Urine drug testing, continued

Heroin tests positive for morphine. This is because heroin is metabolized first from diacetyl morphine, then to 6-monoacetyl morphine (known as 6-MAM) and then into morphine. Codeine is often seen in low levels in the urine drug screens of heroin users.

Heroin is morphine, except with two methyl groups attached. The two acetyl groups were put onto morphine to make it cross the blood-brain barrier more easily. Unlike the rest of the body, the space between capillaries in the brain is much tighter, preventing harmful material from leaking into the fluid that bathes the fragile brain. There’s also a basement membrane at the blood-brain junction, thicker than in other areas of the body. This blood- brain barrier keeps bacteria and large molecules of many drugs from getting access to the brain.

Acetyl groups apparently make it easier for morphine to cross, or be transported, through the  blood-brain barrier. With morphine, even if it’s injected, only five to ten percent of the drug crosses the blood brain barrier to reach the pleasure center, to produce the desired euphoria. However, with the addition of two methyl groups, creating heroin, around eighty to ninety percent of the drug gets across the blood- brain barrier. Thus with heroin, more drug gets to the pleasure centers of the brain. This is what makes most intravenous opioid addicts prefer heroin to injectable morphine, though personal preferences do vary.

On drug screens, we sometimes see 6-monoacetyl morphine (often called 6-MAM) as a metabolic product of heroin, and only of heroin. If this substance is seen in the urine, the person is using heroin, not morphine or other prescription opioids.  This molecule is difficult to detect, since it’s in the urine briefly, from thirty minutes to twelve hours after use.

Yes, poppy seeds can cause a low-level positive for opiates, because they contain tiny amounts of morphine. But unless you eat a mountain of poppy seed muffins, the cut-off for a morphine screening test is usually set high enough to prevent positives opiate tests from poppies. But if you were to decrease the lower limit of detection of morphine, positive tests could be seen in poppy seed eaters.

With heroin, the ratio of morphine to codeine found in the urine is much higher than 2 to 1, but with prescription morphine, this ratio is less than 2:1. Thus the ratio can give an idea whether the person taking a drug test has used prescription opioid medication or heroin.

Urine drug testing for benzodiazepines can also be confusing. On most EIA tests, the antibody in the test is targeted for diazepam (Valium). However, diazepam is metabolized into several compounds, including nordiazepam, temazepam (Restoril), and oxazepam (Serax). Patients who take only Valium as prescribed can be falsely accused of taking Restoril or Serax unless the person interpreting the test results knows this

Many EIA screens don’t test positive for clonazepam, so usually a special test must be added to detect this medication.

Other tidbits: the Z medications don’t cause benzodiazepine positive results on urine drug screen EIAs. False positives for buprenorphine can be seen in patients using codeine, naltrexone, or hydrocodone.

All of these finer points of drug testing illustrate the possible hazards of drug test interpretation. Companies doing drug tests on their employees shouldn’t try to interpret the tests by themselves. They should hire doctors specially trained to interpret these tests. This type of doctor is called an MRO, for Medical Review Officer. To be an MRO, the doctor must take an initial three-day course with about 22 hours of material, and then pass a two-hour written exam to become certified. The course and test must be repeated every five years to remain certified, since the science of drug screening can advance rapidly.

Companies usually contract with MROs to look at all positive tests, and to watch for problems that could affect the integrity of the test process. If a test is positive, the MRO contacts the urine donor, and asks questions about drug use and prescriptions in an effort to decide if there was unauthorized use of a medication or drug. Otherwise, many mistakes can be made and people can lose their jobs over an error in interpretation of the drug test. If the test is positive for a prescribed medication, the only report the employer should get is that the test didn’t show any illicit drugs. In this way, the MRO also acts as a buffer between employee and employer, safeguarding the health information of the employee.

Drug addiction treatment centers usually don’t need MROs, since they are not doing screening tests, but rather tests on patients know to have issues with addiction. At most addiction treatment facilities, the medical directors interpret drug testing results. Counselors shouldn’t be expected to interpret test results on their own, and should always be able to discuss unexpected results with the program physician.

Urine Drug Testing

At April’s ASAM conference, I enjoyed an informative two-hour lecture on the finer points drug testing. Some of the information I knew, some I had forgotten, and some things I thought I knew, but I was wrong. Just goes to show me – again – I have to keep learning, because particularly in this field of medicine, things are always changing.

