Well, greetings again, Tony Decker is a presenter. This is on urine drug testing, biomarkers, and the role of the medical review officer as part of the American Osteopathic Academy of Addiction Medicine CAQ prep course. I'm currently the chief medical officer of the Division of Developmental Disabilities in the state of Arizona. Previously, I had done the walk-in primary care urgent care clinic at Gallup Indian Medical Center in Gallup, New Mexico. I retired after 37 years with the federal government and I'm working as the administrative medical director for DDD. Prior to that, I spent a five-year cycle in the Veterans Administration and prior to that, I was the director of the Department of Addiction Medicine at Fort Belvoir, now known as Fort Alexander in Northern Virginia. And for 12 years prior to that, I was with the Phoenix Indian Medical Center. I went to Michigan State, did a family medicine residency at Chicago, an adolescent and adult medicine fellowship, and then continued in both academic and federal practice. So from a disclosure standpoint, I have no relationships with pharmaceuticals or prohibited donors. I am the past president of the American Osteopathic Academy of Addiction Medicine, and that is the sponsor for this course. Although I've been with the U.S. Public Health Service, Job Corps, Indian Health, Department of Defense, VA, and the Indian Health Service again, and the state of Arizona, I am not representing any state or federal organization. These are simply my opinions on this educational program. So our objectives for this program is to describe the role of screening and confirmatory testing, discuss drug testing for common substances, implement a monitoring program that improves recovery, and to discuss workplace drug testing and the role of the medical review officer. So our clinical issues in testing for substances of abuse is either a patient-centric process, in other words, the people who we are testing, or a medical legal process. That's an important distinction to make because with the Department of Transportation, if there's ever an event, pipeline rupture, a boat that hits a bridge in the Baltimore Harbor, there's a specific protocol that they go through to identify is there an issue. We have many people who are in monitored programs, and they are tested on a regular basis. It's very different to monitor tests for monitoring and monitoring tests for use, in other words, post-accident events and things like that. So substance use peaks between 18 and 26, it decreases with age over time, but no age is protected from the misuse, abuse, and diversion of substances. College graduates are less likely to use than non-graduates, and then those who have not completed high school have the highest use. Now, this is somewhat questionable because as people get further and further up the road of education, they may be more, I would say, intellectually adept to avoiding detection. So that's based on our data sets that we have available to us. It varies significantly by region and by state, and it also varies significantly by substance. So marijuana is much more misused and abused than amphetamines, keeping in mind that most states have made marijuana a legal substance, and then the stimulants are more used than the opiates. However, when we look at overdose events, obviously the opiates are the major contributor, but polysubstance use is the rule, not the exception. Males are identified more often than females in regard to abuse, misuse, and those who are unemployed or part-time employed are more likely than those who are full-time employed. From an occupational standpoint, the highest are in accommodations, in other words, the service industries, the food services, the arts, and the entertainment industries. Mental illness is more likely to be associated with substance misuse and abuse. When we look at drug testing in clinical care, the purpose of toxicology testing is to identify the typically inside of some body secretion or excretion in patients who are enrolled in a substance use disorder program. It's important to identify how we can allow the provider to ensure that the patient's taking the prescribed medications and ensure the patient is not taking other substances. The purpose is not to catch the patient, but rather to advise treatment. It simply shouldn't lead to a discharge to a program, and this is a real issue in regard to medical clinical practice. If you have a person on pain medication and they pop up positive for cocaine, many providers simply say, well, you violated the agreement and you're out. The reality is the patient's telling you they need help because they're not able to avoid the use of cocaine. So I'm hoping that this presentation will allow you, especially since you're looking at certification in addiction medicine, to reconsider that sort of draconian, I caught you mentality and really look at how do we change the way that we're providing services and enhance the intervention strategies. Testing a patient's urine or any body substance will not tell the medical provider how adherent is to their medication or if they have lost the recovery, what the depth of that loss is. Studies show that the treatment participants underreport drug use when compared to urine toxicology screens. That means that people are less likely to provide information. I've got some problems. I saw an old friend. I'm going through a lot of difficult times right now. Not that excuses permit these events, but it should be understood. You're taking care of someone who has a chronic relapsing disorder. The other thing is, what does a positive test mean? There's a window of detection. And so prior to that level, getting to a threshold, and that cutoff is typically identified in the testing process and that when that window of detection becomes positive above the threshold, that's identified as a positive test. If the test is negative, now it could be because you're on the right side of the screen because the metabolite is dropped below the threshold or you're on the left side of the screen that the metabolite has not accumulated to the point of being positive. So I just want to make sure that it's understood that when someone says the drug screen was negative, it doesn't mean that they haven't used, doesn't mean that they won't use. It does mean