Labs face increasing challenges in testing for cannabinoid intake as more states medicalize and legalize marijuana and as new and dangerous synthetic cannabinoids appear in the drug abuse market.

In a review published in Trends in Molecular Medicine, two toxicologists underscore the growing importance of oral fluid as a roadside test and the role of mass spectrometry (MS), presence of minor cannabinoids, and new Breathalyzer technology in assessing an individual’s cannabis intake history.

“There’s a lot of different approaches to this, a lot of new things. You can use multiple matrices to measure an individual’s use of different cannabinoids and improve data interpretation,” Marilyn Huestis, PhD, who co-authored the paper with her business partner, Michael Smith, PhD, of consulting firm Huestis & Smith Toxicology LLC, told CLN Stat. To better understand and interpret cannabinoid concentrations, the authors looked at all of the different matrices and new models that help define drug intake, including blood and plasma, hair, urine, sweat and oral fluid, as well as breath and synthetic cannabinoid markers.

Among all of the issues related to cannabinoid use, documentation of cannabis-impaired driving is perhaps the most timely and critical. Morbidity and mortality rates in states like Washington and Colorado are rising because of this deadly practice, Huestis said. In her view, the best biological matrix for roadside testing is oral fluid.

Measuring Delta-9-Tetrahydrocannabinol (THC), the primary psychoactive component in cannabis, is tricky because it drops so rapidly in the blood within the first few hours. In the United States, it takes between 1.4 and 4 hours from the time of a police stop or crash to collect blood for a sample. “By that time, THC concentration may be even below lab reporting limits,” Huestis said.

Oral fluid tests are easy to use and noninvasive and do an excellent job with evidentiary sample tests in the lab. This type of testing also has a sound track record overseas: Australia exclusively uses oral fluid for assessing impaired driving and Europe has been using this method since the mid- to late-2000s. In the United States, oral fluid testing is just getting started. Several acceptable oral fluid on-site tests are now available, and according to Huestis, between 17 to 20 states have already included oral fluid testing in their laws.

What’s critical is making sure that a second evidentiary oral fluid specimen is analyzed in a laboratory with MS, she emphasized. “If the roadside test is positive for cannabis, cocaine, opiates, or amphetamines, then you always have to confirm an immunoassay screening test with an MS test. But if the roadside test is negative, you still need to send it to a lab because the lab will test for a much broader spectrum of possible analytes.” This is important because if a police officer or other expert on-site documents impairment, the drugs producing that impairment must be identified, Huestis said.

Labs in turn need to validate the method for each oral fluid collection device they use, Huestis advised. The reason for this is the buffers they use potentially interfere with liquid chromatography-tandem MS. “It’s very important to clean up or prepare the sample to remove buffer constituents that can suppress ions in MS,” she said. “This is not a simple dilute and shoot.”

Looking at minor cannabinoid blood markers such as cannabigerol or cannabinol may be another way for labs to improve their interpretive capabilities. Studies have shown that measuring these markers in blood indicates recent cannabinoid use in either occasional or chronic users. “However if you don’t find them, you cannot rule out recent use,” Huestis said. For example, after a person eats cannabinoids these markers don’t always show up on a test due to their low concentrations, compared with markers that are smoked or inhaled.

Scientists are exploring other technologies for measuring recent cannabis intake, including a sensitive and specific Breathalyzer for THC. In her own research, Huestis had success in measuring THC in the breath of frequent and occasional cannabis users. “The problem is, even when we dosed individuals, some people never had any detectable THC, and we used a highly sensitive mass spectrometer to get those results,” Huestis said.

All over the world, different companies are trying to develop a breath test, but they have yet to publish any data that supports their technology, according to Huestis. “Certainly you can measure THC in breath. But right at this moment there’s not a roadside device capable of doing it,” she said.