Methadone And False-Positives On Urine Drug Tests

In our latest question and answer, the pharmacist discusses methadone and false-positives on urine drug screenings.

Question

My daughter is taking and has been takin methadone for migraines for well over a year. She is being tested they sometimes show positive for fentanyl. Sometimes, they are positive for morphine. She is only using methadone. Can methadone break down to give a false-positive for fentanyl?

Asked by Sue On Mar 08, 2019

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Mar 08, 2019
Methadone Molecular Structure Next To Drug Test Cup

False-positive results on urine-drug screenings are, unfortunately, a fairly common event.

Most urine-drug screenings are 'immunoassays', which rely on the reactions of antibodies to determine the presence of a particular drug compound in a sample. Since they are easy to administer, are relatively inexpensive, allow for large-scale testing and provide rapid results, they are commonly used.

Unfortunately, urine-based immunoassays are subject to false-positive results, meaning a substance that isn't actually present in a sample shows up as being there.

In regard to methadone specifically, tests for it are less likely to produce 'false-positives' for other drugs, but it certainly can happen. In the same vein, methadone is unlikely to show up as a false-positive result but there are several documented cases of this happening too.

I explain more in the next sections.

What Are Urine Immunoassay Drug Screenings?

Most urine drug tests are immunoassay tests, specifically EIA (Enzyme Linked Immunoassay) test or CEDIA (Closed Enzyme Donor Immunoassay) tests.

Immunoassay tests are simple, they utilize antibodies to react to a specific drug compound.

When a specified drug is present in a test urine sample, say methadone, an antibody binds to it, and this binding produces a reaction. When a reaction occurs, a 'positive' result is recorded.

How Do False-Positives Happen?

Unfortunately with immunoassay tests, 'false-positives' can result due to 'cross-reactivity'. Antibodies can occasionally react with the wrong substance (i.e. 'cross-react'), producing a reaction that gets recorded as a positive result, but in actuality, is a 'false-positive'.

There are more accurate tests that can be utilized for confirmation of results, such as GC-MS (gas chromatography-mass spectrometry). These tests specifically identify actual drug compounds and don't rely on antibody reactions. If you feel you had a 'false-positive' result, these tests can make a definitive determination if a substance was actually present in a given sample.

Unfortunately, if you did test positive on a urine drug screening, the damage has likely been done. A false-positive test would likely result in some sort of disciplinary action, either from an employer or your doctor but hopefully, you have the option of undergoing a more accurate test.

Methadone Urine Testing

I mentioned that methadone was less likely to produce false-positives than other drugs, and this is because methadone requires a specific test and generally isn't included on 'standard five-panel' urine drug screens.

The United States Department of Health and Human Services (DHHS) workplace drug testing guidelines recommend testing for '5 drugs of abuse' on urine screenings:

  • Amphetamines
  • Cannabinoids (i.e. marijuana)
  • Cocaine
  • Opiates
  • PCP

The class of drugs we are interested in concerning methadone is 'opiates'.

The term 'opiates' and 'opioids' often create confusion and sometimes the terms are even used interchangeably.

Nevertheless, the traditional definition is that opiates are derived from opium, and include opium, thebaine, morphine, and codeine. The term 'opioids' is all-encompassing and includes opiates as well as all the semi-synthetic and synthetic versions of opiates, such as hydrocodone, hydromorphone, oxycodone, fentanyl, and methadone.

Methadone is a synthetic opioid.

Synthetic opioids are not (usually) tested for on standard urine drug screens. Therefore, they require a specific test to be ordered. Two large review studies on urine drug screenings state this specifically.

From 'Urine Drug Screening: Practical Guide for Clinicians':

"Assays for methadone are specific and detect the parent compound because about a third of the drug is excreted unchanged."

'Toxicologic Testing for Opiates: Understanding False-Positive and False-Negative Test Results' states:

"Semisynthetic opiates (oxycodone, hydromorphone, oxymorphone, levorphanol, buprenorphine) and purely synthetic opiates (fentanyl, methadone, propoxyphene, meperidine, tramadol, pentazocine) have their own specifically designed EIA tests that usually need to be specially requested if testing in the inpatient environment."

The overall point is that if a lab is trying to reliably detect a synthetic or semi-synthetic opioid, there needs to be a specific test ordered. To illustrate this point, one study noted the following:

"...in 1 study of 52 standard EIA urine tests for opiates (as compared to GC-MS studies on the same sample), oxycodone was detected only 12% of the time.

So, even during a urine lab screening that was testing for opiates (remember that methadone is not an opiate), oxycodone (a semi-synthetic opioid) was only detected 12% of the time in individuals who were taking it. The chance of a standard urine test causing a false-positive for an individual not taking an opioid is exceedingly low.

False-Positives For Methadone?

While methadone causing false-positives could theoretically happen, simply due to the nature of urine drug testing, other drugs causing false-positives for methadone is far more often reported. 


All the following have been reported to cause methadone false-positives:

  • Chlorpromazine
  • Clomipramine
  • Doxylamine
  • Diphenhydramine
  • Quetiapine
  • Thioridazine
  • Verapamil

Verapamil has extensive published evidence that it can be responsible for false-positive methadone tests. One study, published in Clinical Chemistry, notes that it is likely the most common culprit.

Fentanyl False-Positives

Regarding methadone causing a false-positive for other opioids (like fentanyl you mentioned in your question), again, it's possible, perhaps more-so than other drugs showing up as methadone, but there is no data available to give us an idea of how common it is.

Their respective molecular structures are similar, since they are opioids after all, but they are technically in different chemical groupings:

  • Fentanyl is 'phenylpiperidine'
  • Methadone is a 'diphenylheptane'

Even though their molecular structures are similar, they differ enough that they are usually classified as having a low risk of cross-sensitivity if you are allergic to one or the other. Since cross-reactivity on urine tests is generally due to a similarity in structure, we may surmise that there is a fairly low risk of cross-reactivity between them, but this hasn't been proven.

Methadone Metabolism

Many opioid drugs break-down into familiar compounds as they are metabolized in the body. A notable example is codeine, with morphine being an active metabolite. Another example is hydrocodone, which has many metabolites, one being hydromorphone (which is available as the brand name drug Dilaudid).

It certainly makes sense for drugs like codeine and hydrocodone to cause you to test positive for their metabolites (e.g. hydromorphone if you take hydrocodone).

Methadone does have metabolites, but they are not thought to be pharmacologically active and shouldn't be responsible for causing false-positive for other drugs (although they can be detected in the urine if they are being looked for). The two known metabolites of methadone are:

  • 2-ethylidene-1,5-dimethyl-3,3-diphenypyrrolidine (EDDP)
  • 2-ethyl-5-methyl-3,3- diphenyl-1-pyrroline (EMDP)

What To Do If Methadone Causes A False-Positive

As mentioned earlier in this answer, if you suspect a positive result on a urine drug test for methadone is not accurate, try and request a more specific test, such as GS-MS. These can definitively say whether or not a specific substance is present in a sample, as they don't rely on antibody reactions.


References
  • Commonly prescribed medications and potential false-positive urine drug screens. PubMed
  • False-positive immunochemical screen for methadone attributable to metabolites of verapamil. PubMed
  • False-Positive Interferences of Common Urine Drug Screen Immunoassays: A Review. Journal of Analytical Toxicology
  • Toxicologic Testing for Opiates: Understanding False-Positive and False-Negative Test Results. PubMed
  • Urine Drug Screening: Practical Guide for Clinicians. Mayo Clinic Proceedings
  • Chemical Classes of Opioids. PainDr
  • Elsevier ClinicalKey: Methadone Monograph

About the Pharmacist

Dr. Brian Staiger Pharm.D

Dr. Brian Staiger is a licensed pharmacist in New York State and the founder of PharmacistAnswers.com. He graduated from the University At Buffalo with a Doctor Of Pharmacy degree in 2010. He has been featured in several publications including the Huffington Post as well as a variety of health and pharmacy related blogs. Please feel free to reach out to him directly if you have any questions or want to connect! [email protected]; Office: 716-389-3076

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