that the tested level is below the threshold. Now we start looking at the test type. We have a variety of substances that can be tested. We have advantages and disadvantages for each one. So the urine test is a common test. It's done by several labs. It typically has a longer detection time. It tests for several substances. It is somewhat invasive because you have to excrete urine into a container and then you have to make sure that the substance is actually urine, not scooped out of the toilet, diluted with toilet water, not another substance that was put in a container and then brought into the test site and that person just takes it out of their, out of that container and then puts it into a cup. It can be substituted or adulterated even when observed. They, we have numerous examples of people who have prosthetic penises and have a catheter device down in the genitalia. And we also have people who simply have what's called a shy bladder. They are unable to produce a urine and there may be a medical reason or it simply may be an emotional reason that they cannot produce urine. And then you have a protocol to deal with the shy bladder. More fluid awaiting a time and then going from there. Oral fluid assessment. This has got some brand names. So the proof testing where a person's on videotape so they can see them swabbing their mouth and they put that swab into a sealed container and then into a either FedEx or some other type of overnight delivery package. It's less invasive. It's easy to directly observe with the real-time video. It's better suited for detecting the parent drug rather than the metabolite or the biomarker, although these are possible. It does have a much shorter window of detection because it's based on active salivation and it's only done by certain labs. Some people may have a dry mouth and there may be contamination by things that have been inside the mouth. In recent times, blood testing is always directly observed because you have to do a venipuncture. It's difficult to adulterate or substitute. Another possibility is with the PEF blood spot. The phosphatidyl ethyl blood spot test could be a puncture on any skin area that obtains the blood for the blood spot. I personally feel that getting blood in a container and then taking the blood from the container onto the hard device for blood spot testing is better than simply puncturing and having potential contamination from the site. So, if you're doing a container blood spot test, venipuncture is necessary. It has a very short detection time. It usually shows the parent drug. It is more expensive and it's not commonly used unless testing for alcohol. Hair and nails. So, these are substances that grow on a person. They have a very long detection time and hair can be from not only the head or face, but also from the pubic area, armpit, or chest, body hair. And all of those have different growing capacity. It is directly observed. It's not invasive, but typically they take about 30 to 50 strands of hair and cut it as close as possible to the source. Some people even pull the hair so they can measure from the follicle. But cutting the hair is standardized. So, less than one centimeter cut and then a description of how long the hair is. Obviously, the further the hair is from the follicle, the older that test is. It's not commonly available. It's difficult to interpret results. It cannot detect the use in the last 7 to 10 days, but it can detect older use. And the patient may shave or trim their hair or nails to avoid testing. Sweat testing is possible. It's seldom used for substance use testing. It can detect recent use and this is with a single sweat swipe. It can detect the cumulative use with pads worn for the week. It is non-invasive, not commonly available. Few labs do this. Fewer drugs are available to test. And the patient may remove the sweat patch during that accumulation process, which adulterates the testing process. So, there's limited quantity of the sample for a confirmatory test. Immunoassay testing is typically the test that's done for screening tests. It's the most common type of screening test. It is quite inexpensive. These are the $5 to $7 tests that you can get. It's able to provide a rapid test result. So, many facilities actually do screening test assessment on site. They do provide accurate results that are qualitative, positive or negative. It's similar in a result of an enzyme-multiplied immunoassay, EMITT test, or a enzyme-linked immunosorbent assay, ELISA, and a cloned enzyme donor immunoassay, ACIDIA test. And they're able to be read at the point of care or in a lab. So, what does a negative test mean? It means that the drug screen can be interpreted as negative when there's no drug in the specimen. There is a drug in the specimen, but the concentration is below the threshold level. There is a drug in the specimen, a concentration above the threshold level, but the assay is only weakly positive with certain drugs that are present. There is an interference in the assay created by the administration of other medications or by the addition of adulterants. And so, you need to be able to test for nitrites and other types of adulterants. The sample was submitted, or there's a lab error. I'm sorry, the sample was substituted, such as they came in with their own urine cup and then provided that cup, or there's lab errors. There's lots of reasons that you could have a negative test. And I always try to instruct trainees in addiction medicine to be aware of the lab that is actually doing the test. Is there a chain of custody? Is there a reasonable amount of security? Do they flush the machine between testing? Indicates only recent use, positive test. Does not correlate to impairment, completely independent. Does not indicate the route of administration. So, whether it's taken orally, transderm, IV, inhaled, all those do not tell you. The test does not tell you how it was administered. It does not indicate the route of administration. It cannot tell you the amount used or how often it's used. And there was some laboratory testing that said they could estimate how much a person used, but the person-to-person variation and even the temporal variation in the same person was too great to make those assumptions. The urine drug screens are indicated as a tool to facilitate recovery, but