Tianeptine

updated

Tianeptine is a mu-opioid receptor agonist in cell assays, and it is both a French prescription antidepressant (authorized in 1987) and an unapproved product sold in the US as a supplement and nootropic. FDA says it is not approved for any medical use and reports seizures, loss of consciousness and death with a tianeptine product, and US poison-center exposures rose 1,400% from 2015 to 2023, with dependence and withdrawal in the reports. DEA proposed placing it in schedule I on 8 July 2026, and no trial found tests the supplier's nootropic claim.

Atypical antidepressant with mu-opioid receptor agonist activity

  • In cell assays tianeptine was an efficacious mu-opioid receptor agonist (human EC50 194 +/- 70 nM for G-protein activation) and inactive at the kappa receptor.
  • FDA states tianeptine is not approved for any medical use in the US and does not meet the statutory definition of a dietary ingredient.
  • US poison-center exposures rose 1,400% from 2015 to 2023 (892 single-substance exposures), with major effects in 12.0%, admission in 40.1%, abuse in 40.1% and withdrawal in 22.5%.
  • In a New Jersey series of 37 exposures with acute toxicity, 43% were intubated and 65% were admitted to intensive care, and some products also contained synthetic cannabinoids.
  • France authorized STABLON for major depressive episodes on 6 February 1987, and its label warns of abuse, dependence and withdrawal.
  • DEA proposed placing tianeptine in schedule I on 8 July 2026, and Ohio, Florida, Michigan and Minnesota list it in statute or rule text.

What is tianeptine, and where is it approved?

Tianeptine is a prescription antidepressant authorized in France since 6 February 1987. FDA states it is not approved for any medical use in the US and does not meet the statutory definition of a dietary ingredient, yet it is sold as a supplement and a nootropic.

Tianeptine is authorized in France under a national procedure as STABLON coated tablets (tianeptine sodium, ATC N06AX14) for major depressive episodes, with authorization dated 6 February 1987. The French summary of product characteristics, which showed a last-updated date of 29 September 2026 on 10 October 2026, contraindicates use under age 15 and says safety and efficacy under 18 are not established. French prescribing rules put it on Liste I, with prescriptions limited to 28 days and written in full on a secure prescription form.

DEA's July 2026 notice says tianeptine is approved in European, Asian and Latin American countries as a prescription drug typically used for depression. Only France is confirmed from a primary record here, and no country-by-country list was compiled.

FDA states tianeptine is not approved for any medical use in the US, is not generally recognized as safe for use in food, and does not meet the statutory definition of a dietary ingredient. It is nonetheless marketed as a research chemical, a nootropic cognitive enhancer or a dietary supplement at convenience stores, gas stations, vape shops and online retailers, under names that include Tianaa, Zaza, Neptune's Fix, Pegasus and TD Red. FDA's page was current as of 8 May 2025.

Identity has three records that are not interchangeable by weight. Tianeptine free acid is C21H25ClN2O4S (437.0 g/mol, CAS 72797-41-2, PubChem CID 68870). Tianeptine sodium, the salt in the French tablet, is C21H24ClN2NaO4S (458.9 g/mol, CAS 30123-17-2, CID 23663953). A tianeptine sulfate record also exists (C21H27ClN2O8S2, 535.0 g/mol, CAS 2093109-76-1, CID 68431515). Which forms vendors sell was not established, and supplement products vary in content, so a vendor product may differ from the form studied in the trials.

French STABLON label: authorized 6 February 1987, Liste I, abuse, dependence and withdrawal warnings

Official label

Base de donnees publique des medicaments (France). STABLON (tianeptine sodium) coated tablets, summary of product characteristics, record 65411280. Page last-updated date 29 September 2026, retrieved 10 October 2026.

STABLON is a prescription antidepressant authorized in France under a national procedure on 6 February 1987 (ATC N06AX14). The summary of product characteristics lists major depressive episodes as the indication. Safety text covers suicidality, hyponatremia, and abuse, dependence and withdrawal: after stopping, some patients had anxiety, muscle pain, abdominal pain, insomnia and joint pain. The adverse-event table lists abuse and dependence as uncommon, particularly in people under 50 with a history of drug or alcohol dependence. It is contraindicated under age 15, and its safety and efficacy under 18 are not established. Absorption from the gut is rapid and complete, protein binding is about 94%, metabolism is extensive in the liver by beta-oxidation without CYP450, an active metabolite (MC5) is less potent, and the terminal half-life is about 3 hours. French prescribing rules: Liste I, prescriptions limited to 28 days, written in full on a secure prescription form.

Participants / model
Adults with major depressive episodes in France; label PK participants
Treatment
STABLON coated oral tablets (tianeptine sodium)
Follow-up
Page last-updated date 29 September 2026
Study design
National regulator summary of product characteristics
Funding
not stated in the source

This is a French national authorization, not an FDA approval. The frequency of abuse and dependence given here is for prescription use and does not describe supplement products.

Read the original source
DEA proposed rule, 8 July 2026: tianeptine to schedule I, HHS recommended schedule I

Regulatory record

Drug Enforcement Administration. Schedules of Controlled Substances: Placement of Tianeptine in Schedule I. Proposed rule, 91 FR 42150, document 2026-13821, Docket DEA1596, published 8 July 2026.

On 8 July 2026 DEA published a proposed rule to place tianeptine in schedule I of the Controlled Substances Act. DEA sent its data to HHS on 7 September 2023, and HHS provided an evaluation on 18 July 2025 that recommended schedule I. The notice states there are no tianeptine products approved for medical use in the US, that tianeptine is approved in European, Asian and Latin American countries as a prescription drug typically used for depression, and that NFLIS reported 268 tianeptine encounters from March 2017 to February 2026. Comments were due 7 August 2026. A Federal Register search on 10 October 2026 for tianeptine returned this proposed rule and no final rule or temporary scheduling order.

Participants / model
Not a clinical population
Treatment
Federal drug scheduling
Follow-up
Proposed rule published 8 July 2026; comments due 7 August 2026
Study design
Official proposed rule
Funding
not stated in the source

A proposed rule is not final. Its status may have changed since 10 October 2026.

Read the original source
FDA alert, current as of 8 May 2025: not approved for any medical use, severe adverse events

Regulatory record

U.S. Food and Drug Administration. FDA warns consumers not to purchase or use any tianeptine product due to serious risks. Page content current as of 8 May 2025.

FDA states tianeptine is not approved for any medical use in the US, is not generally recognized as safe for use in food, and does not meet the statutory definition of a dietary ingredient, yet is marketed as a research chemical, a nootropic cognitive enhancer or a dietary supplement at convenience stores, gas stations, vape shops and online retailers. Product names include Tianaa, Zaza, Neptune's Fix, Pegasus and TD Red, and tianeptine has been called gas station heroin. FDA reports severe adverse events with Neptune's Fix, including seizures, loss of consciousness and death, a voluntary recall of all lots by Neptune Resources, and an 11 January 2024 letter urging retailers to stop selling tianeptine products. It also cites case reports of daily intake of 1.3 to 250 times the typical daily dose in labeled foreign products.

Participants / model
Not a clinical population; US consumers of tianeptine products
Treatment
Unapproved oral products (elixirs, tablets, powders)
Follow-up
Page content current as of 8 May 2025
Study design
Official FDA alert
Funding
not stated in the source

A regulator warning and a list of reported events. It gives no incidence figure.

Read the original source
PubChem: tianeptine free acid, sodium salt and sulfate identity

Chemical identity record

National Library of Medicine. PubChem compound records CID 68870 (tianeptine), CID 23663953 (tianeptine sodium) and CID 68431515 (tianeptine sulfate).

Tianeptine (free acid): PubChem CID 68870, C21H25ClN2O4S, 437.0 g/mol, CAS 72797-41-2. Tianeptine sodium, the salt in the French tablet: CID 23663953, C21H24ClN2NaO4S, 458.9 g/mol, CAS 30123-17-2. A tianeptine sulfate record also exists: CID 68431515, C21H27ClN2O8S2, 535.0 g/mol, CAS 2093109-76-1. Which forms vendors sell was not established.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule and salts
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only. The three records are not interchangeable by weight, and supplement products were found to vary in content.

Read the original source

How does tianeptine act on opioid receptors, and what does the body do with it?

In cell assays tianeptine was an efficacious mu-opioid receptor agonist and a full delta-opioid agonist at much lower potency, and it was inactive at the kappa receptor. In the French label its terminal half-life is about 3 hours.

In cell lines expressing human, mouse and rat opioid receptors, tianeptine was an efficacious mu-opioid receptor agonist (human Ki 383 +/- 183 nM, human EC50 194 +/- 70 nM for G-protein activation) and a full delta-opioid agonist at much lower potency (EC50 37.4 +/- 11.2 micromolar), and was inactive at the kappa receptor. Cell-assay potency is not a measure of effect in people.

A follow-up in mice (PMID 28303899) reported that the antidepressant-like effects require the mu-opioid receptor but that tianeptine does not lead to tolerance or withdrawal in those mice. That does not match the withdrawal described in the French label and in the poison-center data below.

In the French label, absorption from the gut is rapid and complete, protein binding is about 94%, and metabolism is extensive in the liver by beta-oxidation without CYP450. An active metabolite (MC5) is less potent, and the terminal half-life is about 3 hours. In a 1996 single-dose study in 16 healthy volunteers, plasma tianeptine peaked at 1 to 2 hours and MC5 at 4 hours. No source found gives tianeptine PK in supplement users.

Cell assays: efficacious mu-opioid agonist, EC50 194 nM, inactive at kappa

Cell study

Gassaway MM et al. Transl Psychiatry. 2014;4(7):e411. PMID 25026323.

In cell assays, tianeptine was an efficacious mu-opioid receptor agonist (human Ki 383 +/- 183 nM, human EC50 194 +/- 70 nM for G-protein activation) and a full delta-opioid agonist at much lower potency (EC50 37.4 +/- 11.2 micromolar), and was inactive at the kappa receptor. A follow-up in mice (PMID 28303899) reported that the antidepressant-like effects require the mu-opioid receptor but that tianeptine does not lead to tolerance or withdrawal in those mice, which does not match the withdrawal described in the French label and in poison-center data.

Participants / model
Cell lines expressing human, mouse and rat opioid receptors; mice in the follow-up
Treatment
In vitro assays; mouse dosing in the follow-up
Follow-up
Not applicable
Study design
Original preclinical study
Funding
not stated in the source

Cell-assay potency is not a measure of effect in people. The mouse follow-up is cited here by its PMID only.

Read the original source
French STABLON label: authorized 6 February 1987, Liste I, abuse, dependence and withdrawal warnings

Official label

Base de donnees publique des medicaments (France). STABLON (tianeptine sodium) coated tablets, summary of product characteristics, record 65411280. Page last-updated date 29 September 2026, retrieved 10 October 2026.

STABLON is a prescription antidepressant authorized in France under a national procedure on 6 February 1987 (ATC N06AX14). The summary of product characteristics lists major depressive episodes as the indication. Safety text covers suicidality, hyponatremia, and abuse, dependence and withdrawal: after stopping, some patients had anxiety, muscle pain, abdominal pain, insomnia and joint pain. The adverse-event table lists abuse and dependence as uncommon, particularly in people under 50 with a history of drug or alcohol dependence. It is contraindicated under age 15, and its safety and efficacy under 18 are not established. Absorption from the gut is rapid and complete, protein binding is about 94%, metabolism is extensive in the liver by beta-oxidation without CYP450, an active metabolite (MC5) is less potent, and the terminal half-life is about 3 hours. French prescribing rules: Liste I, prescriptions limited to 28 days, written in full on a secure prescription form.

Participants / model
Adults with major depressive episodes in France; label PK participants
Treatment
STABLON coated oral tablets (tianeptine sodium)
Follow-up
Page last-updated date 29 September 2026
Study design
National regulator summary of product characteristics
Funding
not stated in the source

This is a French national authorization, not an FDA approval. The frequency of abuse and dependence given here is for prescription use and does not describe supplement products.

Read the original source
Healthy volunteers, single doses: emotional processing changed, no effect on non-emotional cognition

Human study

Cooper CM et al. J Psychopharmacol. 2015;29(5):582-90. PMID 25759404.

In healthy volunteers given a single dose of tianeptine or placebo, tianeptine reduced accuracy in identifying facial expressions, reduced positive affective memory and attentional vigilance to positive stimuli, and had no effect on emotional categorization or non-emotional cognition (working and verbal memory). A 1996 single-dose study of 16 healthy volunteers (PMID 9026373) found a lower dose gave slight EEG activation with mood elevation, and a higher dose gave EEG activation then sedation, lower vigilance and better attention on the Pauli test; plasma tianeptine peaked at 1 to 2 hours and the MC5 metabolite at 4 hours.

Participants / model
Healthy volunteers (number not stated in the 2015 abstract); 16 men and women aged 21 to 35 in the 1996 study
Treatment
Single oral doses of tianeptine or placebo
Follow-up
Single dose
Study design
Original randomized studies
Funding
not stated in the source

Small single-dose studies, not tests of repeated supplement use. Endpoints were emotional processing, working and verbal memory, EEG, attention and PK.

Read the original source

What do the French label and poison centers say about dependence and withdrawal?

The French label warns of abuse, dependence and withdrawal and lists abuse and dependence as uncommon in prescription use. In US poison-center data on unregulated products, abuse accounted for 40.1% of tianeptine exposures and withdrawal for 22.5%.

The French summary of product characteristics carries a warning on abuse, dependence and withdrawal. After stopping, some patients had anxiety, muscle pain, abdominal pain, insomnia and joint pain. Its adverse-event table lists abuse and dependence as uncommon, particularly in people under 50 with a history of drug or alcohol dependence.

In a review of 892 single-substance tianeptine exposures reported to US poison centers (National Poison Data System, 2015 to 2023), abuse accounted for 40.1% of exposures and withdrawal for 22.5%.

The label's frequency applies to prescription use, while the poison-center data come from unregulated products, mostly supplement or gas-station products. No source found gives a dose-response for dependence, and poison-center calls are voluntary reports that do not give incidence.

