# Tianeptine

Rating: Early — Mostly animal or cell studies; few or uncontrolled human data
Type: Compound
Updated: 2026-10-27
Canonical: https://heretic.bio/articles/tianeptine.html

> Tianeptine is a prescription antidepressant in parts of Europe, Asia and Latin America. In 2014 Columbia researchers showed it is a full mu-opioid receptor agonist, and in mice its antidepressant effect depends on that receptor. At prescription doses it treats depression about as well as standard antidepressants. As a cognitive enhancer it has only small single-dose studies in healthy volunteers, with mixed results. The FDA has never approved it, warns against all use, and has linked US products to seizures, overdoses, deaths and opioid-like withdrawal, often at many times the prescription dose.

> Tianeptine is a prescription antidepressant in parts of Europe, Asia and Latin America. In 2014 researchers showed it is a full agonist at the mu-opioid receptor, the same target as morphine. In the United States it was never approved, yet it is sold as a "nootropic" or supplement at gas stations and online, where people take it at up to 250 times the labelled dose. At prescription doses it works for depression about as well as an SSRI. As a cognitive enhancer for healthy people it has only small single-dose studies with mixed results, and the US harm data are some of the worst of any substance sold under the nootropic label.

## What it is

Tianeptine is an atypical tricyclic drug, marketed as Stablon or Coaxil, used for depression outside the US. The FDA has never approved it for any use, and it is not a controlled substance under US federal law (CDC, 2018, [PMID 30070980](https://pubmed.ncbi.nlm.nih.gov/30070980/)). For three decades its mechanism was unclear, and it was usually described as a glutamate modulator, which made it look like a gentle, oddball antidepressant ([PMID 25026323](https://pubmed.ncbi.nlm.nih.gov/25026323/)). That picture changed in 2014.

## The opioid discovery

Gassaway and colleagues at Columbia screened tianeptine against receptor panels and found that it is an efficacious mu-opioid receptor agonist, with a binding constant of about 383 nM and half-maximal G-protein activation at about 194 nM at the human receptor. It is also a full but much weaker delta-opioid agonist and is inactive at the kappa receptor ([PMID 25026323](https://pubmed.ncbi.nlm.nih.gov/25026323/)). In mice, both the acute and chronic antidepressant-like effects disappeared when the mu-opioid receptor was knocked out. Tianeptine also produced opioid-like analgesia and reward in mice, and its main metabolite, MC5, which lasts longer, did the same (Samuels et al., 2017, [PMID 28303899](https://pubmed.ncbi.nlm.nih.gov/28303899/)).

That is the key to understanding everything below. At its labelled dose, tianeptine is a mild opioid that treats depression. At the far larger amounts sold in the US, it is a short-acting opioid with all that implies.

## Depression: real evidence

  * A meta-analysis of five randomized trials (1,348 patients) found tianeptine at least as effective as SSRIs (fluoxetine, paroxetine, sertraline) on depression scores and response rates, with a trend toward better acceptability (Kasper and Olié, 2002, [PMID 15177089](https://pubmed.ncbi.nlm.nih.gov/15177089/)).
  * In the CAMPION trial, 164 Korean adults with major depression were randomized to tianeptine or escitalopram for 12 weeks. After adjusting for the change in depression, tianeptine improved commission errors on an attention test and immediate verbal memory more than escitalopram did (Jeon et al., 2014, [PMID 24525660](https://pubmed.ncbi.nlm.nih.gov/24525660/)).



The CAMPION result is the closest thing to positive "nootropic" evidence: better cognitive scores in depressed patients compared with another antidepressant. It says nothing about healthy people, and the trial compared two active drugs without a placebo arm.