not against the patient, but with the patient. So, this is what we talked about earlier. The key is not to catch people and to push them out of treatment. Patients may verbalize that the urine drug screen, or what's in the urine drug screen, before providing the specimen. One of the things that I do is, we'll be doing urine testing today. Is there anything that I should be concerned about? And many times, patients will simply volunteer that information. Then you can do the test, find out if that presentation is consistent with what the member said. Cross-reactivity. Tests cannot distinguish between substances being tested for and substances that are chemically similar. So, this is a challenge because this would be a false positive if you have someone on a screening test that's positive for a substance after they had taken, for instance, pseudoephedrine and you're testing for amphetamines. Drug class specific immunoassays compared to the structural similarity of a drug or its metabolites with specially engineered antibiotics or antibodies. Substances other than the drug being detected can also cross-react with an antibody and produce a false positive. So, I said pseudoephedrine, false positive for amphetamines. Sertraline, false positive for benzodiazepine. And dextromethorphan, false positive for fencyclidine, for examples. And there are hundreds of false positive possibilities with screening tests. Now, we move to confirmatory testing. So, confirmatory toxicology test samples can be done using gas chromatography, which means they have to heat the sample up, and tandem mass spectrometry, which is the current standard. So, it's GC-MS or GC-MS-MS because it's a tandem mass spectrometer. Or liquid chromatography, which is not as high of a temperature with tandem mass spectrometry, LC-MS-MS and MS sometimes. So, gas chromatography separates and quantifies the drug and the mass spec identifies the drug. These are 99% sensitive and 99% specific. Is it possible for a drug not to be sensitive to all metabolites that are being measured? Yes. And is it possible for them not to be specific? The answer is yes, but extremely low compared to the screening tests. So, substances that are often tested in the clinical setting. So, opiates are obviously one that we test on a fairly regular basis. So, morphine, codeine, and its metabolites are easily measured. The synthetic drugs are measured. They are not detected by the test for opiates. So, if you have a test, a screening test that simply says opiates, it's going to test for morphine, codeine, and metabolites. It will not test for buprenorphine, fentanyl, oxycodone, or methadone. Now, the tests, many times, if you have it actually labeled as methadone, that means that the screening test is testing for the metabolites. For the metabolite of methadone. So, if it has that name on the side of the bottle when you're doing the test, and many of these are calorimetric. So, it's just a plus or minus, a negative or a positive. So, we can also test for benzodiazepines, cannabinoids, amphetamines, cocaine metabolites, and benzoecanine. This is very easy to detect, which is a cocaine metabolite. And alcohol metabolites, and you should be familiar with ethylglucuronide, ethyl sulfate, that's ETG and ETS, and the phosphatidyl ethyl, which is the PEF test. Tests for designer synthetic cannabinoids, the cathinones, which are your bath salts are available, but they are limited, and there are several new drugs on the street. Drugs on the street that, again, you have to test for, such as kratom. So, we look at opiates and opioids. We have in the middle of the morphine molecule, and you can see that codeine can be metabolized by cytochrome 2D6 into morphine. Now, this is an issue because people could be on prescribed codeine, but have a positive morphine test. Now, when you look at this, you can also see the process of codeine metabolism, the process of morphine metabolism, and the process of morphine metabolism into morphine 6-sulfate, morphine 3-sulfate. Now, Bayer made a product called diacetylmorphine in the late 1800s, heroin. And when heroin, which is diacetylmorphine, it crosses the blood-brain barrier faster, but the enzymes cleave off one of those acetyl groups, and then it becomes monoacetylmorphine. Monoacetylmorphine is pathognomonic for exposure to heroin. That's a pretty common test question, so I want you to be aware that diacetylmorphine becomes monoacetylmorphine, and monoacetylmorphine would be pathognomonic or indicates use of heroin. Now, heroin use has actually gone down in the U.S., and fentanyl use has gone up dramatically. Now the other thing is that, what about poppy seeds? Well, poppy seeds actually have morphine in them. It's a very low amount. You see over to the right, you see heroin, diacetylmorphine, is metabolized to 6-monoacetylmorphine, When you cleave off the second acetyl group, it goes back to morphine, because morphine is the active ingredient. The brain does not recognize, as an active substance, diacetylmorphine or monoacetylmorphine. It's just what drives it through the blood-brain barrier faster. So you can see here that morphine can also be metabolized to hydromorphone, hydrocodone also metabolizes into hydromorphone, codeine also metabolizes into hydrocodone, and then hydrocodone can metabolize into dihydrocodone and norhydrocodone, which would indicate the hydromorphone experience, which is dilaudid. And so people on hydrocodone could become positive for hydromorphone. So you need to understand that you put a person on dilaudid, they pop positive for hydrocodone. I'm sorry, you put a person on vicodin, they pop positive for hydrocodone, but they also pop positive for hydromorphone as an expected metabolite. Oxycodone, below the line there, becomes oxymorphone, and you can see that it can become noroxycodone, and that can be metabolized to noroxymorphone. So you have two ways that noroxymorphone can be made. Now is it noroxymorphone or is it naloxone? And this becomes a challenge because it's a very small metabolite, but you can see that at less than 75 nanograms per ml, it's most likely to be associated with the metabolism of naloxone rather than with oxycodone or oxymorphone containing the drug. So it's challenging when you start to look at all the potential metabolites that a person can have. Now