French STABLON label: authorized 6 February 1987, Liste I, abuse, dependence and withdrawal warnings

Official label

Base de donnees publique des medicaments (France). STABLON (tianeptine sodium) coated tablets, summary of product characteristics, record 65411280. Page last-updated date 29 September 2026, retrieved 10 October 2026.

STABLON is a prescription antidepressant authorized in France under a national procedure on 6 February 1987 (ATC N06AX14). The summary of product characteristics lists major depressive episodes as the indication. Safety text covers suicidality, hyponatremia, and abuse, dependence and withdrawal: after stopping, some patients had anxiety, muscle pain, abdominal pain, insomnia and joint pain. The adverse-event table lists abuse and dependence as uncommon, particularly in people under 50 with a history of drug or alcohol dependence. It is contraindicated under age 15, and its safety and efficacy under 18 are not established. Absorption from the gut is rapid and complete, protein binding is about 94%, metabolism is extensive in the liver by beta-oxidation without CYP450, an active metabolite (MC5) is less potent, and the terminal half-life is about 3 hours. French prescribing rules: Liste I, prescriptions limited to 28 days, written in full on a secure prescription form.

Participants / model
Adults with major depressive episodes in France; label PK participants
Treatment
STABLON coated oral tablets (tianeptine sodium)
Follow-up
Page last-updated date 29 September 2026
Study design
National regulator summary of product characteristics
Funding
not stated in the source

This is a French national authorization, not an FDA approval. The frequency of abuse and dependence given here is for prescription use and does not describe supplement products.

Read the original source
892 US poison-center exposures: rate up 1,400%, major effects 12.0%, admission 40.1%

Human study

Quadir M et al. J Med Toxicol. 2025;21(1):30-41. PMID 39724478.

The exposure rate rose 1,400% from 2015 to 2023, with a 525% rise from 2018 to 2023. Effects were moderate in 51.5% and major in 12.0%, and 40.1% required admission, including 22.9% to critical care. Abuse accounted for 40.1% of exposures and withdrawal for 22.5%. People aged 50 or older were more likely to have major effects (RR 1.70, 95% CI 1.13 to 2.56). The authors report that Alabama enacted legislation to regulate tianeptine as a controlled substance in 2021 and that its exposure rate then fell 74.6% from 2021 to 2023 while other southern states kept rising.

Participants / model
892 single-substance tianeptine exposures reported to US poison centers (National Poison Data System)
Treatment
Unregulated tianeptine products, mostly supplement or gas-station products
Follow-up
2015 to 2023
Study design
Poison-center surveillance analysis
Funding
not stated in the source

Poison-center calls are voluntary reports and do not give incidence.

Read the original source

What do FDA and the poison-center and case reports warn about?

FDA reports severe adverse events with Neptune's Fix, including seizures, loss of consciousness and death. US poison-center exposures rose 1,400% from 2015 to 2023 with major effects in 12.0% and admission in 40.1%, and in a New Jersey series 43% of the exposures with acute toxicity were intubated.

FDA reports severe adverse events with the tianeptine product Neptune's Fix, including seizures, loss of consciousness and death, a voluntary recall of all lots by Neptune Resources, and an 11 January 2024 letter urging retailers to stop selling tianeptine products. FDA notes that tianeptine has been called gas station heroin, and it cites case reports of daily intake of 1.3 to 250 times the typical daily dose in labeled foreign products.

A review of 892 single-substance tianeptine exposures reported to US poison centers (2015 to 2023) found the exposure rate rose 1,400% from 2015 to 2023, with a 525% rise from 2018 to 2023. Effects were moderate in 51.5% and major in 12.0%, and 40.1% required admission, including 22.9% to critical care. People aged 50 or older were more likely to have major effects (RR 1.70, 95% CI 1.13 to 2.56). Poison-center calls are voluntary reports and do not give incidence.

In a New Jersey case series, 34 patients became ill after ingesting Neptune's Fix, 4.6 cases a month against a background of 0.5 cases a year. Among 37 exposures with acute toxicity, effects included altered mental status, tachycardia, hypotension and seizures; 43% (16) were intubated and 65% (24) were admitted to intensive care. Analysis of six ingested products found variable composition, including tianeptine, kava alkaloids, natural cannabinoids and the synthetic cannabinoids MDMB-4en-PINACA and ADB-4en-PINACA, and MDMB-4en-PINACA was found in one of two patient blood samples. A supplement-form product may not be tianeptine alone.

In two randomized double-blind placebo-controlled crossover studies in healthy volunteers, oral tianeptine (8 subjects) did not significantly prevent alfentanil-induced respiratory depression, and intravenous tianeptine (15 volunteers) did not stimulate ventilation but worsened remifentanil-induced respiratory depression (minute ventilation 9.6 versus 15.0 L/min, mean difference 5.3 L/min, 95% CI 2.5 to 8.2, P = 0.001). The authors concluded neither route was a respiratory stimulant. This is an opioid-challenge model, not supplement use.

The French label also warns of suicidality and hyponatremia.

FDA alert, current as of 8 May 2025: not approved for any medical use, severe adverse events

Regulatory record

U.S. Food and Drug Administration. FDA warns consumers not to purchase or use any tianeptine product due to serious risks. Page content current as of 8 May 2025.

FDA states tianeptine is not approved for any medical use in the US, is not generally recognized as safe for use in food, and does not meet the statutory definition of a dietary ingredient, yet is marketed as a research chemical, a nootropic cognitive enhancer or a dietary supplement at convenience stores, gas stations, vape shops and online retailers. Product names include Tianaa, Zaza, Neptune's Fix, Pegasus and TD Red, and tianeptine has been called gas station heroin. FDA reports severe adverse events with Neptune's Fix, including seizures, loss of consciousness and death, a voluntary recall of all lots by Neptune Resources, and an 11 January 2024 letter urging retailers to stop selling tianeptine products. It also cites case reports of daily intake of 1.3 to 250 times the typical daily dose in labeled foreign products.

Participants / model
Not a clinical population; US consumers of tianeptine products
Treatment
Unapproved oral products (elixirs, tablets, powders)
Follow-up
Page content current as of 8 May 2025
Study design
Official FDA alert
Funding
not stated in the source

A regulator warning and a list of reported events. It gives no incidence figure.

Read the original source
892 US poison-center exposures: rate up 1,400%, major effects 12.0%, admission 40.1%

Human study

Quadir M et al. J Med Toxicol. 2025;21(1):30-41. PMID 39724478.

The exposure rate rose 1,400% from 2015 to 2023, with a 525% rise from 2018 to 2023. Effects were moderate in 51.5% and major in 12.0%, and 40.1% required admission, including 22.9% to critical care. Abuse accounted for 40.1% of exposures and withdrawal for 22.5%. People aged 50 or older were more likely to have major effects (RR 1.70, 95% CI 1.13 to 2.56). The authors report that Alabama enacted legislation to regulate tianeptine as a controlled substance in 2021 and that its exposure rate then fell 74.6% from 2021 to 2023 while other southern states kept rising.

Participants / model
892 single-substance tianeptine exposures reported to US poison centers (National Poison Data System)
Treatment
Unregulated tianeptine products, mostly supplement or gas-station products
Follow-up
2015 to 2023
Study design
Poison-center surveillance analysis
Funding
not stated in the source

Poison-center calls are voluntary reports and do not give incidence.

