Poster Presentation: Not Your Typical TCA: A Review of Cases Involving Tianeptine
By Stuart Kurtz, D-ABFT-FT
At this year’s annual meeting of NAME, we presented a handful of case reports on tianeptine. We had previously provided some information on tianeptine in a blog post from September 18, 2023. The aim of this poster was to present cases where we detected tianeptine as the primary drug of interest. There were only 2 cases out of 6 presented where this was the case. One of these cases from District 14 Florida had contributing factors of acute pneumonia, chronic pancreatitis, and hepatic steatosis. The other case from Missouri had alcohol as a contributing factor.
Initially, there was a third case that looked to be a tianeptine only fatality. Additional testing by the Lorain County OH crime lab revealed that 2 opened bottles of Neptune’s Fix Tianeptine Elixir found at the scene contained ADB-4en-PINACA and MDMB-4en-PINACA which are synthetic cannabinoids. Using this information, we were able to test the submitted specimens for these drugs via our 42130: Synthetic Cannabinoids panel and confirm the presence of both in the blood.
Due to the current gray area surrounding the sale of products containing tianeptine, scene evidence can be extremely useful. Tianeptine is screened in Axis’ 70510: Comprehensive Panel with Analyte Assurance™ in Blood and confirmed through the 13710: Novel Emerging Compounds Panel but may not be a part of routine screening in all labs. Awareness of what the lab is testing for is important when scene evidence indicates a particular drug. Labeled products can also be tested due to the inconsistent nature of the manufacturing of these products. In the above case from Lorain County OH, additional testing revealed that there were other drugs involved. Product labels are a good starting point but further testing is important to ensure that all factors can be accounted for. The FDA has urged manufacturers of Neptune’s Fix Tianeptine Elixir to recall all products and as of February 2024, all of them have done so.
We would like to thank the following offices for their contribution to this project.
- Office of the District Medical Examiner, District 15 FL, Dr. Terrell Tops & Dr. Natalia Belova
- Office of the District Medical Examiner, District 14 FL, Whit Majors & Dr. Jay Radtke
- Office of the Coroner, Lorain County, OH, Dr. Frank P. Miller
- Southwest Missouri Forensics, Nixa, MO, Carla Yoder & Dr. Ransom Ellis
If you have any questions about this post or want to request a copy of the poster, please reach out to us at 317-759-4869 option 3 or [email protected].
- Published in Drug Classes, General
Axis Experts Present, Fall 2024
By Denise Purdie Andrews
This Fall, Axis’ expert toxicologists can be found speaking in multiple venues, helping to educate our clients and share expertise with other forensic scientists.
The National Association of Medical Examiner (NAME) 2024 Annual Meeting, which will be held in Denver, Colorado, from September 19-23.
- Toxicologist Stuart Kurtz will be presenting a poster on Saturday, September 21st: Not Your Typical TCA: A Review of Cases Involving Tianeptine.
- Laboratory Director Laureen Marinetti will make a platform presentation on Monday, September 23rd at 14:15 local time: Differentiating Emergent Ketamine from Illicit Abuse in Postmortem Cases.
- Axis’ CEO, Phil Roberts, will also be in attendance to answer your product and service questions.
The Society of Forensic Toxicology (SOFT) 2024 Conference will be held October 27 – November 1 in St. Louis, MO.
- Toxicologist Stuart Kurtz will present a poster, An Analysis of Drug Detections in Carfentanil Cases from 2020-2024.
- Laboratory Director Laureen Marinetti will present a poster, The Comparison of Whole Blood and Vitreous Fluid Drug Findings in Fifty Postmortem Cases.
Toxicologist Kevin Shanks has a forthcoming paper in the Journal of Analytical Toxicology:
We will be sharing more information about the content of these presentations in the coming months. If you would like copies of any of the presentations, please email [email protected] and a copy will be provided after they have been presented. If you have the good fortune to attend one of these sessions, please connect with your Axis experts. We’d like to thank you for your business and ensure that we are continuing to serve you well!
