Paul Jannetto, Ph.D., Discusses Cannabis Testing in the Laboratory
Cannabis testing in the laboratory can provide evidence of criminal drug offenses and employee drug use, be an indicator of possible impaired driving, monitor adherence to substance abuse treatment or civil orders or compliance with its use as a therapeutic drug, or provide clinical data in emergency care. A recent CAP TODAY article analyzes the changing methods and usage patterns of cannabis testing, and further explores its place in the laboratory.
According to Paul Jannetto, Ph.D., Director of the Clinical and Forensic Toxicology Laboratory at Mayo Clinic, to meet the demand, “there are new point-of-care technologies and devices, and laboratories continue to expand the list of analytes they measure in their cannabinoid assays.”
However, cannabis can be a complicated drug to deal with, even though sensitivity and specificity have improved. “Cannabis is a very complex drug that contains over a hundred cannabinoids, and it’s quite a challenge from the laboratory standpoint, not to mention the implications for legal testing and judging impairment,” Dr. Jannetto said.
According to the article, most current laboratory test menus offer an immunoassay screen using urine, with mass spectrometry (LC-MS or LC-MS/MS or GC-MS) performed as a confirmatory test. While the biologic matrices of cannabis testing include blood, urine, oral fluid, and hair, the majority of testing testing done now is performed on urine. “Unfortunately, that means most of the assays are looking for the inactive metabolite THC-COOH rather than the psychoactive components of cannabis, and THC-COOH could be an indicator of past use, possibly even several days prior to the collection of the urine sample,” Dr. Jannetto said. “So answering the most frequent questions—did the person recently ingest marijuana, and was the person impaired at a certain point in time?—becomes difficult.”
The correlation between impairment and blood levels of the psychoactive ingredient of marijuana, THC, is not settled, and differing laws set standards across the world as well as within the United States.
“Obviously, testing for alcohol is similar to what we’re trying to do with cannabis,” Dr. Jannetto said. “You have concentrations in samples; you’re using blood, serum, or oral fluid; and just as with alcohol, there are legal deterrents set up so that you would not drive or go to a workplace under the influence. However, one of the key differences is there’s currently no really good way to back-extrapolate to verify THC levels at the time they say someone was being pulled over or after a collision.” In addition, a single set concentration of THC that is directly linked to impairment hasn’t been defined for all users, he said.
So what's the best way to test for cannabis? According to Dr. Jannetto, mass spectrometry is the closest thing to a gold standard and helps compensate for many of the weaknesses of immunoassay and oral fluid testing. “Mass spectrometry gives you that sensitivity and specificity. It also allows you to look at many other analytes and metabolites to differentiate the compounds. So you can look for the parent THC, you can look for 11-hydroxy THC, the other psychoactive component, and THC-COOH. You can also look for other things like CBD, which is not psychoactive but does have more medical use."
In addition, mass spectrometry can look for markers found in natural cannabis but not in synthetics. “But that in itself is a whole analytical nightmare and challenge,” Dr. Jannetto said, “because right now there are more than 50 different synthetic cannabinoids on the street, and those formulations change constantly. So unless our assays are constantly updated for new analytes, you could totally miss it. A negative doesn’t necessarily mean the patient didn’t use a synthetic cannabinoid; they could have used one of the ones I didn’t test for.”
Just as with any laboratory testing, mass spectrometry’s accuracy depends on how the lab sets up and validates its testing, Dr. Jannetto said. “Just because somebody says, ‘I have a mass-spectrometry-based test’ doesn’t mean it’s the gold standard or will give an exact result. The lab still has to have control measures and all of the other things that go along with a properly operated laboratory.”
The bottom line is there are limitations of testing for cannabis. The key issue for laboratories, according to Dr. Jannetto, is understanding the limitations of different matrices, what information you can draw from each specimen type, what analytes you are looking for, and which biomarkers are actually correlated with impairment or use and which aren’t.” This will help ensure that all types of cannabis testing are properly interpreted and used.