windows of detection are important to know. Buprenorphine typically is up to four days, but a person who's stabilized on long-term buprenorphine use may have positive findings of buprenorphine for an extended period of time. Those who are on sublocade or implanted buprenorphine delivery systems will be positive weeks to months later. I've had a patient who had 300 milligrams of buprenorphine injected subdermally and it was still positive four months later. Codeine, one to two days. Heroin metabolites. Now 6-acetylmorphine is gone very quickly, literally hours. So a person who overdoses and they'd stop metabolizing because their body becomes cold may have 6-acetylmorphine, monoacetylmorphine in their system, but a person who is alive, they continue to break down the diacetylmorphine to 6-monoacetylmorphine to just morphine as part of their enzymatic display. And so it's unusual for a person who is using morphine that used last night and comes into your office and tests today. It's unusual for that person to be positive for 6-acetylmorphine or 6am. Hydrocodone is one to two days. Hydromorphone, one to two days. Methadone has an inherent ability. It attaches to the immune receptor, stays on the immune receptor and has to be metabolized. We don't know where methadone stays for people who are in chronic methadone therapy. It could be in the bone marrow, it could be in the brain, it could be in some other organ, but it can be there for many days and it's not unusual for a person who's maintained on methadone and then stops using to still be positive weeks later. Morphine one to two days, oxycodone one to a day and a half, oxycodone with controlled release three days, oxymorphone or PANA one and a half to two and a half days and extended release up to four days. Keep in mind that even fentanyl, which is very short in its transderm delivery system, there's still some fentanyl left in the skin that can be detected a day later, two days later. Most people feel the withdrawal of pulling off the patch and could go into withdrawal because they're used to a higher dose. Poppy seeds contain a small amount of codeine and morphine and that can also cause a positive on the toxicology screen. People who are monitored in drug monitoring programs are told to avoid poppy seeds. However, poppy seeds are not only on bagels, but they're also in everything, crackers are in everything, salad dressing, they're in poppy seed dressing and sometimes they're sprinkled into pastry items and things like that. People need to be keenly aware of this. The poppy seeds are not the sole source of morphine and codeine if the total morphine amount is greater than 5,000 nanograms, if the total codeine amount is greater than 300, if the morphine to codeine ratio is less than two, and if the total morphine amount is greater than 1,000 nanograms without any codeine present. There should be some. However, there's significant variation from the poppy seeds in regard to the amount of codeine or the amount of morphine in the poppy seed. And there's geographic variation from country to country and source of origin, but there's also some hybridized poppy seeds that have, one even has oxycodone in it that's got a pharmaceutical trademark on that particular poppy seed production. And it's a protected, they say it's a protected growth, but it does create challenges because that avenue does exist on a natural hybridized basis. If six monocetylmorphine is present, that's pathogenomata for heroin and that person could be positive for morphine, because remember you cleave off the second acetyl group naturally. But if six MAM is present, that means that they are using heroin too. Buprenorphine and norbuprenorphine levels. So the bup, the norbup to bup is typically 0.2 or less. It indicates that the medication has been dissolved in the specimen. Now why would a person take a small piece of buprenorphine film and put it in their urine sample? Well, it's because they want to show that they're taking their buprenorphine. But if a person has lost their recovery and they want full access to the receptors, many people will simply add a small amount of buprenorphine or a little crumble of a buprenorphine tablet into a sample. And then you have a very high level of norbup to bup. The other thing to remember is that concentrations of norbup generally become higher than bup within a few hours after intake. The metabolite exceeds. And this is because of the first pass effect. 80% of buprenorphine that goes through the gut, goes through the liver, and it is changed into norbup. Norbup to bup ratios less than 0.5 indicate very recent use. Some patients may have a higher bup to norbup level due to lab procedure. The patient's taking some kind of cytochrome 3A4 inhibitor that slows conversion to the metabolite. The patient may be taking a medication that substrates itself through the cytochrome 3A4 system, resulting in competition for the isoenzyme, which gives a higher level of bup. Or the patient may have taken the dose just before the urine test. So norbup to bup ratios, interpreting the quantitative urine buprenorphine and norbup levels in the office-based setting. So samples from patients who report or were suspected of urine adulteration had significantly lower norbup to bup ratios, with a p-value of less than 0.04. Bup levels greater than 700 offered the best accuracy for discriminating between adulterated and non-adulterated specimens. There's a high prevalence of urine tampering in office-based treatment programs based on detecting and evaluating norbup to bup ratios. Now we have a greater number of people prescribing buprenorphine as a treatment for medication assisted treatment. Many of them, because the waiver is no longer required after 2022, may not have the experience or the training to understand the laboratory interpretation, because they want to make buprenorphine more available. And so that creates a challenge, because one of the things that we all try to emphasize is the concurrent use of opioids with buprenorphine may be indicated or may be contraindicated, depending on what you're treating. Is it pain? Is it substance use disorder? Or is it a combination of the two? Let's move on to benzodiazepines. So benzodiazepines are divided into several groups. Some benzodiazepines, so 4-diazepoxide, diazepam, temazepam, are