Read the original source
New Jersey: 34 patients, 43% intubated, synthetic cannabinoids found in some products

Case report

Counts CJ et al. J Med Toxicol. 2025;21(2):253-259. PMID 40102319.

34 patients became ill after ingesting Neptune's Fix, 4.6 cases a month against a background of 0.5 cases a year. Among 37 exposures with acute toxicity, effects included altered mental status, tachycardia, hypotension and seizures; 43% (16) were intubated and 65% (24) were admitted to intensive care. Analysis of six ingested products found variable composition, including tianeptine, kava alkaloids, natural cannabinoids and the synthetic cannabinoids MDMB-4en-PINACA and ADB-4en-PINACA; MDMB-4en-PINACA was found in one of two patient blood samples.

Participants / model
34 patients in one New Jersey cluster; 6 product samples
Treatment
Oral tianeptine-labeled products (Neptune's Fix)
Follow-up
not stated in the source
Study design
Poison-center case series with product analysis
Funding
not stated in the source

A supplement-form product may not be tianeptine alone.

Read the original source
Two crossover studies, 8 and 15 volunteers: tianeptine not a respiratory stimulant

Randomized controlled trial

Algera H et al. Anesthesiology. 2022;137(4):446-458. PMID 35867853.

Oral tianeptine (8 subjects) did not significantly prevent alfentanil-induced respiratory depression. Intravenous tianeptine (15 volunteers) did not stimulate ventilation but worsened remifentanil-induced respiratory depression (minute ventilation 9.6 versus 15.0 L/min, mean difference 5.3 L/min, 95% CI 2.5 to 8.2, P = 0.001). The authors concluded neither route was a respiratory stimulant.

Participants / model
8 and 15 healthy volunteers in two studies
Treatment
Oral tianeptine; intravenous infusion to target plasma concentrations
Follow-up
not stated in the source
Study design
Two randomized double-blind placebo-controlled crossover studies
Funding
not stated in the source

An opioid-challenge model, not supplement use. Endpoints were ventilation at fixed carbon dioxide and minute ventilation.

Read the original source
French STABLON label: authorized 6 February 1987, Liste I, abuse, dependence and withdrawal warnings

Official label

Base de donnees publique des medicaments (France). STABLON (tianeptine sodium) coated tablets, summary of product characteristics, record 65411280. Page last-updated date 29 September 2026, retrieved 10 October 2026.

STABLON is a prescription antidepressant authorized in France under a national procedure on 6 February 1987 (ATC N06AX14). The summary of product characteristics lists major depressive episodes as the indication. Safety text covers suicidality, hyponatremia, and abuse, dependence and withdrawal: after stopping, some patients had anxiety, muscle pain, abdominal pain, insomnia and joint pain. The adverse-event table lists abuse and dependence as uncommon, particularly in people under 50 with a history of drug or alcohol dependence. It is contraindicated under age 15, and its safety and efficacy under 18 are not established. Absorption from the gut is rapid and complete, protein binding is about 94%, metabolism is extensive in the liver by beta-oxidation without CYP450, an active metabolite (MC5) is less potent, and the terminal half-life is about 3 hours. French prescribing rules: Liste I, prescriptions limited to 28 days, written in full on a secure prescription form.

Participants / model
Adults with major depressive episodes in France; label PK participants
Treatment
STABLON coated oral tablets (tianeptine sodium)
Follow-up
Page last-updated date 29 September 2026
Study design
National regulator summary of product characteristics
Funding
not stated in the source

This is a French national authorization, not an FDA approval. The frequency of abuse and dependence given here is for prescription use and does not describe supplement products.

Read the original source

What did the prescription depression trials find?

In a 126-patient placebo-controlled trial, final MADRS scores were better on tianeptine, and in a 5-trial, 1,348-patient meta-analysis tianeptine did not differ significantly from SSRIs. These are short-term prescription trials in patients with depression and do not cover the supplement form.

A multicenter randomized double-blind trial in 126 outpatients with major depression or bipolar depression (MADRS 25 or higher) compared tianeptine with placebo for 42 days. Final MADRS scores were better on tianeptine in the intention-to-treat population, in patients treated 14 days or more, and in completers. Acceptability did not differ from placebo, and headache was more common on tianeptine. The trial dates from 1997. A 16.5-month relapse-prevention trial (PMID 12404534) reported relapse or recurrence in 16% versus 36% of 185 randomized responders, read at abstract level only.

A 2002 meta-analysis of 5 randomized trials in the short-term treatment of depression (1,348 patients: 667 on tianeptine and 681 on an SSRI; two versus fluoxetine, two versus paroxetine and one versus sertraline) found no significant difference between tianeptine and the SSRIs on MADRS total score or responder rate, and concluded tianeptine was at least as effective as an SSRI. The comparator was an SSRI, not placebo, and the abstract does not state who funded the trials.

These data are old and limited to small trials in patients under prescription conditions. They do not test the product sold online.

126 outpatients, 42 days: final MADRS better on tianeptine than placebo

Randomized controlled trial

Costa e Silva JA et al. Neuropsychobiology. 1997;35(1):24-9. PMID 9018020.

Final MADRS scores were better on tianeptine in the intention-to-treat population, in patients treated 14 days or more, and in completers. Acceptability did not differ from placebo, and headache was more common on tianeptine. A 16.5-month relapse-prevention trial (PMID 12404534) reported relapse or recurrence in 16% versus 36% of 185 randomized responders.

Participants / model
126 outpatients with major depression or bipolar depression (MADRS 25 or higher)
Treatment
Oral tianeptine versus placebo
Follow-up
42 days
Study design
1997 multicenter randomized double-blind trial
Funding
not stated in the source

A prescription-use trial in patients with depression. The relapse-prevention trial was read at abstract level only. Endpoints were MADRS, CGI, anxiety and self-rating scales, and adverse events.

Read the original source
Meta-analysis: 5 trials, 1,348 patients, tianeptine not different from SSRIs

Systematic review and meta-analysis

Kasper S et al. Eur Psychiatry. 2002;17 Suppl 3:331-40. PMID 15177089.

There was no significant difference between tianeptine and the SSRIs on MADRS total score or responder rate, and the authors concluded tianeptine was at least as effective as an SSRI.

Participants / model
1,348 patients with depression in 5 randomized trials (667 on tianeptine, 681 on an SSRI)
Treatment
Oral tianeptine versus SSRIs: two trials against fluoxetine, two against paroxetine and one against sertraline
Follow-up
Short-term treatment trials
Study design
2002 meta-analysis of randomized trials with an SSRI comparator
Funding
not stated in the source

The comparator was an SSRI, not placebo, and the abstract does not state who funded the trials. Endpoints were MADRS total score, responder rate and CGI.

Read the original source

Does tianeptine work as a mood or nootropic supplement?

No trial found tests it. Two PubMed searches on 10 October 2026 found no study of repeated tianeptine as a mood or cognitive enhancer in healthy people, and the only healthy-volunteer data, from single doses, showed no effect on non-emotional cognition.

