Labs struggle to keep pace with emerging designer drugs

By Gary Tufel

In the endless battle to combat substance abuse, clinical laboratories are finding themselves involved in a vicious tug-of-war. While researchers struggle to develop laboratory tests that can quickly identify drugs of abuse in emergent and life-threatening situations, the creators of new designer drugs are continuing to find targets of opportunity—often with lethal effect.

According to the National Institute on Drug Abuse (NIDA), a US government research agency, such new drugs and drug use trends often burst on the scene rapidly.

Another US government agency waging battle against such illicit drugs is the Substance Abuse and Mental Health Services Administration (SAMHSA), an agency within the US Department of Health and Human Services. SAMHSA is responsible for public health initiatives that promote the country’s behavioral health, and has oversight of the federal drug-free workplace programs and the national laboratory certification program (NLCP).

Ronald R. Flegel, MT(ASCP), Substance Abuse and Mental Health Services Administration.

Ronald R. Flegel, MT(ASCP), Substance Abuse and Mental Health Services Administration.

NLCP-certified laboratories perform workplace drug testing for federal agencies and federally regulated industries, including the Department of Transportation, the Nuclear Regulatory Commission, and the Department of Defense, says Ronald R. Flegel, MS, MT(ASCP), director of SAMHSA’s division of workplace programs. The focus of the government’s drug-free workplace programs, he adds, is on specific Schedule I and Schedule II drugs, as defined by the Controlled Substances Act.

Other US government efforts have included NIDA’s community epidemiology work group (CEWG), a network of researchers in major metropolitan areas and some US states who reported data on emerging trends and patterns of drug use. CEWG functioned through 2014 but has now been replaced by NIDA’s national drug early warning system (NDEWS), which reports on emerging trends and patterns of drug use in many metropolitan areas and states, as well as from other areas of the nation as problems arise. NIDA offers valuable and up-to-date information on emerging drugs on its Web site (, which includes periodic updates based on NDEWS reports and other reliable information.

Randy Pritchard, Roche Professional Diagnostics.

Randy Pritchard, Roche Professional Diagnostics.

But the problem is global. Due to the growing popularity and spread of illicit substances, more countries are conducting drug testing in order to identify drug use and allow for early intervention and treatment, and also to support patient compliance with drug substitution, addiction treatment, and pain therapy, notes Randy Pritchard, life cycle leader for core reagents with Roche Professional Diagnostics, Rotkreuz, Switzerland.

In clinical settings, drug testing is a useful tool for identifying addiction and the abuse of prescribed drugs, says Pritchard. Such testing supports physician monitoring of patients’ compliance with a medical drug or behavioral therapy, and it also helps to focus the use of scarce therapeutic resources on the regimens that have proven to be most successful and efficient.

In hospital emergency departments (EDs), toxicology drug testing results identify or exclude drug overdose or misuse, Pritchard adds. This practice facilitates and accelerates the start of treatment so that adverse health consequences or even death can possibly be prevented.


Illicit designer drugs—synthetic versions of controlled substances whose altered molecular structures classify them as illicit drugs—are a serious, emerging threat, says Flegel. Designer cocaine derivatives, for example, are about 100 times as strong as cocaine.

Other designer drugs include synthetic cannabinoids such as K2 and spice, synthetic cathinones such as bath salts, and ecstasy. Because FDA has neither reviewed nor approved these designer drugs, their effects on the human body are generally unknown, but they are considered unpredictable and potentially fatal, says Flegel.

According to an April 20, 2015, update from NIDA, “Recent surges in hospitalizations linked to consumption of synthetic cannabinoid products (sold under brand names like ‘spice,’ ‘K2,’ and others) have been reported in some southern states, including Mississippi, Alabama, and Texas, and have prompted health warnings from officials in New York State. New York Governor Andrew Cuomo issued an alert after more than 160 patients were hospitalized following synthetic cannabinoid use in under 2 weeks in mid-April 2015.”

