This page shows what was measured, who it was measured in, and what that does not settle.
What Tianeptine does in the body
A prescription antidepressant elsewhere in the world. In the United States it is sold over a counter as a nootropic, and it is a full agonist at the same receptor as morphine
Tianeptine binds and fully activates the µ-opioid receptor, the receptor morphine works through, at sub-micromolar concentrations. Everything else about it — the antidepressant effect, the euphoria, the dependence, the withdrawal — follows from that. It was prescribed for three decades before anyone tested it against opioid receptors, which is the single most striking fact on this page. Its half-life is short, which is why people who misuse it take it many times a day and why withdrawal arrives quickly.
What happened in people
Full µ-opioid receptor agonism with Ki 383 ± 183 nM and EC50 194 ± 70 nM for human G-protein activation; full δ agonism at ~200-fold lower potency; inactive at κ
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
That approval as a prescription antidepressant abroad implies the exposure obtained from a US supplement-channel product is comparable
Where it acts
µ-opioid receptors in the central nervous system; the antidepressant-like behavioural effects in mice are abolished in animals lacking that receptor
Kind of result
The kind of result is not recorded
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
What the registries record it as
Its recorded molecular formula is C21H25ClN2O4S, weighing 437.
PubChem record · 68870 · read 2026-08-29
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 139 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Protein
A protein is a folded chain your body builds to do a specific job.
A picture of it, and where the picture fails
A protein is like a tool bent into one shape for one task.
Where that stops being true. A tool keeps its shape. A protein can change shape and stop working.
What people get wrong. Protein in food and a protein in the body are related but not the same thing.
A polymer of amino acids folded into a defined structure that determines its function.
Enzyme
An enzyme is a protein that speeds up one chemical change.
A picture of it, and where the picture fails
An enzyme is like a machine on a production line doing one cut.
Where that stops being true. A machine is switched on and off by a person. Enzymes are controlled by the cell.
What people get wrong. Enzymes are thought to be used up. They are not; they work again and again.
A catalytic protein that lowers the activation energy of a specific reaction.
Receptor
A receptor is a part of a cell that a signal fits into.
A picture of it, and where the picture fails
A receptor is like a lock waiting for one key.
Where that stops being true. A lock either opens or does not. A receptor can be half-triggered, or worn out.
What people get wrong. Fitting a receptor is read as causing a benefit. It causes a step, and nothing more.
A protein that binds a specific ligand and converts that binding into a cellular response.
Pathway
A pathway is a chain of steps inside a cell, each one setting off the next.
A picture of it, and where the picture fails
A pathway is like a row of dominoes.
Where that stops being true. Dominoes fall one way. Pathways loop back and can switch themselves off.
What people get wrong. Changing one step is read as changing the outcome. Other steps often absorb it.
An ordered series of molecular interactions producing a defined cellular change.
What happened in people◇Read from sources, not yet reviewed
What was measured, goal by goal
One row for each goal a registered study measured something for. One column for each kind of thing that could be measured.
Registered studies list 10 outcome measures that RNAWiki could read. A registered study says what someone planned to measure. It does not say what they found. 0 of the matched studies tested this substance, and 0 posted a result.
There is no single score. A strong test result and a weak life result are different facts.
Goals down the side, kinds of measurement across the top. Each cell says what kind of thing was registered, not what was found.
Goal
Life outcome
What a body can do
How a person feels
A test result
A step in the body
Harms
How long
Who was studied
Mood
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
…Waiting for a reviewer1 registered symptom measure.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Which registered measures put each goal on this table
Mood
montgomery asberg depression rating scale
Sorted by fixed word lists, version v1. A name the rules do not recognise stays unsorted rather than moving to the nearest column.
What each mark on this table means
∅ Nothing in the sources checked
No registered study lists a life outcome for this goal.
… Waiting for a reviewer
1 registered symptom measure.
