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Kenosha County, Wisconsin, was one of the first counties in Wisconsin – and Wisconsin is still the only state in the nation – to use direct biomarker testing to help the population of impaired drivers served by the local assessment agency, the Hope Council on Alcohol and Other Drug Abuse, where I was Executive Director. Starting in July 2011 with the help of Pamela Bean, PhD, who had dedicated herself to reducing the number of drunk drivers on Wisconsin’s roads, the Hope Council, with the help of USDTL, implemented testing of convicted impaired drivers who were assessed for three or more offenses. In 2014 we expanded testing to include any person convicted and assessed for any number of offenses who was referred to treatment.

Testing the intoxicated driver population was the single most impactful change made in this programming since assessments were mandated in the late 1970s, and I truly don’t understand how every county in every state in the nation hasn’t jumped on board.

Dr. Bean laid the groundwork for Wisconsin counties by securing permission for the use of direct biomarker testing, but these aren’t just any tests. These tests specifically identify those who use alcohol problematically. We aren’t looking to “catch” drinkers. We’re looking to help those who have significant substance use disorders to recognize that their use is problematic and then guide them into treatment and provide tools for them to begin a life of abstinence…or at least to not drink during the Driver Safety Plan (DSP) that’s developed with them at the assessment.

Clients at the Hope Council with three or more offenses are required to have at least three Ethyl Glucuronide (EtG) tests during the one-year duration of their DSPs. EtG is detected in fingernails and shows a window of approximately 90 days of use. For those clients who have deliberately underplayed their use at the time of assessment, it’s likely that a follow-up Phosphatidylethanol (PEth) test would be scheduled within a month of the surprise positive test results. The PEth test uses dried blood spots and shows a window of about 30 days of use. Many clients are surprised by the quality of these tests, so they may not be truthful at the assessment. The follow-up PEth allows the clients the opportunity to show that they are abstaining, as required by the assessment.

And if they aren’t? Well, that gives the assessment agency the opportunity to provide additional support and oversight for those who are having a hard time remaining abstinent. Addiction is a chronic, progressive, lethal disease, and it needs to be treated as such. Every other disease uses tests to provide valuable information for disease management, so why not the disease of addiction? Finger sticks for diabetes determine if blood sugar levels are balanced. Blood tests for international normalized ratio (INR) for heart disease determine if the blood is clotting properly. Direct biomarker tests should be used to determine if those assessed as having significant substance use disorders are maintaining appropriate levels of substances – specifically none – in their systems.

These tests are the best tools to help those suffering from the disease of addiction to recognize it and move toward treating it.

Click here to learn more on Guided by Guida. Click here to learn more about Alcohol by the Numbers.

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1) What is the difference between a clinical test and a forensic test?

• Forensic testing includes confirmation testing, which uses a second portion/aliquot of the original specimen run on different, more sophisticated instruments when possible to duplicate positive screening results. This is a fail-safe to prevent false positives.
  
  
• Forensic testing also includes a clearly documented chain of custody, which ensures the specimen collected is the specimen that was tested and, in turn, reported out. This is because forensic testing has processes to ensure that the evidence created is defensible in a court of law, potentially mitigating issues associated with the testing.

2) How do I know if a laboratory is a good option for forensic newborn drug testing?

You should seek a laboratory that has forensic accreditations. Forensic drug testing laboratories work with the oversight of forensic accrediting bodies. These accrediting bodies review the laboratory processes regularly for accuracy and compliance. Laboratories that don’t have proper oversight can put an organization’s reputation and integrity at risk if their processes are determined to be forensically indefensible. This can lead to extensive and costly reevaluation. USDTL holds one of the highest international accreditations for forensic toxicology as an ANSI-ASQ National Accreditation Board (ANAB) ISO 17025 forensic testing laboratory. This means that every test completed by USDTL is done under the highest standards available for a forensic drug testing laboratory.

3) What is the best way to reduce the chances of missing newborn drug exposure while reducing testing bias?

Standardized collection of umbilical cord tissue at every birth ensures equity in the newborn drug testing process. No newborn will be left without the documented exposure they need for their lifetime and no hospital is left without the data they need to make the best decisions. This process streamlines staff training and reduces issues of missed collection because every umbilical cord is collected even if it is not tested. Stored specimens can be sent out for testing based on hospital protocol or if the neonate starts showing unexpected symptoms of withdrawal hours or days after birth. Specimens that do not need testing are simply discarded. See our blog The Onset of Newborn Withdrawal Symptoms is Highly Variable, which shows the different times onset can occur. According to the study, some barbituates could take up to 14 days for withdrawal to present.

