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Tianeptine

Extensively Studied

Functionally a μ-opioid agonist sold as an "antidepressant nootropic" — at biohacker doses it produces opioid-tier euphoria, opioid-class… | Pharmaceutical · Oral

Aliases (11)
Stablon · Coaxil · Tatinol · Tianna · Tianna Red · Zaza · Zaza Red · TD Red · Neptune's Fix · Pegasus · gas station heroin
TYPICAL DOSE
12.5-25 mg
ROUTE
Oral (tablet)
CYCLE
None
STORAGE
Room temp; original container
✎
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▸Brand options8 known
StablonCoaxilTatinolTiannaTianna RedZazaZaza RedTD Red

StatusRx in France/EU/Asia (Stablon 12.5mg); Schedule I or controlled in 15+ US states (MI, AL, MN, TN, GA, IN, KY, OH, FL, MS, NC, LA, VA, DE, TX as of 2026); FDA Class I warning letter 2024 + reissued 2025; not federally scheduled in US (regulatory gap that fueled the gas-station epidemic)

▸ Overview TL;DR

Functionally a μ-opioid agonist sold as an "antidepressant nootropic" — at biohacker doses it produces opioid-tier euphoria, opioid-class dependence, opioid withdrawal, and opioid-mechanism deaths (naloxone-reversible). The 12.5 mg TID French Rx use is medically defensible under monitoring; everything else (US gas-station "Zaza Red," 50-2000+ mg/day "nootropic" stacks, research-chem powders) is opioid abuse with extra steps. SKIP-PERMANENT for all archetypes. Better non-opioid antidepressants and AMPA/BDNF neuroplasticity tools exist (TAK-653, agomelatine, ketamine for treatment-resistant depression).

▸ Mechanism of action

The original Servier marketing story (1983-2014) was that tianeptine was a "selective serotonin reuptake enhancer" — a backwards SSRI that increased serotonin uptake into neurons. That mechanism turned out to be wrong, or at best a downstream artifact.

What it actually is (Gassaway et al. 2014, Translational Psychiatry; replicated 2017, 2021, 2025):

  • Full μ-opioid receptor (MOR) agonist — Ki ~383 nM, EC50 ~194 nM for G-protein activation. Same target as morphine, heroin, fentanyl, oxycodone, hydrocodone. Lower affinity than classical opioids but full efficacy (it activates the receptor as completely as morphine does once bound).
  • Full δ-opioid receptor (DOR) agonist at higher concentrations.
  • Negligible direct activity at serotonin transporters, monoamine oxidases, or classical antidepressant targets.

Downstream effects (all MOR-dependent — knock out MOR in mice and they vanish):

  • Increased phosphorylation of AMPA receptor GluA1 subunit at Ser831/Ser845 → enhanced AMPA-mediated glutamate transmission
  • Reduction in dendritic atrophy in chronic stress models (the "neurorestorative" claim)
  • BDNF upregulation in hippocampus
  • Reduced GABA release from inhibitory interneurons in CA1, disinhibiting pyramidal neurons (2025 preprint, Bauer lab)
  • Antidepressant-like behavior in mouse forced-swim and tail-suspension — abolished by naloxone or MOR knockout

Translation: every "atypical neuroplasticity" effect tianeptine is marketed for is downstream of opening μ-opioid receptors. This is an opioid antidepressant. The structural distinction from classical opiates (it's a tricyclic dibenzothiazepine, not a phenanthrene like morphine) is chemically real but functionally irrelevant — the biology is opioid biology.

▸ Pharmacokinetics No data
Pharmacokinetics data not available for this compound.
No half-life mentions found in the source notes.
▸Research indications1 use cases

Full μ-opioid receptor (MOR) agonist

Most effective

Ki ~383 nM, EC50 ~194 nM for G-protein activation. Same target as morphine, heroin, fentanyl, oxycodone, hydrocodone. Lower affinity than…