— Not recorded
Harms were not a registered measure for this goal.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Binding affinity and functional potency of tianeptine at µ, δ and κ opioid receptors
✓ The study showed what it set out to show
Who was studied
Gassaway et al. 2014 receptor characterisation (Columbia University)
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The result reassigns the mechanism of a drug that had already been prescribed for three decades. No clinical study preceded it, and none of the licensing decisions abroad were made with this information.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet or capsule; abroad a 12.5 mg prescription tablet, in the US an unregulated supplement serving
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Characteristics and trend of tianeptine exposure calls
✓ The study showed what it set out to show
Who was studied
CDC National Poison Data System analysis, 2000-2017
How many people
218
Study design
National surveillance analysis
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Statistically significant increase in exposure calls and in intentional abuse or misuse calls from 2014 to 2017 (p < 0.001 for each); 5 calls in 2014 rising to 81 in 2017
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. No deaths were recorded in this dataset, which reflects the reporting system rather than the drug — poison-centre data capture calls made, and fatal cases are frequently identified through medical-examiner systems instead.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet or capsule; abroad a 12.5 mg prescription tablet, in the US an unregulated supplement serving
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Clinical presentation and management of tianeptine misuse, toxicity and withdrawal
✓ The study showed what it set out to show
Who was studied
Anand et al. 2026 systematic review of tianeptine misuse
How many people
1055
Study design
PRISMA 2020 systematic review
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
53 publications included (48 case reports, 5 retrospective series); of 52 extractable individual cases, 26 (50%) withdrawal and 23 (44%) overdose
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. A case-report-dominated evidence base cannot estimate incidence and carries publication bias. Study quality was assessed with Joanna Briggs Institute tools and findings synthesised narratively rather than pooled.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet or capsule; abroad a 12.5 mg prescription tablet, in the US an unregulated supplement serving
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 3 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What happened in people◇Read from sources, not yet reviewed
How close this is to real life
The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.
□Living longer, or avoiding a major eventNo evidence recorded. Death, a heart attack, a stroke, a hospital stay.No registered study measures this.
□What a body can do day to dayNo evidence recorded. Walking, dressing, breathing, recovering.No registered study measures this.
□Measured performanceNo evidence recorded. How much was lifted, how far was run, how fast.No registered study measures this.
■Symptoms and quality of lifeEvidence recorded. Pain, tiredness, mood, sleep, as the person rated it.1 registered measure of this kind.
□A number that stands in for healthNo evidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.No registered study measures this.
■A step measured inside a personEvidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
■AnimalsEvidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.Stored records in Mouse. A result in animals says what to test next. It does not say what happens in people.
■Cells in a dishEvidence recorded. Cells or chemistry on a bench, far from a whole body.Stored mechanism abstracts describe steps measured in cells or tissue.
□A guess from softwareNo evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.
Higher on these steps means closer to something a person would feel. It does not mean better done.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Tianeptine
What a person takes: Oral tablet or capsule; abroad a 12.5 mg prescription tablet, in the US an unregulated supplement serving.
The measurement behind this step
The licensed pharmaceutical is a 12.5 mg tablet taken three times daily. The products driving the US case literature are capsules, tablets and liquid shots sold as nootropics with no verified content, sometimes containing undeclared additional psychoactive substances. The delivery system is the retail channel as much as the dosage form.
Getting in
Swallowed — 12.5 mg abroad, far more in the US products
The licensed antidepressant dose is 12.5 milligrams three times a day. Products sold as supplements have contained many multiples of that in a single serving.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Oral tianeptine sodium. Rapid absorption with a short elimination half-life for the parent compound, which is why the licensed regimen is three times daily and why misuse patterns involve frequent redosing through the day.
Reaches the brain and is converted to a longer-lived metabolite
The parent drug clears quickly; a metabolite called MC5 lasts longer and does the same thing at the same receptor.
╌╌Measured in animals. A result in animals says what to test next. It does not say what happens in people.
The measurement behind this step
Beta-oxidation of the heptanoic acid side chain produces MC5, the principal metabolite, which has a longer half-life and reproduces tianeptine's behavioural effects in a µ-opioid-receptor-dependent manner in mice.
It switches on the morphine receptor completely, not partially. That is the finding that rewrote the drug's pharmacology in 2014.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Full µ agonist, Ki 383 ± 183 nM and EC50 194 ± 70 nM for human G-protein activation. Full δ agonist at roughly 200-fold lower potency, inactive at κ. Antidepressant-like behavioural effects are abolished in µ-opioid receptor knockout mice.
Antidepressant effect, analgesia and reward — all through the same receptor
The mood effect and the opioid effects are not separate. Removing the receptor removes both.
╌╌Measured in animals. A result in animals says what to test next. It does not say what happens in people.
The measurement behind this step
Both acute and chronic antidepressant-like effects in mice require µ. The same receptor mediates the analgesia and reward the drug also produces. This is a single-target pharmacology, which is why it is not possible to describe tianeptine as an antidepressant that happens to have opioid side effects.
Dependence, withdrawal and critical-care admissions
People taking large doses repeatedly become dependent, and withdrawal is a common reason for presenting to hospital.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Withdrawal accounted for 13.3% of US poison-centre exposure calls and 26 of 52 extractable individual cases in the 2026 systematic review. Among tianeptine-only exposures with a recorded level of care, 24% were admitted to critical care; clinical effects were neurologic in 48.3% and cardiovascular in 32.5%.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What it would be like to take◇Read from sources, not yet reviewed
Felt, measured, or meaningful
Three different things that get called the same word. Registered studies measured all three, and mixing them is how a blood test becomes a health claim.
Felt
Things a person could notice without a test.
montgomery asberg depression rating scale
Measured
Things only a test, a scale or a device shows.
No registered study measured anything of this kind.
Meaningful
Things that change how a life goes, not only a number.
No registered study measured anything of this kind.
A registered study says what someone planned to measure. It does not say what they found. A number moving is not the same as a life going better. The two are shown apart here.
Felt, but not shown to help. A person notices a change. No study showed it leads anywhere good.
Measured, but not felt. A number moves. The person notices nothing. Both can be true.
Measured, but not shown to matter. A number moves in the good direction. Nobody showed that lives went better.
Matters, but takes years. The result that counts may take longer than anyone would keep watching.
Names that fit none of the three (9)
changes in raven progressive matrices total from baseline
medication possession during first 180 days of treatment
persistence during first 180 days of treatment
who adhered to treatment measured by mpr
experiencing recurrence during the acute treatment phase
experiencing recurrence after the acute treatment phase
adverse events within maintenance phase of treatment
average daily dosage at index date
average daily dosage during the acute treatment phase
These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Abroad: patients with depression, on prescription, at conventional doses. In the US poison-centre series: predominantly men (82.3%) aged 21 to 40 (56.8%), taking it deliberately and often alongside phenibut.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
Where the result stopped carrying
Three decades of pharmacological investigation failed to identify the drug's molecular target, because opioid receptors were not among those tested
A targeted tianeptine assay would have found tianeptine in the New Jersey cluster and missed the synthetic cannabinoids that were also present
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied for a different goal
The studies measured something else entirely.
On this record: Some registered studies measured things that match no goal on this page.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (10)
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Varies by country
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral tablet or capsule; abroad a 12.5 mg prescription tablet, in the US an unregulated supplement serving
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
RNAWiki has not recorded a supervision or regulatory status for this substance.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
No register row and no identity class settled the question.
No source is stored against this line.
What is in the pack
5 mg tablet taken three times daily. The products driving the US case literature are capsules, tablets and liquid shots sold as nootropics with no verified content, sometimes containing undeclared additional psychoactive substances. The delivery system is the retail channel as much as the dosage form.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
Because it is a full µ-opioid agonist, the acute toxidrome is an opioid one: sedation, miosis and respiratory depression, with naloxone the relevant antidote. In US poison-centre data, tianeptine-only exposures produced neurologic effects in 48.3% and cardiovascular effects in 32.5%, with fluids, benzodiazepines and oxygen the commonest treatments and 24% of those with a recorded level of care admitted to critical care. Physical dependence develops with regular use and withdrawal is a common presentation. Co-exposure is frequent, phenibut most often. Products from the unregulated channel have contained undeclared synthetic cannabinoids. At licensed doses and under prescription abroad, the drug has an established tolerability record that does not describe any of the above.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
These are reports people sent to a regulator. They do not show the medicine caused the reaction.
Nobody counted how many people took the medicine and reported nothing.