metabolized to oxazepam. Oxazepam is conjugated into an inactive glucuronibetabolite. So when we're testing these, we're using tests for the metabolites and sometimes even for the biomarkers. Nitrobenzodiazepines, such as clonazepam, is primarily reduced to an aminoclosaclonazepam, which is further metabolized, and it's usually reduced to a corresponding amino compound, but not converted to oxazepam. So you need to understand that for certain substances, oxazepam is a measured metabolite. Triazolobenzodiazepines, such as alorazepam and estazolam and triazolam tend to form hydroxyl derivatives that are separated and distinct from oxazepam. And other benzodiazepines, such as lorazepam and flurazepam, have unique metabolism that does not result in the formation of oxazepam. So this is a good diagram to see. Clonazepam can become temazepam. Diazepam can become nordiazepam. Now chlorodiazepoxide and chlorazepate can become nordiazepam also, and they all end up as oxazepam on the bottom right. When we look at benzodiazepine metabolism, clonazepam, alprazolam, or Xanax, and lorazepam, and Ativan move into those metabolites. And so, again, recognizing these become important in the ability to go backwards and say, well, this is consistent with the use of Xanax, but that's my psychiatrist's medication, and I need to have that. That's okay, I have a prescription for it, but we need to be able to measure it. There's also a concern because the use of alprazolam and benzodiazepine has been associated with sedation. Have you noticed any changes in the way that you function during the day? You're taking naps, falling asleep, do you fall asleep when the car stops at a stoplight, that kind of thing. Benzodiazepine window of detection, so our short actings like triazolam is up to 24 hours. Intermediate acting is up to 12 days. And that's important to understand because that means your alprazolam, clonazepam, lorazepam, and temazepam can be detected for 1 to 12 days. Long actings, such as diazepam, can be up to 3 weeks plus. And then chronic abuse of opioids can be up to 30 days after their last use. So these are detected longer than our typical opiates. Sertraline is structurally similar to diazepam. It does cross-react on the screening test. Therefore, you could get a false positive for benzodiazepines. But then when you do the gas chromatograph or liquid chromatography with the tandem mass spectrometry, it'll distinguish between sertraline and the benzodiazepines. Cannabinoids have become a significant challenge in the clinical picture. One of the reasons is that the availability of high-potency THC has become ubiquitous rather than difficult. And the effect it has on individuals is much greater. So there's a presentation on cannabis use. THC is stored in the fatty tissue. It gradually re-enters the bloodstream at lower levels and then becomes metabolized and excreted. This means that a person who's using a significant amount of THC and stops, but they have significant body fat, it can be in the body fat. And as they lose weight, it'll release the THC. It'll also be gradually released, even if they're not losing weight, and cause them to be positive for several days later. So the window of detection is dependent on the quality or the potency of THC in the marijuana. And keep in mind that the hybrid marijuana, I mean, marijuana in the 70s was between four percent up to maybe 14 percent for very high concentrate. Now it's not unusual to have anywhere between 30 to 60, 70 percent with hybrid marijuana bud or flower. Obviously hashish and THC oil is even higher than that. And there is a product in the Phoenix area called Shatter, which is 90 plus percent THC. Now that amount of stimulation of CB1 and CB2 receptors has been associated with degradation of people who have serious mental illness, bipolar disorders, bipolar 1, bipolar 2, schizoaffective schizoid, and schizophrenia. And it's also been associated with degradation of other forms of major depressive disorder or psychotic depression. So when you look at the chronicity of use, this becomes a challenge because after single use you should be able to detect up to three days. For moderate use, at least four days, and for heavy use, at least 10 days after their last use. So let's say a person was in a motor vehicle accident, was hospitalized, they're positive when they go in, but they get released from the hospital, they come to your office, and they're positive again. What does that indicate? That indicates that there's THC in their system. And that can indicate, do they use it just before they came to your office, or did they use it 10 days ago when they were significantly on heavy use of marijuana back then? 30 to 36 days for chronic heavy use, hydration when the urine sample is collected has an impact, and the lab cutoff also has an impact too. Every lab's a little different. So therapeutic cannabinoid products, so there's Dornival or Marinol for nausea, that's a normal positive test for a person on prescribed Marinol, Sativex for muscle spasms, and that also contains cannabidiol, and Navolone, which is a treatment for nausea and vomiting, Casameth. Danger to hemp liquid or hemp liquid gold, and then CBD for vaping. Should be noted that in the state of Arizona, if the CBD is less than 0.3%, it can be sold as non-THC CBD. Every state has their own acceptable level of THC in CBD, which includes levels as low as 0.1% and as high as 1%. Well, those obviously would cause a person to be positive for THC too. So a gas chromatograph mass spectrometry greater than 15 nanograms per ml would indicate that they're getting some kind of THC exposure. I know that the monitoring programs that I run with, typically if a person's higher than five nanograms, it's consistent with marijuana use. This would be for monitoring physicians and other health professionals. Synthetic cannabinoids need to be tested for, specifically, there's over 600 different synthetic CB1 and CB2 receptor agonists. So K2 and Spice, which were legal until 2012, when they became illegal, Schedule 1 for the DEA, and many others. There was significant use. The primary source of the synthetic cannabinoids was gas stations and sex shops, but that use has gone down dramatically. Unfortunately, it's been replaced with fentanyl use, which also in Phoenix, the number one