In new era, cannabis testing a mixed bag

Create PDF

Dr. Jannetto

Specimen collection by lesser trained personnel can be a further error source. “Obviously, for any sample collection, you need trained individuals. It’s much easier to train someone to do good oral fluid collection than to do a good blood collection, but they do need to know what they’re doing. They have to follow the chain of custody appropriately, keep the person under surveillance, and make sure they do not have anything to eat or drink 10 minutes prior to collecting the sample.”

Mass spectrometry is the closest thing to a gold standard for cannabis testing and helps compensate for many of the weaknesses of immunoassay and oral fluid testing, Mayo’s Dr. Jannetto says. “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 says, “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 cautions. “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.”

January 2017—When the new federal rules are finally published, Dr. Huestis says, they will not allow for on-site screens in the federally regulated workplace. “They require that you have a trained and certified collector collect the sample, which is immediately sent to the laboratory for both screening and confirmation, for the federally regulated workplace in general.” However, she adds, there are many employers not federally regulated “that absolutely love roadside or on-site tests. Because you’ll be at a construction site, say, and you can screen and if the result is positive, take a second sample and send it to the lab, and avoid hiring the person if it comes back positive.”

Drug treatment programs also set a lower standard, Dr. Huestis adds. “They don’t in many cases confirm urine tests. But we always say they should confirm if the test will have any negative consequence. For example, in drug court, they’ll do the screen, they’ll talk to the person, and many times the person will admit use and will have consequences for being positive, although it usually is not going to mean they are kicked out of the program or put back in jail. If they deny using, the treatment programs will run a confirmation test.”

The specificity of THC testing is quite good for on-site tests, Dr. Huestis says. “However, obviously anytime there’s going to be a potential adverse consequence, whether that’s losing your license, losing children, or losing a job, it needs to be confirmed. I think that in most forensic cases, you always have a mass spectrometry confirmation.”

The federal rule to regulate cannabis workplace testing came close to publication in 2004, she recalls. “It went all the way through, but it got kicked back when there was a paper that came out and said there could be false-positive results if you weren’t smoking but the person next to you was. So it did not get signed; that killed the entire law.” But when that particular study was repeated, researchers found that the positive results occurred because they had left all the collection devices inside the area where people were smoking, and the devices became contaminated from the drug in the air. Unfortunately, she says, “That is the kind of preanalytical error source that people seize upon to say there really is a problem.”

No federal initiative is underway to make marijuana legal at this point, she notes. “The Drug Enforcement Administration reviews the controlled list every year, and a lot of people, including myself, thought maybe what would happen is they might move THC from Schedule I to Schedule II. Then the FDA would come in and regulate it.”

After doing decades of research on cannabis, Dr. Huestis believes there are therapeutic applications for the drug, but the big problem is the lack of well-designed, controlled, double-blind studies to demonstrate those uses. “All the things you’d normally have to do to get a drug approved by the FDA—those have not been in place.”

Just in the last couple of months, however, two well-designed studies have shown that Epidiolex, which is a purified cannabis plant extract high in CBD and low in THC, has shown significant results for reducing seizures in individuals who have severe seizure disorders like Dravet syndrome or Lennox-Gastaut syndrome.

Dr. Huestis agrees with the Institute of Medicine recommendation in 1999 that there is now enough evidence that more research is needed to discover potential medical uses. “But we should not be smoking it,” she says firmly. “We need to figure out not only safety but also efficacy, and we need to see how we can standardize potency. Because whenever you have a natural product, it’s difficult to control potency.”

What can laboratories expect from the current climate for cannabis? “I think most hospital and clinical laboratories are going to be in the oral fluid market in the near future, whether from the workplace or from treatment facilities, or in the ER,” Dr. Huestis predicts. “Oral fluid is absolutely coming as a very prominent alternative matrix for the labs. They’re even talking about using it postmortem for autopsy cases. So we will see a lot more test volume.”

“And I think there is going to be a lot more interest in blood cannabinoids that will be of interest to hospital laboratories. It will depend on what the test mix is for the laboratory—many might not do any blood testing for cannabinoids—but blood will be involved where there’s any kind of impairment testing, DUID, or crashes.”

She forecasts that laboratories’ repertoire will be changing. “Right now, labs that are doing blood cannabinoids are doing THC and THC-COOH, and if they’re really good they’re also doing the 11-hydroxy-THC. But I think labs in the future will want to be able to test for some of these other markers of recent use to help them interpret results.”

Also likely to be a big area is therapeutic drug monitoring. “As we get more and more medical marijuana, and you have people on seizure medications, for example, you have to know whether they’ve got adequate concentrations to prevent the seizures,” Dr. Huestis explains. Studies of marijuana as treatment for neuropathic pain and migraines are underway. “So they will start doing therapeutic drug monitoring to test what the concentrations of THC are and whether they’re in therapeutic ranges.”

Amid the expanding universe of cannabis testing, Dr. Jannetto warns, people must continue to be aware of one of the core features of any laboratory test: limitations. “The testing that is locally available for law enforcement or physicians—they are going to use whatever devices are accessible to them. They have to understand the limitations of the technology and test.”

For laboratories, “given the new legal frameworks, the key issue 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.” Keeping those limitations in mind, Dr. Jannetto says, will help ensure that all types of cannabis testing are properly interpreted and used.
[hr]

Anne Paxton is a writer and attorney in Seattle.