In March 2018, a report was released that involved two cases of adult men being found alone, having suffered a fatal overdose. Unfortunately, it’s a common story, but what makes this report unique is the drug that was found in their system. Tianeptine is a psychoactive substance that originated in France in the 1960s. The drug is primarily used to treat depression, but it may also be used to treat anxiety, asthma, and irritable bowel syndrome. But tianeptine isn’t approved by the U.S. Food and Drug Administration, and it’s not federally scheduled in the country. So how did it turn up in the systems of these two men?

The 2018 tianeptine deaths were the first time the drugs were recorded to cause a fatal overdose in the U.S. No other drugs were found in toxicology screens, but one man was known to use drugs recreationally, and the other was found with other drug paraphernalia. The drug is rarely used recreationally. When it comes to achieving a euphoric high, there are more viable options. However, the drugs are used for another purpose that goes beyond the treatment of depression.

Tianeptine is sometimes used for supposed nootropic properties, which means users believe the drug has cognitive-enhancing properties. The nootropic culture typically centers around medications and supplements that are unregulated, legal, or in legal gray areas. Nootropic users often experiment with different substances and combinations to find the best brain-boosting results.

Other people may use tianeptine to self-medicate for issues like anxiety or depression. However, self-medication, mixing medications, and experimenting with psychoactive substance can be dangerous. Though the drug has shown to be safe and useful in some studies, when it’s taken as prescribed, users report becoming chemically dependent and even addicted to the substance.

In high doses, and when the tianeptine is combined with other drugs, it can lead to a deadly overdose. Learn more about how tianeptine works and what happens when it’s mixed with other drugs.

What is Tianeptine?

Tianeptine is a drug that’s used to treat depression around the world, and it’s sold under the names Stablon and Coaxil abroad. In the United States, the drug isn’t approved by the FDA to be used as a prescription drug. However, the fact that the drug is unregulated opened it up to be sold as a supplement. In the U.S., the drug was sold as a nootropic supplement, which means that it’s said to have cognitive-enhancing effects. However, unregulated nootropics may not be as effective in improving cognitive functions as they claim to.

In other countries, tianeptine is used to treat major depressive disorder, but it may also be used to treat anxiety, asthma, and irritable bowel syndrome. It’s also said to achieve anti-anxiety effects without significant sedative or cardiovascular effects. Because it offers some of the same benefits as accepted depressant drugs with fewer side effects, it’s considered a promising medication for treating common mental health issues. 

The drug has been found to bind to mor-opioid receptors, which is similar to the way prescription opioids act in the body. Because of this, people may use tianeptine recreationally. According to the Drug Enforcement Administration, tianeptine has been found in bulk powders. Tianeptine pills are used to create counterfeit hydrocodone and oxycodone. Some may have been found mimicking illicit heroin. 

In the United States, there are no accepted medical uses for tianeptine, and the DEA considers it to have no commercial uses. However, as a supplement that’s purchased online, the drug is sold on what is called “the grey market.” The grey market involves the trade of a commodity through means that circumnavigate the law. Drugs that aren’t considered controlled substances are sometimes bought and sold as other items and marked “not for human consumption.” For instance, they may be sold as plant food, but buyers intend to use them as a nootropic or recreational drug. In 2018, the FDA issued a warning to marketers of products that contain tianeptine not to make unproven claims about the drug. Some marketers claimed that tianeptine could help treat serious conditions, including opioid use disorders.

How Tianeptine Works in the Brain

Tianeptine is referred to as an atypical antidepressant because it works in the brain in a way that’s different from most other depression medications. Most antidepressants are either selective serotonin reuptake inhibitors (SSRI) or monoamine oxidase inhibitors (MAOI).

SSRIs affect serotonin, which is a chemical that’s tied to reward and motivation, and it’s one of the main “feel-good” chemicals that your brain produces. Reuptake is a process in which your brain removes excess serotonin from your system. SSRIs stop or slow that process so that a build-up of the drug creates a more pronounced, mood-lifting effect. However, Tianeptine seems to enhance the reuptake of serotonin.