source of getting fentanyl, these are the tablets, is from gas stations. Testing is limited to rapid development of new molecules. Cocaine, amphetamine, and synthetic cathinones. Cocaine is quickly metabolized to benzyl echinine. Benzyl echinine is very easy to detect. It is not stored in the body. The window of detection, which when the cutoff is 300 nanograms, is one to three days. Immunoassay tests are very specific for benzyl echinine. There are very few false positives for the screening test for cocaine, which is really a test for benzyl echinine. You should know that name, benzyl echinine. Now ingestion of teas made with coca leaves can cause a person to be positive for benzyl echinine. You can get inca teas or coca teas, which you can receive on the internet right now because they do contain small amounts of cocaine. Amphetamines, when testing for amphetamines, it's important that methylphenidate will not test positive for an amphetamine. Vicks Vapel inhaler is 80% L-methamphetamine. So racemic mixture testing is a challenge because if a person has been using the old Vicks Vapel inhaler, so this is the one that's in the kitchen drawer that's been there for several years, and the person uses it, now it's in the vernacular of people that misuse or abuse amphetamines, and so many times people will say, well, I've got chronic allergies and I've got to use my Vicks Vapel inhaler. They need to stop using that. Now the methamphetamine of abuse is the D-methamphetamine, but the decongestant is the L-methamphetamine. The mixtures are not 100%, so you can get L-methamphetamine in some methamphetamine products. Remember, there's wide variations of the synthesis of methamphetamines. Selenogine has equal amounts of L-methamphetamine and D-methamphetamine, but the 80% rule still applies. 80% of L-methamphetamine on the GC-MS racemic evaluation, that would indicate use of decongestants. MDMA can trigger positives for amphetamines, and there's literally dozens of amphetamine metabolites, acetyl amphetamines, which are the most common in the illicit use that result in positive amphetamines. Bath salts are bath salts. They need to be tested specifically. Testing is limited to rapid development of new molecules. And so this is a challenge. Fortunately, we're not seeing as much bath salts, but this comes and goes. It's very regionally based. So it depends on what the supply system has. If they have more of the cathinones, people try to move product. Alcohol testing is a bit challenging. So I want to go over this in detail. Blood alcohol concentration is a direct marker for ethanol. A breathalyzer and blood are typically the two ways that that's tested. One standard drink, this is something that you need to know, has 14 grams of ethanol. In an hour, it raises the blood alcohol to 0.01 or to 0.05. So that's interesting that one drink in an hour can raise the blood alcohol by 0.01 to 0.05. Now, keep in mind that 0.08 is the level of intoxication in all states. That was a change that the addiction groups mobilized with the Department of Transportation in the early 2000s, because it was clear that even with one serving of alcohol, it does change the psychomotor reaction time. But if a person has four as a female or five servings as a male, their reaction time is significantly impaired. The breathalyzer is sensitive for about 24 hours. The blood alcohol is sensitive for about 12 hours. So you have a very rapidly declining level of blood alcohol. Now, ETG, ethyl glucuronide, and ETS, ethyl sulfide, are direct biomarkers. So these are analytes of a non-oxidative breakdown of alcohol. We have tests that are highly sensitive to these biomarkers. They can detect even a single drink. They can detect even alcohol in a non-alcoholic beverage. I'll give you examples. Kombucha is fermented tea. It could be between 1% to 5% ethanol. Remember, beer is 5%. People typically drink kombucha in 0.5 to 1 liter servings. Kiffer. Kiffer is fermented camel's milk. It stays firm even at room temperature. So a lot of people who have smoothies, and again, they typically drink 32 ounces of smoothies, may have some kiffer in it. It's in the dairy department in most grocery stores. Apple cider vinegar. The Dr. Bragg's apple cider vinegar, yellow label on a dark brown bottle, says right on the bottle, does not need refrigeration. But it has cider in it. When you open the seal, you contaminate the cider with yeast. And if you leave it on the table for a week, the cider can ferment. The thing that's important is that it only takes three things to make alcohol, yeast, sugar, and water, and heat. So if you have that combination, and we're talking room temperature heat, you can facilitate the fermentation process. So when we look at ETS and ETG, it can be affected by extraneous alcohol products that we've talked about. Listerine and scope mouthwash is 58% ethanol. 158, 116 proof. People gargle and spit. People gargle and swish. And some people gargle and swallow. So you're swallowing, and your mouth can easily hold 50 cc's or 100 cc's. That's the size of a shot when a person's drinking a 40% or 80 proof shot of distilled spirits. But I've already told you that mouthwash can be 58% ethanol, so that's even higher in alcohol content. So people who are in monitored programs need to use non-alcohol mouthwash. 1,000 nanograms per ml heavy drinking recently. That would be if your ETS or ETG is above 1,000. Between 500 and 1,000 is low positive. From 100 to 500, you could have heavy drinking that's old or recent light drinking. And again, those levels that are between the lowest detection and 100 to 200, you have to think of, is it possible that other non-alcoholic beverage could have caused this presentation? Phosphatidyl ethyl, which is the PEF direct marker, is a minor metabolite. Alcohol concentration and incubation time are directly proportional to the quantity of PEF produced. The PEF in the blood is a standard test that we use. The test is based on 44 grams of ethanol. So that would be three servings of alcohol over the course of 72 hours. And that would cause a positive PEF of 20. So when a person has a PEF that is in the 60s, 80s, 100s, in the 100s, the likelihood that they have had a significant ethanol exposure is very high. And yet, keep in mind that part of the disease of addiction is denial, that I don't