Drug Addiction AbuseThe mass spectrometry issue of Clinical Chemistry, the journal of AACC, features pioneering research that could enable screening for two synthetic cannabinoids that are on the rise. This study could also help to reduce the popularity of designer drugs overall by making it easier to develop tests for the myriad of new, dangerous substances that emerge every year.

Experts have likened keeping up with designer drugs to a game of whack-a-mole — each time a designer drug is identified and outlawed, chemists simply create a new one. From 2009 to 2012 alone, the number of these substances rose from 166 to 251 in the member states of the United Nations Office on Drugs and Crime. The result is that forensic and clinical toxicology labs have become overwhelmed trying to develop methods to detect these unknown drugs.

Certain types of designer drugs such as synthetic cannabinoids are particularly difficult to test for because they don’t show up in measurable amounts in urine, the sample type most widely used for drug screening. This is one of the main reasons why users turn to designer drugs, despite the risk of severe consequences such as kidney damage, psychosis or even death.

For the first time, a team of researchers led by Marilyn A. Huestis, PhD, of the National Institute on Drug Abuse, has identified metabolites of two new synthetic cannabinoids that could potentially be detected by a urine drug test. The substances they investigated, known as THJ-018 and THJ-2201, were initially found in 2014 and drug-user forums suggest their abuse is becoming increasingly prevalent.

Although synthetic cannabinoids don’t appear in urine, they are broken down by the liver and the body typically excretes the byproducts of liver breakdown, known as metabolites, with urine. Identifying these metabolites presents a challenge, however, as it can be difficult to find positive cases of new designer drugs to study. To get around this problem with THJ-018 and THJ-2201, Huestis’s group incubated human liver cells known as hepatocytes in solutions of each of these drugs. Using a relatively new lab technique known as high-resolution mass spectrometry (HR-MS), the researchers then identified the major metabolites produced by the liver cells that are unique to each drug and could serve as targets for a test.

“These data empower clinical laboratories to target markers of

[new psychoactive substance (NPS)] intake,” said Huestis. “Our analysis strategy, HR-MS data acquisition, and processing and hepatocyte incubation, is also applicable to further studies of newly emerging NPSs.”

In an editorial in the same issue of Clinical Chemistry, Svante Vikingsson and Henrik Gréen, PhD, of Sweden’s Linköping University comment further on the significance of these findings. They note that, because designer drugs spread quickly around the globe, this research on THJ-018 and THJ-2201 is very timely. Even more important, they believe, is the fact that the method developed by Huestis’s group could be used to develop urine tests for the future designer drugs that will inevitably crop up.

“To properly assess the metabolism of a synthetic cannabinoid, different approaches need to be combined and the results must be interpreted carefully,” wrote Vikingsson and Gréen. “The work of [Huestis’s team] shows how this process can be carried out successfully and sets the standard for future studies.”