- Published in Announcements
Drug Primer: Designer Benzodiazepines
By Kevin Shanks, D-ABFT-FT
What are Designer Benzodiazepines?
Designer benzodiazepines are substances synthesized to mimic the effects of traditional benzodiazepines, which are commonly prescribed for anxiety, insomnia, and other conditions. Unlike their pharmaceutical counterparts, designer benzodiazepines are often created in clandestine laboratories with the intention of circumventing the controlled substances act and other legal restrictions. These benzodiazepine compounds have similar sedative and anxiolytic effects but may also come with unpredictable purity, potency, and adverse effects mainly due to their unregulated production. Their emergence and proliferation on the illicit market present significant challenges for public health officials, coroners and medical examiners, and law enforcement, as they can lead to substance abuse, pose serious health risks to users, and potentially cause death in overdose.
Benzodiazepines work by affecting the central nervous system, primarily through action via gamma-aminobutyric acid (GABA). GABA is an inhibitory neurotransmitter that helps reduce excitability of neurons and essentially calms the brain’s activity. When the substance binds to the GABA receptor, chloride channels in the receptor open – this allows chloride ions to enter the nerve cell. This influx of chloride ions makes the neuron more negatively charged, which makes it less likely to relay a signal and slows down brain activity, which results in sedative, muscle relaxant, and anxiety reducing effects. While effective for their intended pharmaceutical uses as medications, benzodiazepines can also lead to tolerance, dependence, and withdrawal symptoms if used for prolonged periods or at high doses. Common adverse effects of the use of these compounds include drowsiness, tiredness, sedation, loss of motor coordination, slurred speech, amnesia, and respiratory depression.
Some examples of designer benzodiazepines are:
- Bromazolam – Bromazolam is a drug that has a history in pharmaceutical drug development as it was first synthesized in the 1970s as XLI-268, but it was never approved for medicinal use. The first emergence of bromazolam on the illicit drug market in the United States was in 2019, but it did not become prevalent until more recently. The substance is the brominated analog of alprazolam, meaning it has a bromine atom in the place of the typical chlorine atom. It is not currently considered a controlled substance by the United States Federal government.
- Clonazolam – Clonazolam is a drug that was first reported in 1971 in scientific research, but it did not become a pharmaceutical medication. Reports include strong sedative effects. It has recently been sold online as a novel psychoactive substance and in 2023, it was made a Schedule I controlled substance in the United States by the Federal government.
- Etizolam – Etizolam is a substance that was first patented in 1972, but is currently used as a pharmaceutical medication for the treatment of anxiety and insomnia in Italy and India. It is not authorized for use as a medicine in the United States and was first detected in the States in 2015-2016. It became a Schedule I controlled substance at the Federal level in 2023.
- Flubromazepam – Flubromazepam is a drug that also has a history in pharmaceutical drug development. It was first synthesized in 1960, but it did not receive any further study as a medicine. It appeared on the illicit drug market in 2012, but didn’t gain any traction for several years. Flubromazepam is a fluorinated analog of phenazepam, a benzodiazepine used as a medicine in Russia, meaning it has a fluorine atom in the place of the typical chlorine atom. It is not currently considered a controlled substance by the United States Federal government.
- Gidazepam (Desalkylgidazepam) – Gidazepam is a benzodiazepine used in Russia as a pharmaceutical medication for anxiety and certain cardiovascular disorders such as cardiac arrhythmias. Gidazepam acts as a prodrug and is rapidly metabolized to an active metabolite, desalkylgidazepam, which has a very long half-life (87 hours). Gidazepam is not currently considered a controlled substance by the United States Federal government.