want to be caught. I don't want to lose my license. I don't want to get in trouble. And so denial is a common experience. I work with my members that I serve in a way that tries to help them acknowledge that their explanation is inconsistent with the lab result. And so we go from that standpoint and go from there. And I always give people the option, is there anything that you feel could have caused this? Or do you feel that something you've told me is something you'd like to change editorially? And I give them that out so they can say, you know, I just remembered. Something like that. When we look at alcohol biomarkers, you can start to see several things that we have here. So CDT is a screening for heavy drinking. The time to return to normal is two to three weeks. ETS and ETG is only the past one to three days. A GGT is for the past two to four weeks. Mean corpuscular volume on a CBC can take several months to change because of vitamin changes. Phosphatidyl ethyl is for the past two to four weeks. So if I'm looking at someone who had a phosphatidyl ethyl positive today, and I'm presenting this on April 5th, I would go back to March 5th and say, during the past month, can you tell me if you've had any exposure to alcohol and what that exposure was? A sensor device is a continual level. So that goes along with, for instance, the breathalyzer that's used in a car. The SGOT and SGAT, I'm sorry, SGOT and the AST are two to four weeks, and the SGPT and LT are also in the past two to four weeks. Looking at other substances, LSD, the clearance half-life of LSD is about three hours. The half-life for the metabolites, about 12 hours. LSD is a rather new substance that we can test for. The LSD is higher than the LOQ, indicates exposure in the past day. Hallucinogens have become a popular therapeutic avenue. Ketamine, LSD, and psilocybin are showing up in a variety of settings. Oregon has approved psilocybin. There is a bill in the Arizona House right now to approve psilocybin. Typically what we saw with ketamine was a whole bunch of ketamine and S-ketamine clinics pop up across the country. There was complications because the entrepreneurial mentality is, I have a product, I have a territory, I wanna use this product, but we do know that the hallucinogens do have a significant negative effect on some individuals. So the presence of 2-oxy-3-hydroxy-LSD greater than the LOQ indicates exposure within the past two to five days. PCP, club drugs, inhalants. Phencyclidine does have a cross-reactivity on the screening tests with dextromethorphan. And other false positives could be from imotrazine and venlafaxine. Club drugs, which include GHB, ketamine, rofenol, MDMA, MDA, MDEA. Most screening tests do not test for these. However, confirmatory tests do. GHB has a detection level that's less than 12 hours. That's a club drug that's used to sedate victims. And then the methamphetamine analogs can cross-react with just amphetamines. Inhalants, there's a variety of inhalants. Some are stimulatory, some are sedative. Right now, the most common way that people misuse, abuse, or are dependent to fentanyl is take a fentanyl tablet, fold over the heavy tinfoil, and just put a Bic lighter under it, and then just chase the white tail. Also, the way that the heroin, black tar heroin, is used. You have a little bead of black tar heroin. It melts with the flame. And then the tail is a dark purple or a black tail, and that's chasing the dragon's tail. You have to have some knowledge of the vernacular in your community regarding this. Drug testing in the workplace. Patty. Sorry about that. Key points are there's a wide use of alcohol, tobacco, marijuana, prescription opioids, cocaine, and hallucinogens in the US. There are many factors for substance use that have to be taken into consideration, age being one of them. Unfortunately, now in the childhood years, gender, geography, education, occupation, and work status, recreational use of marijuana has risen dramatically with legalization. Opioid overdose and deaths are absolutely epidemic with over 88,000 deaths in 2022. That number may be going down this year, but the amount of fentanyl coming into the US right now is higher than ever before, as is the amount of cocaine coming into the US. The peak ages for use, abuse, and sadly even overdoses is now 18 to 25. Two thirds of drug users are employed. Workplace environments, job turnover, absenteeism, on-the-job injuries, healthcare utilization, and lost productivity are all impacted by substance use. When we look at annual positive drug tests by year, this is looking at the tests that were done for job placement. That number has gone down in the late 1990s, mostly from marijuana use. But with the legalization of marijuana over the past five years, going beyond medical marijuana, I do see this going up in the near future. Comprehensive drug-free workplace. You have formal written policies. Employee assistance plans, which does not provide feedback to the supervisory staff. Supervisor training on recognition and support. Employee education and methods of detection. The Department of Transportation has a safety-sensitive position. So that includes the FAA, flight crew, attendants, mechanics, dispatch, ground security, instruction, air traffic control, aviation screening, and operations and control specialists. That means anything that goes up in one piece and comes back in one piece, all the people that work for that item are in the FAA safety-sensitive positions. The FMCSA, the overland drivers, are also being done, and that does require testing. The FRA, which is the rail service, that includes anyone who works in the rail areas. That's the train crew, signal and switch crew, train dispatch, maintenance of way. All those people are being monitored in the Federal Department of Transportation safety-sensitive positions. FTA, vehicle operations, maintenance, control, dispatch, armed security personnel. The PHMSA are pipeline operations, maintenance and emergency response, the pipelines, and the U.S. Coast Guard, vessel operation, navigation, and emergency response. These are all staff that are tested on a regular basis. I know in the military, it was not unusual. Today's test day, you find out when you check in in the morning, and you just go down the hall and stand in line. There'll be a guy