According to the Food and Drug Administration (FDA), companies are making dangerous claims that tianeptine can improve brain function and treat depression, anxiety, pain opioid disorder, and other conditions. In the illicit drug market, it has been found in counterfeit pills mimicking hydrocodone and oxycodone and in small packets commonly used to distribute heroin. It is not approved in the United States for any medical use, despite its approval to treat certain conditions in other countries.
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References to non-CDC sites on the Internet are provided as a service tianeptine products linked to serious harm, overdoses, death to MMWR readers and do not constitute or imply endorsement of these organizations or their programs by CDC or the U.S.
Engineering
Whether withdrawal of tianeptine is a unique syndrome, results from exacerbation of anxiety or depression, or is related to changes in neurotransmitter signaling from physiological dependence remains undefined. I am writing to draw your attention to a dangerous and growing health trend facing our nation and particularly young people– the increasing number of adverse events involving products containing tianeptine, which can lead to serious harm, including death. Tianeptine, which is often called “gas station heroin” because of its availability in gas station stores, is not approved by the FDA for any use. Despite its lack of FDA approval, tianeptine has made its way to the shelves of convenience stores and gas stations, branded as “Zaza” and “Tianna Red.” It can also be obtained online from independent vendors without a prescription. Of note, this article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.
What are the risks of using tianeptine?
Tianeptine is an antidepressant drug that is not approved by the Food and Drug Administration (FDA). Clinical effects of tianeptine abuse and withdrawal can mimic opioid toxicity and withdrawal. Uzbay and colleagues found that tianeptine reduced the intensity 27 and delayed the onset 192 of pentylenetetrazole-induced seizures in rodents.
- In support of this hypothesis, clinical studies on depressed patients have reported that morphological changes in the amygdala precede those that are observed in the hippocampus 117.
- Tianeptine is also called “gas station heroin.” Some products claim tianeptine can help treat depression, anxiety, and pain, and can improve brain function.
- Misuse of tianeptine can lead to euphoric, opioid-like highs with the potential for chronic users to develop dependence and tolerance.
- The funding organization was not involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
- The samples were sent to the Center for Forensic Science Research and Education (Horsham, PA) for comprehensive chemical analysis of drugs and toxicants.
Systematic Review of Clinical Case Reports Involving Tianeptine Products: “Gas Station Heroin” Hype or Fact?
Tianeptine’s ability to prevent the effects of chronic stress on neurogenesis may involve blocking the stress-induced reduction of neurotrophic factor levels in the hippocampus 3. Another study, although reporting no effect of stress or tianeptine on hippocampal BDNF, found that chronic tianeptine treatment significantly increased BDNF levels in the rat amygdala, independent of whether or not the rats were exposed to stress 157. According to Reagan and colleagues, the amygdala may be the site of initiation of chronic stress-induced morphological changes in other brain regions, such as the hippocampus and prefrontal cortex 157,159. In support of this hypothesis, clinical studies on depressed patients have reported that morphological changes in the amygdala precede those that are observed in the hippocampus 117. Therefore, tianeptine’s effectiveness as antidepressant treatment may result from its stabilization of neurotrophin levels in the amygdala. This case series describes an outbreak of 41 cases of tianeptine exposure reported to NJPIES from June 2023– February 2024, a marked increase compared with the poison center’s historical average.
Almost unintuitively, tianeptine was thought to stimulate rather than inhibit the reuptake of 5-hydroxytryptophan (5-HT) in the synaptic cleft; its therapeutic effects were partially due to neuronal remodeling and plasticity 5, 6. This theory has since been disproven and will be discussed later in this picture. Interestingly, tianeptine weakly interacts with the mu- and delta-opioid receptors, producing many similar clinical effects as other opioid agonists 4, 6. Further discussion of tianeptine’s mechanisms of action and off-target effects are highlighted below. Chronic stress has been shown to increase expression of the glutamate transporter, GLT-1, which is important for removing excess glutamate from synaptic regions 158.
Wisconsin DHS Health Alert #59: Adverse Health Effects Linked to Neptune’s Fix and Other Products with Tianeptine
In contrast to the hippocampus and prefrontal cortex, amygdala volumes of depressed patients are larger than those of healthy individuals following the first episode of depression 54. However, with recurrent episodes, amygdala volumes in depressed patients tend to be smaller than those of controls 175. Nevertheless, most work has reported that activity of the amygdala is increased in depressed individuals 43 and with successful treatment, significantly declines 178. Extensive research has shown that acute stress impairs hippocampus-dependent learning and memory in humans and rodents 37,39,41,83,85.