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The Center for Disease Control and Prevention defines substance use disorders (SUDs) as ‘treatable, chronic diseases characterized by a problematic pattern of use of a substance or substances leading to impairments in health, social function, and control over substance use’¹. Addiction at times can be incorrectly thought of as ‘a moral failing instead of what we know it to be: a chronic treatable brain disease’², which results in the body sending signals in the absence of the drug. These signals cause the user to ‘crave’ the substance, much like the body sends signals when we are hungry or tired. These physiological changes are related to our body’s natural messengers, neurotransmitters.

Neurotransmitters are the body’s natural chemical messengers that control bodily functions such as breathing, heartbeat and blood pressure, muscle movement, sleep, digestion, and thoughts and memories³. Some examples of neurotransmitters are dopamine, glutamate, serotonin, norepinephrine, GABA, epinephrine, and histamine. The volume and storage of neurotransmitters within the body is highly regulated. The body can sense when there is too little or too much of a neurotransmitter and responds by creating more or destroying the neurotransmitter.  Any change of this homeostasis can have severe consequences on the body’s ability to react to external stimuli and can be referred to as intoxication⁴.

The effects experienced by drugs is related to neurotransmitters. Neurotransmitters work on the body by binding to receptors. Neurotransmitters and their receptors work very similarly to a lock and key. The neurotransmitter perfectly fits into a specific receptor just like a key fits into a specific lock.

Some drugs, referred to as agonists, mimic neurotransmitters causing the body to think neurotransmitters are present, when in fact they are not. In our lock and key model, this would be like using an object to pick a lock in the absence of a key.

Some other drugs can increase or decrease the level of natural neurotransmitters in the body resulting in an increased or decreased level of signals. For example, the drugs can ‘copy’ the set of keys, allowing the lock to be opened more freely, or destroy the keys, preventing the lock from being opened.

Other drugs, called antagonists, block the body’s natural neurotransmitters causing no signal even when the stimuli are present. In our model, this would be equivalent to breaking a key off in the lock, preventing future keys from opening the lock (infographic ⁴). The effects of the drugs can be desirable such as euphoria or relaxation, while others are not desirable, like paranoia or increased blood pressure.

Over time with repeated drug usage, the body will compensate for the imbalance of neurotransmitters to restore the homeostasis. For instance, amphetamine increases the level of dopamine in the body. With chronic amphetamine use, the body recognizes the unnaturally high levels of dopamine.  As a response, the body starts producing less dopamine. If the user then suddenly stops using amphetamine, they can experience side effects of low dopamine in the body, such as lack of motivation, lethargy, moodiness, or difficulty sleeping⁵. This phenomenon is referred to as withdrawal, and at times, for some substances, can be life-threatening.

Tolerance is similar to withdrawal in that it is also related to the body compensating for the imbalance of neurotransmitters. In the prior example, chronic amphetamine use causes the body to produce less dopamine. However, the ‘high’ experienced by amphetamine use is caused by the unnaturally high level of dopamine. If the body is producing less dopamine naturally, the user will need to take more amphetamine to experience the same ‘high’. This phenomenon is referred to as tolerance. Both tolerance and withdrawal are related to imbalance of the body’s neurotransmitters.

SUDs are more than just the psychological need to use a substance. They are complex diseases which affect the natural chemistry of the user’s body. Due to this complexity, individuals suffering from SUDs are recommended to seek treatment from professionals.

References

1. https://www.cdc.gov/dotw/substance-use-disorders/index.html#:~:text=Substance%20Use%20Disorders%20(SUDs)%20are,and%20control%20over%20substance%20use.
2. https://nida.nih.gov/nidamed-medical-health-professionals/health-professions-education/words-matter-language-showing-compassion-care-women-infants-families-communities-impacted-substance-use-disorder
3. https://my.clevelandclinic.org/health/articles/22513-neurotransmitters#:~:text=Neurotransmitters%20are%20chemical%20messengers%20that,muscle%20cell%20or%20a%20gland.
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3628948/#:~:text=Neurotransmitter%20expression%20can%20be%20transient,compensation%20to%20the%20changing%20environment.
5. https://my.clevelandclinic.org/health/articles/22588-dopamine-deficiency 

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Benzodiazepines are a group of drugs which act as a central nervous system depressant and are used for the treatment of insomnia and anxiety. Although benzodiazepines are prescribed by doctors, they are also misused, most commonly in combination with opioids and alcohol. USDTL is excited to announce the addition of several benzodiazepines to the benzodiazepine panel in our umbilical cord assay beginning July 5th, 2023. Two of these added analytes are the designer benzodiazepines etizolam and flualprazolam, which can be purchased online. 

The structures of medically approved benzodiazepines can be modified to create new compounds, commonly referred to as designer benzodiazepines, which are not medically approved. Etizolam and flualprazolam are two such designer benzodiazepines. Many times, these designer benzodiazepines are more potent than the medical benzodiazepines. Additionally, changing the structure to create these designer benzodiazepines affects the ability of this drug to be detected. Therefore, laboratories must update their methods to effectively detect new designer benzodiazepines.   

Etizolam has recently emerged in the illegal drug market in Europe and the United States, but it is an approved medication in Japan, India and Italy¹. In 2018, the DEA reported 1,716 cases involving etizolam, but in 2021 that number rose to 4,252. Clinical studies have indicated that etizolam is about 10 times more potent than the medical benzodiazepine, diazepam. Common negative side effects of etizolam include drowsiness, sedation, muscle weakness and incoordination, fainting, headache, confusion, depression, slurred speech, visual disturbances, and changes in libido¹.  

Flualprazolam is another such designer benzodiazepine which is not approved for use in the United States. Less is known about the potency of flualprazolam, but it is thought to create severe sedation and coma². Flualprazolam is thought to be misused for its sedative and hypnotic effects, and users report the effects are similar to clonazepam and alprazolam². The DEA only reported one case involving flualprazolam in 2017, but there were 1,624 cases in 2019.    

The DEA released an intent to temporarily schedule these two designer benzos as Schedule 1 substances in December 2022³.  

 References:

1. ETIZOLAM (usdoj.gov) 
2. Flualprazolam (Street Name: Flualp) (usdoj.gov) 
3. Federal Register :: Schedules of Controlled Substances: Temporary Placement of Etizolam, Flualprazolam, Clonazolam, Flubromazolam, and Diclazepam in Schedule I 

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Diphenhydramine is an antihistamine often used to treat allergies, insomnia, and other conditions. However, there has been an alarming rise in diphenhydramine misuse in recent years, particularly among young people. The “Benadryl Challenge” on TikTok led the FDA to put out a statement in 2020 warning about the risk of using high doses.

What is Diphenhydramine?

Diphenhydramine (also known as DPH, Dimedrol, and Benadryl) is an antihistamine commonly used to treat allergy symptoms such as itching, sneezing, and runny nose. It is also used as a sleep aid and to treat other conditions such as motion sickness and Parkinson’s disease.

What are the Risks of Diphenhydramine Misuse?

Diphenhydramine is often misused in two ways, to induce sleep and to experience euphoria. Misusing diphenhydramine can have serious consequences. When taken in large doses, it can cause hallucinations, delirium, and seizures. It can also cause rapid heartbeat, high blood pressure, and difficulty breathing. In some cases, it can even be fatal.

In addition to the physical risks, diphenhydramine misuse can also have psychological effects. People who misuse the drug may experience anxiety, paranoia, and other mental health issues.

Are There Drug Tests for Diphenhydramine?

Yes. Though diphenhydramine is a legal substance, like alcohol, misuse can become a larger problem for some individuals, especially if they are in legal programs to get on the road to recovery. In these circumstances, drug testing for any mind-altering drug might be a consideration regardless of its status as legal or illicit. 

USDTL offers diphenhydramine testing in hair and nail specimens to organizations that administer drug testing. Diphenhydramine can build up and remain in hair and nail specimens for up to approximately three months. 

If your organization would benefit from offering this type of detection, please get in touch with us at 1-800-235-2367 or fill out our contact us form. Please note we are a business-to-business forensic laboratory only, and we do not offer toxicology testing to the general public. Due to confidentiality obligations, we cannot answer questions from parties not explicitly authorized by our business-to-business clients.

References:

1. U.S. Food and Drug Administration. (2019). Diphenhydramine (Benadryl): Drug Safety Communication – Serious Problems with High Doses from Over-the-Counter (OTC) Use. Retrieved from https://www.fda.gov/safety/medwatch-safety-alerts-human-medical-products/diphenhydramine-benadryl-drug-safety-communication-serious-problems-high-doses-over-counter-otc-use

2. National Institute on Drug Abuse. (2021). Misuse of Prescription Drugs. Retrieved from https://www.drugabuse.gov/publications/drugfacts/prescription-cns-depressants

3. Substance Abuse and Mental Health Services Administration. (2020). Key Substance Use and Mental Health Indicators in the United States: Results from the 2019 National Survey on Drug Use and Health. Retrieved from https://www.samhsa.gov/data/sites/default/files/reports/rpt29393/2019NSDUHFFRPDFWHTML/2019NSDUHFFR1PDFW090120.pdf

4. American Academy of Pediatrics. (2019). Diphenhydramine (Benadryl). In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2018 Report of the Committee on Infectious Diseases. 31st ed. Elk Grove Village, IL: American Academy of Pediatrics; 2019:364-365.

