I’m behind the curve again, having had final exams to grade and such, but with all the talk about Jeremy Mayfield’s suspension for failing a drug test, I had to write something about drug tests and what you can reliably conclude from them. Disclaimer: I’m not a medical doctor, but even a casual perusal of the drug-testing literature suggests to me that drug testing is a lot more complicated than the black-and-white results people would have you belive. NASCAR has a drug-testing policy that allows them to test urine, blood, saliva, hair or breath if there is “reasonable suspicion”. Random competitor tests are also done on a weekly basis.
What is Being Tested For?
NASCAR crews (not drivers) were given a list that includes:
- Seven different amphetamines, including methamphetamine and PMA, a synthetic psychostimulant and hallucinogen.
- Three drugs classified under ephedrine.
- 13 different narcotics, including codeine and morphine.
- Ten different benzodiazepines and barbituates.
- Marijuana, cocaine, zolpidem, nitrites, chromates and drugs that can increase specific gravity.
Amphetamines are ‘uppers’, which decrease fatigue by increasing levels of the stress hormones norepinephrine (attention and responding/fight-or-flight reactions), and the neurotransmitters serotonin (modulates anger, aggression, mood, metabolism, etc.), and dopamine (increases heart rate and blood pressure).
Ephedrines are stimulants, appetite suppressants, decongestants. The molecule Ephedrine looks very similar to amphetamine. Psuedoephedrine is like the left-handed version of ephedrine and that’s what’s in over-the-counter decongestants like Sudafed.
Narcotics is an imprecise term that usually refers to anything that deadens the senses. Codeine, morphine, heroin, etc. fall in this category.
Prohibiting marijuana, cocaine and zolpidem (a sleep aid that is in things like Ambien) is obvious, but the last part doesn’t make sense at first reading. I believe the idea is that nitrites and chromates can be used to adulterate a urine sample to try to hide drug use. “Drugs that can increase specific gravity” means the specific gravity of urine (as was pointed out by a poster on rowdy.com). One way of checking for adulterated samples is measuring the pH, temperature and specific gravity (the density of the sample relative to water). If the values are outside of a specified expected range, then the sample is suspect. So the latter part of that rule isn’t about illegal substances, it’s about things that you might take in order to hide the use of illegal substances. For example, if you drink large quantities of water (1-2 liters), most of it comes out in the urine and that dilutes anything elkse in there.
Needless to say, you don’t want anyone in a position of responsibility on one of these substances. Note that this list is for the crews. The drivers don’t have a list, but you could safely assume that all of the substances mentioned are off-limits, plus some. NASCAR reserves the right to test for anything they think could potentially impair a driver on the track.
How Do You Tell If Someone’s Used These?
A sample (usually urine) is collected and split into two parts called the ‘A’ sample and the ‘B’ sample. The A sample is tested with a chemical test called an immunoassay. Immunoassay (IA) tests, as I’ll describe in a moment, are more general tests. The B sample is stored and there are specific protocols for how the sample must be stored. If the IA test shows one or more positives, then the B sample is brought out and tested using a more sophisticated test called Gas Chromatography-Mass Spectroscopy. If the B sample tests negative, then the test is generally regarded as negative. If the B sample tests positive for one of the banned substances, then the driver is notified and disciplinary action is taken.
Immunoassays work sort of like a jigsaw puzzle. There are antibodies (detectors) and antigens (targets). The two types of molecules bind to each other.
The molecule in the upper left of the picture above is our detector molecule. The circle represents something that can be detected – a fluorescent molecule, a magnetic bead or something similar. The molecules on the right-hand side are the molecules in the sample to be analyzed. Our detector molecule has a binding site – the fork pointing to the right, and that binding site will allow it to only link to specific shapes of molecules. (In reality, the binding is chemical, not by shapes, but I find the analogy to shapes easier to understand.) Our detector will only bind to triangle shapes, but there’s a problem here in that there are blue triangles and green triangles. Immunoassays are very sensitive – they’re good at detecting things, but they are not always as specific as we might like. The green triangles might represent a banned drug, while the blue ones are harmless — but both bind to our detector molecule.