Tianeptine is sold online as a mood and nootropic supplement. Because it is an approved antidepressant in some countries, the mood claim rests on prescription trials that do not cover supplement use, and the nootropic claim has no trial behind it.

In healthy volunteers given a single dose of tianeptine or placebo (number not stated in the 2015 abstract), tianeptine reduced accuracy in identifying facial expressions, reduced positive affective memory and attentional vigilance to positive stimuli, and had no effect on emotional categorization or non-emotional cognition (working and verbal memory). A 1996 single-dose study of 16 healthy men and women aged 21 to 35 found a lower dose gave slight EEG activation with mood elevation, and a higher dose gave EEG activation then sedation, lower vigilance and better attention on the Pauli test. Both are small single-dose studies, not tests of repeated supplement use.

A PubMed search on 10 October 2026 for tianeptine with nootropic, cognitive enhancement, cognitive performance, cognitive function or memory in healthy people, volunteers or humans returned 10 records: neurochemistry and stress-biology papers, a Delphi consensus on depression in Alzheimer's disease, a misuse systematic review and the two single-dose volunteer studies above. A second search for tianeptine with nootropic, dietary supplement or gas station returned 18 records: poison-center and misuse reports, case reports, narrative reviews, rat mitochondria studies and a neonatal withdrawal case report. None tested repeated tianeptine as a mood or cognitive enhancer in healthy people.

A supplement-form product may also differ from the form and content studied: in the New Jersey series, six ingested products varied in composition.

PubMed searches, 10 October 2026: 10 records and 18 records, none testing repeated use as an enhancer

PubMed search record

PubMed searches run on 10 October 2026: (1) tianeptine[tiab] AND (nootropic*[tiab] OR cognitive enhanc*[tiab] OR cognitive performance[tiab] OR cognitive function[tiab] OR memory[tiab]) AND (healthy[tiab] OR volunteer*[tiab] OR human*[tiab]); (2) tianeptine[tiab] AND (nootropic*[tiab] OR dietary supplement*[tiab] OR gas station[tiab]). 10 and 18 records returned.

The first search returned 10 records: neurochemistry and stress-biology papers, a Delphi consensus on depression in Alzheimer's disease, a misuse systematic review, and the two single-dose volunteer studies described on this page. The second search returned 18 records: poison-center and misuse reports, case reports, narrative reviews, rat mitochondria studies and a neonatal withdrawal case report. None tested repeated tianeptine as a mood or cognitive enhancer in healthy people.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source
Healthy volunteers, single doses: emotional processing changed, no effect on non-emotional cognition

Human study

Cooper CM et al. J Psychopharmacol. 2015;29(5):582-90. PMID 25759404.

In healthy volunteers given a single dose of tianeptine or placebo, tianeptine reduced accuracy in identifying facial expressions, reduced positive affective memory and attentional vigilance to positive stimuli, and had no effect on emotional categorization or non-emotional cognition (working and verbal memory). A 1996 single-dose study of 16 healthy volunteers (PMID 9026373) found a lower dose gave slight EEG activation with mood elevation, and a higher dose gave EEG activation then sedation, lower vigilance and better attention on the Pauli test; plasma tianeptine peaked at 1 to 2 hours and the MC5 metabolite at 4 hours.

Participants / model
Healthy volunteers (number not stated in the 2015 abstract); 16 men and women aged 21 to 35 in the 1996 study
Treatment
Single oral doses of tianeptine or placebo
Follow-up
Single dose
Study design
Original randomized studies
Funding
not stated in the source

Small single-dose studies, not tests of repeated supplement use. Endpoints were emotional processing, working and verbal memory, EEG, attention and PK.

Read the original source
New Jersey: 34 patients, 43% intubated, synthetic cannabinoids found in some products

Case report

Counts CJ et al. J Med Toxicol. 2025;21(2):253-259. PMID 40102319.

34 patients became ill after ingesting Neptune's Fix, 4.6 cases a month against a background of 0.5 cases a year. Among 37 exposures with acute toxicity, effects included altered mental status, tachycardia, hypotension and seizures; 43% (16) were intubated and 65% (24) were admitted to intensive care. Analysis of six ingested products found variable composition, including tianeptine, kava alkaloids, natural cannabinoids and the synthetic cannabinoids MDMB-4en-PINACA and ADB-4en-PINACA; MDMB-4en-PINACA was found in one of two patient blood samples.

Participants / model
34 patients in one New Jersey cluster; 6 product samples
Treatment
Oral tianeptine-labeled products (Neptune's Fix)
Follow-up
not stated in the source
Study design
Poison-center case series with product analysis
Funding
not stated in the source

A supplement-form product may not be tianeptine alone.

Read the original source

Why does tianeptine sit in F tier?

F grades tianeptine as it is sold and used. The French prescription record is real but narrow and tightly regulated, while the product sold online is unapproved in the US, with documented dependence, withdrawal, poison-center exposures and seizures, and no trial behind the nootropic claim.

The French prescription record is real: authorization since 1987, one 126-patient placebo-controlled trial and a meta-analysis matching SSRIs. It is old, limited to small trials, and sits under French prescribing rules (Liste I, a 28-day limit, a secure prescription) with a label that already lists dependence and withdrawal.

The form people buy online is a different exposure. FDA says it is not approved for any use and ties tianeptine products to seizures, loss of consciousness and death. US poison-center exposures rose 1,400% from 2015 to 2023 with major effects in 12.0% and admission in 40.1%, a New Jersey cluster included 43% intubated and synthetic cannabinoids in some products, and DEA proposed schedule I on 8 July 2026.

The published downside outweighs any reported upside for the product as sold, and the only healthy-volunteer cognition data showed no effect on non-emotional cognition after a single dose.

French STABLON label: authorized 6 February 1987, Liste I, abuse, dependence and withdrawal warnings

Official label

Base de donnees publique des medicaments (France). STABLON (tianeptine sodium) coated tablets, summary of product characteristics, record 65411280. Page last-updated date 29 September 2026, retrieved 10 October 2026.

STABLON is a prescription antidepressant authorized in France under a national procedure on 6 February 1987 (ATC N06AX14). The summary of product characteristics lists major depressive episodes as the indication. Safety text covers suicidality, hyponatremia, and abuse, dependence and withdrawal: after stopping, some patients had anxiety, muscle pain, abdominal pain, insomnia and joint pain. The adverse-event table lists abuse and dependence as uncommon, particularly in people under 50 with a history of drug or alcohol dependence. It is contraindicated under age 15, and its safety and efficacy under 18 are not established. Absorption from the gut is rapid and complete, protein binding is about 94%, metabolism is extensive in the liver by beta-oxidation without CYP450, an active metabolite (MC5) is less potent, and the terminal half-life is about 3 hours. French prescribing rules: Liste I, prescriptions limited to 28 days, written in full on a secure prescription form.

Participants / model
Adults with major depressive episodes in France; label PK participants
Treatment
STABLON coated oral tablets (tianeptine sodium)
Follow-up
Page last-updated date 29 September 2026
Study design
National regulator summary of product characteristics
Funding
not stated in the source

This is a French national authorization, not an FDA approval. The frequency of abuse and dependence given here is for prescription use and does not describe supplement products.