The same event can be reported more than once, and many reports are incomplete.
News coverage, lawsuits and new warnings change how often people report.
A count is not a rate and not a risk.
Tianeptine appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 146 reaction mentions were counted. One report can name several reactions.
The recorded terms (10)
confusional state — 24 reaction mentions
lethargy — 20 reaction mentions
fall — 18 reaction mentions
toxicity to various agents — 18 reaction mentions
serotonin syndrome — 15 reaction mentions
agitation — 13 reaction mentions
hyponatraemia — 11 reaction mentions
cytolytic hepatitis — 9 reaction mentions
epilepsy — 9 reaction mentions
loss of consciousness — 9 reaction mentions
open-targets-adr · recorded 2026-06-24 · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral tablet or capsule; abroad a 12.5 mg prescription tablet, in the US an unregulated supplement serving
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
5 mg tablet taken three times daily. The products driving the US case literature are capsules, tablets and liquid shots sold as nootropics with no verified content, sometimes containing undeclared additional psychoactive substances. The delivery system is the retail channel as much as the dosage form.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
1 product lists this as an active ingredient in the United States drug directory. 1 of them contain it and nothing else.
FDA National Drug Code directory · 53069-0940 · read 2026-08-29
They are sold as powder.
FDA National Drug Code directory · 53069-0940 · read 2026-08-29
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.
Questions worth asking
Which of the trials of Tianeptine studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That the absence of tolerance and withdrawal in mice indicates a low human dependence liability
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That approval as a prescription antidepressant abroad implies the exposure obtained from a US supplement-channel product is comparable
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That "no deaths reported" in the poison-centre dataset means no deaths have occurred; that dataset counts calls, not fatalities
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the serotonin-reuptake-enhancement mechanism described in the pre-2014 literature is a partial account rather than a superseded one
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
How much did people take in the studies?
The sources RNAWiki checked hold nothing for this field.
Why it matters. A result belongs to an amount. Without the amount the result floats free.
What would answer it
A stored source that records it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
How fast does the body clear it?
The sources RNAWiki checked hold nothing for this field.
Why it matters. Without this, nothing on this page can say how long anything lasts.
What would answer it
A stored source that records it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Tianeptine are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
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A thirty-year-old antidepressant turned out to be an opioid
In plain words
Tianeptine had been prescribed since the 1980s and described as working by enhancing serotonin reuptake — a mechanism unlike any other antidepressant. In 2014 it was tested against opioid receptors for the first time and turned out to be a full agonist at the morphine receptor.
What was measured
Ki and EC50 at human and rodent µ, δ and κ opioid receptors, with µ-receptor knockout confirmation of the behavioural effects
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Gassaway et al. characterised tianeptine as an efficacious µ-opioid receptor agonist using radioligand binding and cell-based functional assays including BRET-based G-protein activation and cAMP accumulation: Ki 383 ± 183 nM at the human receptor, EC50 194 ± 70 nM for human and 641 ± 120 nM for mouse G-protein activation. It was also a full δ-opioid agonist at far lower potency (EC50 37.4 ± 11.2 µM human) and inactive at κ in both human and rat. The authors note that despite three decades of basic and clinical investigation the molecular target had remained elusive. Samuels et al. then showed that both the acute and the chronic antidepressant-like behavioural effects in mice require the µ-opioid receptor, that tianeptine also produces analgesia and reward, and that its principal metabolite MC5 mimics its behavioural effects in a µ-dependent fashion. The conclusion shift recorded here is unusually complete: not a refinement of a mechanism but its replacement, after the drug had been in clinical use for a generation.
Written into the record, not signed off as a reviewed claim
Poison-centre calls rose from five in 2014 to 81 in 2017
In plain words
US poison centres logged eleven tianeptine calls in the whole of 2000 to 2013. Then five in 2014, 38 in 2015, 83 in 2016 and 81 in 2017.