Dr. Peter Tenore, assistant professor at Albert Einstein College of Medicine, gave the two-hour presentation. He began with basic information about urine drug screening, and how to detect adulteration of a urine sample. Checking the urine creatinine and urine specific gravity are cheap and easy ways to see if a sample was adulterated. If the urine creatinine and/or urine specific gravity are below what is physically possible, it’s not human urine. These tests are fairly good, and detect most sample adulterations.

But besides these two methods, labs that do drug testing use ever more sophisticated ways to look for methods to thwart drug testing. These companies want to have good reputations. They want to be able to say they are savvy to the latest ways drug users try to cheat drug tests. These companies go to the same place drug users go for new ideas and technology – the internet. Testing companies buy the same products, advertised to beat drug tests, that the drug users do, in order to find ways to counter them. It’s a continuing game of cat-and-mouse.

Dr Tenore outlined the two types of tests done on samples to detect drugs. The first is cheap, quick, and fairly accurate, called the EIA, which stands for enzyme immunoassay. This test uses antibodies to identify the different classes of drugs. These tests are good for quick screening, but can have false positives. This mean a person has not used the drug, but the tests shows positive for the drug. In such a case, the same sample can be sent for more specific testing that won’t give a false positive, called GC/MS testing. This second test, more complex and more expensive, will show positive only if the drug really does exist in the sample. This second test meets the legal standard of beyond a reasonable doubt so if it’s positive…it’s positive.

Dr. Tenore took pains to remind us about the limits of drug testing, too. For example, oxycodone is a partially man-made molecule. The standard EIA (electroimmuno assay) tests for the morphine molecule, and oxycodone’s side chains, added to give it different opioid properties, often prevent the morphine antibody from attaching to the oxycodone molecule. In fact, if a patient prescribed only oxycodone is continually positive for opiates, oxycodone may not be the only opiate the patient is taking. Fortunately, there’s a specific EIA test for oxycodone, and most opioid treatment programs know to include this test, lest they miss important information.

I already knew that oxycodone doesn’t always show up as a positive for opiates, but surprisingly, many doctors who prescribe oxycodone don’t know this.

A few years ago, a patient being treated for chronic pain with oxycodone came for intake at the opioid treatment center where I worked at the time. His doctor, who prescribed oxycodone to treat a chronic pain condition, had just “fired” him. The patient was told only that there was a problem with his drug test. After talking with the patient, I didn’t feel he had the disease of addiction, and thus was not appropriate for admission to methadone maintenance at an opioid treatment center. This guy had never snorted pills, never used more than prescribed, never got extras from other doctors or off the street. He vehemently denied selling or giving away any of his oxycodone prescription, and said he took it as prescribed. This was puzzling.

I decided to call the testing lab, who said his sample was negative for opiates. I asked if the sample had been tested for oxycodone specifically, and was told “no.” Then with the patient’s permission, I called his pain management doctor, who was horrified at his mistake, and asked me to send the patient back to him immediately, which I did. Small errors like that can make big problems for patients.

The standard opiate EIA test works great for detecting drugs that get metabolized to morphine, such as heroin, codeine, and, of course, morphine. But special EIA screening tests must be done to detect the fully synthetic opioids like buprenorphine (Suboxone, Subutex), methadone, fentanyl, meperidine (Demerol), and tramadol. Other semi-synthetics are often negative for opiates on the standard EIA: oxycodone as described above, (name brands such as OxyContin, Roxicodone, Oxy IR, Percodan, and Percocet), hydromorphone (Dilaudid), and oxymorphone, (Opana). Hydrocodone usually does test positive on routine screening EIA.

Some drugs are metabolized into other drugs, which sometimes confuses doctors into thinking that two drugs have been used. For example, hydrocodone (Lortab, Vicodin) is metabolized into hydromorphone. So if I have a patient for whom I’m prescribing hydrocodone, I shouldn’t be surprised if, for some reason, I do a GC/MS test, and hydromorphone is also present. It does not mean the patient took Dilaudid. Similarly, oxycodone is metabolized to oxymorphone, and isn’t unexpected in the GC/MS of a patient prescribed Percocet.

In my next blog entry, I’ll explain how labs can tell whether a drug test is positive for opiates because the patient used heroin, or because the patient took prescribed medication.

Drug Testing Information

When people think of drug tests, they usually think of urine drug testing, though this isn’t the only option. In my office, where I prescribe buprenorphine to treat opioid addiction, I use both urine and saliva drug testing. I’ve rarely recommended hair drug testing, because it has limitations.