NIDA’s update noted that synthetic cannabinoids are chemically related to tetrahydrocannibinol (THC), the active ingredient in marijuana, and are sometimes called “synthetic marijuana” or “legal marijuana,” but actually the effects can be considerably more powerful and more dangerous than marijuana. Users can experience anxiety and agitation, nausea and vomiting, high blood pressure, shaking and seizures, and hallucinations and paranoia, and they may act violently. The list goes on, including the recent appearance of flakka (?-pyrrolidinopentiophenone, or alpha-PVP), which scientists at the Scripps Research Institute have found to be as potent as a stimulant, and therefore as addictive, as its chemical cousin, bath salts (methylenedioxypyrovalerone, or MDPV).1

In 2012, the Synthetic Drug Abuse Prevention Act classified 26 types of synthetic cannabinoids and cathinones as Schedule I designer drugs, thus giving SAMHSA the authority to test for them. But unfortunately, says Flegel, designer drug chemists have proven to be adept at synthesizing other biologically active drug analogs that do not have the illicit drug classification. And contributing to the drug threat is the constant influx of newer designer drugs for which tests have not yet been developed.


The protocol for forensic drug testing involves an initial screening assay. A specimen producing a positive result is further subjected to confirmation testing for a very specific analyte, using gas chromatography-mass spectrometry (GC-MS) or liquid chromatography–mass spectrometry (LC-MS) technology. But because designer drug analytes are continually changing, says Flegel, test manufacturers have been reluctant to allocate the funds necessary to develop new immunoassays for those drugs.

Most nonmedical users of drugs—including illicit drugs, synthetic opiates, designer drugs, and prescription drugs—are young adults aged 16 to 30. Drug use often occurs at parties, Flegel says, and in some instances individuals are unknowingly exposed to the drugs. When they subsequently present to a hospital ED with toxicity symptoms, they often cannot provide any recent drug use history.

For such individuals, says Flegel, patient care is jeopardized when the resources are not available to identify the drug substance, so that an appropriate treatment can be administered. For clinical laboratories that serve EDs, there is a great need for new and improved designer drug tests with rapid turnaround times for test results. “For routine drug testing, the typical laboratory turnaround time is 2 to 3 days,” says Flegel. “But the test result turnaround time required in the ED is minutes.”

Flegel cites a recent “rave” party near Baltimore that resulted in 20 young partygoers being admitted to the local ED because of drug toxicity, with two fatalities. One of the fatalities may have occurred when a partygoer unknowingly ingested the drug from a water bottle. “The problem isn’t getting better, and it may be even getting worse,” he says.

Many designer drugs are used in combination with other drugs or alcohol. Polypharmacy poses an additional challenge for the laboratory. “This ongoing battle with drugs is taking a toll on families and on physicians. Someone needs to step up to the plate and develop new tests,” says Flegel. “Some test manufacturers have developed general toxicology screens for acid-based drugs that are a step in the right direction.”

The cost of developing new drug tests is high. “Is it worth the expense? Companies have to weigh the cost,” says Flegel, “but human lives are at stake.”

Flegel is hopeful that new tests will be developed. But as new designer drugs are synthesized and state laws become more lenient about marijuana, he expects that testing for drugs of abuse will continue to be a challenge.


Kelli Mogush, Siemens Healthcare Diagnostics.

Kelli Mogush, Siemens Healthcare Diagnostics.

The most significant challenge in testing for drugs of abuse is that the drugs are constantly evolving and changing, and test developers are hard-pressed to keep pace with the constant changes. Although laboratory-developed tests for drugs of abuse do not currently require FDA approval, a commercial test that does require FDA review can take a year to go through the agency’s entire approval process, says Kelli Mogush, senior marketing manager at Siemens Healthcare Diagnostics, responsible for Siemens’ Syva line of drug testing products. “Many of the new and dangerous designer drugs may have come and gone by then,” she says.

The number of designer drugs entering the US from Asia and India is so large that testing for a given drug sometimes simply doesn’t exist. This presents problems for EDs and clinical labs when they are trying to diagnose and treat a patient who is suspected of drug overdose, and all laboratory drug screens are negative.

Most drug testing identifies 60% to 70% of tested drugs, says Mogush, but more new drugs are constantly entering the market, often within days of their being discovered and scheduled by the US Drug Enforcement Agency (DEA). DEA is doing its best to schedule all of the designer drugs that have entered the United States, but with hundreds of compounds to test, the task is daunting.

One group of drugs that experts are especially concerned about is synthetic cannabinoids, a class of diverse chemical compounds that act on the cannabinoid receptors of cells that repress neurotransmitter release in the brain. In April, the American Association of Poison Control Centers and experts at America’s 55 poison centers warned the public about a group of dangerous new synthetic cannabinoids that have led to a dramatic spike in poison center calls in the United States. The experts cite several reasons for concern.

Synthetic cannabinoids affect every sector of the brain. They were originally created for use in receptor research. But these drugs soon made their way onto the streets from clandestine labs in Asia and India. The first such drugs were identified and scheduled by the DEA. But with slight changes in their molecular structure to make them legal, new versions of these drugs are now continuing to flood into the United States.

According to Mogush, what began as a trickle has now grown to a flood of hundreds of synthetic compounds manufactured for recreational use. The drugs are made into powders, solvents, sprays, and other forms, and are often ingested by young people—sometimes unknowingly—at “rave” parties. Users often wrongly suppose these compounds to be milder drugs, partly because the term “synthetic cannabinoids” suggests a relation to “cannabis,” which is legally available for either medical or recreational use in many states.

“It’s a nightmare for diagnostics suppliers and in vitro diagnostics companies because each of these drugs is different from the others, even if only slightly. They have nothing to do with the original synthetic cannabinoids or with marijuana; they are structurally different from marijuana,” says Mogush. “The DEA is still one step behind the manufacturers of these drugs, but the situation is getting better.”

Sample drugs-of-abuse test kits that run on the Cobas modular platform by Roche Diagnostics.

Sample drugs-of-abuse test kits that run on the Cobas modular platform by Roche Diagnostics.

The designer drug known as spice is a synthetic cannabinoid whose effects illustrate the gulf between such compounds and marijuana. “Pot smokers are usually mellow, benign, and sedentary,” notes Mogush. “But users of the synthetic drug spice, which can be up to 800 times as potent as marijuana, are the opposite.”

The difference, says Mogush, lies in how the brain’s cannabinoid receptors react to the drug when it takes full effect. “Marijuana in its natural state contains a compound—cannabidiol—which has a mitigating effect on the brain’s receptors; but that compound is not present in synthetic versions. Also, the body cannot metabolize the synthetics, which can rebind with brain receptors, thus making the effects last for a much longer period.

“It’s very, very scary. Users often don’t know what they’re getting and sometimes even ingest the drug without knowing it,” Mogush says. “Bath salts and other such drugs are equally frightening.”

Some “head shops” and other sellers of such compounds make customers sign releases acknowledging the danger when they purchase potpourri and other designer drugs, but the customers still smoke it, says Mogush. When the experience ends up with the user in a hospital ED, many don’t know what they took. “If the testing is negative, and the drug isn’t one that can be tested for yet, the physicians just have to let the drug run its course for however long it lasts—a terrifying experience for many who have taken these drugs.”

To forestall such experiences, public health officials around the world have become increasingly active in testing users for new substances. In Vienna, an effort called “CheckIt!” uses a van equipped with LC-MS equipment that travels to concerts, clubs, and parties, and tests those who have fears about what they’ve ingested; results are provided in 30 minutes. There’s no involvement by police or any law enforcement. And it’s also a way to track what’s hitting the streets from Asia and India.


Despite the challenges, clinical labs are playing a significant testing role. “Laboratorians know what drugs are popular in a certain region, which narrows the possibilities,” says Mogush. “In the District of Columbia, for example, marijuana joints are sometimes dipped in liquefied phencyclidine (PCP). So regionally, labs do have an idea.

An operator places test kits into a Cobas c analyzer, by Roche Diagnostics.

An operator places test kits into a Cobas c analyzer, by Roche Diagnostics.

“A patient’s behavior and symptoms can also provide a clue,” Mogush adds. “The symptoms of someone on synthetic cannabinoids (perspiring heavily, hallucinations) look different from those of someone on hashish brownies. So if a patient is obviously having a bad drug reaction and the tests are negative for all drugs, it has to be a synthetic. That offers guidance for treatment.”

In another example, says Mogush, “in the United States, more than 80% of what’s sold as ecstasy is not actually ecstasy, but a synthetic version. Knowing this, labs are somewhat equipped. But if all tests are negative, the labs have to look further.”

As a positive sign, it’s believed that current testing will reveal the presence of 80% to 90% of the bath salts on the market. Testing won’t detect 100% of synthetic cannabinoids, says Mogush, but it will pick up the most popular ones.