5. Drug Enforcement Administration. (2021). Drugs of Abuse: A DEA Resource Guide. Retrieved from https://www.dea.gov/sites/default/files/2021-01/Drugs%20of%20Abuse%202020%20Edition%20Digital%20Download.pdf

6. https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-problems-high-doses-allergy-medicine-diphenhydramine-benadryl

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What is Buprenorphine?

Buprenorphine is a derivative of thebaine, an extract of opium. Buprenorphine is an opioid partial agonist, meaning it can activate the opioid receptors in the brain, but to a lesser degree than opioids such as heroin.

Partial agonist drugs like buprenorphine, butorphanol, and tramadol can be helpful for treating pain and can assist in treating opioid use disorder, as they can help minimize withdrawal symptoms. Buprenorphine has a ceiling effect, causing a plateau in the sedative effects, which helps protect the individual from negative respiratory and/or cardiovascular effects when taken as prescribed.

Buprenorphine has been used internationally for several years to assist people suffering from opioid dependency. Subutex, which is pure buprenorphine, is designed to be used in the initial stages of addiction treatment.¹

Buprenorphine Misuse and Diversion

As the opioid crisis started growing, treatment drugs such as buprenorphine were being looked at for misuse and diversion. In 2014, the Food and Drug Administration required new safety labeling on prescribed opioids, indicating they are a Schedule III drug and warning of “risks of addiction, abuse, and misuse, which can lead to overdose and death.”³

According to the National Drug Intelligence Center, Suboxone (buprenorphine and naloxone)–because of its ceiling effect and ability to precipitate withdrawal systems if taken in high doses– is more susceptible to misuse by individuals who are addicted to low doses of opioids or individuals in the early stages of opioid addiction.¹

Misuse may include mixing buprenorphine with other drugs, such as heroin or methamphetamine, for a more intense high. Buprenorphine misuse is extremely dangerous even though it is used in clinical settings. In those settings, buprenorphine is administered in small, specifically curated doses based on the patient’s substance use history.

Diversion of buprenorphine, or nonmedical use by people it is not prescribed for, is another potential risk for consideration. According to the Center for Disease Control’s (CDC) 2022 Clinical Practice guidelines for prescribing opioids, toxicology tests can assist clinicians in identifying when patients are not taking opioids prescribed for them, which may indicate diversion or other clinically important issues such as difficulties with adverse effects.³ Advanced specimen drug testing may be the link to identifying the misuse or diversion of buprenorphine.

USDTL Advanced Specimen Testing

As an innovative leader offering alcohol and other drug testing, we understand the importance of being able to test for drugs of concern when it is most feasible for your organization. We offer buprenorphine testing, along with testing for many other drugs of concern, in urine, nail, and hair specimens. Contact us at adultandchild@usdtl.com with any questions.

References:

1. https://www.justice.gov/archive/ndic/pubs10/10123/index.htm
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154701/
3. https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm

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Xylazine is a sedative which causes analgesic and muscle-relaxing properties and is approved for veterinary medicine. Xylazine was first produced in 1962 by the Bayer company¹. It has been studied for human use, but clinical trials had to be terminated due to severe adverse side effects, including central nervous system (CNS) depression¹. Xylazine is not approved for human consumption, but it has been found as an adulterant being added to drugs, and it has been used in drug facilitated crimes to induce sleep. According to the DEA, there were 149 reported cases from federal and state laboratories involving xylazine in 2015, but that number jumped to 8,938 in 2021¹. 

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Some individuals exposed to xylazine may not be aware of its presence. Xylazine has been found as an adulterant in white powder drugs. Primarily xylazine has been detected in heroin and fentanyl supply, though it has also been discovered in some stimulant supply such as methamphetamine and cocaine². Other users actively seek out and use xylazine along with speedball, the street name for a mixture of heroin and cocaine, to mitigate some of xylazine’s negative effects. Xylazine containing products can be marketed on the street as tranq, sleep-cut, Philly-dope, or zombie drug.  

Negative side effects of xylazine include CNS and respiratory depression, hypotension, hypothermia, high blood glucose levels, miosis, hypotension, and necrotic skin ulcerations that can lead to amputation if not treated. Additionally, because xylazine is not an opioid, naloxone is ineffective in the event of an overdose. The FDA issued a safety alert warning in November 2022 about the severe risks associated with the drug³.  

