growing problem of designer drugs. Although some of these compounds are new to the illicit drug scene, they aren’t necessarily new molecules, Baumann says. “These drugs are being pulled from the scientific and patent literature.” For example, John W. Huffman, professor emeritus of organic chemistry at Clemson University, has published studies on hundreds of chemicals that interact with cannabinoid receptors. This research has provided valuable insight into the brain’s endocannabinoid system, which affects appetite, mood, memory, and pain sensation. But rogue chemists have hijacked Huffman’s research, synthesizing vast quantities of the cannabinoids and selling them to people who want to get high—or more accurately, Baumann says, to people who want to get high on the sly. For example, a report published in September 2013 by the Office of National Drug Control Policy found that more than one-quarter of a sampling of DC area men in the criminal justice system, such as parolees and probationers, tested positive for synthetic cannabinoids, many of whom had passed the standard drug test panel. As with well-known drugs, these designer molecules can cause real harm. During the second half of 2013, a new street drug called 4,4′-dimethylaminorex (4,4′-DMAR) was responsible for a wave of 26 overdose deaths in Europe. To figure out what they were dealing with, European scientists contacted Baumann. A few months later, Baumann and his colleagues reported that 4,4′-DMAR had potent interactions with transporter proteins in the brain which normally take up neurotransmitters from the extracellular space. Specifically, 4,4′-DMAR produced transporter-mediated release of dopamine, norepinephrine, and serotonin into the synapses between neurons. This spike in neurotransmitter release likely contributes to increasing a user’s heart rate and body temperature, with deadly consequences. Baumann’s data helped authorities from several European countries outlaw 4,4′-DMAR. Michael Baumann and his team at NIDA study the neurochemistry of designer drugs. Courtesy Michael Baumann. Meanwhile, Baumann’s collaborator at Memorial Sloan Kettering Cancer Center, Gavril W. Pasternak, is about to initiate a program to study newly emerging opioid analogues. The opioid epidemic is already worrying drug enforcement in the U.S.: The New York Times reported that the opioid fentanyl, a powerful prescription painkiller that’s also synthesized in illegal laboratories, is now killing more people than heroin in some parts of New England. Acetyl fentanyl, a derivative with no legitimate usage, was responsible for more than 50 confirmed fatalities between 2013 and 2015. At least six other fentanyl derivatives have been identified as well. “The danger there is the potency of that material and the ease in which people can obtain it”, says Jill M. Head, a supervisory chemist with the DEA’s Special Testing & Research Laboratory.