No reaction
No reactionWARNINGDANGER OF DEATH
Most cases of fatal overdose occur when depressants like opioids are combined with other depressants such as alcohol, benzodiazepines or gabapentinoids. It is highly discouraged to combine these substances.
Tianeptine
Tianeptine
Stablon, Coaxil, Tatinol, ZaZa, Tianna Red
Tianeptine is an atypical tricyclic antidepressant of the dibenzothiazepine class.1 Unlike typical tricyclics, it is thought to act primarily through glutamatergic modulation rather than direct monoaminergic regulation. Clinically prescribed for depression and anxiety, it also exhibits anxiolytic and purported nootropic properties. At supratherapeutic doses, tianeptine produces opioid-like effects, contributing to its recreational misuse potential. It is considered habit-forming and is most commonly available in its sodium salt form.
Dosage & Duration
Dosage
Threshold~3 mg
Light3-12 mg
Moderate12-35 mg
Strong35-100 mg
Heavy100+ mg
Bioavailability
~99%
Tianeptine occurs commonly in 2 salts, sodium and sulfate. The duration of sulfate is much longer.
Duration
Onset30-60 minutes
Come Up15-30 minutes
Peak1-1.5 hours
Offset0.5-1 hours
After Effects1-8 hours
Total2-3 hours
Half-life
2.5-3 hours
Subjective Effects
Effects vary widely by individual, dose, and context.
Physical
Cognitive
Visual
Pharmacology
Pharmacodynamics
Tianeptine acts primarily as a full agonist of the μ-opioid receptor (MOR) and may function as a biased agonist at this site.23 It also shows full agonism at the δ-opioid receptor with approximately 200-fold lower potency, while κ-opioid receptor activity is clinically negligible.2 Tianeptine indirectly modulates glutamatergic neurotransmission through effects on AMPA and NMDA receptors and promotes the release of brain-derived neurotrophic factor (BDNF), influencing neuroplasticity.4 Additional actions include allosteric modulation of the serotonin transporter (SERT) that enhances rather than inhibits serotonin reuptake,4 modest enhancement of mesolimbic dopamine release with indirect potentiation of D2 and D3 receptor signaling (without direct receptor affinity), and high-efficacy agonism at the nuclear receptor PPAR-δ.5
Pharmacokinetics
Tianeptine has an oral bioavailability of approximately 99% and reaches peak plasma concentrations within about one hour, with approximately 95% plasma protein binding.6 Metabolism is hepatic via β-oxidation, and CYP enzymes are not involved, limiting the potential for drug-drug interactions.17 The elimination half-life is 2.5 to 3 hours, increasing to 4 to 9 hours in elderly individuals.6 Two active metabolites are produced: MC5, which retains μ-opioid but not δ-opioid agonist activity and has a longer half-life of approximately 7.6 hours, and MC3, which is a much weaker μ-opioid agonist. MC5 takes about one week to reach steady-state under daily dosing. Approximately 65% of tianeptine is excreted renally and 15% in feces.6
Interactions
Interactions not written up yet
An unlisted combination is an unknown one, not a safe one. Check a dedicated combination chart before mixing.
Tolerance
Full Tolerance
Tolerance to many of tianeptine's effects develops with prolonged and repeated use, including its therapeutic benefits. This necessitates progressively larger doses to achieve equivalent effects. The compound's short duration of action may encourage frequent redosing, and the euphoric properties at high doses (above 100mg) can accelerate tolerance development.
Baseline Reset
1-2 weeks
Half Tolerance
3-7 days
Cross Tolerance
Opioids, Tricyclic antidepressants
Harm Potential
Addiction & Dependence
Psychological
ModerateTianeptine has moderate abuse potential, particularly at doses exceeding the therapeutic range. Its short duration of action may compel frequent redosing, and the opioid-like euphoria at high doses (above 100mg) can drive compulsive use patterns.8 Between 1989 and 2004, France identified 141 cases of recreational use, representing 1 to 3 cases per 1000 treated patients.
Physical
ModeratePhysical dependence develops with chronic use at high doses. Withdrawal symptoms resemble those of typical opioids including agitation, nausea, vomiting, tachycardia, hypertension, diarrhea, tremor, and diaphoresis, along with emotional instability.9 Withdrawal severity correlates with daily dosage and duration of use, with high doses described as extremely difficult to quit.
Toxicity
Cardiovascular
Unlike other tricyclic antidepressants, tianeptine produces significantly fewer cardiovascular effects and does not appear to affect heart function at therapeutic doses.1
Vascular
Intravenous injection of crushed tablets can cause thrombosis and severe necrosis due to silica and other undissolved particles blocking capillaries; this harm is associated with improper administration of oral formulations rather than inherent compound toxicity.
Seizure Risk
Research indicates possible anticonvulsant activity via downstream modulation of adenosine A1 receptors, suggesting tianeptine may have seizure-protective rather than seizure-promoting properties.
History & Culture
Discovery and Medical Development
Tianeptine was developed and patented by the French Society of Medical Research during the 1960s.10 Following clinical development, it was introduced for therapeutic use in France in 1983, becoming available through Laboratories Servier…
Legality
By Country
United StatesRestrictedUnapproved drug
Tianeptine is not approved by the Food and Drug Administration for any medical use in the United States. Under the Federal Food, Drug, and Cosmetic Act, a new drug may not be introduced or delivered for introduction into interstate commerce unless an approved application is effective; FDA states that some companies are illegally marketing and selling tianeptine products to consumers. Tianeptine does not appear in the current federal controlled-substance schedules in 21 CFR Part 1308.
By state
0 United States jurisdictions were confirmed to treat tianeptine consistently with the federal FDA-unapproved-drug baseline. 6 jurisdictions have a source-backed divergent controlled-substance classification. The remaining 50 jurisdictions are preserved as research gaps rather than inferred from federal law.
AlabamaIllegalSchedule I controlled substance
FloridaIllegalSchedule I controlled substance
North CarolinaIllegalSchedule II controlled substance
OhioIllegalSchedule I controlled substance
TennesseeIllegalSchedule II controlled substance
VirginiaIllegalSchedule I controlled substance
GermanyPrescription onlyAnlage 1
Tianeptine and its esters are listed in Anlage 1 of the Arzneimittelverschreibungsverordnung. Medicinal products that are or contain listed substances may be dispensed only on a medical, dental, or veterinary prescription, unless the regulation provides otherwise. The rule regulates dispensing of medicinal products and does not itself make possession generally contingent on holding a prescription.
SwedenControlledCitation needed
Not approved as a prescription medicine in Sweden, and is therefore classified as a controlled substance. Possession without authorization is illegal.
TurkeyPrescription only (green prescription)Citation needed
Designated as a 'green prescription' substance, indicating controlled distribution through pharmacies. Illegal when sold or possessed without a valid prescription.
CanadaNot scheduledNot controlled
Legal to possess without any license or prescription. Not scheduled under federal controlled substances legislation.
RussiaSchedule IIICitation needed
Classified as a Schedule III controlled substance since 2010.11 Possession, distribution, and production without authorization is prohibited.
SwitzerlandUncontrolledCitation needed
Not listed under controlled substance categories Buchstabe A, B, C, or D. Generally considered legal to possess.
References
Source Pages
Citations
- Tianeptine: a review of its use in depressive disorders. CNS Drugs, 15(3), 231–59 (March 2001). https://doi.org/10.2165/00023210-200115030-00006123
- <br /> |- | || 10000+ (K<sub>i</sub>)<br />37400 (. (n.d.). https://doi.org/10.1038/tp.2014.30123
- The Behavioral Effects of the Antidepressant Tianeptine Require the Mu-Opioid Receptor. Neuropsychopharmacology, 42(10), 2052–2063 (September 2017). https://doi.org/10.1038/npp.2017.6012
- The neurobiological properties of tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation. (n.d.). https://pmc.ncbi.nlm.nih.gov/articles/PMC2902200/12
- Activity Screening of Fatty Acid Mimetic Drugs Identified Nuclear Receptor Agonists. International Journal of Molecular Sciences, 23(17) (September 2022). https://doi.org/10.3390/ijms2317100701
- R J Royer, H Albin, D Barrucand, C Salvadori-Failler, & A Kamoun. (1988). Pharmacokinetic and metabolic parameters of tianeptine in healthy volunteers and in populations with risk factors. Clinical Neuropharmacology, 11(Suppl 2), S90-6. https://pubmed.ncbi.nlm.nih.gov/3180120/123
- Bernard Fromenty, Eric Freneaux, Gilles Labbe, Dominique Deschamps, Dominique Larrey, Philippe Letteron, & Dominique Pessayre. (1 Nov 1989). Tianeptine, a new tricyclic antidepressant metabolized by beta-oxidation of its heptanoic side chain, inhibits the mitochondrial oxidation of medium and short chain fatty acids in mice. Biochem Pharmacol, 38(21), 3743–3751. https://doi.org/10.1016/0006-2952(89)90580-71
- Tianeptine Abuse and Dependence in Psychiatric Patients: A Review of 18 Case Reports in the Literature. Journal of Psychoactive Drugs, 50(3), 275–280 (March 2018). https://doi.org/10.1080/02791072.2018.14386871