Several clinical models have shown that glutamate levels are decreased in various brain regions in people with MDD compared to those without the disease 12. Tianeptine is thought to stabilize glutaminergic signaling and exerts opposing effects on N-methyl-d-aspartate (NMDA) and aminomethylphosphonic acid (AMPA) receptors; these interactions potentiate anti-depressive effects 4, 8, 11. It is now known that tianeptine’s primary mechanism of action is glutamate modulation 4, 11. This mechanism of action is where the anti-depression action occurs rather than in the serotonin system. The FDA has issued warning letters to companies distributing and selling unlawful tianeptine products as dietary supplements and unapproved drugs.
- Some people have turned to tianeptine as an opioid alternative, or to self-treat anxiety or depression.
- Nevertheless, most work has reported that activity of the amygdala is increased in depressed individuals 43 and with successful treatment, significantly declines 178.
- Consumers are usually taking a gamble when they buy tianeptine products because they can’t know for sure how much of the drug they’re getting.
- All six bottles contained a dark liquid and were labeled with an ingredients list containing tianeptine, kava (Piper methysticum), magnesium, solvents (propylene glycol, vegetable glycerin, and/or water), and flavoring.
- Tianeptine has made its way to convenience stores and gas station shelves, branded as “Zaza” and “Tianna Red.” It can also be obtained online from independent vendors without a prescription.
- Researchers have postulated that the up-regulation of GLT-1 levels in this region is a compensatory response to chronic elevations of extracellular glutamate levels.
For more information about tianeptine, please read the factsheet from DEA included below, along with the recent trend alert, warning, and article from FDA. Tianeptine is licensed in some countries and marketed as an atypical antidepressant meant to treat depression through three daily 12.5 mg oral doses, according to Makary. In 2023, the FDA warned consumers not to use or purchase any products from Neptune’s Fix after receiving multiple reports of severe reactions, including seizures and hospitalizations. In 2024, Neptune’s Fix products sold nationwide were recalled because of their use of tianeptine. Last year, Calello and her colleagues published a study documenting a cluster of emergency calls in New Jersey tied to a flavored elixir called Neptune’s Fix. People experienced distress, rapid heartbeat, low blood pressure and seizures after drinking it.
Despite increasing reports of tianeptine, few studies guide treating patients who use this substance. Case reports have suggested success in treating tianeptine use similar to opioid use, with naloxone for acute overdose and buprenorphine to treat dependence. Furthermore, unregulated distribution has made monitoring usage rates, adverse effects, and gathering information about those who use tianeptine extremely challenging.
Because of its high potential for drug abuse, those who regularly misuse the pills may exhibit withdrawal symptoms such as stomachaches and anxiety if they try to quit. Consumers are usually taking a gamble when they buy tianeptine products because they can’t know for sure how much of the drug they’re getting. This increases the risk of an unintentional overdose, along with other adverse side effects like lethargy, elevated blood pressure and heart rate, agitation, abdominal pain, tremors, and hallucinations. Tianeptine, an atypical antidepressant not approved in the United States, is readily purchased from unregulated markets such as the internet and gas stations. We became aware of a cluster of 34 patients in New Jersey who became ill following ingestion of the tianeptine containing-product Neptune’s Fix, the rate of which (4.6 cases per month) far exceeded the background rate for this substance of 0.5 cases per year.
New “Gas Station Heroin” Tianeptine Product Trend
Support for this hypothesis was based on the incidental finding that efficacious antidepressants, such as monoamine oxidase inhibitors and tricyclics, increased monoamine neurotransmitter levels 127. Sometimes called “gas station heroin,” the products are usually marketed as energy shots or cognitive supplements but actually contain tianeptine, an unapproved drug that can be addictive and carries risks of serious side effects. The FDA issued a consumer warning about using tianeptine products in 2022 and has sent warning letters to two marketers, but hasn’t taken further action in the wake of more recent overdoses. In an email to PopSci, an agency representative wrote that “a drug sponsor would need to submit an application to the agency for review” for it to be approved for medical use, either as a controlled or uncontrolled substance. “The FDA generally cannot confirm or deny the existence of any possible product application,” he added. Johnson-Arbor further warns that people may experience more unwanted side effects, including breathing difficulties, hallucinations, and excessive sleepiness, when combining tianeptine with other medications.