This publication was prepared by the Substance Abuse and Mental Health Services Administration (SAMHSA), Center for Substance Abuse Prevention (CSAP) Division of Workplace Programs.

The authors are Walter F. Vogl, Ph.D., and Donna M. Bush, Ph.D.

The primary objective of the technical report series is to facilitate the transfer of prevention and intervention technology between and among researchers, administrators, policy makers, educators, and providers in the public and private sectors.

All material appearing in this book, except quoted passages from copyrighted sources, is in the public domain and may be used or reproduced without permission from CSAP or the authors. Citation of the source is appreciated.

DHHS Publication No. (SMA) 97-3164

Printed 1997

5. Specific Drug Class Issues

7. MRO Documentation and Recordkeeping

8. Additional MRO Responsibilities

A. National Laboratory Certification Program

C. Sample MRO Forms

As set forth in the Mandatory Guidelines for Federal Workplace Drug Testing Programs initially published in the Federal Register on April 11, 1988 (53 FR 11970-11989) and revised in the Federal Register on June 9, 1994 (59 FR 29908-29931), an essential part of the drug testing program is the final review of results. A positive laboratory test result does not automatically identify an employee or job applicant as an illegal drug user. An individual with a detailed knowledge of possible alternative medical explanations is essential to the review of results. The Medical Review Officer (MRO) fulfills this function by reviewing the results with the donor and protecting the confidential nature of a donor’s medical information.

Not only is the MRO a critical safeguard in Federal drug testing programs, the MRO also represents the first formal role of the physician in the prevention and deterrence of substance abuse. It is a new and important area of medical practice. The direct involvement of the physician in prevention opens new opportunities and approaches in deterring substance abuse.

The MRO's responsibility does not include ensuring that every aspect of an agency's drug testing program meets or exceeds regulatory requirements. The MRO can only ensure that his or her involvement in the review and interpretation of results is consistent with the regulations and will be forensically and scientifically supportable.

As with any clinical specialty, to ensure that current practice guidelines are followed, an MRO must keep abreast of new information and the regulations. It is recommended that practicing MROs maintain a Standard Operating Procedure to ensure consistency and improve overall quality of the review process. It is further recommended that MROs participate in continuing education activities and actively request and review current regulations and guidelines for any specific agency for which an MRO has professional responsibility. MROs may also have additional responsibilities according to contractual arrangements and should ensure familiarity with such requirements as well.

From initial requirements that an MRO be a licensed physician with knowledge of substance abuse disorders, practical requirements have evolved regarding the availability of various training programs and certification examinations. These programs ensure that MROs are familiar with current regulations and receive the latest information on interpreting drug testing results. Although there is no regulatory requirement for formal certification at the present time, the training courses offered by the various professional organizations have served a very important role in providing continuing education programs.

Note: The listing of these three organizations is not an endorsement of their programs by the Federal government nor is attendance at one of their courses a regulatory requirement before a licensed physician can serve as an MRO. Although certification is not required, it is encouraged to ensure that an MRO is familiar with all regulatory policies and procedures.

The Mandatory Guidelines (section 1.2) define an MRO as:

HHS has determined that only individuals holding either a Doctor of Medicine (M.D.) or Doctor of Osteopathy (D.O.) degree may serve as MROs. Individuals with other degrees are not permitted to serve as MROs for federally regulated programs. With regard to knowledge of substance abuse disorders, the MRO must be knowledgeable in the medical use of prescription drugs and the pharmacology and toxicology of illicit drugs.

An additional requirement has been included in the revised Guidelines (paragraph 2.6(b)):

The purpose of this requirement is to prevent any arrangement between a laboratory and an MRO that would prevent the MRO from reporting a problem identified with a laboratory’s test results or testing procedures. Similarly, the laboratory is prohibited from entering into any agreement with an MRO that could be construed as a conflict of interest.

In all cases, the MRO must ensure that no compromise of confidentiality with respect to drug test results or medical information learned in the review of drug test results occurs due to circumstances within the scope of the MRO's control.

The MRO has the following responsibilities:

Note: A positive test result does not automatically identify a donor (i.e., an employee or job applicant) as an illegal drug user. The MRO must assess and determine whether an alternative medical explanation could account for the positive test result and that documents associated with the test result are forensically and scientifically supportable.

All urine specimens must be collected while maintaining chain of custody. Chain of custody is the term used to describe the process of documenting the handling and storage of a specimen from the time a donor gives the specimen to the collector to the final disposition of the specimen. Chain of custody is also used to document the handling, storage, and disposition of an aliquot during its testing in the laboratory.

For specimens collected under the Mandatory Guidelines, an Office of Management and Budget (OMB) approved Custody and Control Form (CCF) must be used to document the collection of a specimen (Appendix B is an example of the CCF) at the collection site. The OMB-approved CCF can be supplied by a number of different sources (e.g., laboratories, collectors, MROs); however, it is usually provided by the laboratory.