            Urine drug testing has been around for some time. This type of testing is reliable and accurate, though it’s possible to falsify a urine drug test in several ways: by adding something to the urine sample, and by ingesting a compound and then drinking plenty of water to dilute the concentration of drug in the urine sample. Fortunately, labs that do drug testing use the internet to buy the same items advertised to help people “pass” urine drug screens, to find ways to detect the adulterants. But people are clever, and new ways of falsifying have evolved. The cat and the mouse are ever learning new ways to do their jobs better.

Urine tests have the advantage of being much cheaper than saliva and hair testing.

            Saliva testing is difficult, if not impossible, to adulterate. The only way I’ve seen patients try to falsify these tests is by trying not to get enough saliva on the mouth swab. This doesn’t work with the kits I now use, since there must be enough saliva to give 5 drops of saliva, and it that’s not obtained, it’s not a valid test.

Saliva tests are particularly excellent at detecting marijuana and cocaine, because those drugs are concentrated in the saliva. In fact, saliva may detect these drugs at a lower intake level than urine testing. But saliva tests can cost more than twice urine drug tests.

            Hair testing isn’t an exact science, and it’s not used for routine testing. Theoretically, drugs are concentrated in the hair shaft as it grows, giving a record of drug use over time. Depending on the length of hair, we can get information for six months or more. But hair testing can be thwarted by hair treatments. Plus, it’s much more expensive.

            Then there’s a racial issue. Naturally dark hair concentrates drugs much more than naturally blonde hair. Thus, a blonde Caucasian and an African-American may ingest the same amount of drug, and it’s more likely for the dark-haired African-American to have a positive test, detecting the drug. Most people hesitate to use a racially skewed test like this.

            What about these substances advertised to “flush out your system?” They work by dilution. Save your money, because you’d get the same results by drinking large quantities of water. But do be careful, as it’s actually possible to overdose on water. This occurs if you drink so much water that your electrolyte levels drop, and it can be fatal.

            The most amusing device I’ve seen used to falsify a urine drug screen is something called “The Whizzinator.” This is a prosthetic penis-type device that contains a heated sample of negative urine, which is funneled through the fake penis and into the collection cup. These are used when observed urines are requested, but also have their flaws.

            At one clinic where I worked, the device purchased by the patient was a great deal larger than the real member, and was a different color. This was a give-away that something was amiss, and the patient’s ruse was detected. Apparently the Whizzinator comes in five colors and sizes, so one must be careful to get a fake penis closely resembling one’s own skin tone. And one should take pains to make sure the fake penis doesn’t fall off, as happened to another patient during an observed urine collection.

            But why go to all that effort and expense? As I’ve said before, the best way to have a negative drug test is…don’t use drugs.

Urine Drug Screens for methadone and Suboxone (buprenorphine)

Many patients who are prescribed methadone or buprenorphine (better known to some as Suboxone) are concerned about their employment drug screens. Because of the stigma attached to opioid addiction and its treatment with methadone or buprenorphine, patients don’t want their employers to know about these medications, and thus about their history of addiction.

Most companies who do urine drug screening hire a Medical Review Officer (MRO), who is a doctor specifically trained to interpret drug screen results. This doctor is a middle man between the employer and the employee, and though this doctor may ask for medical information, and information about valid prescriptions, this doctor usually can’t tell the employer this personal information. The MRO reports the screen as positive or negative, depending on information given to her.

Most employment urine drug screens check for opiates, meaning naturally-occurring substances from the opium poppy, like codeine and morphine. Man-made opioids like methadone, buprenorphine, and fentanyl, to name a few, won’t show as opiates on these drug screens.

A few employers do drug screening that specifically checks for hydrocodone or oxycodone. This is infrequent. It’s rare for employers to screen for methadone, and they almost never screen for buprenorphine, unless the patient is a healthcare professional being monitored by a licensing agency. The screen for buprenorphine is pricey, so the only doctors who tend to screen for it regularly are the ones prescribing buprenorphine. These doctors want to make sure their patients are taking, not selling, their medication.

Patients ask if they should tell their employer they are on methadone or buprenorphine. In general, that’s probably a bad idea, unless it’s a special situation. So long as you can do your job safely, your medical problems aren’t any of your boss’s business.

