More information is becoming available about one new “gas station” substance and a veterinary medication that are being abused. The first is Tianeptine, also known as ZaZa or Tianna Red, which is an antidepressant similar in structure to the tricylics that is approved in Europe, but not here in the US. It has a strong affinity for mu and delta opioid receptors, and it increases extracellular dopamine. Though similar in some ways to tricyclics, it is also quite different. It is more involved in modulating the glutamate system via indirect actions on NMDA and other receptors. Currently it is legal in Kentucky. Several other states have banned it. When it is abused, the withdrawal symptoms are similar to opioid withdrawal. Tianeptine was discussed at the spring 2022 ASAM meeting. It is very prevalent in states around us, particularly in larger suburban areas. Clinicians there were using short courses of suboxone to detox patients off tianeptine. Tianeptine is not new to the US. It has been available and shown abuse potential since 2000. But for whatever reason, there seems to be an increase in patients showing up in the ER exhibiting withdrawal symptoms from stopping it.
According to the article cited below from Practical Pain Management, there is not a POC or gas chromatography urine test available for Tianeptine. There is only a blood test. The article was written in 2020, so perhaps that has now changed.
A second substance being increasingly abused is Xylazine. A PowerPoint presentation, sent to KYSAM from ASAM and put together by Kelly Ramsey, MD,MPH,MA, FACP, DFASAM has been prepared. Since this newsletter format will not allow a file of that size to be downloaded, our administrative coordinator, Miranda Sloan, will send it separately, so watch for the email. It is a great overview of the history, pharmacology, and abuse potential of Xylazine. Xylazine is a non-opioid sedative, analgesic, muscle relaxant used by veterinarians for procedures. It is an alpha 2-adrenergic receptor agonist. It is not a controlled substance. It is not manufactured illicitly, but it is probably diverted from the veterinary supply chain. It has been used to extend the effects of fentanyl. It is also known as “tranq." It is increasingly involved in opioid overdoses. If you look at Dr. Ramsey's slide 31, you will see that the role of benzodiazepines in overdoses has declined somewhat while the role of Xylazine has increased. There is an increased incidence of skin ulcers when Xylazine is used as an adulterant with fentanyl or heroin.
Slide 55 lists signs of a Xylazine overdose. Those include BP and heart rate instability, heavy sedation, respiratory depression, and elevated glucose with rebound hypoglycemia. Avoid CNS depressants when treating Xylazine overdoses. Xylazine cannot currently be detected via point of contact, office based, testing, but it can be detected via gas chromatography (GC/MS or LC/MS or Thin Layer Chromatography). However, those results take several days to come back.
Obviously, a pure Xylazine overdose won’t respond to Narcan because Xylazine is not an opioid. However, most overdoses are from polysubstance use, so the standard of care when the substances are not known, is still to use Narcan.
Of course, Kratom, an herbal supplement, is still available in gas stations as well. Historically, the FDA has regulated it as an herbal. The FDA did consider banning it but held off because of public outcry from users who felt it was beneficial. It has opioid like effects, and users can become physiologically dependent on it if they use it regularly. Recently there has been an increase in adulterated Kratom with reports of seizures, tachycardia, and liver damage. Several states have banned it, but it is still legal in Kentucky.
Here are some links to articles about tianeptine.
From the University of Alabama. Toxicologist unravels the dangerous medical mystery of ZaZa, Alabama’s ‘gas station dope’. click here
Bettinger J, Cleary J. The Rise in Tianeptine Abuse: Our Next Kratom Problem?. Pract Pain Manag. 2020;20(2). click here.
Springer J, Cubała WJ. Tianeptine Abuse and Dependence in Psychiatric Patients: A Review of 18 Case Reports in the Literature. J Psychoactive Drugs. 2018 Jul-Aug;50(3):275-280. doi: 10.1080/02791072.2018.1438687. Epub 2018 Mar 1. PMID: 29494783.
Trowbridge P, Walley AY. Use of Buprenorphine-Naloxone in the Treatment of Tianeptine Use Disorder. J Addict Med. 2019 Jul/Aug;13(4):331-333. doi: 10.1097/ADM.0000000000000490. PMID: 30550394.