Note: See the Urine Specimen Collection Handbook for Federal Workplace Drug Testing Programs (CSAP Technical Report 12, DHHS Publication No. (SMA) 96-3114, dated 1996) for a detailed discussion of the procedure used to collect a urine specimen. It may be ordered by contacting the National Clearinghouse for Alcohol and Drug Information (NCADI) at 1-800-729-6686 or downloaded through the Internet at the NCADI web site (www.health.org/workpl.htm).

The CCF consists of the following seven copies with the color of each copy noted in parentheses:

Copy 1 accompanies the specimen to the testing laboratory and serves as the testing record maintained by the laboratory, Copy 2 goes initially to the laboratory and then to the MRO with the test results from the laboratory, Copy 3 accompanies the split specimen (if collected) to the testing laboratory, Copy 4 is sent to the MRO directly from the collection site with donor identifying information, Copy 5 is given to the donor at the collection site, Copy 6 is retained by the collector, and Copy 7 is forwarded to the employer.

Note: Upon completion of laboratory testing, the laboratory may send Copy 2 of the CCF to the MRO a number of different ways (e.g., express mail, courier, facsimile, electronic transmission). The MRO may not report results to the employer until the original Copy 2 is received.

After a specimen is collected, the collector sends the specimen bottle along with the appropriate copies of the CCF to the laboratory for testing and Copy 4 is sent directly to the MRO. For single specimen collections, Copy 1 and Copy 2 accompany the specimen bottle to the laboratory. For split specimen collections, Copy 1, Copy 2, and Copy 3 are sent to the laboratory.

The CCF is completed as follows:

Step 1. This step is completed by the collector. The following information is required: name, address, and identification number (if applicable) of the employer; specific name and address of the MRO; donor's social security number or other employee identification number; reason for the test; and tests to be performed.

Step 2. This step is completed by the collector. The collector is required to measure the temperature of the specimen within four minutes after receiving the specimen from the donor. If the temperature is within the acceptable range, the "Yes" box is checked. If the temperature is outside the acceptable range, the "No" box is checked and the actual temperature is recorded. When this occurs, it may only be possible to indicate that the actual temperature is greater than or less than the highest or lowest temperature indicated on the measuring device.

Step 3. This step is completed by the collector and donor.

Step 4. This step is completed by the donor. On Copy 4 of the CCF, the donor provides a daytime phone number, evening phone number, date of birth, printed name, signature, and date of collection. The donor should read the statement on the CCF before providing a signature.

Step 5. This step is completed by the collector. The following information is provided: name, address, and phone number of the collection facility; printed name and signature of the collector; date of collection; time of collection; a block to check whether the collection was a single or split specimen collection. This section also has a "REMARKS" line to allow the collector to annotate any problems that may have occurred during the collection.

Step 6. This step is initiated by the collector and completed as necessary thereafter. This section is used to document the transfer and handling of the specimen(s) at the collection site. The first transfer of the specimen occurs when the donor gives the specimen container/bottle to the collector. On the first line, the collector records the date and prints and signs his or her name in the column labeled "SPECIMEN RECEIVED BY." This should occur contemporaneously (i.e., immediately before or after receiving the specimen from the donor). After sealing the single specimen bottle or split specimen bottles, the collector must complete the second line of Step 6 and indicate the specific name of the carrier to which the specimen package will be released before sealing the specimen/split specimens and copies of the CCF in a shipping container/package.

Step 7. This step is completed by the laboratory after testing the specimen. The laboratory must report the result as either "NEGATIVE," "POSITIVE" for a specific drug, or "TEST NOT PERFORMED." For "TEST NOT PERFORMED," the laboratory must document the reason by providing an appropriate comment on the "REMARKS" line in Step 7.

Step 8. This step is completed by the MRO.

The MRO and the laboratory have separate and independent responsibilities to review the CCF because each has access to some information that is not available to the other (e.g., Copy 4 of the CCF (the MRO copy) contains the donor’s name and telephone number while the laboratory receives the specimen bottle and must inspect the bottle for evidence of tampering).

The MRO must review Copy 4 of the CCF to ensure that:

If Copy 4 of the CCF contains all the required information, it indicates that the collector followed the appropriate collection procedure. At this point, the MRO waits to receive Copy 2 of the CCF from the laboratory.

Copy 2 of the CCF is similar to Copy 4 of the CCF with the following differences:

The consistency of the information on Copy 2 of the CCF, Copy 4 of the CCF, and any additional laboratory report must be established.

After receiving Copy 2 of the CCF from the laboratory, the MRO is required to make a determination regarding the test result. The action taken by the MRO will depend upon whether the test result reported by the laboratory is "NEGATIVE," "POSITIVE" for a specific drug, or "TEST NOT PERFORMED." Additionally, there may be other information on the CCF provided by the collector and/or the laboratory that might suggest a problem exists with the specimen.

The action taken by the MRO for each type of result reported by the laboratory is as follows:

The MRO review of a negative laboratory test result includes a review of Copy 2 of the CCF, any additional laboratory report provided by the laboratory, and a comparison of this information to the information on Copy 4 of the CCF which was received directly from the collection site.

