Something Old: Tianeptine

I first blogged about this drug in 2016, when I first heard about it. Recently some addiction medicine physicians were talking about it again. These physicians, who treat opioid use disorder, occasionally encounter patients who buy tianeptine at gas stations, head shops, and online. These patients are seeking an alternative to traditional opioids, and the tianeptine is advertised as being useful for a variety of effects.

Internet ads say it treats anxiety and depression, ADHD, and seizures, among other things. The ads boast that this drug can “reduce stress-induced atrophy of neuronal dendrites.” Other ads offer to sell it but say it is “not for human consumption,” with a wink and a nod, to protect sellers.

It’s an interesting medication, but not available in the U.S., Canada, or the United Kingdom. It is sold in Europe under the brand names Coaxil and Stablon. It’s used to treat depression, though some sources say it is more toxic to the liver than other antidepressants. Though structurally similar to tricyclic antidepressants, it exerts its action in a different way, via glutamate receptors. Other antidepressants are thought to work because they increase serotonin and norepinephrine levels, so tianeptine is novel in this sense.

Scientists know depression causes structural and functional changes in the brain, and some articles about tianeptine say this medication can reverse some of the stress-induced changes seen in depressed brains. We don’t fully understand all aspects of neurotransmitters and mood, and this medication shows us that serotonin and norepinephrine are not the only determiners of mood. [1, 2]

But what about this medication’s addictive potential? Why would people take it compulsively?

According to internet forums, people described a euphoria similar to opioids, though the described dose was usually far in excess of the recommended 12.5mg three times daily. One person took 500mg and described euphoria. Other people mixed it with other drugs, so it’s hard to know what effect the tianeptine had. Other people described a difficult withdrawal from tianeptine.

Kesa et. al., 2007, says tianeptine has some stimulating activity at the mu opioid receptors, thought it has a low affinity for those receptors. Apparently it takes high doses to produce euphoria, moderated through those opioid receptors.

In the Annals of Internal Medicine, 2003, Leterme et al describe five cases of tianeptine abuse. Withdrawal was said to be difficult, due mostly to anxiety.

From the collective experiences I read, it seems tianeptine is a weak opioid agonist, but at high doses gives an opioid effect. It sounds like people describe a typical opioid addiction after using these high doses daily for more than a few weeks. They described classic signs and symptoms of opioid withdrawal. At least one case report described neonatal abstinence syndrome in a baby born to a woman who regularly used tianeptine.

Most people taking tianeptine use other drugs, including opioids. It’s rare that people use only tianeptine.

Tianeptine is being sold as a dietary supplement in places like gas stations, so it’s easily available. is sometimes called, “Za-Za” or “Tianna Red,” and packaging says it promotes attention and energy.  These dietary supplements don’t require any FDA approval or any inspections by state or federal agencies, so there’s no quality control. Potency and purity could vary considerably between lots from the same manufacturer. Or the product may not contain any tianeptine.

Earlier this year, Alabama was the second state to make the substance illegal to sell at convenience stores, by making it a Schedule II controlled substance.

Should this drug be illegal in all states?

I think so, given the potential for physical dependency, which has been described in case reports. There have also been reports of tianeptine overdoses, though it’s often mixed with other drugs, making it hard to tell how much tianeptine contributed to the overdose. Tianeptine can be reversed with naloxone,

  1. Kasper et. al., “Neurobiological and clinical effects of the antidepressant tianeptine,” CNS Drugs, 2008;22(1);15-26.
  2. McEwen et. al., “The neurobiological properties of Tianeptine (Stablon): From hypothesis to glutamatergic modulation,” Molecular Psychiatry 2010 March;15(3): 237-249.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

%d bloggers like this: