NPR: 8 things to know about the drug known as 'gas station heroin'

Jul 18
Decades before it became known as "gas station heroin," tianeptine was prescribed to treat depression in dozens of countries. Now, U.S. poison control centers are reporting a dramatic spike in cases involving tianeptine — a drug that isn't FDA approved, and one that authorities warn poses overdose and dependency risks.

Tianeptine inhabits a murky space in U.S. drug regulation. It's illegal to market or sell the drug, but it's also not on the list of federally controlled substances. And while it's in products sold at gas stations and other stores, it's also available to buy online.

A growing number of states have now banned tianeptine, most recently, Florida. But millions of people in Europe, Asia and South America have used the drug — despite the fact that for years, no one was sure exactly how it worked.

"This is kind of a mistaken identity type of drug," Todd Hillhouse, an associate professor at the University of Wisconsin-Green Bay who studies antidepressants' mechanisms and history, told NPR. "And it's kind of wild."
The drug's true identity emerged after researchers figured out it's a type of opioid — one that does, in fact, work in a way that's similar to heroin. Another similarity? People who abuse tianeptine report that it has left them wrestling with addiction.


Here's more to know about tianeptine and its unusual history:
It's available in the U.S., despite lack of FDA approval
Launched in Europe in the 1980s, tianeptine has never been cleared by the U.S. Food and Drug Administration for medical use. It's sold in the U.S. as a nootropic, a substance promising to enhance users' mood and cognitive function.

Experts warn that it's dangerous to consume any unapproved drug, particularly one that poses the risk of dependency and withdrawal, and that in the case of tianeptine, can cause respiratory depression and severe sedation. Often packaged in colorful, shot-sized bottles, these rogue tianeptine products contain the drug in varying concentrations and have also been found to include dangerous synthetic cannabinoids.

"Imagine if you're [at a] truck stop, you take two bottles of that and you're driving down the road — now you're high on opioids," Hillhouse says. "It's not a safe situation to be in. And it could be accidental. So I think it's good to get this out there and keep people vigilant. Just because you see it in a gas station doesn't mean it's safe."

People who use more pure forms of tianeptine often face another danger: addiction. A Reddit forum for people trying to quit the drug many of them call "tia" has grown to some 5,500 members. They describe taking full grams of the drug each day — in some cases, more than 100 times the manufacturer's recommended daily dose.

It was developed in France
In the late 1980s, Tianeptine gained its first market approval as an antidepressant: in France, where it was sold under the trade name Stablon.

The drug eventually spread to at least 66 countries, sometimes under the trade names Coaxil and Tatinol. Its recommended dose was small — one 12.5 mg tablet — and because the body clears it quickly, doses were to be taken three times a day. It also was advertised as having minimal side effects.

Tianeptine came out as Prozac was becoming a sensation, bringing a new era of selective serotonin-reuptake inhibitor drugs, or SSRIs. Tianeptine was lumped in with older drugs called tricyclics.

"Its chemical structure has three rings, so people thought that it was a tricyclic antidepressant," Jonathan Javitch, a professor at Columbia University and a research psychiatrist at the New York State Psychiatric Institute who is an authority on tianeptine, told NPR.

The drug worked, but no one knew how
Researchers soon realized tianeptine didn't seem to work like any other antidepressant. Even in 2012 — 25 years after its initial authorization — France's Transparency Committee, an advisory panel that assesses medicines for the government, described tianeptine as "an antidepressant, the exact mechanism of action of which is not known."

Both tricyclics and SSRIs work by targeting receptors for neurotransmitters such as serotonin, aiming to block neurotransmitters from being reabsorbed so they can boost levels of our bodies' key behavioral and mood regulators. But in tests, tianeptine didn't attach to those receptors.

"It didn't work at a whole variety of receptors," Javitch said. "And it was basically a mystery of how this compound worked."

Hillhouse of the University of Wisconsin compares it to having a key that fits a lock — but not knowing which lock the key opens.

It showed promise of broad benefits to the brain
Tianeptine caught Javitch's eye about 10 years ago, after a colleague at Columbia, Dali Sames, suggested they take a look at the drug. Studies had suggested it can improve memory and ease anxiety and bring other benefits.

Javitch's interest grew when he saw research by the late scientist Ben McEwan, outlining the drug's seeming "neurorestorative" ability to correct damage in the brain. Tianeptine was described as modulating one of the major neurotransmitters in the brain and promoting neuroplasticity, the brain's vital ability to adapt.

"This antidepressant is rich in future possibilities," both for its own application and to improve our understanding of depression, McEwan and his fellow researchers wrote.

A 'shocking' breakthrough showed it worked like an opioid
In their work, Javitch, Dali and their colleagues found that tianeptine targets the mu opioid receptor, which is named for morphine and controls pleasure, pain relief and need. The finding was shocking, Javitch said, given the ongoing opioid crisis. Even more surprising: Tianeptine didn’t just bind to the opioid receptor.

"It actually activates the receptor like other opioids do, like morphine or like oxycodone or like fentanyl," Javitch said.

A middle-aged man smoking crack cocaine in Rhode Island. The state had the country’s fourth-highest rate of overdose deaths involving cocaine in 2022.

Stimulant users caught up in fatal 'fourth wave' of opioid epidemic
They were also shocked because it's not the way other antidepressants work — and at the time of their research in 2014, there were few signs of tianeptine abuse, Javitch said.

The researchers’ findings brought a swirl of competing emotions. They were excited to discover a unique antidepressant mechanism — but they were also well aware of surging opioid addiction in the U.S. Their hopes for the drug's future were immediately tempered.