If all of the information appears correct and complete and no problems are noted by either the collector or the laboratory on the CCF, a negative laboratory test result is simply determined as a "NEGATIVE" by the MRO. The MRO completes Step 8 on Copy 2 of the CCF and reports the "NEGATIVE" result to the employer using the reporting procedure described later in this chapter (Section F).

If the MRO finds an administrative error on Copy 2 of the CCF or on Copy 4 of the CCF, the MRO reports a "NEGATIVE" result to the employer and includes an appropriate comment to describe the administrative error.

If a laboratory provides information to suggest that a specimen may have been diluted or adulterated (e.g., the specific gravity, creatinine concentration, or pH may be outside the normal range for a urine specimen, or the urine contains an unspecified adulterant) along with the negative result, the MRO should verify the test result as "NEGATIVE" and provide the information to the employer regarding possible dilution or adulteration.

The MRO review of a positive laboratory test result includes a review of Copy 2 of the CCF and any additional laboratory report provided by the laboratory, a comparison of this information to the information on Copy 4 of the CCF which was received directly from the collection site, and an interview with the donor.

If all of the information on the CCF appears correct and complete, no problems are noted by either the collector or the laboratory on the CCF, and the donor is unable to provide a valid alternative medical explanation, a positive laboratory test result is determined as a "POSITIVE" by the MRO. The MRO completes Step 8 on Copy 2 of the CCF and reports the "POSITIVE" result to the employer.

If the MRO finds that the laboratory made an administrative error on Copy 2 of the CCF or failed to identify an administrative error made by the collector, the MRO should contact either the collector or the laboratory (whichever made the administrative error) to determine if the administrative error can be recovered/corrected by a Memorandum For Record (MFR) from the collector or the laboratory.

If a laboratory provides information to suggest that a specimen may have been adulterated or diluted (e.g., the specific gravity, creatinine concentration, or pH may be outside the normal range for a urine specimen, or the urine contains an unspecified adulterant) along with the positive result, the MRO should verify the test result as "POSITIVE" and provide the information to the employer regarding possible dilution or adulteration.

The MRO review of a "TEST NOT PERFORMED" result includes a review of Copy 2 of the CCF and any additional laboratory report provided by the laboratory and a comparison of this information to the information on Copy 4 of the CCF which was received directly from the collection site. Additionally, an interview with the donor may be necessary depending on the reason for the "TEST NOT PERFORMED" result.

A laboratory will report a "TEST NOT PERFORMED" result for any of the following reasons:

When a "TEST NOT PERFORMED" result is reported, the laboratory must provide an appropriate comment on the "REMARKS" line (Step 7, Copy 2 of the CCF) to explain why the "TEST NOT PERFORMED" result was reported.

Note: Although a laboratory reports a "TEST NOT PERFORMED" result when it may have actually conducted tests on a specimen, the CCF only allows reporting a "NEGATIVE," a "POSITIVE," or a "TEST NOT PERFORMED" result.

An MRO will make a "TEST NOT PERFORMED" determination when the laboratory reports a "TEST NOT PERFORMED" result except as noted above.

An essential element of the MRO review process is the opportunity given the donor to explain why the specimen tested positive or to explain why there may have been a problem regarding the validity of the specimen.

The MRO contact and interview with the donor should include the following steps:

Appendix C contains some sample forms to document the contact with the donor. These are only examples, but an MRO may find them useful in developing his or her own forms.

Before making a determination on a positive test result, the Mandatory Guidelines permit an MRO to request a retest of a single specimen or the Bottle A specimen from a split specimen collection if there is any question regarding the accuracy or validity of the test result.

Note: The MRO’s request must be based on a review of technical information (provided by the laboratory or donor) that makes the MRO believe that the result may be scientifically insufficient and, therefore, believes that a retest would be useful before making the determination.

To ensure that a specimen is available if a retest is requested either by an MRO or by an official administrative or judicial proceeding, HHS requires laboratories to place all specimens confirmed positive in properly secured frozen storage for a minimum of one year. This is generally a sufficient amount of time to allow for a retest to occur; however, the time may be extended beyond one year by either the employer or an administrative/judiciary official to allow completion of any litigation/arbitration that may be ongoing with the donor.

For a split specimen collection, the MRO must inform the donor of his or her right to request an analysis of the split specimen (Bottle B). The donor’s request to have the split specimen tested must be made through the MRO. Although the time allowed for a retest request may vary among agencies, the donor is normally given a maximum of 72 hours to initiate the request. This will ensure that the analysis of the split specimen is performed in a timely manner.

The MRO must request the retest of a single specimen or the testing of a split specimen in writing (i.e., a memorandum or letter format). The written request may be mailed, faxed, or electronically sent to the laboratory where the specimen was tested.

The request to retest a single specimen should contain the following information:

The request to test a split specimen (Bottle B) should contain the following information:

If the retesting of the original specimen fails to reconfirm the original laboratory result, the MRO will report the result as "NEGATIVE" to the employer.

