Reprinted from MedReview

Is it Poppy Seeds or Opiates?
Distinguishing between the two bagel breakfast and opiate abuse.

Laboratories have many requests to report quantitative urinary opiate (morphine/codeine) to assist in distinguishing poppy seed products from the use of heroin (morphine metabolite) or codeine. Possibly one of the most difficult tasks for Medical Review Officers (MROs) and others interpreting urine drug screening results, is the opiate positive. It is estimated that 70% of DOT opiates positives are due to poppy seeds. An applicant or employee whose drug screen is held up for confirmation of opiates or follow-up quantitation due to dietary poppy seeds, know they are not abusers of illicit drugs and may be hostile toward the collection site, laboratory, and MRO. For non-SAMHSA (non-NIDA) assays performed by certified laboratories, all positive opiates will be quantitatively reported the first time, giving additional information immediately to our clients and obviating follow-up requests. (MRO’s can also have written standing orders for SAMHSA (NIDA) opiate levels, but must request this in writing.) This will assist our clients in the proper and timely interpretation of opiate positives.

Laboratories have demonstrated that poppy seeds contained in bakery products, such as bagels, can result in positive opiate (morphine) results at low levels (below 3000 ng/ml). Codeine may also be found after poppy seed ingestion, however morphine is predominant. Although morphine is an ordinary metabolite of codeine, the presence of codeine in poppy seeds probably comes from the poppy seeds themselves rather than as a metabolite. Generally high levels of codeine, above the morphine level, probably indicate codeine ingestion. However, terminal elimination of morphine following codeine use, long after the codeine was taken, may reveal only morphine. Interpretation of urinary opiate results is fairly complex. The US Department of Health and Human Services (NIDA) issues guidelines for MRO.

THE TWO BAGEL BREAKFAST

A preplacement urine screened positive for opiates by radioimmunoassay and EMIT. Gas chromatography/mass spectrometry (GC/MS) identified 487 ng/ml morphine. The individual denied opioid abuse. Inquiry by the examining medical center revealed a diet consisting of a Burger King hamburger the night before the specimen was taken and a breakfast, apparently usual, of two bagels from the university snack bar. The individual appeared to be quite normal. Scientists obtained a bagel from the snack bar. Pulverization of a few poppy seeds used as decoration on the bagel resulted in positive immunoassay (RIA and EMIT) responses. A toxicologist volunteered to eat the bagel and collect urine post dose. The first urine, three hours post dose, resulted in an opiate level, as determined by Roche radioimmunoassay (RIA), of 250 ng/ml. By six hours post dose the level had dropped to about 60 ng/ml and was negative (sensitivity 30 ng/ml) by 12 hours post dose.

Thus, using the DHHS opiate cutoff of 300 ng/ml, a person ingesting a single bagel would be reported negative. The individual in question ate a two bagel breakfast and had urine levels at approximately 500 ng/ml, an unusually good correspondence between the experiment and the subject's history. Since the two poppy seed bagel breakfast is probably rare, clients may retain the usual 300 ng/ml cutoff, but may wish a higher level cutoff of 3000 ng/ml, corresponding the present US military opiate cutoff designed to avoid dietary positives.

We obtained a bottle of Schillings poppy seeds, imported from the Netherlands, from a local market and had the laboratory volunteer eat three teaspoons, six grams, of the seeds. The first urine was collected six hours post dose and had the highest opiate level, approximately 1200 ng/ml as determined by the Roche radioimmunoassay (RIA). Levels twelve hours post dose dropped to about 250 ng/ml, and the urine was negative by twenty-four hours post dose (sensitivity 30 ng/ml).

INTERPRETATION

Urine drug screening is primarily useful simply to detect the presence of a drug. Urinary presence does not necessarily relate to the degree of influence being demonstrated by an individual. Methods of urinary detection are sufficiently sensitive to detect even poppy seeds, certainly not having any observable effects at all. Blood levels correspond much better to the effect or degree of influence for many drugs. Thus, the preferred specimen for a determination of degree of effect (influence), is blood, while urine is the preferred sample for drug screening due to concentration in the urine and relative ease of sample preparation.

Opiates are a very old class of drugs derived from the exudate of the opium poppy and used for centuries for pain relief. Morphine is the principal alkaloid in opium and the name morphine was derived from the Greek god of dreams - Morpheus. The psychological effects of opium were known to the ancient Sumerians, but the first undisputed reference to the opium poppy dates from the third century B.C. Like so many drugs, modern chemistry has extensively experimented with the drug's chemistry, resulting in more useful, potent, and addictive opioid derivatives. The invention of the hypodermic needle increased the abuse of morphine. The smoking of opium by the Chinese workers in the late 1800's, use of morphine for Civil War casualties, and lack of regulation until the first part of the 20th century all contributed to the rise of opioid abuse. Heroin, a very potent opioid, was synthesized for use during the Civil War resulting in the addiction of many Civil War soldiers.

6-MONOACETYLMORPHINE - HEROIN METABOLITE

The use of opium and its derivatives dates back to the third century B.C. where reference was made to "poppy juice" with its analgesic and euphoric properties. Over the centuries, opium has passed through periods of popularity for both its medicinal and intoxicating effects. Eras of peak opiate use and abuse include 16th century Europe, 18th century China, the American Civil War, and the late 1960's through today. With the advent of the hypodermic needle, the severity of addiction and the extent of tolerance has made opiate abuse a widespread social problem.

Derivatives of the opium poppy along with synthetic analogs, make up the group of drugs classified as opiates. These compounds are characterized by their analgesic properties, their structural similarity, and their tendency to form a physical dependency and develop tolerance with extended use. Included in this class are morphine, codeine, and heroin. Morphine is used primarily in hospital settings as a powerful short term pain killer and is administered parenterally. Codeine is a commonly prescribed analgesic taken orally and frequently in combination with aspirin or acetaminophen. Heroin is an illicit drug no longer used therapeutically in the United States but its abuse persists despite the severe addiction and physical debilitation associated with long term use.

In the realm of employee drug testing, an initial screening will identify those specimens that are positive for opiates as a class. The method used in opiate confirmation is capable of identifying both codeine and morphine. Because heroin (diacetylmorphine), codeine (methlymorphine), and some varieties of poppy seeds can result in the identification of morphine, a problem arises when morphine only is identified by the confirmation. Has the patient used a prescribed medication, ingested a fair amount of poppy seeds (they contain traces of morphine but will not produce any clinical effect), or is this evidence of heroin abuse? An assay is now available that can identify a metabolite unique to heroin: 6-0-monoacetylmorphine or 6-MAM.

METABOLISM AND METHOD

Heroin or diacetylmorphine, metabolizes rapidly after entering a person's system. Due to this rate of break down, heroin is rarely, if ever, picked up in clinical specimens and one must rely on identification of its metabolites. It is first broken down to monoacetylmorphine and further to morphine. Because monoacetylmorphine (MAM) is a metabolite unique to heroin, its presence can be considered evidence of recent heroin use. The procedure for MAM incorporates GC/MS (gas chromatography/mass spectrometry) technology using a deuterated MAM internal standard and scanned in the Selected Ion Mode (SIM). This is the most sensitive and specific technique available through commercial laboratories today. The sensitivity for this assay is 2 ng/ml with most specimens falling between 5 and 500 ng/ml. Levels as high as 10,000 ng/ml have been reported.

Although this assay is useful in pinpointing the opiate source, the absence of MAM in a specimen does not necessarily rule out the use of heroin and the physician must rely on clinical evidence such as needle marks, a valid prescription, or a dietary history.