That’s OK because we have the B sample and if the A sample shows that there might be something there, we then analyze the B sample using a more specific technique. Gas chromatography is used to separate molecules by weight. The sample is run through a column so that all the molecules with the same weight as the target substance are collected. We do this in elementary school with kids and pens. The analogy we use is to make two rows of kids the same length. Two kids are chosen to be ‘sample molecules’. The first kids is allowed to just walk down the row. The second kid must shake hands with everyone in the row as he walks. We start both kids at the same time and, not suprisingly, the student who has to shake hands takes a lot longer to travel the same lengths as the student who doesn’t. In GS, the sorting is done by weight, so all the molecules with the same weight as the suspicious molecule are separated.
The molecules are then heated. All molecules break into fragments in rather predictable manner when heated, so the mass spectrometer detects fragments and you can infer what the molecule was before it was broken up, and how much of it there was.
A false positive is when you find that the molecule you’re testing for is there, but it isn’t really. There are A LOT of things that cause false positives. For example, buproprion (an anti-depressant) can cause a false positive for amphetamine. So can an awful lot of other things. Apparently, if a driver has a prescription for one of the conflicting substances, they just have to have their doctor contact the drug testing doctor and things are OK.
To make it more complicated, some drugs are quickly metabolized (broken up) by the body. Amphetamine passes through the body into the renal system (the urine) mostly unadulterated by the body; however, other drugs are transformed by the body and what you test for are the products of metabolizing the drug. Some drug tests are therefore very indirect.
Chain of Custody
The lab handling the analysis must follow proper procedures and be very careful to make sure that they don’t mix up samples or cross-contaminate one sample with another. While you hope that all labs are careful, there are plenty of incidences in which labs have been found to have shoddy procedures.
A problem, of course, is the time scale of the tests: urine tests can detect drug use from timescales of hours to days. NASCAR didn’t relate that there was a problem with the test for a few days, so taking another urine test after notification wasn’t a possibility. It is, however, possible to test for drug use in hair, which can reflect drug use over a period of weeks to months. NASCAR allows no appeal, which seems to me very misguided. NOTE ADDED: ESPN is reporting that Mayfield is having hair samples tested.
Conflict of Interest
The doctor that NASCAR has contracted with to conduct the drug testing also owns the lab at which the tests are done. This seems to me to be a clear conflict of interest. At the very least, NASCAR should have an independent person versed in drug testing overseeing the test. If I were NASCAR, I would have the samples tested at two different labs, preferably one lab chosen by the person being tested. This is too important an issue to leave to the possibility of a lab screw up – and the papers are full of people being let out of jail because of mess ups in testing laboratories. There are a lot of places for things to go wrong. It doesn’t sound like that’s what happened here because of Mayfield’s defense that an interaction between a prescription drug and an over-the-counter drug is responsible for the positive; however, sometimes the perception of unfairness – totally independent of the reality – is damning.
The other conflict of interest issue is whether NASCAR should make the drug for which the positive test was found public or not. One the one hand is Mayfield’s right to privacy. He may be taking antidepressants and not wish to have that revealed; however, if Mayfield waives that right, this isn’t an issue. The latest statement Mayfield issued (from an infield hospitality trailer during the All-Star Race) says that NASCAR hasn’t told him what drug he tested positive for, while NASCAR claims that he’s been told verbally on three occasions the identity of the drug. This is extremely troublesome for two reasons. First, if he’s found guilty, he ought to at least know the evidence against him. Second, how can he claim a reason for why he tested positive if he doesn’t know what he tested positive for?
Can We Make a Judgement?
No, we can’t because there simply hasn’t been enough data released to make a determination. The people who are assuming guilt or innocence are doing so based on their opinions, not on evidence. More balanced are the writers calling for greater transparency. If Mayfield follows up on his threat of legal action, the truth may come out. Until then, we are pretty much stuck in the dark, trying to make decisions based on who we deem to be most trustworthy – a pretty poor way to do science, especially when a man’s reputation is at stake here. Let’s hope that the facts are brought to light and we can all make a conclusion based on real evidence
NOTES Added: Jeremy claims he doesn’t know what substance he tested for. Dr. Black claims he’s told Jeremy personally. Jeremy says he hasn’t gotten it in writing. Dr. Black says that NASCAR issues written reports, not him. NASCAR says that they aren’t aware Jeremy wanted a written report. Come on folks. Argh!
Also see: Marc at Full Throttle has a great post on the issue – well worth reading.