Tianeptine
Tianeptine sodium / sulfate
Also known as: Neptune's Fix, ZaZa Red, Tianna, TD Red
This ingredient is classified as unclassified risk (GIRI score: 9.5/10).
Safety Profile
Known Safety Concerns
- Unapproved drug — marketed illegally as a supplement in the US
- Opioid-like dependence and severe withdrawal syndrome
- Fatal overdoses documented — often combined with other substances
- Banned in Alabama, Georgia, Indiana, Michigan, Minnesota, Mississippi, Ohio, and others
- FDA import alert and safety warnings issued
Contraindications
- Unapproved drug — marketed illegally as a supplement in the US
- Opioid-like dependence and severe withdrawal syndrome
Interactions
Information not yet available for this ingredient profile.
Evidence and Scientific Findings
Ingredient Overview
Tianeptine is an atypical antidepressant with opioid agonist activity at mu-opioid receptors, marketed in the US as a dietary supplement despite being unapproved as a drug. At high doses it produces opioid-like euphoria, rapid tolerance, severe physical dependence, and a withdrawal syndrome indistinguishable from opioid withdrawal. Multiple US states have banned it. The FDA has issued warnings and import alerts. Overdose fatalities have been documented.
Biological and Chemical Classification
- Scientific Name
- Tianeptine sodium / sulfate
Mechanism of Action
Information not yet available for this ingredient profile.
Clinical Evidence of Effectiveness
Information not yet available for this ingredient profile.
Pharmacokinetics
Information not yet available for this ingredient profile.
Recommended Dosage
Information not yet available for this ingredient profile.
SETI — Scientific Evidence Transparency Index
Executive Summary — Ingredient Assessment
- 10 studies reviewed
- 0 high-quality studies (meta-analysis or RCT)
- Evidence consistency: High consistency across studies (100%)
- Unapproved drug — marketed illegally as a supplement in the US
- Opioid-like dependence and severe withdrawal syndrome
- Fatal overdoses documented — often combined with other substances
- Banned in Alabama, Georgia, Indiana, Michigan, Minnesota, Mississippi, Ohio, and others
- FDA import alert and safety warnings issued
The available scientific evidence for Tianeptine indicates notable safety signals that warrant caution. Use should be considered carefully and monitored, particularly in sensitive populations or alongside other medications.
Total SETI Score
High risk| Evidence quality | 10/40 |
| Evidence consistency | 20/20 |
| Safety signals | 0/20 |
| Study recency | 10/10 |
| Evidence transparency | 10/10 |
Evidence Summary
- 10 studies reviewed
- 0 high-quality studies (meta-analysis or systematic review)
- 0 studies identified benefits or no safety concern (GREEN)
- 10 studies reported limited or advisory safety evidence (YELLOW)
Evidence Policy
Only peer-reviewed scientific literature indexed in PubMed or comparable databases is included in this evaluation. Commercial websites, blogs, and marketing materials are excluded. All references include direct traceable links to source documents.
Last updated: 23 მარ 2026, 14:49
Evidence Distribution
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Observational / other LOW evidence YELLOWImproving Cognition in Bipolar Disorder: A Systematic Review of Current Pharmacological and Nutraceutical Approaches. ↗Yalin N et al.. Improving Cognition in Bipolar Disorder: A Systematic Review of Current Pharmacological and Nutraceutical Approaches.. Neuropsychobiology. 2026. PMID:41843701.PMID 41843701 ↗Journal NeuropsychobiologyYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41843701/
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Observational / other LOW evidence YELLOWDifferential inhibition of the diverse behavioural effects of mu-opioid receptor agonists by progressive receptor depletion. ↗Brown L et al.. Differential inhibition of the diverse behavioural effects of mu-opioid receptor agonists by progressive receptor depletion.. Neuropharmacology. 2026. PMID:41796936.PMID 41796936 ↗Journal NeuropharmacologyYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41796936/
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Observational / other LOW evidence YELLOWu03bc Opioid Modulation of Sensorimotor Functional Connectivity in Autism: Insights From a Pharmacological Neuroimaging Investigation Using Tianeptine. ↗Dimitrov M et al.. u03bc Opioid Modulation of Sensorimotor Functional Connectivity in Autism: Insights From a Pharmacological Neuroimaging Investigation Using Tianeptine.. Biol Psychiatry Glob Open Sci. 2026. PMID:41630828.PMID 41630828 ↗Journal Biol Psychiatry Glob Open SciYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41630828/
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Observational / other LOW evidence YELLOWPrediction of 12-Week Remission in Patients With Depressive Disorder Using Reasoning-Based Large Language Models: Model Development and Validation Study. ↗Park JH et al.. Prediction of 12-Week Remission in Patients With Depressive Disorder Using Reasoning-Based Large Language Models: Model Development and Validation Study.. JMIR Ment Health. 2026. PMID:41576265.PMID 41576265 ↗Journal JMIR Ment HealthYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41576265/
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Observational / other LOW evidence YELLOWEmerging Substances and Perinatal Health: A Narrative Review. ↗Jones CW et al.. Emerging Substances and Perinatal Health: A Narrative Review.. Obstet Gynecol. 2026. PMID:41166713.PMID 41166713 ↗Journal Obstet GynecolYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41166713/