Tianeptine also seems to affect specific opioid receptors. It acts as a full agonist to two of the three types of opioid receptors, which causes opioid-like effects like pain relief. It also activated the reward system in the brain like opioids do, which is one of the reasons opioids are so addictive. However, some studies show that tianeptine has a lower likelihood of causing tolerance or withdrawal symptoms than opioids. For that reason, some users turn to the drug as a way to treat opioid addiction.

What Causes a Tianeptine High?

Because tianeptine works in such a unique way, some researchers believe that it’s a promising medication for people who are resistant to other forms of antidepressant treatment. However, there is some controversy as to the potential effects of abuse and misuse. A normal dose of tianeptine won’t cause a euphoric high. People who are treated with prescription pain relievers can sometimes experience pleasant euphoric symptoms. While the number of people who become addicted through normal therapeutic use of opioids, the euphoric potential of the drug is enticing to many.

Though tianeptine is less likely to result in euphoria, it can cause a high when used in larger doses. Likewise, heavier doses can also lead to dependence, withdrawal, and overdose. Like in the case of the two men from the 2018 report, overdose can be deadly.

How Dangerous is Tianeptine on its Own?

Tianeptine can cause some uncomfortable and potentially dangerous side effects. People that take it may experience confusion, tachycardia, nausea, and vomiting. In a high tianeptine dosage, it could cause some potentially life-threatening effects that are similar to opioid overdose. In high doses, opioid agonists can slow down vital functions of the nervous system, including respiratory depression. Slowed breathing is one of the most common causes of coma and death in opioid overdoses, and it may be possible when taking high doses of tianeptine. 

Mixing Tianeptine With Other Antidepressants

Tianeptine doesn’t currently have a long list of contraindications; however, mixing any medications of psychoactive substances can be dangerous and should be avoided or done with extreme care. One potentially dangerous combination that involves tianeptine is MAOIs. Both drugs have some cardiovascular effects that can be dangerous when combined. An unsafe combination of the drug can cause hypertension, convulsions, hyperthermia, and death. However, one study looked at the potential therapeutic effects of a combination of MAOIs and tianeptine and found that, at the proper levels, the mixture could be safe and effective.

Mixing Tianeptine With Opioids

Opioids are a common medication used in pain relief, and the abuse of opioids poses a major public health risk in the United States. Since tianeptine is an unregulated drug that can cause opioid-like effects, it may be attractive to illicit drugs users as an alternative opioid or as a way to treat addiction.

However, mixing high doses of tianeptine with opioids can be deadly. A combination could result in something called potentiation, which is when one substance interacts with another to magnify their effects. Mixing opioids and tianeptine can cause extreme confusion, difficulty maintaining consciousness, slowed breathing, and oxygen deprivation.

During an overdose, breathing may slow to the point where your brain and body aren’t getting the oxygen they need, causing brain damage, poor circulation, coma, and death. Opioid overdoses can be reversed with a drug called naloxone that is carried by many first responders and sold over the counter in some states. If you see the signs of opioid overdose, seek medical attention immediately.

Mixing Tianeptine With Alcohol

Because tianeptine is similar to opioids in the way it affects the brain, it could potentially potentiate the effects of alcohol. If the two drugs are taken together, they could suppress your nervous system to a dangerous degree. Alcohol doesn’t act on opioid receptors, but it does work on a chemical in the brain that’s designed to control excitability in the nervous system called gamma-Aminobutyric acid (GABA).

Alcohol increases the efficacy of GABA, which causes your nervous system to slow down. Opioids achieve similar effects by a different chemical process. But taking both together could slow down your heart rate and breathing. Most people who overdose on alcohol or opioids stop breathing and experience deadly oxygen deprivation, coma, and death. Always check with your doctor or pharmacist before mixing alcohol with medication.

Mixing Tianeptine with Benzodiazepines

Benzodiazepines are a class of medications that are used to treat anxiety and sleep disorders. However, some benzodiazepines like Xanax and Valium are used as recreational drugs. Benzodiazepines are central nervous system depressants that work similarly to alcohol. Xanax is often sold by illicit sources. Counterfeit pills are often sold that are made to look identical to Xanax. Fake pills may contain any number of other adulterants, including tianeptine. Benzodiazepines are dangerous to take with tianeptine for the same reason alcohol is. The drugs may potentiate each other, leading to more profound depressant effects than when the drugs are taken separately. Mixing them could lead to coma and respiratory depression.

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