- Tharwat El Zahran, Joshua Schier, Emily Glidden, Stephanie Kieszak, Royal Law, Edward Bottei, Cynthia Aaron, Andrew King, & Arthur Chang. (August 2018). Characteristics of Tianeptine Exposures Reported to the National Poison Data System - United States, 2000-2017. MMWR. Morbidity and Mortality Weekly Report, 67(30), 815–818. https://doi.org/10.15585/mmwr.mm6730a21
- Classics in Chemical Neuroscience: Tianeptine. (n.d.). https://doi.org/10.1021/acschemneuro.4c00519123
- Characteristics of Tianeptine Exposures Reported to the National Poison Data System - United States, 2000-2017. (n.d.). https://www.cdc.gov/mmwr/volumes/67/wr/mm6730a2.htm123
- Drug Enforcement AdministrationDiversion Control DivisionDrug & Chemical Evaluation Section - Tianeptine. (n.d.). https://www.deadiversion.usdoj.gov/drug_chem_info/tianeptine.pdf123
- Novel Psychoactive Substances: Tianeptine (LAPPA Fact Sheet, March 2023). (n.d.). https://legislativeanalysis.org/wp-content/uploads/2023/03/Tianeptine-Fact-Sheet-FINAL.pdf12345
- FDA Warns Consumers Not to Purchase or Use Neptune's Fix or Any Tianeptine Product Due to Serious Risks. (n.d.). https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-consumers-not-purchase-or-use-neptunes-fix-or-any-tianeptine-product-due-serious-risks1
- Senate Bill 801 of 2018 (Public Act 107 of 2018) - Michigan Legislature. (n.d.). https://www.legislature.mi.gov/Bills/Bill?ObjectName=2018-SB-08011
- Controlled Drugs and Substances Act. canada.ca (n.d.). https://www.canada.ca/en/health-canada/services/publications/healthy-living/new-psychoactive-substances-canada-2024.html1
- Controlled Drugs and Substances Act. laws.justice.gc.ca (n.d.). https://laws.justice.gc.ca/eng/acts/C-38.8/FullText.html1
- Anlage 1 AMVV (Arzneimittelverschreibungsverordnung) — gesetze-im-internet.de. gesetze-im-internet.de (n.d.). https://www.gesetze-im-internet.de/amvv/anlage_1.html1
- Arzneimittelverschreibungsverordnung (AMVV). gesetze-im-internet.de (n.d.). https://www.gesetze-im-internet.de/amvv/__1.html1
- Arzneimittelverschreibungsverordnung (AMVV). gesetze-im-internet.de (n.d.). https://www.gesetze-im-internet.de/amvv/index.html1
- Psychoactive Substances Act 2016. (2016). https://www.legislation.gov.uk/ukpga/2016/2/contents/enacted12
- Tianeptine. fda.gov (n.d.). https://www.fda.gov/consumers/health-fraud-scams/tianeptine1
- 21 U.S.C. 355 — New drugs. uscode.house.gov (n.d.). https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title21-section355&num=0&edition=prelim1
- 21 CFR Part 1308 — Schedules of Controlled Substances. ecfr.gov (n.d.). https://www.ecfr.gov/current/title-21/chapter-II/part-13081
- Alabama Administrative Code r. 420-7-2-.01, Schedule I. admincode.legislature.state.al.us (n.d.). https://admincode.legislature.state.al.us/administrative-code/420-7-2-A1
- Fla. Stat. § 893.03, Schedule I. leg.state.fl.us (n.d.). https://www.leg.state.fl.us/statutes/index.cfm?App_mode=Display_Statute&Search_String=&URL=0800-0899/0893/Sections/0893.03.html1
- N.C. Gen. Stat. § 90-90, as amended by S.L. 2024-43. ncleg.gov (n.d.). https://www.ncleg.gov/EnactedLegislation/SessionLaws/HTML/2023-2024/SL2024-43.html1
- Ohio Admin. Code 4729:9-1-01. codes.ohio.gov (n.d.). https://codes.ohio.gov/ohio-administrative-code/rule-4729%3A9-1-011
- Tenn. Code Ann. § 39-17-408, as amended by 2022 Tenn. Pub. Acts, ch. 1090. wapp.capitol.tn.gov (n.d.). https://wapp.capitol.tn.gov/apps/BillInfo/Default?BillNumber=SB1997&ga=1121
- Code of Virginia § 54.1-3446, Schedule I. law.lis.virginia.gov (n.d.). https://law.lis.virginia.gov/vacode/title54.1/chapter34/section54.1-3446/1
Further Reading
Drugs-Forum: recreational use experiences (2012)
FDA consumer warning (2024)
IV toxicity case report (2017)
Mississippi withdrawal cases (2022)
Opioid-system mechanisms review (2023)- Pain Therapy narrative review (2023)
PBS NewsHour FDA warning coverage (2023)
Pharmacology and use review (ResearchGate 2018)
Reddit: community experiences (r/QuittingTianeptine)- Reddit: dosage discussion (r/researchchemicals 2023)
- Reddit: high-dose habit report (r/QuittingTianeptine 2024)
- Reddit: social media analysis (PMC 2021)
- Severe withdrawal case management (2023)
UIC Pharmacy FAQ on tianeptine misuse (2024)
VICE article on Reddit withdrawal support
- Reviewed & approved
Reviewed, edited, and approved by subject-matter expert Lyrea.
Automated synthesisInformation aggregated and synthesized using an autonomous workflow built by Josie Kins.
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