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Observational / other LOW evidence YELLOWTargeting Cend1-Atp5f1b interaction rescues mitochondrial dysfunction and ameliorates ischemic brain injury. ↗Li H et al.. Targeting Cend1-Atp5f1b interaction rescues mitochondrial dysfunction and ameliorates ischemic brain injury.. Commun Biol. 2025. PMID:41469760.PMID 41469760 ↗Journal Commun BiolYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41469760/
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Observational / other LOW evidence YELLOWReal-World Effects of Home-Based Transcranial Direct Current Stimulation in Depression: A Randomized Controlled Trial of 3-Week Versus 6-Week Protocols. ↗Park HY et al.. Real-World Effects of Home-Based Transcranial Direct Current Stimulation in Depression: A Randomized Controlled Trial of 3-Week Versus 6-Week Protocols.. Brain Behav. 2025. PMID:41376187.PMID 41376187 ↗Journal Brain BehavYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41376187/
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Observational / other LOW evidence YELLOWGas station heroin- tianeptine and its impact: a systematic review and exploratory analysis. ↗Parnia S et al.. Gas station heroin- tianeptine and its impact: a systematic review and exploratory analysis.. BMC Public Health. 2025. PMID:41136982.PMID 41136982 ↗Journal BMC Public HealthYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41136982/
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Observational / other LOW evidence YELLOWGas Station Heroin: A Case Report of Tianeptine Use Disorder and a Literature Review. ↗Kandra K et al.. Gas Station Heroin: A Case Report of Tianeptine Use Disorder and a Literature Review.. Cureus. 2025. PMID:41132482.PMID 41132482 ↗Journal CureusYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41132482/
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Observational / other LOW evidence YELLOWConcomitant Tianeptine and Alcohol Use Disorders: Diagnosis and Treatment with Buprenorphine-Naloxone. ↗Krause Q et al.. Concomitant Tianeptine and Alcohol Use Disorders: Diagnosis and Treatment with Buprenorphine-Naloxone.. Kans J Med. 2025. PMID:41127130.PMID 41127130 ↗Journal Kans J MedYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41127130/
Score Transparency
0 of 10 approved references (score saturates at 10). More peer-reviewed studies = stronger evidence base.
Method: Q = number of approved references ÷ 10 (capped at 1.0)
Limited — mostly case reports or animal studies
Method: L = mean study-level weight across approved references. Level 1 (meta-analysis / systematic review) = 1.0; Level 2 (RCT) = 0.8; Level 3 (cohort/case-control) = 0.6; Level 4 (case report) = 0.4; Level 5 (animal / in-vitro) = 0.2.
Mixed or neutral — roughly equal benefit and risk signals
Method: D = (sum of risk-scored references − sum of benefit-scored references) ÷ total evidence score, then scaled from [−1, 1] to [0, 1]. 0.0 = pure benefit; 0.5 = neutral; 1.0 = pure risk.
One or more monitoring-level safety signals active
Method: S = 0.5 (neutral baseline) + sum of active signal severity deltas ÷ 10. Severity deltas: Critical = +2.0, High = +1.5, Moderate = +1.0, Low = +0.5. Capped at 1.0.
Final GIRI Score for Tianeptine. Risk level thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.
Full methodology & data sources
The GIRI Score is computed entirely from structured data — no editorial scoring or subjective weighting is applied at any step.
- References: Only approved references are counted. Each reference is assigned an evidence level (L1–L5) and a direction (risk / neutral / benefit) by the reference manager or AI classifier.
- Safety Signals: Sourced from regulatory agencies (FDA, EMA, Health Canada, TGA, and others) and pharmacovigilance databases. Only active signals count toward the score.
- Formula version: GIRI Score v3.7.0 — Q × L × D × S × 10.
- Limitations: The score reflects published evidence and recorded signals as of the last update date. It is not a clinical risk assessment and should not replace advice from a qualified healthcare professional.
Risk Level Classification
Based on available regulatory signals and scientific evidence, this ingredient presents a critical safety concern. Regulatory restrictions or bans are in place in multiple jurisdictions.
0–3.0
3.0–5.5
5.5–7.5
7.5–10
The score pin shows exactly where this ingredient falls on the fixed risk scale.
What drove the Critical classification for Tianeptine
A score of 9.5 places this ingredient in the Critical band. Thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.
0 approved references.
Limited — mostly case reports or animal studies (Level 4–5).
Neutral or mixed — benefit and risk signals roughly balanced.
No active signals — S component is at neutral baseline (0.5), contributing no extra risk weight.
No major regulatory restrictions or advisories recorded across monitored jurisdictions (FDA, EMA, Health Canada, TGA, and others).
How are the Low / Moderate / High / Critical thresholds defined?
The four risk levels are fixed score bands. A score is assigned to exactly one level based on where it falls:
| Level | Score | Meaning |
|---|---|---|
| LOW | 0.0 – 2.9 | Sparse or predominantly beneficial evidence. No active safety alerts. |
| MODERATE | 3.0 – 5.4 | Mixed signals — some risk alongside benefit. Caution at high doses or in sensitive groups. |
| HIGH | 5.5 – 7.4 | Multiple studies or regulatory alerts documenting adverse effects. Professional oversight recommended. |
| CRITICAL | 7.5 – 10 | Regulatory restrictions in one or more major jurisdictions. Serious documented harm. Avoid without specialist supervision. |
Thresholds are fixed constants (GIRI_Score_Utils::LEVEL_THRESHOLDS). They do not change per ingredient and are never subject to editorial adjustment.