What was measured
Tianeptine exposure calls to US poison control centres by year, with demographics, co-exposures, clinical effects and level of care, 2000-2017
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
CDC analysed all tianeptine exposure calls in the National Poison Data System from 2000 to 2017: 218 calls in total. The first fourteen years produced 11 calls between them; from 2014 to 2017 the increase in both total exposure calls and intentional abuse or misuse calls was statistically significant (p < 0.001 for each), rising from 5 in 2014 to 38, 83 and 81 in the following three years. 91.2% of calls came from health-care providers. Callers were 82.3% male, with 56.8% aged 21 to 40 and a mean age of 35. Exposure was intentional in 54.6% and specifically a withdrawal presentation in 13.3%. Among the 83 calls reporting co-exposures, the most common was phenibut (31.3%), then ethanol (15.7%), benzodiazepines (12.0%) and opioids (12.0%). Among 114 tianeptine-only exposures excluding withdrawal calls, clinical effects were neurologic in 48.3%, cardiovascular in 32.5% and gastrointestinal in 10.5%; 25 of 105 with a recorded level of care (24%) were admitted to critical care, and 50 of 93 with a known outcome (54%) had a moderate outcome. No deaths were reported in this dataset.
Written into the record, not signed off as a reviewed claim
Systematic review: half of individual cases present in withdrawal
In plain words
A 2026 systematic review pooled every published human report of tianeptine misuse. Of the individual case reports, half were people in withdrawal and just under half were overdoses.
What was measured
Presentation type across 52 extractable individual cases from 53 included publications (N=1,055)
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Anand et al. searched MEDLINE, Embase, Cochrane, PsycInfo and Scopus from inception through July 2025 following PRISMA 2020, for human studies describing tianeptine misuse, toxicity, withdrawal or overdose. Fifty-three publications met inclusion criteria — 48 case reports and 5 retrospective series, N = 1,055 in total. Among the 52 individual cases with extractable detail, 26 (50%) presented with withdrawal and 23 (44%) with overdose. A literature dominated by case reports cannot establish incidence and is subject to publication bias in both directions, but the ratio of withdrawal to overdose presentations is itself informative: it describes a drug people are taking regularly enough to become dependent on, not one taken once.
Written into the record, not signed off as a reviewed claim
A severe-illness cluster caused by what else was in the bottle
In plain words
In New Jersey in 2023, a group of people became seriously ill after taking a tianeptine product. The cause was not only the tianeptine — the product also contained synthetic cannabinoids.
What was measured
Identification of synthetic cannabinoids alongside tianeptine in a product linked to a severe-illness cluster
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
CDC reported a cluster of severe illness linked to the tianeptine product Neptune's Fix in New Jersey between June and November 2023, in which synthetic cannabinoids were identified in the product alongside tianeptine. The episode demonstrates a failure mode specific to unregulated supplement-channel drugs: the labelled active ingredient is not the whole exposure, and clinicians treating an apparent tianeptine toxidrome were dealing with something else as well. It also demonstrates why the analytical workflow on this page includes an untargeted screen rather than a targeted tianeptine confirmation — a targeted assay would have returned a correct result and the wrong answer.
Written into the record, not signed off as a reviewed claim
Not scheduled federally, and not approved either
In plain words
Tianeptine appears nowhere in the US federal drug schedules and has no FDA approval. It occupies the gap between the two: legal to sell as a supplement, illegal to sell as a medicine.
What was measured
Absence from the federal drug schedules combined with absence of any FDA approval
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Tianeptine appears in no schedule of 21 CFR part 1308. It also holds no FDA approval, and CDC described it in 2018 as "not approved by the Food and Drug Administration for medical use and an unscheduled pharmaceutical agent". That combination — a licensed pharmaceutical abroad, an unapproved unscheduled substance domestically — is what allows it to be sold in the United States through the supplement and "nootropic" retail channel. Control has been enacted at state level instead, which produces the same patchwork the salvinorin A record describes. This is filed as measured because it is a checkable regulatory fact, and because readers routinely infer approval from availability.
Written into the record, not signed off as a reviewed claim
The mouse finding of no tolerance or withdrawal does not describe the case series
In plain words
In mice, tianeptine produced opioid-like analgesia and reward but not tolerance or withdrawal. In humans it plainly produces both, and half the published case reports are withdrawal presentations.