## As a nootropic: small studies, mixed results

The placebo-controlled studies in healthy people are small and used single doses. In a 1996 Viennese study of 16 volunteers, tianeptine produced mild EEG activation and mood lift, and the higher of two doses improved attention test scores over several hours (Saletu et al., 1996, [PMID 9026373](https://pubmed.ncbi.nlm.nih.gov/9026373/)). In a 2015 Oxford study, a single prescription-strength dose left working memory and verbal memory unchanged and shifted emotional processing in a negative direction, the opposite of what conventional antidepressants do (Cooper et al., 2015, [PMID 25759404](https://pubmed.ncbi.nlm.nih.gov/25759404/)). Neither tested the repeated use people buy it for. Its online reputation, mood lift, calm, social ease and pain relief, is what a mu-opioid agonist does. Users chasing that effect escalate the dose, and the opioid side takes over.

## The US harm wave

  * **Poison centers, 2015 to 2023:** 892 exposures involving tianeptine alone, a 1,400% rise. 40% needed hospital admission and 23% intensive care. Withdrawal accounted for 22.5% of calls. People over 50 were 70% more likely to have major effects (Quadir et al., 2025, [PMID 39724478](https://pubmed.ncbi.nlm.nih.gov/39724478/)).
  * **Earlier data:** exposure calls rose across 2014 to 2017, with opioid-like toxicity and withdrawal. The most common co-exposures were phenibut, alcohol, benzodiazepines and opioids ([PMID 30070980](https://pubmed.ncbi.nlm.nih.gov/30070980/)).
  * **Doses taken:** case reports describe US users taking 1.3 to 250 times the labelled foreign dose ([FDA, May 2025](https://www.fda.gov/consumers/health-fraud-scams/new-gas-station-heroin-tianeptine-product-trend)).
  * **Systematic review, 2026:** 53 publications covering 1,055 people. Of 52 individual cases, half presented in withdrawal and 44% with overdose. Overdose meant central nervous system depression, respiratory failure and muscle breakdown; naloxone was given in 6 of 22 detailed overdose cases, and 7 of those 22 died. 22% of patients in the larger case series needed intensive care. Buprenorphine was used to manage withdrawal in some patients (Anand et al., 2026, [PMID 42177839](https://pubmed.ncbi.nlm.nih.gov/42177839/)).
  * **Adulteration:** between June 2023 and February 2024, the New Jersey poison centre recorded 37 acute poisonings in 34 people, a cluster linked to the tianeptine product Neptune's Fix. Six product samples varied in content, and some contained synthetic cannabinoids. Seizures, low blood pressure and altered consciousness were common; 16 of the 37 exposures ended in intubation and 24 in intensive care (Counts et al., 2025, [PMID 40102319](https://pubmed.ncbi.nlm.nih.gov/40102319/)).



## Legal status

Where | Status  
---|---  
United States, federal | Not approved for any medical use and not federally scheduled. The FDA says it is not a lawful dietary ingredient and is an unsafe food additive, so supplements containing it are adulterated ([FDA](https://www.fda.gov/food/information-select-dietary-supplement-ingredients-and-other-substances/tianeptine-dietary-supplements)). Warning letters since 2018, the Neptune's Fix recall in 2023 to 2024, a letter urging retailers to stop selling it in January 2024, and a nationwide warning to clinicians in May 2025 ([FDA](https://www.fda.gov/drugs/drug-alerts-and-statements/fda-warns-consumers-not-purchase-or-use-any-tianeptine-product-due-serious-risks))  
United States, states | A growing number of states schedule or ban it. Alabama made it a controlled substance in 2021; its poison-center exposure rate then fell 75% while it kept rising in neighbouring states ([PMID 39724478](https://pubmed.ncbi.nlm.nih.gov/39724478/))  
Countries where it is approved | Prescription antidepressant. Some have tightened how it is prescribed or added addiction warnings to the label ([FDA](https://www.fda.gov/consumers/health-fraud-scams/new-gas-station-heroin-tianeptine-product-trend))  
  
