An increase in use [of designer drugs] would not necessarily be relevant to acute healthcare professionals if these substances were not harmful. However, existing data shows that this is not the case. In 2012 alone, 52 deaths in England and Wales were directly attributable to novel psychoactive substances, with no other drugs listed on the death certificate. Many more deaths reference co-ingestion of these substances.

Smith & Robert, 2014

Testing and assessment of patients admitted for designer drug use presents a number of challenges. Urine and other screening tests cannot yet identify or even detect specific designer drugs, particularly because their chemical structures are changed rapidly. Because of this, clinicians must be alert for signs and symptoms of designer drug use during the screening and assessment of new patients.

Testing Challenges

Urine or serum toxicology screens are unable to detect all of the designer drugs that have been synthesized, posing a major diagnostic and monitoring challenge for clinicians. Although laboratory testing is expanding, widespread standardized designer drug testing is not yet available in most clinical practice settings and laboratories. The analytical challenge is compounded by differences in designer drug product contents, concentration, and chemical constituents, all of which may vary between and within products (Weaver et al., 2015).

Illicit manufacturers have demonstrated remarkable flexibility in altering the psychoactive components of designer drugs to evade regulation and detection. It is common practice to modify functional groups, change substitutions, and alter moieties* of substances in a rapid and iterative process to evade legal restriction. This practice also poses significant challenges for detection of compounds or metabolites through urine drug screening (Weaver et al., 2015).

*Moiety: a part or a functional group of a molecule, part of a molecule.

Individuals frequently report that the lack of detection on standard urine drug screening tests is a reason for designer drug product use. For example, populations under criminal justice supervision may use designer drugs to evade detection by probation officers. Among the U.S. military, where most soldiers referred for addiction treatment are identified through urine drug screening, synthetic cannabinoids are consumed by those seeking cannabis-like mood-altering effects but with much lower risk of detection (Weaver et al., 2015).

Even though most emerging designer drugs will not be picked up on routine urine drug screening in a healthcare setting, collection of urine is still valuable clinically to test for unreported, co-occurring substance use. A general laboratory screening battery of urine or serum should be sent to screen for common drugs of abuse. This helps the clinician to be aware of potential toxicity due to drug interactions, and to the need for closer or prolonged monitoring due to the presence of other, non-designer substances. When comprehensive designer drug testing is unavailable or pending, familiarity with the most common designer drugs and other substances of abuse in a given locality can help clinicians rapidly recognize intoxication and begin management of serious complications (Weaver et al., 2015).

In the clinical and forensic toxicology settings, detection of designer stimulants and synthetic cannabinoids presents a complicated challenge. Detection of these designer drugs using mass spectrometry* is one method under investigation. Screening immunoassays** based on amphetamine, methamphetamine, or MDMA as the target molecules cross-react with only a small subset of designer amphetamine-like drugs and are thus unreliable for detection of designer amphetamine-like drugs (Krasowski & Ekins, 2014).

*Mass spectrometry: a technique that measures the mass or weight of atoms and molecules and uses this information to identify the amount and type of chemicals present in a sample.

**Screening immunoassays: a biochemical test that measures the presence or concentration of a macromolecule in a solution through the use of an antibody or immunoglobulin.

Immunoassays designed for THC metabolites generally do not cross-react with the synthetic cannabinoids that do not share the classic cannabinoid backbone found in THC. This suggests complexity in understanding how to detect and correctly identify whether a patient has taken a molecule of one class or another and it ultimately impacts clinical care. Recently, enzyme-linked immunosorbent assays (ELISAs)* for bath salts and synthetic cannabinoids have been developed and analyzed for cross-reactivity. The use of immunoassays such as ELISA for detection of designer drugs raises the question of how well such assays will detect a variety of compounds while avoiding false positives caused by cross-reactivity with unrelated compounds (Krasowski & Ekins, 2014).

*Enzyme-linked immunosorbent assay (ELISA): a test that uses antibodies and color change to identify a substance.

Clinical Assessment

Young adults are the most common demographic among those seeking emergency medical services related to designer drug use; hence, clinicians should consider direct inquiry about designer drug use, particularly among young adults presenting for acute medical care with signs or symptoms that could indicate substance-related toxicity (Weaver et al., 2015).

Since designer drugs are not detected by routine drug screens, healthcare providers relying solely on laboratory testing may be misled that illicit drugs have not been used. Conversely, the presence of routinely detectable illicit substances does not rule out the presence of designer drugs, since polysubstance use is typical in the population using designer drugs. Clinicians should be alert for inconsistencies between observed and expected intoxication syndrome from a self-reported or detected class of drugs. Such discrepancies could indicate recent designer drug use (Weaver et al., 2015).

Clinicians can be alert for clinical clues based on variations in patient presentation that may help identify designer drug use (see table below). Conjunctival injection is an indicator of synthetic cannabinoid intoxication as well as other cannabis products. Some patients presenting for emergency treatment may still have the package that contained the designer drug. This can be examined for possible identification of common brand names for a specific class of designer drug (see earlier table) and, potentially, any remaining content can be sent to a laboratory for analysis (Weaver et al., 2015).

Internet sites may be helpful for identification of specific substances ingested due to their rapidly changing appearance. However, the lack of research-based information on the adverse effects of designer drugs has led to the emergence of a range of websites that may or may not provide accurate information. The presence of paraphernalia such as a pipe for smoking could indicate designer drug or other smokable drug use, and a strong smell of perfume or cologne may be an attempt to mask the smell of recent smoking (Weaver et al., 2015).

Routine inquiry about designer drug use is prudent, particularly among patients with a history of substance use disorder, those who are undergoing mandated urine testing (eg, criminal justice supervisees), or among those who have reported a history of designer drug use of a different chemical class. Different classes of designer drugs may be used concurrently, which could increase the incidence of adverse effects and toxicity (Weaver et al., 2015).

It is helpful for clinicians to ask about specific products by name, or perhaps “synthetics” in general, since patients may not be aware of designations used by medical personnel, or of different street names for similar products. For each affirmative response, followup questions should be asked about frequency, patterns of use, and subjective effects. Careful inquiry about subjective effects could help provide insight into the designer drug class, particularly when the brand–compound association is less well established and with wide variation in contents. Although our first table lists brand names along with the designer drug compound or class, the list is not comprehensive; there are likely thousands of different trade-name brands sold internationally (Weaver et al., 2015).

Further clinical inquiry should include specific questions about factors associated with designer drug use and the potential consequences, whether related to medical sequelae, interpersonal difficulties, or financial/legal problems. Chronic designer drug use may lead to physiologic dependence with tolerance and abstinence-related withdrawal, as well as a designer drug use disorder. Comprehensive inquiry about such factors regarding the patient’s designer drug use helps the clinician make an initial determination about potential severity and provides insight into treatment needs (Weaver et al., 2015).

Among patients presenting for acute medical complications of designer drug use, routine laboratory testing should include—in addition to standardized urine drug testing—a complete blood cell count and complete metabolic panel. Cardiac enzymes should be obtained if cardiac symptoms are present. Creatine phosphokinase is helpful if rhabdomyolysis is suspected on the basis of severe muscle spasms, swelling and pain in the extremities, or severe seizures. Additional diagnostic studies may be selected on the basis of the initial presentation (Weaver et al., 2015).