Xylazine is not currently scheduled, though legislation was proposed in March 2023 to make xylazine a Schedule III Substance⁴. Congress has considered scheduling the substance prior to this legislation, but scheduling the drug would significantly impede the veterinary use of the medication⁵. Currently, the FDA is working to more strictly regulate the importation of xylazine and verify the legitimate veterinary supply⁶.  

1. https://www.deadiversion.usdoj.gov/drug_chem_info/Xylazine.pdf 
2. https://www.fda.gov/media/162981/download 
3. https://www.empr.com/home/news/safety-alerts-and-recalls/fda-restricts-unlawful-import-of-xylazine-containing-products/#:~:text=In%20November%202022%2C%20the%20FDA,and%20high%20blood%20glucose%20levels. 
4. https://abc7chicago.com/xylazine-effects-in-humans-congress-controlled-substance/13043734/ 
5. https://www.avma.org/blog/congressional-offices-consider-making-xylazine-controlled-substance 
6. https://www.fda.gov/news-events/press-announcements/fda-takes-action-restrict-unlawful-import-xylazine 

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What is Ketamine? 

Ketamine (ketamine hydrochloride) is a dissociative anesthetic with some hallucinogenic effects, meaning it distorts perceptions of sight and sound and makes the user feel disconnected from their environment and any pain.¹ It has one-tenth the potency of PCP, and its original use is as an injectable, short-acting anesthetic for use in humans and animals.⁵ Ketamine can induce a state of sedation (feeling calm and relaxed), immobility, relief from pain, and amnesia (no memory of events while under the influence of the drug).¹ It can be used for the induction (the transition from an awake to an anaesthe-tized state) of general anesthesia as a pre-anesthetic to other general anesthetic agents.² 

Potential Therapeutic Use 

Studies from Yale research labs showed that ketamine triggers “glutamate production,” which can prompt the brain to form new neural connections. This makes the brain more adaptable and able to create new pathways, giving patients the opportunity to “develop more positive thoughts and behaviors.” This was an effect that had not been seen before, even with traditional antidepressants.⁴ For the last two decades, researchers at Yale have led ketamine research by experimenting with using small doses of ketamine delivered intravenously in controlled clinical settings for patients with severe depression who have not improved with standard antidepressant treatments. In several studies, more than half of participants (who felt other antidepressant medications were ineffective) showed a significant decrease in depression symptoms after just 24 hours. The study states that ketamine “needs to be part of a more comprehensive treatment plan.”⁴ Studies are continuing to explore the possibilities of ketamine in therapeutic settings. It is not unlikely to assume that as ketamine gets clinically used, it will unfortunately also be under threat of being abused or misused. 

Ketamine Misuse 

Much like its intended use, ketamine can be misused recreationally for its ability to produce dissociative sensations and hallucinations. In 2022, the American Addiction Centers reported that nonmedical misuse is relatively low, with 0.7% of the U.S. population using it illegally.⁶

Since ketamine can be used in powdered form, it has been known to be snorted as a “party drug” at festivals or rave events.³ The street name for ketamine is “K” or “Special K.” 

Ketamine has also been used to facilitate sexual assault because of its hallucinogenic effects known to make the user feel disconnected from their surroundings. A number of individuals have abused this drug or have been instrumental in others using this drug as a “date-rape” drug.¹ 

Recreational use of ketamine can result in a number of internal complications including:

• gastrointestinal issues; 
• depression; 

• respiratory problems and; 
• amnesia 

Serious debilitating urinary tract symptoms are also seen frequently in those individuals who abuse ketamine.³ A study on ketamine in the National Institutes of Health predicts that ketamine toxicity and addiction “pose significant risks to a small segment of the population, and given increasing utilization, the prevalence of these phenomena is expected to increase.⁵” As ketamine use increases both recreationally and clinically, it will continue to be a substance worth testing for. 

USDTL Testing 

As an innovative leader offering alcohol and other drug testing, we understand the importance of being able to test when it is most feasible for your organization. We offer extended panel testing for ketamine in alternative specimens including hair, nail, and urine. 

References:  

• 1: https://www.dea.gov/factsheets/ketamine 
• 2: https://www.ncbi.nlm.nih.gov/books/NBK470357/  

• 3: https://clinmedjournals.org/articles/ijda/international-journal-of-depression-and-anxiety-ijda-1-006.php?jid=ijda  
• 4: https://www.yalemedicine.org/news/ketamine-depression  
• 5: https://www.ncbi.nlm.nih.gov/books/NBK541087/  
• 6: https://americanaddictioncenters.org/ketamine-abuse