Note: Since this retest was performed because the MRO had concerns regarding the validity of the positive test result initially reported by the laboratory, the MRO cannot make a final determination before the retest result is reported to the MRO by the laboratory.

If the testing of Bottle B reconfirms the presence of the drug/drug metabolite, the MRO verifies the result for Bottle B as "RECONFIRMED" on Copy 3 of the CCF.

If the testing of Bottle B fails to reconfirm the result reported by the laboratory that tested the Bottle A specimen, the MRO shall report "FAILED TO RECONFIRM - BOTH TESTS CANCELED" on Copy 3 of the CCF

There is a technical problem that very occasionally occurs when Laboratory B retests an aliquot of a single specimen or tests a split specimen (Bottle B) that had been reported "POSITIVE" by Laboratory A. The drug is present in the specimen; however, Laboratory B is unable to reconfirm the presence of the drug or metabolite reported by Laboratory A because it uses a different analytical procedure and/or instrumentation. These differences occasionally prevent a Laboratory B from reconfirming the presence of a drug or metabolite because the analytical results do not satisfy all the criteria required to make a positive identification of the analyte.

Occasionally, if the MRO has serious concerns regarding the validity of a test result, the MRO will need to review the complete package of analytical data, chain of custody records, and other administrative documents associated with a particular specimen. The MRO may request the laboratory to provide this information, generally referred to as a "full documentation package." A full documentation package should include copies of the batch test results that contain the test result for the donor’s specimen, internal and external chain of custody documents for the batch of specimens that contain the donor’s specimen, and any other relevant information pertaining to the testing of the donor’s specimen.

The MRO should review: the chain of custody documents for the specimen bottles to ensure that their handling was properly documented during accessioning, storage and disposal; the internal chain of custody documents associated with the handling of the aliquots to ensure that their handling was properly documented during the testing; and the batch test results to ensure that they contain the test results for the calibrators and controls that were analyzed with the donor specimens.

The MRO must report all verified results in writing to the employer. The written report may be sent by mail, courier, facsimile, or secured electronic means to the employer. However, if secured electronic means or a facsimile is used to quickly report a result, a hard-copy of the report must also be mailed or sent by courier.

The MRO report must include, at a minimum, the following: donor name and/or SSN, specimen I.D. number from the CCF, the verified test result (if positive, list specific drug(s)), the MRO’s printed name and signature, and the date the determination was made.

If a memorandum or letter format is used, the MRO may list results for several specimens on one memorandum or letter. There is no requirement that a separate report be prepared for each result reported to an employer.

The OMB-approved Federal Drug Testing Custody and Control Form requires the MRO to verify the result reported by the laboratory as either "NEGATIVE," "POSITIVE," "TEST NOT PERFORMED," or "TEST CANCELED."

Note: A verified result may not be reported to the employer until the MRO has completed the review process.

If the MRO review includes a need to discuss the result with the donor, the following exceptions allow the MRO to verify a result without discussing it with the donor:

Executive Order 12564 used the term "illegal drugs" to refer to any controlled substance that was included in Schedule I or II of the Controlled Substances Act. The Executive Order also stated that the term illegal drugs "does not mean the use of a controlled substance pursuant to a valid prescription or other uses authorized by law."

Note: The purpose of this policy is to ensure that in a drug-free workplace program, drug testing does not identify an individual who is receiving legitimate medical care and, thereby, provides confidential medical information to an employer or anyone else.

However, there is a public safety issue associated with information that a donor may provide to an MRO during the review of a drug test result. That is, the donor may be taking a legal prescription medication as treatment for a medical condition. This medication may have possible side effects that may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks (e.g., driving a car or truck, operating machinery).

State initiatives and laws which make available to an individual a variety of illicit drugs by a physician’s prescription or recommendation do not make the use of these illicit drugs permissible under the Federal Drug-Free Workplace Program. These State initiatives and laws are inconsistent with Federal law and put the safety, health, and security of Federal workers and the American public at risk.

The use of any substance included in Schedule I of the Controlled Substance Act, whether for non-medical or ostensible medical purposes, is considered a violation of Federal law and the Federal Drug-Free Workplace Program. These drugs have no currently accepted medical use in treatment in the United States and their uses are inconsistent with the performance of safety-sensitive, health-sensitive, and security-sensitive positions, and with other testing circumstances.

Note: Medical Review Officers shall not accept a prescription or the verbal or written recommendation of a physician for a Schedule I substance as a legitimate medical explanation for the presence of a Schedule I drug or metabolite in a Federal employee/applicant specimen.

Chapter 5. Specific Drug Class Issues

Amphetamine and methamphetamine are substances regulated under the Controlled Substances Act (CSA, 21 U.S.C. § 801 et seq.), and implementing regulations as Schedule II stimulants (see 21 CFR § 1308.12(d)). Schedule II substances have legitimate medical uses, but also have a high potential for abuse. Both drugs have been used for treating attention deficit disorder in children, obesity, and narcolepsy.

Amphetamine and methamphetamine are central nervous system stimulants. A single therapeutic dose often enhances attention and performance, but exhaustion eventually occurs and performance deteriorates as the effects wear off. Frequently, repeated high-dose use produces lethargy, exhaustion, mental confusion, and paranoid thoughts.

Tolerance can develop to the effects of amphetamine and methamphetamine. Therapeutically administered amphetamine and methamphetamine are usually taken orally as tablets or capsules. Absorption from the gastrointestinal and respiratory tract is good and they are distributed throughout the body. Abusers inject the drugs intravenously, sometimes take them by intranasal "snorting," and by smoking. A typical therapeutic dose is five milligrams. Individuals who abuse these drugs are reported to inject up to one gram in a single intravenous dose. Physical dependence is modest. Lethargy, drowsiness, hyperphagia, vivid dreams, and some mental depression may persist for a few days to several weeks after abrupt termination of repeated high doses.

Nearly half of a methamphetamine dose is recovered from urine unchanged. A small percentage is demethylated to amphetamine and its metabolites. The excretion rate of methamphetamine is also increased when urine is acidic.

Amphetamine is excreted as both unchanged amphetamine and as hydroxylated metabolites. Typically, about one-quarter of an administered dose is excreted as unchanged amphetamine, but this varies widely with urinary pH; the drug stays in the body longer when urine is alkaline, allowing reabsorption and thus allowing more of it to be metabolized. In 24 hours, about 80 percent of a dose will be excreted if urine is acidic, while less than half is excreted if urine is alkaline.

A single therapeutic dose of amphetamine or methamphetamine can produce a positive urine for about 24 hours, depending upon urinary pH and individual metabolic differences. High-dose abusers may continue to generate positive urine specimens for 2 to 4, or more, days after last use.

Methamphetamine and amphetamine exist in two isomeric structural forms known as enantiomers. Enantiomers are non-superimposable mirror images. The two isomers of each substance are designated as d- (dextro) and l- (levo), indicating the direction in which they rotate a beam of polarized light. As do many pharmacological enantiomers, the d- and l- isomers have distinct pharmacological properties with different sites of action. In this case, the d- isomer of each substance has a strong central nervous system stimulant effect while the l- isomer of each substance has primarily a peripheral action. It should be noted that d-methamphetamine is metabolized to d-amphetamine and l-methamphetamine is metabolized to l-amphetamine.

The enantiomer identification may be useful in determining if a donor has been using a Vicks Inhaler®, a prescription medication, or abusing an illegal drug. The presence of the l- isomer of either amphetamine or methamphetamine does not by itself rule out illegal use.

Note: Illegally manufactured amphetamine and methamphetamine often contain significant amounts of the l- isomer of each substance. This depends on the starting materials used and the technical proficiency of the clandestine laboratories.

The following prescription medications contain d-amphetamine or racemic d,l-amphetamine (i.e., equal amounts of d- and l-amphetamine):

Adderall®

Benzedrine®

Biphetamine®

Dexedrine®

Durophet®

Obetrol®

The following prescription medication contains d-methamphetamine:

Desoxyn® (Gradumet®)

The following substances are known to metabolize to methamphetamine (and amphetamine):

Benzphetamine (Didrex®)

Dimethylamphetamine

Famprofazone

Fencamine

Furfenorex

Selegiline (Deprenyl, Eldepryl®)

The following substances are known to metabolize to amphetamine:

Amphetaminil

Clobenzorex (Dinintel®, Finedal®)

Ethylamphetamine

Fenethylline (Captagon®)

Fenproporex (Tegisec®)

Mefenorex (Pondinil®)

Mesocarb

Prenylamine

The donor provides the following response:

Cocaine is an alkaloid from the coca plant, Erythroxylon coca. It usually is obtained as cocaine HCl, but those who smoke the drug prepare the "freebase" or "crack" form, chemically removing the HCl. This form better survives the high temperatures involved in smoking. Cocaine is widely used in the United States.

Cocaine produces psychomotor and autonomic stimulation with a euphoric subjective "high." Larger doses may induce mental confusion or paranoid delusions, and serious overdoses cause seizures, respiratory depression, cardiac arrhythmias, and death.

Cocaine abusers, even if they do not use the drug at work, often report vocational impairment due to exhaustion; they use the drug until late at night. Among chronic users, exhaustion, lethargy, and mental depression appear, and the stimulant effect may seem progressively weaker. But the drug is highly reinforcing; repeated experiences with it tend to drive further episodes of self-administration. After repeated exposures, many patients say that although the drug no longer produces much of a "high," they are unable to abstain.

Short-term tolerance (tachyphylaxis) develops when several doses of cocaine are administered over a brief period. Reports of weaker "highs" with repeated use also suggest tolerance. However, animal studies show "reverse tolerance," with certain behavioral effects becoming stronger upon repeated administration. So the question of tolerance to cocaine remains an area for further research. Patients withdrawing from cocaine experience moderate lethargy and drowsiness, severe headaches, hyperphagia, vivid dreams, and some mental depression. These symptoms usually abate within a few days to a few weeks.