The most recent data from the Drug Enforcement Administration’s (DEA) National Forensic Laboratory Information System in 2022 showed that the designer benzodiazepines clonazolam (5th), bromazolam (6th), etizolam (8th), flualprazolam (10th), and flubromazepam (14th) were now in the top 15 reported tranquilizers and depressants in the United States. Each of these compounds have been previously implicated in human intoxication cases involving driving motor vehicles as well as being involved in or associated with toxicity leading to fatality.
Because of these trends, Axis recently introduced an all-encompassing Designer Benzodiazepines panel of testing. This panel scope includes adinazolam, bromazolam, clonazolam and metabolite 8-aminoclonazolam, etizolam, flualprazolam, flubromazepam, flubromazolam, gidazepam (as desalkylgidazepam). This streamlined panel allows for easier potential identification of designer benzodiazepines in your medical-legal investigation.
As always, if you have questions about these substances and how they may apply to your toxicology casework or investigation, please reach out to our forensic toxicology experts by email ([email protected]) or phone (317-759-4869, Option 3).
- Published in Drug Classes
New Designer Benzodiazepine Panel
- Published in Operations
Drug Primer: Psilocybin
By Kevin Shanks, D-ABFT-FT
Psilocybin is a compound most commonly found naturally in the Psilocybe genus of mushrooms, but also can be found in some species of Panelous and Concybe genera of mushrooms. In all, there are greater than 200 species of mushroom that contain the substance. These mushrooms have been used by Native Americans throughout Central and South America for thousands of years in cultural practices.
Psilocybin is rapidly dephosphorylated in the liver to the pharmacologically active compound psilocin, a 4-hydroxy derivative of N,N-dimethyltryptamine (DMT). Pharmacologically, psilocin is a 5-hydroxytryptamine (5-HT) receptor agonist. It binds to those receptors and aids in the release of serotonin in the body. Effects of psilocin include tachycardia, hyperthermia, hypertension, cardiomyopathy, vomiting, paresthesia, anxiety, dilated pupils, euphoria, disorientation, depersonalization, delusions, and hallucinations involving visual and perceptual alterations including distortion of shapes and colors. When consumed orally, onset of effects is normally 30-90 minutes with primary effects lasting 4-6 hours and potential residual effects lasting 2-6 hours longer.
Neuropsychopharmacologist Alexander Shulgin wrote about psilocybin mushrooms and its effects in his book TiHKAL [Tryptamines I Have Known And Loved]: The Continuation.
From chapter 5 of TiKHAL titled ‘Shrooms:
“First effects felt at 10 minutes after eating the little devils. Shortly after that, the world erupted into patterns. Patterns over everything. They seemed to fill all the space between me and my surroundings. The most prevalent design was that of a sort of squarish amoeba with a central black dot, like a nucleus, repeated endlessly and in three dimensions. Actually, it began to look most of all like chickenwire, with a small black dot in the middle of each square. In three dimensions.”
While psychedelic mushrooms have not been commonly implicated in fatality due to overdose and toxicity, they have been associated with behavioral effects and changes that have contributed to fatality such as driving under the influence traffic collisions, pedestrian-vehicle encounters, jumping from heights such as tall buildings and bridges, and other situations involving psychotic episodes and changes in the overall state of consciousness.
Both psilocybin and psilocin are considered to be Schedule I controlled substances in the USA – this includes the chemicals and the actual mushrooms themselves. The amount of mushrooms seized and identified by the United States Drug Enforcement Administration (DEA) has been relatively steady over the last 20 years, but an upward trend has been observed in identifications by the DEA during the past 4-5 years.
Psilocybin has been the subject of research in academia and industry for the last several decades for its potential use in treatment of personality and mood disorders, obsessive-compulsive disorder, anxiety, nicotine and alcohol dependence, and cluster headaches. In 2018, the substance was named a breakthrough therapy for use in treatment-resistant depression.