Read the original source
FDA alert, current as of 8 May 2025: not approved for any medical use, severe adverse events

Regulatory record

U.S. Food and Drug Administration. FDA warns consumers not to purchase or use any tianeptine product due to serious risks. Page content current as of 8 May 2025.

FDA states tianeptine is not approved for any medical use in the US, is not generally recognized as safe for use in food, and does not meet the statutory definition of a dietary ingredient, yet is marketed as a research chemical, a nootropic cognitive enhancer or a dietary supplement at convenience stores, gas stations, vape shops and online retailers. Product names include Tianaa, Zaza, Neptune's Fix, Pegasus and TD Red, and tianeptine has been called gas station heroin. FDA reports severe adverse events with Neptune's Fix, including seizures, loss of consciousness and death, a voluntary recall of all lots by Neptune Resources, and an 11 January 2024 letter urging retailers to stop selling tianeptine products. It also cites case reports of daily intake of 1.3 to 250 times the typical daily dose in labeled foreign products.

Participants / model
Not a clinical population; US consumers of tianeptine products
Treatment
Unapproved oral products (elixirs, tablets, powders)
Follow-up
Page content current as of 8 May 2025
Study design
Official FDA alert
Funding
not stated in the source

A regulator warning and a list of reported events. It gives no incidence figure.

Read the original source
892 US poison-center exposures: rate up 1,400%, major effects 12.0%, admission 40.1%

Human study

Quadir M et al. J Med Toxicol. 2025;21(1):30-41. PMID 39724478.

The exposure rate rose 1,400% from 2015 to 2023, with a 525% rise from 2018 to 2023. Effects were moderate in 51.5% and major in 12.0%, and 40.1% required admission, including 22.9% to critical care. Abuse accounted for 40.1% of exposures and withdrawal for 22.5%. People aged 50 or older were more likely to have major effects (RR 1.70, 95% CI 1.13 to 2.56). The authors report that Alabama enacted legislation to regulate tianeptine as a controlled substance in 2021 and that its exposure rate then fell 74.6% from 2021 to 2023 while other southern states kept rising.

Participants / model
892 single-substance tianeptine exposures reported to US poison centers (National Poison Data System)
Treatment
Unregulated tianeptine products, mostly supplement or gas-station products
Follow-up
2015 to 2023
Study design
Poison-center surveillance analysis
Funding
not stated in the source

Poison-center calls are voluntary reports and do not give incidence.

Read the original source
New Jersey: 34 patients, 43% intubated, synthetic cannabinoids found in some products

Case report

Counts CJ et al. J Med Toxicol. 2025;21(2):253-259. PMID 40102319.

34 patients became ill after ingesting Neptune's Fix, 4.6 cases a month against a background of 0.5 cases a year. Among 37 exposures with acute toxicity, effects included altered mental status, tachycardia, hypotension and seizures; 43% (16) were intubated and 65% (24) were admitted to intensive care. Analysis of six ingested products found variable composition, including tianeptine, kava alkaloids, natural cannabinoids and the synthetic cannabinoids MDMB-4en-PINACA and ADB-4en-PINACA; MDMB-4en-PINACA was found in one of two patient blood samples.

Participants / model
34 patients in one New Jersey cluster; 6 product samples
Treatment
Oral tianeptine-labeled products (Neptune's Fix)
Follow-up
not stated in the source
Study design
Poison-center case series with product analysis
Funding
not stated in the source

A supplement-form product may not be tianeptine alone.

Read the original source
DEA proposed rule, 8 July 2026: tianeptine to schedule I, HHS recommended schedule I

Regulatory record

Drug Enforcement Administration. Schedules of Controlled Substances: Placement of Tianeptine in Schedule I. Proposed rule, 91 FR 42150, document 2026-13821, Docket DEA1596, published 8 July 2026.

On 8 July 2026 DEA published a proposed rule to place tianeptine in schedule I of the Controlled Substances Act. DEA sent its data to HHS on 7 September 2023, and HHS provided an evaluation on 18 July 2025 that recommended schedule I. The notice states there are no tianeptine products approved for medical use in the US, that tianeptine is approved in European, Asian and Latin American countries as a prescription drug typically used for depression, and that NFLIS reported 268 tianeptine encounters from March 2017 to February 2026. Comments were due 7 August 2026. A Federal Register search on 10 October 2026 for tianeptine returned this proposed rule and no final rule or temporary scheduling order.

Participants / model
Not a clinical population
Treatment
Federal drug scheduling
Follow-up
Proposed rule published 8 July 2026; comments due 7 August 2026
Study design
Official proposed rule
Funding
not stated in the source

A proposed rule is not final. Its status may have changed since 10 October 2026.

Read the original source
PubMed searches, 10 October 2026: 10 records and 18 records, none testing repeated use as an enhancer

PubMed search record

PubMed searches run on 10 October 2026: (1) tianeptine[tiab] AND (nootropic*[tiab] OR cognitive enhanc*[tiab] OR cognitive performance[tiab] OR cognitive function[tiab] OR memory[tiab]) AND (healthy[tiab] OR volunteer*[tiab] OR human*[tiab]); (2) tianeptine[tiab] AND (nootropic*[tiab] OR dietary supplement*[tiab] OR gas station[tiab]). 10 and 18 records returned.

The first search returned 10 records: neurochemistry and stress-biology papers, a Delphi consensus on depression in Alzheimer's disease, a misuse systematic review, and the two single-dose volunteer studies described on this page. The second search returned 18 records: poison-center and misuse reports, case reports, narrative reviews, rat mitochondria studies and a neonatal withdrawal case report. None tested repeated tianeptine as a mood or cognitive enhancer in healthy people.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source
126 outpatients, 42 days: final MADRS better on tianeptine than placebo

Randomized controlled trial

Costa e Silva JA et al. Neuropsychobiology. 1997;35(1):24-9. PMID 9018020.

Final MADRS scores were better on tianeptine in the intention-to-treat population, in patients treated 14 days or more, and in completers. Acceptability did not differ from placebo, and headache was more common on tianeptine. A 16.5-month relapse-prevention trial (PMID 12404534) reported relapse or recurrence in 16% versus 36% of 185 randomized responders.

Participants / model
126 outpatients with major depression or bipolar depression (MADRS 25 or higher)
Treatment
Oral tianeptine versus placebo
Follow-up
42 days
Study design
1997 multicenter randomized double-blind trial
Funding
not stated in the source

A prescription-use trial in patients with depression. The relapse-prevention trial was read at abstract level only. Endpoints were MADRS, CGI, anxiety and self-rating scales, and adverse events.

Read the original source
Meta-analysis: 5 trials, 1,348 patients, tianeptine not different from SSRIs

Systematic review and meta-analysis

Kasper S et al. Eur Psychiatry. 2002;17 Suppl 3:331-40. PMID 15177089.

There was no significant difference between tianeptine and the SSRIs on MADRS total score or responder rate, and the authors concluded tianeptine was at least as effective as an SSRI.