## Claims audit

Claim | Verdict | Why  
---|---|---  
"A nootropic that improves focus and memory" | Unsupported | Two small single-dose placebo studies in healthy volunteers: one found better attention scores, the other no effect on memory. No study of repeated use in healthy people  
"An antidepressant, so it's safe" | False at gram doses | Acceptable at labelled doses under prescription; an opioid with overdose and withdrawal risk at the amounts people buy it for  
"Not an opioid" | False | Full mu-opioid agonist; its antidepressant effect in mice needs the mu receptor  
"Helps people get off opioids" | No evidence | FDA warns specifically against products making this claim; withdrawal from tianeptine itself is often treated with buprenorphine  
  
## What would change the rating

A placebo-controlled trial of repeated labelled doses for cognition, in depression or in healthy adults, would move the cognitive rating. Nothing in the pipeline suggests one is coming. The depression evidence is better than the rating implies, but this entry rates tianeptine as people actually encounter it in the nootropic market.

Tianeptine often turns up together with [phenibut](phenibut.html) in poison-center data. For the class of drugs actually designed as cognitive enhancers, see the [nootropics overview](nootropics-and-smart-drugs-overview.html); for the history of Soviet and Western antidepressant thinking, [Russian pharmacology](russian-pharmacology.html).

## Sources

1. El Zahran T, Schier J, Glidden E et al. Characteristics of tianeptine exposures reported to the National Poison Data System, United States, 2000-2017. MMWR. 2018;67(30):815-818. PMID 30070980 (PubMed 30070980)
2. Gassaway MM, Rives ML, Kruegel AC et al. The atypical antidepressant and neurorestorative agent tianeptine is a μ-opioid receptor agonist. Transl Psychiatry. 2014;4:e411. PMID 25026323 (PubMed 25026323)
3. Samuels BA, Nautiyal KM, Kruegel AC et al. The behavioral effects of the antidepressant tianeptine require the mu-opioid receptor. Neuropsychopharmacology. 2017;42(10):2052-2063. PMID 28303899 (PubMed 28303899)
4. Kasper S, Olié JP. A meta-analysis of randomized controlled trials of tianeptine versus SSRI in the short-term treatment of depression. Eur Psychiatry. 2002;17 Suppl 3:331-40. PMID 15177089 (PubMed 15177089)
5. Jeon HJ, Woo JM, Lee SH et al. Improvement in subjective and objective neurocognitive functions in patients with major depressive disorder: a 12-week, multicenter, randomized trial of tianeptine versus escitalopram, the CAMPION study. J Clin Psychopharmacol. 2014;34(2):218-25. PMID 24525660 (PubMed 24525660)
6. Saletu B, Grünberger J, Anderer P et al. Comparative pharmacodynamic studies with the novel serotonin uptake-enhancing tianeptine and -inhibiting fluvoxamine utilizing EEG mapping and psychometry. J Neural Transm. 1996;103(1-2):191-216. PMID 9026373 (PubMed 9026373)
7. Cooper CM, Whiting DA, Cowen PJ, Harmer CJ. Tianeptine in an experimental medicine model of antidepressant action. J Psychopharmacol. 2015;29(5):582-90. PMID 25759404 (PubMed 25759404)
8. Quadir M, Rine NI, Badeti J et al. Tianeptine exposures reported to United States poison centers, 2015-2023. J Med Toxicol. 2025;21(1):30-41. PMID 39724478 (PubMed 39724478)
9. Anand A, Alessi MR, Toussi RA et al. Tianeptine misuse and addiction: a systematic review of withdrawal, toxicity, and clinical management. Drug Alcohol Depend. 2026;285:113196. PMID 42177839 (PubMed 42177839)
10. Counts CJ, Spadaro AV, Cerbini TA et al. An outbreak of synthetic cannabinoid-adulterated tianeptine products in New Jersey: case series. J Med Toxicol. 2025;21(2):253-259. PMID 40102319 (PubMed 40102319)