What was measured
That the absence of tolerance and withdrawal in mice indicates a low dependence liability in humans
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Samuels et al. reported that while tianeptine produces opiate-like behavioural effects including analgesia and reward in mice, it did not lead to tolerance or withdrawal in their experiments. That finding is often quoted as evidence that tianeptine carries a lower dependence liability than conventional opioids. The human record does not support extending it: 13.3% of US poison-centre exposure calls were specifically withdrawal presentations, and 26 of 52 extractable individual cases in the 2026 systematic review presented in withdrawal. The discrepancy is most plausibly explained by dose and dosing frequency — licensed human use is 12.5 mg three times daily, while the misuse pattern involves far larger and more frequent doses — but that explanation is itself an inference, and the mouse result should not be carried across as a safety claim.
Written into the record, not signed off as a reviewed claim
Phenibut is the commonest thing taken alongside it
In plain words
Of the tianeptine poison-centre calls that recorded another substance, the most frequent was phenibut — another drug sold in the same shops and also unscheduled.
What was measured
Co-exposure frequencies among tianeptine poison-centre calls
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Among the 83 tianeptine exposure calls reporting co-exposures in the CDC analysis, phenibut was the commonest at 26 calls (31.3%), ahead of ethanol (15.7%), benzodiazepines (12.0%) and opioids (12.0%). Both tianeptine and phenibut are unapproved, unscheduled and sold through the same supplement and smoke-shop channel, and both produce dependence with a withdrawal syndrome; phenibut has its own record on this site. The pairing is a property of the retail channel rather than of the pharmacology, and it matters clinically because the two withdrawal syndromes are managed differently — an opioid-type withdrawal and a GABA-B-type withdrawal presenting in the same patient.
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What is not here
4 questions this page could not answer
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The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
An antidepressant prescribed in around sixty countries that turned out, in 2014, to be a full µ-opioid receptor agonist — and which in the United States is unapproved, unscheduled, sold over a counter, and behind a rise in poison-centre calls from five in 2014 to 81 in 2017.
Recorded evidence blocks (10)
Q1
What did Tianeptine's largest trial (370212 people) and its longest (8.5 years) measure?
370212 people in Tianeptine's largest registered study, 8.5 years in its longest registered window, measuring Maximum Observed Plasma Concentration (Cmax) of JNJ-39823277. ClinicalTrials.gov · 2026-09-01
2 na, 2 phase2, 2 phase4, 1 na or unstated, 1 phase1, 1 phase3; NCT04145076; 2023-05-31; no ageing endpoint recorded. Last human test completed 2025, NCT05935059.
Interpretation These counts include studies where Tianeptine was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.
Show the evidence
na
2
phase2
2
phase4
2
na or unstated
1
phase1
1
phase3
1
1 more recorded row
Last recorded human testNCT05935059
2025-03-01
recorded 2026-09-01 · last checked 2026-09-04
Q2
From mouse to human: where has Tianeptine shown biomarker?
13; NCT00879372; PHASE3; the smallest recorded human enrolment at or below 30; the registry states no direction of its result; UNKNOWN
Q5
Which of adverse events within maintenance phase of treatment, average daily dosage at index date and average daily dosage during the acute treatment phase did Tianeptine's trials measure?
adverse events within maintenance phase of treatment, average daily dosage at index date and average daily dosage during the acute treatment phase lead 10 outcome terms across Tianeptine's trials. ClinicalTrials.gov · 2026-09-01
Interpretation who adhered to treatment measured by mpr, experiencing recurrence during the acute treatment phase, experiencing recurrence after the acute treatment phase, adverse events within maintenance phase of treatment, average daily dosage at index date and average daily dosage during the acute treatment phase follow.
Show the evidence
changes in raven progressive matrices total from baseline
1
medication possession during first 180 days of treatment
1
persistence during first 180 days of treatment
1
who adhered to treatment measured by mpr
1
experiencing recurrence during the acute treatment phase
1
experiencing recurrence after the acute treatment phase
1
4 more recorded rows
adverse events within maintenance phase of treatment
1
average daily dosage at index date
1
average daily dosage during the acute treatment phase
1
montgomery asberg depression rating scale
1
recorded 2026-09-01 · last checked 2026-09-04
Q6
What will the one ongoing trial of Tianeptine report, and when?
