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12 Articles in this Series
Central Post-Stroke Pain – How Central Is It?
False-Positive Urine Drug Monitoring Results and Aspirin
Medical Marijuana & Pain
More Potential Uses for Low-Dose IV Naloxone
On the Horizon: A Brief Look at Potential Analgesics of the Future
Preview of PAINWeek 2018 - Know Before You Go
Stem Cells & Beyond
Underlying Causes of Small Fiber Neuropathies
Understanding Sexual Pain – A Physical Therapist’s Perspective
Video: Drs. Gudin & Fudin on PAINWeek 2018 and PPM's Future
Where Does the Patient-Centered Pain Practitioner Stand Today?
Why Interventional Tactics Should be Used for Chronic Pain Patients Now, Not Later

False-Positive Urine Drug Monitoring Results and Aspirin

In a well-attended poster session at PAINWeek 2018, researchers led by Jeffrey Bettinger, PharmD, made a case for using prompt definitive testing methods in patients on opioid therapy.


The patient, a 48-year-old woman with a history of lumbar spinal, hip, and lower extremity pain, was prescribed a variety of pain relievers, along with aspirin. But when a private pain management clinic requested an initial evaluation, including an oral fluid drug test, that's when the confusion started.

"It came back positive for 6-mono acetyl morphine (6-MAM),'' a unique metabolite of heroin, explained Jeffrey Bettinger, PharmD, a pharmacy resident at Albany Stratton VA Medical Center, Albany, NY. He presented the case report at PAINWeek 2018 in Las Vegas.1 His poster, titled “False Positive 6-Mono Acetyl Morphine (6-MAM) Saliva Test Results in a Patient Taking Morphine and Aspirin,” was completed with Jeffrey Fudin, PharmD, Erica Wegrzyn, PharmD, and Jacqueline Cleary, PharmD, all at the Stratton VA Medical Center. While the test did show 6-MAM, the patient was believed not to be taking heroin.

Patient Profile

When the patient was evaluated in late 2016, her medication regimen included:

  • Aspirin, 81 mg PO once daily for cardioprotection
  • Gabapentin, 400 mg PO Q4H, for neuropathy
  • Methocarbamol, 750 mg PO Q8hr for muscle spasms
  • Morphine extended-release, 15 mg PO Q 12 hours, for pain
  • Oxycodone-acetaminophen, 10/325 mg PO Q6H for pain.

The initial saliva test was conducted in the office, co-author Dr. Fudin explained. Later, a urine test was done, but not by the same provider and not in close proximity to the saliva test.  The urine test was negative. The saliva test showed the following.

First, the expected results:

  • Morphine
  • Noroxycodone
  • Oxycodone
  • Oxymorphone

Then, the unexpected results:

  • Buprenorphine
  • 6-MAM
  • Codeine

Test Results & Followup

According to Mayo Clinic laboratories, 6-MAM has a short half-life and is the only definitive metabolite of heroin use.2 So, when the drug monitoring analysis came back, the patient's medications were tapered to discontinuation due to the results pointing to heroin use.

The researchers suspected that the co-administration of morphine and aspirin partly explained the results. Information obtained about the patient’s eating habits helped to fill to answer a few questions about the disconcerting results; she reported eating at a chain Italian restaurant often, favoring its salad with an oil-and-vinegar house dressing. She also consumed honey, and additional vinegar and cinnamon for their supposed health benefits.

Explaining the Chemistry

Chemically, heroin is diacetylmorphine, two morphine molecules connected by a 2-carbon or acetyl chain. Heroin is then metabolized into two morphine molecules. One molecule retains the acetyl group at the 6 position, 6-MAM metabolite. This same acetyl chain, according to Dr. Bettinger, is seen in molecules including vinegar, or acetic acid, and aspirin, or acetyl salicylic acid.

Reports of false-positive 6-MAM in those patients taking morphine are often seen when tested by gas chromatography/mass spectrometry (GC/MS), the researchers shared, but generally LC/MS is more accurate, usually coming up negative. However, the researchers did find reports of in vitro studies showing 6-MAM formation by co-administration of morphine and aspirin. Aspirin donated the acetyl group to morphine to form 6-MAM.3,4 (They also shared that 6-MAM can cause a false-positive for buprenorphine).

In the case of the 48-year-old pain patient, the researchers' plausible conclusion was that the aspirin, along with the vinegar on the salad eaten soon before the test, or vinegar in her tea, another habit, interacted with the morphine and donated its acetyl groups to the morphine molecules, forming 6-MAM in the saliva in the process.

This is a true 6-MAM test result, Dr. Bettinger clarified, technically not a false-positive; however, the 6-MAM was not thought to originate from heroin.

Bottom Line

The case report pointed out the need to conduct additional confirmatory testing. If a saliva test in office showed these results, with no reason to believe the patient was a problem patient, the best action to take would be to conduct a followup urine test promptly, Dr. Fudin advised.  For this particular case, the researchers said they would “Bring the patient back in, do a urine drug screen, and possibly a serum test. Don't immediately assume things, especially in this environment."

Dr. Bettinger reported being a consultant to Remitigate, LLC, a software development company with a focus on opioid safety. Dr. Fudin is the owner/CEO of Remitigate.



1Fudin J, Bettinger J, Wegrzn E, Clear J. “False Positive 6-Mono Acetyl Morphine (6-MAM) Saliva Test Results in a Patient Taking Morphine and Aspirin,” poster presented at: PAINWeek 2018, September 4-8, in Las Vegas, Nevada.

2Mayo Clinic Medical Laboratories: Test ID: 6 MAM.

3MRO Advisory: Possible in vitro synthesis of 6-AM from morphine in GC-MS analytical procedures. October 2009. Volume XX, No. 8. Official publication of the American Association of Medical Review Officer.

4Naso-Kaspar CK, et al. In vitro formation of acetylmorphine from morphine and aspirin in postmortem gastric content and deionized water. Journal of Analytical Toxicology. 2013;15;37(8):500-506.


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