Participants / model
1,348 patients with depression in 5 randomized trials (667 on tianeptine, 681 on an SSRI)
Treatment
Oral tianeptine versus SSRIs: two trials against fluoxetine, two against paroxetine and one against sertraline
Follow-up
Short-term treatment trials
Study design
2002 meta-analysis of randomized trials with an SSRI comparator
Funding
not stated in the source

The comparator was an SSRI, not placebo, and the abstract does not state who funded the trials. Endpoints were MADRS total score, responder rate and CGI.

Read the original source

Studies and sources

Cell assays: efficacious mu-opioid agonist, EC50 194 nM, inactive at kappa

Cell study

Gassaway MM et al. Transl Psychiatry. 2014;4(7):e411. PMID 25026323.

In cell assays, tianeptine was an efficacious mu-opioid receptor agonist (human Ki 383 +/- 183 nM, human EC50 194 +/- 70 nM for G-protein activation) and a full delta-opioid agonist at much lower potency (EC50 37.4 +/- 11.2 micromolar), and was inactive at the kappa receptor. A follow-up in mice (PMID 28303899) reported that the antidepressant-like effects require the mu-opioid receptor but that tianeptine does not lead to tolerance or withdrawal in those mice, which does not match the withdrawal described in the French label and in poison-center data.

Participants / model
Cell lines expressing human, mouse and rat opioid receptors; mice in the follow-up
Treatment
In vitro assays; mouse dosing in the follow-up
Follow-up
Not applicable
Study design
Original preclinical study
Funding
not stated in the source

Cell-assay potency is not a measure of effect in people. The mouse follow-up is cited here by its PMID only.

Read the original source
French STABLON label: authorized 6 February 1987, Liste I, abuse, dependence and withdrawal warnings

Official label

Base de donnees publique des medicaments (France). STABLON (tianeptine sodium) coated tablets, summary of product characteristics, record 65411280. Page last-updated date 29 September 2026, retrieved 10 October 2026.

STABLON is a prescription antidepressant authorized in France under a national procedure on 6 February 1987 (ATC N06AX14). The summary of product characteristics lists major depressive episodes as the indication. Safety text covers suicidality, hyponatremia, and abuse, dependence and withdrawal: after stopping, some patients had anxiety, muscle pain, abdominal pain, insomnia and joint pain. The adverse-event table lists abuse and dependence as uncommon, particularly in people under 50 with a history of drug or alcohol dependence. It is contraindicated under age 15, and its safety and efficacy under 18 are not established. Absorption from the gut is rapid and complete, protein binding is about 94%, metabolism is extensive in the liver by beta-oxidation without CYP450, an active metabolite (MC5) is less potent, and the terminal half-life is about 3 hours. French prescribing rules: Liste I, prescriptions limited to 28 days, written in full on a secure prescription form.

Participants / model
Adults with major depressive episodes in France; label PK participants
Treatment
STABLON coated oral tablets (tianeptine sodium)
Follow-up
Page last-updated date 29 September 2026
Study design
National regulator summary of product characteristics
Funding
not stated in the source

This is a French national authorization, not an FDA approval. The frequency of abuse and dependence given here is for prescription use and does not describe supplement products.

Read the original source
FDA alert, current as of 8 May 2025: not approved for any medical use, severe adverse events

Regulatory record

U.S. Food and Drug Administration. FDA warns consumers not to purchase or use any tianeptine product due to serious risks. Page content current as of 8 May 2025.

FDA states tianeptine is not approved for any medical use in the US, is not generally recognized as safe for use in food, and does not meet the statutory definition of a dietary ingredient, yet is marketed as a research chemical, a nootropic cognitive enhancer or a dietary supplement at convenience stores, gas stations, vape shops and online retailers. Product names include Tianaa, Zaza, Neptune's Fix, Pegasus and TD Red, and tianeptine has been called gas station heroin. FDA reports severe adverse events with Neptune's Fix, including seizures, loss of consciousness and death, a voluntary recall of all lots by Neptune Resources, and an 11 January 2024 letter urging retailers to stop selling tianeptine products. It also cites case reports of daily intake of 1.3 to 250 times the typical daily dose in labeled foreign products.

Participants / model
Not a clinical population; US consumers of tianeptine products
Treatment
Unapproved oral products (elixirs, tablets, powders)
Follow-up
Page content current as of 8 May 2025
Study design
Official FDA alert
Funding
not stated in the source

A regulator warning and a list of reported events. It gives no incidence figure.

Read the original source
DEA proposed rule, 8 July 2026: tianeptine to schedule I, HHS recommended schedule I

Regulatory record

Drug Enforcement Administration. Schedules of Controlled Substances: Placement of Tianeptine in Schedule I. Proposed rule, 91 FR 42150, document 2026-13821, Docket DEA1596, published 8 July 2026.

On 8 July 2026 DEA published a proposed rule to place tianeptine in schedule I of the Controlled Substances Act. DEA sent its data to HHS on 7 September 2023, and HHS provided an evaluation on 18 July 2025 that recommended schedule I. The notice states there are no tianeptine products approved for medical use in the US, that tianeptine is approved in European, Asian and Latin American countries as a prescription drug typically used for depression, and that NFLIS reported 268 tianeptine encounters from March 2017 to February 2026. Comments were due 7 August 2026. A Federal Register search on 10 October 2026 for tianeptine returned this proposed rule and no final rule or temporary scheduling order.

Participants / model
Not a clinical population
Treatment
Federal drug scheduling
Follow-up
Proposed rule published 8 July 2026; comments due 7 August 2026
Study design
Official proposed rule
Funding
not stated in the source

A proposed rule is not final. Its status may have changed since 10 October 2026.

Read the original source
State statutes and rules in Ohio, Florida, Michigan and Minnesota list tianeptine

Regulatory record

Ohio Administrative Code 4729:9-1-01 (https://codes.ohio.gov/ohio-administrative-code/rule-4729:9-1-01); Florida Statute 893.03 (https://www.leg.state.fl.us/statutes/index.cfm?App_mode=Display_Statute&URL=0800-0899/0893/Sections/0893.03.html); Michigan Compiled Laws 333.7214 (https://www.legislature.mi.gov/Laws/MCL?objectName=mcl-333-7214); Minnesota Statute 152.02 (https://www.revisor.mn.gov/statutes/cite/152.02). Read directly on 10 October 2026.

Ohio Administrative Code 4729:9-1-01 lists tianeptine as item (71) among schedule I narcotics-opiates (rule effective 8 November 2025 as shown on the page). Florida Statute 893.03 lists tianeptine as item 57 in schedule I, subsection (1)(a). Michigan MCL 333.7214(f) lists tianeptine sodium in schedule 2. Minnesota Statute 152.02, subdivision 2 (schedule I), lists tianeptine under central nervous system depressants in paragraph (f). Alabama's 2021 controlled-substance action is described only in the poison-center paper. Georgia, Tennessee and Indiana were not confirmed.

Participants / model
Not a clinical population
Treatment
State controlled-substance schedules
Follow-up
Texts read on 10 October 2026
Study design
Official state statute and rule text
Funding
not stated in the source

Only the four states named were confirmed from primary text. Other states may also schedule tianeptine.

Read the original source
892 US poison-center exposures: rate up 1,400%, major effects 12.0%, admission 40.1%

Human study

Quadir M et al. J Med Toxicol. 2025;21(1):30-41. PMID 39724478.