As previously reported, Axis Forensic Toxicology added testing for psilocybin (as psilocin) to the 70510: Comprehensive Panel, Blood with Analyte AssuranceTM on July 1, 2024. Reporting limit for the compound is 5 ng/mL and it is reported as qualitative only (i.e. not quantified). It is important to note that psilocin’s stability in blood is pH and light dependent. Please collect in a vial containing a preservative such as sodium fluoride, protect from exposure to light, and store in refrigerated conditions (2-8°C).
As always, if you have questions about psilocin and how it may play a role in your medical-legal investigation, please reach out to our subject matter experts by email ([email protected]) or phone (317-759-4869, Option 3).
References
Baselt, R. Psilocybin. Disposition of Toxic Drugs and Chemicals in Man. Twelfth Edition. Biomedical Publications: Seal Beach, CA. Pages 1795-1796. (2020)
Baselt, R. Dimethyltryptamine. Disposition of Toxic Drugs and Chemicals in Man. Twelfth Edition. Biomedical Publications: Seal Beach, CA. 675-676. (2020)
Levine, B. Hallucinogens and Psychedelics. Principles of Forensic Toxicology. Fifth Edition. Pages 467-489. AACC, Inc. (2020)
Shulgin, A. and Shulgin, A. TiHKAL, The Continuation. Transform Press, Page 112. (1997)
National Forensic Laboratory Information System. Annual Drug Report. (2022).
- Published in Drug Classes
Addition of Psilocin to Comprehensive Panel with Analyte Assurance™, Blood
We are thrilled to share some exciting news with you. Thanks to your valuable feedback and our unwavering dedication to research and development, we are pleased to announce that Psilocin will be included in our Comprehensive Panel with Analyte Assurance™, Blood, effective July 1st, 2024.
At Axis Forensic Toxicology, your needs are our priority, and we continuously strive to enhance our services to better serve you. This addition is a direct result of your feedback and our commitment to providing you with the most comprehensive testing solutions available.
Should you have any questions or require further information regarding this exciting development, please don’t hesitate to reach out to us at [email protected]. Our dedicated team is here to assist you.
Thank you for your continued trust and partnership. We look forward to serving you with excellence and providing you with the best possible testing solutions.
Sincerely,
Matt Zollman
Director of Operations & Product Management
- Published in Operations
The Newest Drug in the Illicit Drug Supply – Medetomidine
By Kevin Shanks, D-ABFT-FT
Medetomidine, an alpha-2-adrenergic receptor agonist, similar to the prescription medications clonidine and tizanadine and the veterinary medicine xylazine, is approved for use in human and veterinary medicine and has found its way into the illicit drug supply. The adverse effects of medetomidine use are consistent with central nervous system depression and include analgesia, sedation, muscle relaxation, hypotension, bradycardia, and hyperglycemia. It is thought that adding this substance as an adulterant to the current illicit opioid drug supply (e.g. fentanyl) increases potential bradycardia, sedation, and respiratory depression. Medetomidine is not currently a controlled substance in the United States.
The substance was first detected in the United States in Maryland in mid-to-late 2022 and was also sporadically detected in various states, such as California, Colorado, Missouri, and Pennsylvania, into 2023. Reports of the substance spread to Canada in early 2024 when alerts regarding its detection in the drug supply were published out of Toronto, Ontario and Vancouver, British Columbia. In 2024, medetomidine has also been observed in additional states including Florida, Illinois, North Carolina, and Ohio.
Axis Forensic Toxicology has monitored for this substance in Analyte Assurance™ as part of the Comprehensive Panel testing (order code 70510) since January 2024. Over the last 6 months, the laboratory has not detected medetomidine in casework, but we remain vigilant in surveillance for this drug and other newly emerging substances.
If you have any questions or concerns regarding the role of medetomidine or any other newly emerged substance in your toxicology case, please reach out to our Axis Forensic Toxicology subject matter experts at [email protected]. To stay current with the scope of testing for all services offered by Axis, please consult the online catalog.
References
Randall C. Baselt (2020). Dexmedetomidine. Disposition of Toxic Drugs and Chemicals in Man, 12th Edition. Biomedical Publications. Pages 600-601.
The Center for Forensic Science Research and Education, NPS Discovery (2024) Medetomidine Rapidly Proliferating Across USA – Implicated in Recreational Opioid Drug Supply And Causing Overdose Outbreaks. https://www.cfsre.org/nps-discovery/public-alerts/medetomidine-rapidly-proliferating-across-usa-implicated-in-recreational-opioid-drug-supply-causing-overdose-outbreaks?emci=c7a462cb-8617-ef11-86d0-6045bdd9e096&emdi=086973c5-5c18-ef11-86d0-6045bdd9e096&ceid=10243135
National Public Radio (2024) Gangs Mix Another Potent Sedative Into US Street Drugs Causing “Mass Overdoses”. https://www.npr.org/2024/05/31/nx-s1-4974959/medetomidine-overdose-fentanyl-sedative
- Published in Drug Classes
Axis Forensic Toxicology Confirms Transition of Chief Toxicologists and Appointment of New Laboratory Director Effective June 1, 2024
- Published in Uncategorized
Axis Recognizes Postdoctoral Fellows
Axis is pleased to recognize the four Forensic Medicine Fellows that recently completed Axis’ toxicology rotation. The rotation is a week-long virtual program where participants reviewed many aspects of a modern forensic toxicology operation, including the instrumentation and methods, critical processes, and a survey of major illicit and pharmaceutical drugs and emerging compounds, their action upon the body and relevance to cause of death.
The 2024 follows were:
- Joshua Smith, DO, from the Jackson County, MO, Medical Examiner’s Office is a graduate of the Texas College of Osteopathic Medicine in Fort Worth, TX. He is board certified in anatomic and clinical pathology. At the conclusion of his fellowship, he will be serving as a deputy medical examiner with the Jackson County MEO.
- Shamaya Creagh Winters, MD, from the Fulton County, GA, Medical Examiner’s Office is a graduate of Wayne State University School of Medicine in Detroit, MI. She took her anatomic pathology exam this month. At the conclusion of her fellowship training, she will join the Fulton County MEO as an Associate Medical Examiner.
- Geunyoung Jung, MD, from the Marion County, IN, Coroner’s Office is a graduate of Pusan National University College of Medicine in Busan, South Korea. He is board certified in anatomic pathology. At the conclusion of his fellowship, he will join the Bexar County Medical Examiner’s Office (San Antonio, TX) as a deputy medical examiner.
- Ryan Bruhns, MD, from the Forensic Science Center (Pima County) in Tucson, AZ, is a graduate of the University of Arizona College of Medicine in Tucson, AZ. He is board certified in anatomic and clinical pathology. At the conclusion of his fellowship, he will remain with the Forensic Science Center.
Our fellows were very engaged in the presentations and topics. We are confident that they will serve our industry well and we wish them the best in their careers!
Axis is pleased to be able to offer this program to its clients in support of a well-functioning death investigation system. The rotation is typically offered each Spring. If you have or anticipate having a Fellow in your office and would like to participate, please contact our toxicologists at [email protected].
- Published in Announcements
Change to Third Party Storage Requests
Axis Forensic Toxicology has historically offered a service to store casework for a third party (typically a family member or law office) once our clients authorize a release. This has effectively been a behind-the-scenes service that benefits third parties, but creates a great deal of complexity for case transfer and storage on our end.
We wanted to communicate that we will no longer be offering this service for third parties. If our submitting client requests additional storage beyond the 1-year of storage that is provided with all cases, we will continue to offer that service as we always have. This change is specific to storage for third parties only.
The options that will be provided to those third parties will be to perform testing (which would also provide 12 months of storage) or to ship the case to a location of the third party’s choosing (either a dedicated storage facility that they have coordinated with or any other location they choose).
If you have any questions, please contact us at [email protected].
We look forward to serving you.
Sincerely,
Matt Zollman
Director of Operations & Product Management
- Published in Operations