On the other hand, synthetic cannabinoid makers are cocktailing some of the original synthetic cannabinoids, which are now resurfacing because they’re considered the best of their kind.

Synthetic cannabinoids and synthetic benzodiazepines are on the rise, says Roche’s Pritchard, and new synthetic drugs are definitely a challenge for the classic hospital laboratory. The large number of analytes that cannot be identified with existing drug tests makes it hard to diagnose an overdose. This is why forensic labs often analyze these drugs with sophisticated MS methods or send specimens to specialized forensic laboratories.

According to Pritchard, the popularity of amphetamine-type stimulants is also increasing. These include amphetamine and methamphetamine agents such as d-methamphetamine, use of which is currently on the rise in Europe. Although many people believe that such substances are safe and not harmful, amphetamine-type stimulants and their derivatives cause serious health problems. Today, amphetamine-type drugs are the world’s second-most used stimulants after cannabis.

“From many laboratories, we know that the use of synthetic drugs is increasing remarkably—and especially among young people,” says Pritchard. “These rapidly evolving new drugs challenge national authorities, as they are simply too numerous. However, there has been early discussion about scheduling drug classes according to their potential of hazardousness and individual impairment.”


Table 1. Drugs-of-abuse tests using the enzyme-multiplied immunoassay technique (EMIT) and marketed by Siemens Healthcare Diagnostics under its Syva brand. Siemens sells and distributes the assays for use on the Viva family of dedicated drug-testing systems as well as for use on Beckman Coulter AU systems. The company also offers applications for many other general chemistry analyzers. Contact Siemens for information on availability. Source: Siemens Healthcare Diagnostics.

Table 1. Drugs-of-abuse tests using the enzyme-multiplied immunoassay technique (EMIT) and marketed by Siemens Healthcare Diagnostics under its Syva brand. Siemens sells and distributes the assays for use on the Viva family of dedicated drug-testing systems as well as for use on Beckman Coulter AU systems. The company also offers applications for many other general chemistry analyzers. Contact Siemens for information on availability. Source: Siemens Healthcare Diagnostics.

What’s next? Siemens’ goal is to offer the broadest possible spectrum of tests, giving labs the greatest array of tools to detect designer drugs (see Table 1). “Even though we know it’s not possible to detect 100% of the dangerous illegal drugs out there, Siemens is committed to helping physicians combat this societal problem,” says Mogush. “We have been providing these types of tests for 50 years, and we’re well aware of the drugs-of-abuse issues facing labs. We are working on innovative ways to address these issues.”

The recent “Syva Scientific Days” symposium held in Rome, May 19–20, addressed the evolution of drugs, emerging trends in abuse, and strategies for combating new synthetic and psychoactive substances. Hosted by Siemens, the symposium featured experts and key opinion leaders in the field of toxicology and brought together more than 100 experts from around the world to focus on the latest trends in drugs-of-abuse testing. Topics included how drug abuse continues to evolve and escalate globally from the US law-enforcement perspective, and expert panels considered drug-abuse history and developing trends, the area of new psychoactive substances, and how some regions are dealing with the continuing evolution of drug abuse.

At Roche, the current portfolio for drugs-of-abuse testing and therapeutic drug monitoring comprises more than 19 different drug tests plus a panel for specimen validity tests. A set of dedicated solutions exists for applications such as toxicology analysis, court-mandated sobriety programs, anti-doping reports, and crime scene investigations using serum and urine specimens.

Pritchard says Roche’s emphasis is on offering a complete menu that supports laboratories in achieving efficient testing for the volume demanded by all departments the lab serves. “Roche focuses on offering a complete menu of drugs-of-abuse tests that support clinical laboratories to achieve efficient on-demand results,” he says. “Our interest is to deliver fully automated and reliable high-performance tests, available on our Cobas modular platforms.

“Availability of automatic and efficient tests with good performance is the main motive for Roche,” he adds. “We always follow the science and medical need and direct our research to where we believe we can make the greatest impact for patients.”

Gary Tufel is a contributing writer for CLP. For further information, contact CLP chief editor Steve Halasey via [email protected].


  1. Scientists Find Hyped New Recreational Drug ‘Flakka’ Is as Addictive as ‘Bath Salts.’ The Scripps Research Institute News & Views (May 8, 2015); available at: Accessed May 27, 2015.