The exposure rate rose 1,400% from 2015 to 2023, with a 525% rise from 2018 to 2023. Effects were moderate in 51.5% and major in 12.0%, and 40.1% required admission, including 22.9% to critical care. Abuse accounted for 40.1% of exposures and withdrawal for 22.5%. People aged 50 or older were more likely to have major effects (RR 1.70, 95% CI 1.13 to 2.56). The authors report that Alabama enacted legislation to regulate tianeptine as a controlled substance in 2021 and that its exposure rate then fell 74.6% from 2021 to 2023 while other southern states kept rising.

Participants / model
892 single-substance tianeptine exposures reported to US poison centers (National Poison Data System)
Treatment
Unregulated tianeptine products, mostly supplement or gas-station products
Follow-up
2015 to 2023
Study design
Poison-center surveillance analysis
Funding
not stated in the source

Poison-center calls are voluntary reports and do not give incidence.

Read the original source
New Jersey: 34 patients, 43% intubated, synthetic cannabinoids found in some products

Case report

Counts CJ et al. J Med Toxicol. 2025;21(2):253-259. PMID 40102319.

34 patients became ill after ingesting Neptune's Fix, 4.6 cases a month against a background of 0.5 cases a year. Among 37 exposures with acute toxicity, effects included altered mental status, tachycardia, hypotension and seizures; 43% (16) were intubated and 65% (24) were admitted to intensive care. Analysis of six ingested products found variable composition, including tianeptine, kava alkaloids, natural cannabinoids and the synthetic cannabinoids MDMB-4en-PINACA and ADB-4en-PINACA; MDMB-4en-PINACA was found in one of two patient blood samples.

Participants / model
34 patients in one New Jersey cluster; 6 product samples
Treatment
Oral tianeptine-labeled products (Neptune's Fix)
Follow-up
not stated in the source
Study design
Poison-center case series with product analysis
Funding
not stated in the source

A supplement-form product may not be tianeptine alone.

Read the original source
Two crossover studies, 8 and 15 volunteers: tianeptine not a respiratory stimulant

Randomized controlled trial

Algera H et al. Anesthesiology. 2022;137(4):446-458. PMID 35867853.

Oral tianeptine (8 subjects) did not significantly prevent alfentanil-induced respiratory depression. Intravenous tianeptine (15 volunteers) did not stimulate ventilation but worsened remifentanil-induced respiratory depression (minute ventilation 9.6 versus 15.0 L/min, mean difference 5.3 L/min, 95% CI 2.5 to 8.2, P = 0.001). The authors concluded neither route was a respiratory stimulant.

Participants / model
8 and 15 healthy volunteers in two studies
Treatment
Oral tianeptine; intravenous infusion to target plasma concentrations
Follow-up
not stated in the source
Study design
Two randomized double-blind placebo-controlled crossover studies
Funding
not stated in the source

An opioid-challenge model, not supplement use. Endpoints were ventilation at fixed carbon dioxide and minute ventilation.

Read the original source
Meta-analysis: 5 trials, 1,348 patients, tianeptine not different from SSRIs

Systematic review and meta-analysis

Kasper S et al. Eur Psychiatry. 2002;17 Suppl 3:331-40. PMID 15177089.

There was no significant difference between tianeptine and the SSRIs on MADRS total score or responder rate, and the authors concluded tianeptine was at least as effective as an SSRI.

Participants / model
1,348 patients with depression in 5 randomized trials (667 on tianeptine, 681 on an SSRI)
Treatment
Oral tianeptine versus SSRIs: two trials against fluoxetine, two against paroxetine and one against sertraline
Follow-up
Short-term treatment trials
Study design
2002 meta-analysis of randomized trials with an SSRI comparator
Funding
not stated in the source

The comparator was an SSRI, not placebo, and the abstract does not state who funded the trials. Endpoints were MADRS total score, responder rate and CGI.

Read the original source
126 outpatients, 42 days: final MADRS better on tianeptine than placebo

Randomized controlled trial

Costa e Silva JA et al. Neuropsychobiology. 1997;35(1):24-9. PMID 9018020.

Final MADRS scores were better on tianeptine in the intention-to-treat population, in patients treated 14 days or more, and in completers. Acceptability did not differ from placebo, and headache was more common on tianeptine. A 16.5-month relapse-prevention trial (PMID 12404534) reported relapse or recurrence in 16% versus 36% of 185 randomized responders.

Participants / model
126 outpatients with major depression or bipolar depression (MADRS 25 or higher)
Treatment
Oral tianeptine versus placebo
Follow-up
42 days
Study design
1997 multicenter randomized double-blind trial
Funding
not stated in the source

A prescription-use trial in patients with depression. The relapse-prevention trial was read at abstract level only. Endpoints were MADRS, CGI, anxiety and self-rating scales, and adverse events.

Read the original source
Healthy volunteers, single doses: emotional processing changed, no effect on non-emotional cognition

Human study

Cooper CM et al. J Psychopharmacol. 2015;29(5):582-90. PMID 25759404.

In healthy volunteers given a single dose of tianeptine or placebo, tianeptine reduced accuracy in identifying facial expressions, reduced positive affective memory and attentional vigilance to positive stimuli, and had no effect on emotional categorization or non-emotional cognition (working and verbal memory). A 1996 single-dose study of 16 healthy volunteers (PMID 9026373) found a lower dose gave slight EEG activation with mood elevation, and a higher dose gave EEG activation then sedation, lower vigilance and better attention on the Pauli test; plasma tianeptine peaked at 1 to 2 hours and the MC5 metabolite at 4 hours.

Participants / model
Healthy volunteers (number not stated in the 2015 abstract); 16 men and women aged 21 to 35 in the 1996 study
Treatment
Single oral doses of tianeptine or placebo
Follow-up
Single dose
Study design
Original randomized studies
Funding
not stated in the source

Small single-dose studies, not tests of repeated supplement use. Endpoints were emotional processing, working and verbal memory, EEG, attention and PK.

Read the original source
PubChem: tianeptine free acid, sodium salt and sulfate identity

Chemical identity record

National Library of Medicine. PubChem compound records CID 68870 (tianeptine), CID 23663953 (tianeptine sodium) and CID 68431515 (tianeptine sulfate).

Tianeptine (free acid): PubChem CID 68870, C21H25ClN2O4S, 437.0 g/mol, CAS 72797-41-2. Tianeptine sodium, the salt in the French tablet: CID 23663953, C21H24ClN2NaO4S, 458.9 g/mol, CAS 30123-17-2. A tianeptine sulfate record also exists: CID 68431515, C21H27ClN2O8S2, 535.0 g/mol, CAS 2093109-76-1. Which forms vendors sell was not established.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule and salts
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only. The three records are not interchangeable by weight, and supplement products were found to vary in content.

Read the original source

Why is Tianeptine in F tier?

F fits tianeptine as it is sold and used. It has a real prescription record in France and short-term depression trials, but FDA says it is not approved for any medical use in the US, poison centers report dependence, withdrawal and major effects, a New Jersey cluster included intubation and synthetic cannabinoids in some products, and no trial tests the nootropic claim.