standing in the bathroom for me, and I've got to pee in a cup, hand him the cup, he puts on the top, and it goes into a container, and then I walk out. This is all part of the deal in many federal and state programs. Workplace drug testing. There's a pre-employment test. There's an annual physical test. There can be a test for reasonable cause for suspicious situations. Post-accident testing is the rule, not the exception. And post-treatment, after a person goes into treatment, which is highly encouraged, they can be tested too and be in a monitored system. Healthcare, same thing. So if you're a licensed healthcare worker and you ask for help, typically that population does very well. 95% complete the program, but it's expensive. Not unusual to spend about $10,000 a year to be in that program. Accuracy of workplace drug testing results. You need to use a HHS-certified lab to test specimens. There needs to be a chain of custody documented well. The medical review officer interprets those results. So MROs are licensed physicians of a knowledge and training of substance use disorders and federal drug testing regulations. They are trained to interpret and evaluate test results in concert with the employee's medical history and other relevant history. So if a person has a prescription for let's say hydromorphone dilaudid, you should expect that they will have hydromorphone in their system. If they have a prescription for vicodin, hydrocodone, you should expect that there will be hydrocodone and hydromorphone in that sample. SAMHSA targets five drug families of abuse. That's the amphetamines, cocaine, marijuana, which is a THC assessment, opiates, which includes opium and opioids and the semi-synthetics, and phencyclidine. The DOT mandatory testing cutoffs, and I would recommend that you know these. Marijuana, the initial cutoff is 50, but the confirmatory is 15. And then keep in mind in monitored programs for physicians, our cutoff is five. Cocaine metabolites, which is always benzoalkanine, codeine, morphine, hydrocodone, hydromorphone, oxycodone, oxymorphone, 6-acetylmorphine. Remember, 6-monoacetylmorphine is a metabolite of heroin. That's why the level is so low, that if a person has a level of 10, it is consistent with use. Any detectable level is consistent with use of heroin. Then we have the phencyclidine is at 25, amphetamines, the methamphetamines, 500 and 250 as the confirmatory cutoff. And then the other amphetamine analogs are the same, 500 for screening and 250 for confirmatory cutoff. So confirmatory testing with the MRO, it's a second analytical procedure performed on a different aliquot. So when a person gives a urine sample, or actually any sample, there should be a second sample taken. So they split the sample, seal it in a container, and then they have to save it, they freeze it, so that if there's a reason to do a second sample on that same sample, it's available. So the method must be used that combines the chromatographic separation and the mass spec identification. So GC or LC, gas chromatograph or liquid chromatograph, and then tandem mass spectrometry is typically the standard that's being used. Methamphetamine must be at least 250 nanograms and at least 100 nanograms of amphetamine to be positive. So there are some things that occur because amphetamine is a metabolite of methamphetamine. Drugs that are currently not on the HHS panel are the synthetic cannabinoid mimetics. Cannabinoid mimetics, so Spice K2, John W, John WH, and then the Hebrew University samples. Keep in mind that the U.S. government paid universities to make these synthetic cannabinoids to see if there was a way to treat marijuana dependence. Turns out that the agonism at the CB1 and CB2 receptor was much higher and the formulas escaped the university settings and now they're out in the community. The bath salts currently that are common, mephedrone, MDPV, methylone, these are not being tested on a routine panel, but you can test them. And you should know from your confirmatory testing site what tests are available for the synthetic cannabinoids and the cathinones, the bath salts, in addition to the amphetamines and the opioids. Fentanyl, sufentanil, carfentanil, alpha, methylfentanyl, a variety of things. I mean, we still have acetylfentanil as our leading drug of abuse. The U47700 and U50488 are other opioids. They have even a greater agonism at the mu receptor and these new phenylethylamines, the NBOMEs, not the National Osteopathic Board of Medical Examiners, but a phenylethylamine, which is used as a stimulant and a hallucinogen. Benzodiazepines are also not currently screened, but your private screening labs will have those. Validity testing from the MRO, check the creatinine. I mean, typically a creatinine of 100 in the urine is consistent with normal creatinine. So if you have a person who has a creatinine of 10, it's a very dilute urine, which would be suspicious. Did the person just scoop the water out of the toilet? Most people put stain in the water, so they can't do that. Specific gravity, any specific gravity less than a 1001 or 1.001 or 1030, if it's greater than that, would be considered outside of the range of appropriate testing. And then you have to ask yourself, why so concentrated or why so dilute? The pH of every specimen needs to be between four and 11. Any type of oxidizing adulterants such as nitrites greater than 500 nanograms would be consistent with a adulterant being used. And then additional things, reaction responses, characteristics of the adulterant. And typically most confirmatory labs will identify whether there's any of those that are listed there, surfactant, pyridine, chromium, halogens, things like that. We have our references here in regard to urine drug screening and testing. And I wanna thank you for your willingness to go through the process of studying for the examination and taking the exam, being a contributor for our patient population who has addiction and substance related issues. My name is Anthony Decker. I am available if you have any questions regarding this program by emails in the system. Thank you very much.

urine drug testing

biomarkers

medical review officer

addiction medicine

workplace drug testing

screening and confirmatory testing

substance use

DOT mandatory testing

synthetic cannabinoids

sample integrity