The only exceptions to this are if you work in a “safety sensitive” job. This includes medical professionals, transit workers, pilots, and the like. These jobs may require disclosure of medical issues to protect public safety. For example, to get a commercial driver’s license (CDL), you have to be free from illnesses which may cause a sudden loss of consciousness behind the wheel.

The Dept. of Transportation still says that if you are taking methadone for the treatment of addiction, you can’t be granted a CDL. However, most of the studies done on methadone-maintained patients shows their reflexes are the same as a person not on methadone, so there’s no real scientific reason for the DOT’s decision. (1, 3, 4) Besides, since the urine drug screen for a driver’s physical doesn’t include methadone, they won’t know unless you tell them.

Patients can be impaired, and unable to drive safely, if they have just started on methadone, haven’t become accustomed to it, or are on too high a dose. These patients shouldn’t be behind the wheel until they are stable, even in a car, let alone an 18-wheeler. Methadone patients are likely be impaired and unable to drive if they abuse benzodiazepines. They shouldn’t drive any kind of vehicle. Ditto for alcohol. (2, 5)

1. Baewert A, Gombas W, Schindler S, et.al., Influence of peak and trough levels of opioid maintenance therapy on driving aptitude, European Addiction Research 2007, 13(3),127-135. This study shows that methadone patients aren’t impaired at either peak or trough levels of methadone.

2. Bernard JP, Morland J et. al. Methadone and impairment in apprehended drivers. Addiction 2009; 104(3) 457-464. This is a study of 635 people who were apprehended for impaired driving who were found to have methadone in their system. Of the 635, only 10 had only methadone in their system. The degree of impairment didn’t correlate with methadone blood levels. Most people on methadone who had impaired driving were using more than just methadone.

3.Cheser G, Lemon J, Gomel M, Murphy G; Are the driving-related skills of clients in a methadone program affected by methadone? National Drug and Alcohol Research Centre, University of New South Wales, 30 Goodhope St., Paddington NSW 2010, Australia. This study compared results of skill performance tests and concluded that methadone clients aren’t impaired in their ability to perform complex tasks.

4.Dittert S, Naber D, Soyka M., Methadone substitution and ability to drive. Results of an experimental study. Nervenartz 1999; 70: 457-462. Patients on methadone substitution therapy did not show impaired driving ability.

5.Lenne MG, Dietze P, Rumbold GR, et.al. The effects of the opioid pharmacotherapies methadone, LAAM and buprenorphine, alone and in combination with alcohol on simulated driving. Drug Alcohol Dependence 2003; 72(3):271-278. This study found driving reaction times of patients on methadone and buprenorphine don’t differ significantly from non-medicated drivers; however, adding even a small amount of alcohol (.05%) did cause impairment.

More About Drug Screens

Working at an opioid treatment center, I get questions frequently from patients who are concerned about their positive urine drug tests. Overall, the tests are pretty good, but false positives can, and do, occur. Every different lab tests the urine samples with different reagents, or chemicals, so the doctor at your opioid treatment center should know what can cause a false positive at your particular lab.

First, a little about cocaine. The test for cocaine is very specific. The only thing that causes a positive for cocaine is cocaine. Despite similarities in the name, Novocain and lidocaine don’t cause a drug test to be positive for cocaine. No, it can’t be absorbed through the skin enough to give a positive, and if you are so close to cocaine that you’re handling it, I would say that counts as a positive anyway. Yes, it can be absorbed through mucosal lining – oral, vaginal, rectal – and again, that’s a true positive.

Benzodiazepines are a different story. I’ve worked at clinics where diphenhydramine (Benadryl) causes false positive results. That is, the patient didn’t take benzos, but the diphenhydramine made their test positive, so it looked like they are using benzos.

I tell patients to avoid diphenhydramine, which can be difficult, since it’s in most of the over the counter sleep aids. But diphenhydramine does interact with the metabolism of methadone, and needs to be avoided.

I had a patient test positive repeatedly for benzos, and she swore she wasn’t taking them. I believed her, and had her gather all the medications she had at home, prescription and over the counter. When we looked at them, she had a bottle of some kind of herbal stress-relief medication. On a hunch I asked her to stop this pill. Within two weeks her urine drug screen was negative.

I’m convinced this herbal remedy either contained a benzo, or a substance that caused a positive for benzos. There’s no FDA oversight with these herbal remedies, so the contents may or may not actually be what’s listed on the label.

So if you are testing positive for benzos, and know you haven’t taken any, consider stopping any herbal medicines that you are taking.