In the days when marijuana was illegal throughout the United States, testing was simple. If cannabinoid metabolites showed up in urine, a person clearly had broken the law. Now that 23 states and the District of Columbia have laws legalizing marijuana in some form, testing has gotten trickier. Police and employers need to know not just whether someone used marijuana, but if the individual did so recently and in amounts enough to cause impairment.

Yet the traditional urine drug test, which detects the inactive carboxy tetrahydrocannabinol (THC) metabolite, cannot do that. “There’s really no good relationship between [metabolite] concentrations and impairment,” said Gwendolyn McMillin, PhD, medical director of the toxicology laboratory and pharmacogenetics at ARUP Laboratories. “Any attempt to monitor impairment is going to require analysis of the active components themselves.”

THC, the main active component of marijuana, can be measured in blood, but blood poses a challenge for clinical laboratories that have been set up for urine drug tests, according to Sarah Urfer, MS, D-ABFT-FT, laboratory director of ChemaTox in Boulder, Colorado. “It is a totally different method,” Urfer said. “You have to have different controls, different standard operating procedures, and different disposal techniques.” The switch was easy for ChemaTox because it was already both a clinical and forensic laboratory, she said, but other clinical laboratories in the state now outsource blood testing.

The Switch to Oral Fluid

THC can also be detected in oral fluid. Some employers have switched to oral fluid tests for cannabinoid screening simply for the ease of collection and to reduce the opportunity for sample adulteration. The U.S. Substance Abuse and Mental Health Services Administration updated its guidelines for federal workplace drug testing programs in May 2015 to include oral fluid testing. “Many people say that currently about a third of companies doing urine drug testing have switched to oral fluid testing,” said Marilyn A. Huestis, PhD, chief of the Chemistry and Drug Metabolism Section at the National Institute on Drug Abuse. “So urine testing is going down and oral fluid testing is coming up in the workplace.”

Oral fluid testing is also an option for police or employers looking to quantify THC concentrations and detect recent use. Oral fluid has the advantage that it can be collected quickly and easily by an officer at the scene of a crash, Huestis said. In contrast, it typically takes 1.5 to 4 hours for a suspect to get a blood draw after a traffic stop. In that time THC levels fall rapidly. Her own studies have found that THC in blood can decrease 90% within 1 to 2 hours.

Some oral fluid devices can even screen a sample on-site and detect several categories of drug, including cannabinoids. Police are exploring using these devices like a breath test for alcohol. Colorado State Patrol is in the process of field-testing on-site oral fluid devices, according to Urfer. If the result is positive they back up the test with a blood sample, not oral fluid.

“There is limited literature discussing the relationship between oral fluid THC concentrations and impairment. This makes interpretation of oral fluid THC results very difficult,” Urfer said. “I’ve been hearing in this field for ten years, ‘Oh, oral fluid is going to be the new big thing.’ So maybe it really is going to be the new big thing, I don’t know. But you know what? We haven’t gotten there yet.”

No Easy Answers for Interpretation

Regardless of whether the sample is blood or oral fluid, laboratories can accurately measure THC. The problem lies in interpreting the result. “It is not that the testing can’t be done well,” Huestis said. “It is trying to make the leap and the decision on, ‘What does the number mean? And at what number are you intoxicated or impaired?’ That’s where cannabinoids are completely different from, for instance, alcohol.”

Cannabinoids are lipophilic. Unlike alcohol, which is hydrophilic and tends to stay in blood, cannabinoids ultimately accumulate in fatty tissue. Chronic, frequent cannabis users can build up a heavy body burden of THC. Huestis’ studies showed THC is still detectable in some chronic users’ blood 30 days after last use.

But cannabinoids cause problems for infrequent users, too, who will be impaired at much lower concentrations, according to Huestis. “No one in our studies had a blood concentration greater than 5 ng/mL 24 hours after last cannabis use,” she said. “Drivers at this concentration of THC are over 6 times more likely to cause a fatal crash” (Clin Chem 2015;61:1223–5). However, many occasional users are impaired at just 1 or 2 ng/mL. “Everybody wants one number and there isn’t one number [as a threshold indicating intoxication],” Huestis said. “And it doesn’t matter how much more research we do, we’re never going to get to one number.”

Some states, such as Washington and Colorado, have set 5 ng/mL as the limit for driving under the influence. Others, such as Oregon, have not set a limit and rely instead on police officers’ observations. Legal limits are still debated even in alcohol impairment, noted Douglas Berman, a law professor at Ohio State University. Some lawyers specialize in challenging breathalyzer results by questioning the tests or how well they are administered, he said.

“Not only am I not sure there’s anything close to a resolution here, but if you get deep into the nitty gritty of even the debates over blood alcohol content and the way in which the law has handled that, you’ll hear lots of competing perspectives,” Berman said. Obviously there is a demand among law enforcement for clear results in roadside tests, he said, “but whether that will hold up in court ... it’s going to be as much a choice made by lawmakers as it is something driven by science.”

Having testified in Colorado’s marijuana legalization hearings, Urfer urges laboratory professionals to get involved in the legalization process to help ensure that any new regulations will be realistic and based in science. “The biggest thing that they can do to help themselves is to try to be aware of the laws as they come down and try to give input,” Urfer said. Also, any laboratory that needs to add testing functionality because of legalization should reach out to colleagues in states that have already gone through the process. “Do not try to reinvent the wheel,” she said. “The methods already exist.”

Legalization ultimately will create new opportunities for laboratories, predicted Adam Jansen, director of laboratory operations at Assurance Drug Testing Laboratories in Wisconsin, where a marijuana legalization bill has been introduced twice in the state legislature.

“Overall, the legalization of marijuana in some states will have a positive effect on the growth of the drug testing industry,” Jansen said. “The increasing need for monitoring ongoing patient history (medicinal) and in-the-field testing (law enforcement) will increase testing beyond what we see as the probable loss in pre-employment screenings due to legalization of marijuana.”

Julie Kirkwood is a freelance writer who lives in Rochester, New York. +Email: julkirkwood@gmail.com