Cocaine usually is taken by one of three routes: intranasal "snorting" is the most common; its "freebase" or "crack" form of the drug is smoked, utilizing the pulmonary route; and intravenous injections.

Cocaine is rapidly and extensively metabolized by liver and plasma enzymes. The major metabolite, benzoylecgonine, is more persistent; it usually is detected for 2 days after a single dose. Cocaine and benzoylecgonine are not significantly stored in the body; therefore, even after heavy, chronic use urine specimens will be negative when collected a few days after last use.

The donor provides the following response:

1. Background

Marijuana comes from the hemp plant, Cannabis sativa. The principal psychoactive agent in marijuana is delta-9-tetrahydrocannabinol (THC).

Marijuana produces a pleasant euphoria or "high," commonly followed by drowsiness. Intoxication temporarily impairs concentration, learning, and perceptual-motor skills. Thus, for at least 4-6 hours after a dose of marijuana, employees probably function with reduced abilities. Preliminary studies suggest that performance is impaired long after the acute subjective effects have ended. Experienced pilots in a flight simulator were impaired for at least 24 hours after a dose, long after the subjective "high" had disappeared. Functional impairments are less well understood in cases of prolonged, heavy marijuana use, because although THC accumulates in the body, behavioral and physiological tolerance also develops.

In addition to tolerance, a mild abstinence syndrome may follow abrupt termination of very high-dose, chronic marijuana use. Withdrawal signs include irritability, sleep disturbance, diminished appetite, gastrointestinal distress, salivation, sweating, and tremors. Marijuana abstinence syndromes are uncommon at the doses at which the drug is usually taken in this country.

Marijuana is usually smoked; transpulmonary absorption rapidly gets psychoactive drugs to the brain. Since the drug also is absorbed from the gastrointestinal tract, although much more slowly, marijuana sometimes is eaten. THC leaves the bloodstream and is distributed into different parts of the body where it is metabolized, excreted, or stored. The THC that is stored in fatty tissue gradually reenters the blood stream at very low levels, permitting metabolism and eventual excretion. THC is metabolized extensively in the liver and the major metabolite is 11-nor-D⁹-tetrahydrocannabinol-9-carboxylic acid (delta-9 THCA).

The immunoassay procedures detect multiple metabolites of marijuana, while the GC/MS procedure specifically identifies and quantitates the delta-9 THCA metabolite. To be reported positive, a specimen must screen positive at or above the 50 ng/mL cutoff and have a concentration of the delta-9 THCA that is equal to or greater than the 15 ng/mL confirmatory cutoff level. Considering these cutoffs, a person with no marijuana experience who smokes a single marijuana cigarette may be positive for 1-3 days. But with repeated smoking, THC accumulates in fatty tissue; so frequent, chronic smokers slowly release THC over a longer time and may continue to produce detectable levels below the cutoff values for longer periods of time (depending upon the assay cutoff).

The donor provides the following response:

Opioids are a large class of analgesic drugs, the effects of which are stereospecifically antagonized by naloxone. Opiates refer to natural products derived from the juice of the opium poppy (loosely applied to morphine derivatives). The opium poppy flower is the source of the natural opiate prototype alkaloid, morphine. The opium poppy is also the source of the naturally occurring alkaloid codeine; codeine is also synthesized chemically for inclusion in medications available through prescription and over-the-counter. Heroin (or diacetylmorphine) is a semisynthetic opiate obtained by reacting natural morphine with acetic acid. Heroin has no legitimate medical uses in the United States and is only available illegally (DEA Schedule I).

Opioid intoxication may cause miosis, a dull facies, confusion or mental dullness, slurring of speech, drowsiness, partial ptosis, or "nodding" (the head drooping toward the chest and then bobbing up).

Tolerance develops to opioid effects, and abusers escalate doses when possible. Physical dependence results in a moderate, nonlethal, "flu"-like abstinence syndrome with nausea, diarrhea, coryza, occasional vomiting, weakness, malaise, "gooseflesh," and mydriasis. Also flu-like symptoms are common during opiate withdrawal, e.g., watery eyes, nausea and vomiting, muscle cramps, and loss of appetite. All opiates are physically and psychologically addictive, and produce withdrawal symptoms that differ in type and severity.

Heroin and morphine are usually injected, but may be smoked as opium once was, or "snorted" (insufflated) onto the nasal mucosa.

Cognitive and psychomotor performance can be impaired by opiates, although the duration and extent of impairment depend on the type of opiate, the dose, and the experience and drug history of the user. Ingestion of low to moderate amounts produces a short-lived feeling of euphoria followed by a state of physical and mental relaxation that persists for several hours.