▸Quality indicators4 checks
✓
FDA-approved manufacturer
NDC code on the bottle matches FDA registration. Generic OK; backyard not OK.
✓
Brand vs generic listed
Pharmacy fills should disclose substitution. AB-rated generics are bioequivalent.
✓
Tamper-evident packaging
Pharmacy seal intact, lot number + expiry visible on the bottle and the box.
!
Schedule labeling correct
C-II / C-IV warnings on label match the medication; report any mismatch to the pharmacist.
▸ What to expect Generic
  1. 1
    Day 1
    PK-driven acute peak per administration. Verify dose tolerated.
  2. 2
    Week 1
    Steady-state reached for most daily-dosed pharma.
  3. 3
    Week 2-4
    Therapeutic effect established; titration window if needed.
  4. 4
    Long-term
    Periodic monitoring per drug class (labs, BP, ECG as applicable).
▸ Side effects + safety

  • Common (>10% even at therapeutic dose):

    • Dry mouth, constipation, nausea (opioid GI signature)
    • Drowsiness, dizziness
    • Headache
    • Insomnia (paradoxical — short half-life crash)
    • At higher doses: itching, pinpoint pupils, sedation

  • Less common (1-10%):

    • Hepatotoxicity (rare elevations in transaminases; cases of hepatitis reported)
    • Mood swings on the post-dose crash
    • Tachycardia, hypertension during withdrawal even at therapeutic-dose discontinuation

  • Rare-serious (<1% but clinically critical):

    • Respiratory depression at high doses → ICU admission, mechanical ventilation, naloxone reversal documented
    • Death — 6 fatalities NJ June 2023-March 2024; 2 fatalities TX with pulmonary edema; ongoing per FDA reporting; often co-detected with kratom (mitragynine), buprenorphine, benzodiazepines (multi-substance overdose physiology)
    • Seizures at high doses (FDA Neptune's Fix advisory specifically lists seizures + loss of consciousness)
    • Severe withdrawal — autonomic storm, suicidal ideation during PAWS, ICU-level detox in heavy users
    • Full opioid use disorder by DSM-5 criteria

  • Specific watch periods:

    • All of them. There is no safe biohacker window. Dependence physiology starts within days at supra-therapeutic doses.
▸Interactions7 compounds
  • None should be considered.Synergistic
    All "synergies" amount to "stacking opioids with other CNS depressants" → respiratory depression risk multiplies.
  • kratomAvoid
    mitragynine + 7-OH-mitragynine are also μ-opioid agonists. Co-use is the most common pattern in tianeptine fatality case series. Stacking μ-agonists is how p…
  • phenibutAvoid
    GABA-B agonist + μ-opioid agonist = compounded sedation, respiratory depression, and two simultaneous severe withdrawals if both are run chronically. This is…
  • Any opioid (Rx or otherwise)Avoid
    additive μ-agonism, additive respiratory depression.
  • Benzodiazepines, Z-drugs, GHB/GBL, alcohol, gabapentinoidsAvoid
    additive respiratory depression. The CDC respiratory-depression-death warning for opioid + benzo applies fully.
  • MAOIsAvoid
    historically contraindicated; risk of serotonin/hypertensive interaction unclear given the corrected mechanism, but the warning stands.
  • Tramadol, tapentadolAvoid
    both have opioid + monoamine effects; stacking is doubly bad.
▸References23 sources

The atypical antidepressant and neurorestorative agent tianeptine is a μ-opioid receptor agonist (Gassaway et al. 2014, Translational Psychiatry)

2014

Original mechanism reversal paper. Ki ~383 nM at human MOR, full agonist at MOR + DOR.

nature.comView →

The Behavioral Effects of the Antidepressant Tianeptine Require the Mu-Opioid Receptor (Samuels et al. 2017, Neuropsychopharmacology)

2017

MOR-knockout mice lose all antidepressant-like behavioral response.

nature.comView →

Mu opioid receptors on hippocampal GABAergic interneurons are critical for the antidepressant effects of tianeptine (2021)

2021

Localizes the MOR-dependent mechanism to GABAergic interneurons.

pubmed.ncbi.nlm.nih.govView →

Tianeptine causes opioid-receptor-dependent beta oscillations in rat hippocampus (2025 bioRxiv preprint)

2025

Replication of MOR-mediated effects in 2025.

biorxiv.orgView →

Tianeptine disinhibits hippocampal CA1 pyramidal neurons by reducing GABAergic neurotransmission (2025 bioRxiv preprint)

2025

Mechanistic refinement: MOR on inhibitory interneurons → disinhibition → AMPA enhancement.

biorxiv.orgView →
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