"Randomized, Double-blind, Placebo-controlled Trial of the Efficacy and Safety of Tianeptine in the Treatment of Covid Fog Symptoms in Patients After COVID-19."; n 140; "Improvement in covid fog symptoms"; 2027-10-31
recorded 2026-09-01 · last checked 2026-09-04
Q7
Which 2 trials of Tianeptine posted no result?
Posted no result
2 of 2 completed trials
Registrations
NCT02103985 and NCT01309776
Completion dates
oldest 2009-06; newest 2012-09
Show the evidence
Trial
NCT02103985
2009-06
NCT01309776
2012-09
Q8
At the median, Tianeptine's trials enrolled 100 people — anything larger?
Median enrolment
100
Largest enrolment
370212
Registered trials counted
9
Q9
What do 146 spontaneous reports say about Tianeptine — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Tianeptine appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 146 reaction mentions were counted: confusional state 24; lethargy 20; fall 18; toxicity to various agents 18. open-targets-adr · CHEMBL1289110 · 2026-06-24
Show the evidence
confusional state
24
lethargy
20
fall
18
toxicity to various agents
18
serotonin syndrome
15
agitation
13
4 more recorded rows
hyponatraemia
11
cytolytic hepatitis
9
epilepsy
9
loss of consciousness
9
recorded 2026-06-24 · last checked 2026-09-04
Q10
What is recorded about Tianeptine and mTOR?
"The aim of this study was to investigate the effects of the antidepressant tianeptine on the mechanistic target of rapamycin complex 1(mTORC1)-mediated autophagy pathway in primary hippocampal neurons exposed to B27-deprived conditions." — where Tianeptine and mTOR appear together. Europe PMC · pathway abstract search · 2025-04-25
mTOR, autophagy; PMID 40280952, 27129862
Show the evidence
mTORPMID 40280952
"The aim of this study was to investigate the effects of the antidepressant tianeptine on the mechanistic target of rapamycin complex 1(mTORC1)-mediated autophagy pathway in primary hippocampal neurons exposed to B27-deprived conditions."
autophagy
PMID 40280952
"The aim of this study was to investigate the effects of the antidepressant tianeptine on the mechanistic target of rapamycin complex 1(mTORC1)-mediated autophagy pathway in primary hippocampal neurons exposed to B27-deprived conditions."
PMID 40280952
"When primary hippocampal neurons were treated with tianeptine at doses of 1, 10, 50, and 100 µM for 3 days under B27-deprived conditions, we observed that it activated autophagy and increased the formation of autophagosomes through the upregulation of autophagic proteins, including autophagy-activating kinase 1 (ULK1), Beclin 1, LC3B-II/I, and p62."
PMID 40280952
"Changes in the expression of autophagic proteins induced by B27 deprivation were reversed by tianeptine treatment in a concentration-dependent manner, and tianeptine significantly reduced the increase in LC3B membrane number induced by B27 deprivation, an effect that was blocked by pretreatment with rapamycin."
mTOR
"<title>Abstract</title> <p>The aim of this study was to investigate the effects of the antidepressant tianeptine on the mechanistic target of rapamycin 1(mTORC1)-mediated autophagy pathway in primary hippocampal neurons exposed to B27-deprived conditions."
PMID 27129862
"Tianeptine increased BDNF, dendritic outgrowth, spine density, and synaptic proteins; all of these effects were blocked by the mTORC1 inhibitor."
recorded 2025-04-25 · last checked 2026-09-04
Where it is registeredIdentifiers, relations and other names
Gas station heroin, Jnj-39823277, Stablon, Tianeptina
Trade name
Stablon, Coaxil, Tatinol — prescription antidepressant brands in Europe, Asia and Latin America. In the United States it is sold unapproved as a "nootropic" under names such as Zaza and Neptune's Fix
Sources (6)
Sources
ClinicalTrials.govClinicalTrials.gov API v2 snapshot 2026-09-01T09:00:05 ·
ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · Europe PMC — metadata only, under the recorded legal gate · Open Targets 26.06 — CC0 · derived from this page's own recorded fields; no external licence
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✓ source coverage passed: 6 source rows
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