The following prescription medications contain morphine:

Astramorph PF®

MSIR®

MS Contin Tablets®

Roxanol®

The following prescription medications contain codeine:

Actifed with Codeine Cough Syrup®

Codimal PH® Syrup

Dimetane-DC Cough Syrup®

Emprin with Codeine®

Fiorinal with Codeine®

Phenaphen with Codeine®

Robitussin A-C®

Triaminic Expectorant with Codeine®

Tussar-2®

Tylenol with Codeine(#1, 2, 3, or 4)®

Note: The above lists are only a representative sample of the prescription medications that contain codeine or morphine.

The following nonprescription products contain opium (i.e., morphine):

Amogel PG®

Diabismul®

Donnagel-PG®

Infantol Pink®

Kaodene with Paregoric®

Paregoric

Quiagel PG®

The following nonprescription product contains codeine:

Kaodene with Codeine®

The following substances metabolize to morphine:

Codeine

Heroin

Heroin (diacetylmorphine) is rapidly deacetylated to 6-acetylmorphine (6-AM; also called 6-monoacetylmorphine, 6-MAM), and, therefore, heroin itself is rarely ever detected in the urine. Heroin's characteristic metabolite, 6-AM, is rapidly deacetylated to morphine, and will likely not be detected in most urine specimens of heroin users. Since codeine is a naturally occurring alkaloid in the same opium poppy juice that is the source of morphine used as the starting material for heroin synthesis, codeine may be found in the urine of heroin users.

Morphine is rapidly absorbed and excreted as unchanged morphine and as conjugated glucuronides (i.e., morphine-3-glucuronide, morphine-6-glucuronide). The primary metabolite is morphine-3-glucuronide. Morphine and its metabolites can be detected in urine up to about 4 days after its use.

Codeine (methylmorphine) is also rapidly absorbed and is excreted as unchanged codeine, morphine, and glucuronide conjugates.

Since the body metabolizes codeine to morphine, both substances (i.e., codeine and morphine) may occur in the urine following the use of codeine. Recently ingested codeine explains the presence of both drugs in the urine specimen (i.e., parent drug codeine and morphine metabolite). After the ingestion of a legitimate medical preparation containing codeine, there comes a time when parent codeine has been completely excreted or metabolized to morphine, so that morphine only is detected in the urine.

Ingestion of morphine in any form will never account for the presence of codeine in the urine (codeine is not a metabolite of morphine).

3. Interpreting Laboratory Result

The opiate drug class poses some unique challenges with regard to interpreting a positive test result. A positive for codeine or morphine may be a result of a donor having taken a prescription medication that contains codeine or morphine or a donor consuming normal dietary amounts of poppy seeds. In addition, for the opiate drug class, there is a requirement to document clinical evidence of illegal use.

Note: Quantitative test results may not be requested by the MRO from the testing laboratory on a routine basis for the other drug categories, but may be requested on a case-by-case basis.

The donor provides the following response:

Phencyclidine (PCP), an arylcyclohexylamine, was first synthesized in the 1950's as a general anesthetic. Street names include Angel Dust, Crystal, Killer Weed, Supergrass, and Rocket Fuel. PCP's synthesis is relatively simple for clandestine laboratories. Phencyclidine's use as a human anesthetic was discontinued because it produced psychotic reactions ("emergence delirium"), and its more prolonged use as a veterinary tranquilizing agent also has stopped. PCP is currently a DEA Schedule II controlled substance, has no current therapeutic role, and all uses are illegal. The preferred route of ingestion is smoking, but it may be eaten, snorted, or injected intravenously.

PCP is best classified as a hallucinogen and has a variety of effects on the central nervous system. Intoxication begins several minutes after ingestion and usually lasts eight hours or more. PCP is well known for producing unpredictable side effects, such as psychosis or fits of agitation and excitability. PCP clearly has drastic effects on performance. Clinical cases have documented the severe debilitating physical and psychological effects of PCP abuse and the extremely unpredictable behavior caused by the drug.

Intoxication may result in persistent horizontal nystagmus, blurred vision, diminished sensation, ataxia, hyperreflexia, clonus, tremor, muscular rigidity, muteness, confusion, anxious amnesia, distortion of body image, depersonalization, thought disorder, auditory hallucinations, and variable motor depression or stimulation, which may include aggressive or bizarre behavior.

PCP is well absorbed by any route and is excreted as unchanged PCP and as conjugates of hydroxylated PCP. About 10 percent of the PCP dose is excreted in the urine as the parent compound. PCP is a weak base which concentrates in acidic solutions in the body. Because of gastric acidity, PCP repeatedly reenters the stomach from plasma, later returning into plasma from the basic medium of the intestine.

Generally, PCP is considered detectable in urine for several days to several weeks depending on the frequency of use.

The donor provides the following response:

During the collection procedure, a donor may attempt to adulterate, dilute, or substitute the specimen that he or she gives the collector. In most cases, the collector should be able to identify when a potential problem exists and take immediate action to correct it (e.g., the specimen is clearly adulterated and the collector gets permission to conduct a second collection using direct observation). If the collector does not suspect that there is a problem with the donor’s specimen but the donor was able to tamper with the specimen, the problem with the specimen may be identified by the laboratory during the testing. When this occurs, the laboratory will provide an appropriate comment on the "REMARKS" line in Step 7 on the CCF.

Substitution refers to a donor’s attempt to replace his or her urine specimen with "clean" urine, synthetic urine, water, or other fluid during the collection procedure. Generally, it is difficult for a donor to substitute an entire urine specimen and ensure that the substituted specimen is within the required temperature range. If the specimen temperature is not within the acceptable range, the collector knows that substitution may have occurred. The collector must provide an appropriate comment on the CCF, and the collector will normally be given permission to collect a second specimen using direct observation. Although the substituted specimen will be submitted to the laboratory for testing, the laboratory results will probably indicate that it did not appear to be a valid urine specimen.

A donor may attempt to adulterate/dilute a specimen either in vivo (i.e., the donor intentionally ingests a substance in an attempt to affect the drug test) or in vitro (i.e., the donor externally adds something to the specimen in an attempt to affect the drug test).

Common approaches used to adulterate/dilute a specimen include:

Accurate recordkeeping is essential in documenting all aspects of the MRO review process. All communications, written or oral (including, but not limited to, those with donors, employer representatives, laboratory personnel, and collectors) must be appropriately documented.

Although the Guidelines do not specify the length of time that MROs should retain these records, it is recommended that they be maintained for a minimum of two years from the date of collection, or as otherwise provided by law or contract with the employer.

No regulatory requirements exist requiring MROs to use a specific procedure to review drug tests; however, using a standard procedure is likely to ensure that each MRO review is complete and thorough. The use of a simple checklist will ensure that certain activities are always documented.

Documentation should normally include such things as copies of prescriptions or labels on prescription bottles, or notes that a prescription was verified at a pharmacy or by the treating physician. Any letters or notes received from an employee, relative, or physician providing treatment should be retained in the file.

Finally, MRO records must be separated from other medical and personnel records kept on an individual. For example, some physicians may also serve as a primary care provider and retain medical records related to that function.

The Mandatory Guidelines state (paragraph 2.6(h)):

The MRO must provide a final verified urine test result to the employer and may be required to provide such results to other agencies by regulation or law. However, the MRO has a responsibility to maintain confidentiality of the information received during the review process including information related to the donor's medical condition, medications, medical diagnosis, and medical history. This role is particularly important with respect to laboratory positive urine drug test results, especially those that may be verified by the MRO as negative due to an alternative legitimate medical explanation. The MRO must also maintain the confidentiality of certain information associated with the testing process, such as quantitative test results, except that the MRO may reveal the quantitation of a positive test result to the employer or the decision maker in a lawsuit, grievance, or other proceeding initiated by or on behalf of the donor resulting from a verified positive drug test.

Despite this general requirement to maintain the confidentiality of medical information, there are certain circumstances in which the MRO may provide such information to other parties. In these instances, the MRO should inform the donor, prior to the medical interview, that disclosure of information learned as part of the medical review process may occur if, in the judgment of the MRO, the information suggests there is a significant safety hazard associated with the information or there is a medical disqualification of the donor under an applicable regulation.

Even when the MRO releases otherwise confidential information due to such concerns, the MRO should attempt to release as little specific information as possible and release such information only to parties with a clear need-to-know. Such parties include physicians responsible for medical certification of the donor, Federal agency officials as required by regulation, or designated employer representatives.

Diagnoses or other specific details of medical information do not need to be provided to non-medical personnel. For example, employer representatives may only need to be informed that a safety hazard may exist and that the MRO needs to provide specific information to the physician responsible for making medical qualification decisions regarding the donor. In general, unless required by regulation or law, the MRO should only discuss specific medical information with other physicians or qualified health professionals.

The Mandatory Guidelines require each Federal agency to ensure that a minimum of 3 percent blind quality control samples are submitted with the donor specimens.

The blind quality control samples must be certified by immunoassay and GC/MS and have stability data which verifies their performance over time. The requirement to have certification data ensures that the blind quality control samples purchased from different sources are acceptable.

Generally, the employer will request the collector to purchase the blind samples or may provide them to the collector. In either case, the collector must submit each quality control sample as if it were a donor specimen. This requires completing a CCF and properly labeling a specimen bottle. Since there is no donor associated with a quality control sample, the collector must generate a fictitious social security number or employee identification number and fictitious initials to be written on the specimen bottle label/seal. The collector must complete the CCF as for any other specimen, with the exception of Copy 4 of the CCF (i.e., the MRO copy). The collector should indicate that the specimen is a "Quality Control Sample" where a donor would normally print his or her name.

In addition, the collector or the employer, whichever purchased the blind samples, should forward that information to the MRO. This will allow the MRO to determine if the laboratory reported the correct result when the Copy 2 of the CCF is received from the laboratory.

If the laboratory reports a result different from the one expected based on information provided by the manufacturer of the blind sample, the MRO should contact the laboratory to determine if there is an obvious reason why the laboratory did not report t