Tianeptine
Tianeptine is an atypical antidepressant prescribed in parts of Europe, Asia and Latin America, with an unusual glutamatergic and mu-opioid mechanism. At therapeutic doses it treats depression, but at supratherapeutic doses it acts as a mu-opioid agonist, and it is increasingly sold in the US as an unregulated "gas station" supplement with a clear potential for opioid-like dependence and withdrawal.
01 Overview
At therapeutic doses (around 12.5 mg three times daily) tianeptine has decades of use as an antidepressant, with a side-effect profile historically considered favourable. Its mechanism is atypical: it modulates glutamatergic signalling and synaptic plasticity and is a full agonist at the mu-opioid receptor, which is now understood to underlie both its antidepressant action and its abuse potential.
Outside approved medical use, tianeptine is sold in the US in capsules and "supplements" (e.g. under brand names marketed near cash registers) and misused at many times the therapeutic dose to produce opioid-like euphoria. At these doses it causes tolerance, compulsive use, and a genuine opioid-type withdrawal syndrome on cessation; US poison-control calls and FDA warnings have risen sharply. This dependence liability is the central honest point: at high doses tianeptine behaves like an opioid, and stopping abruptly can produce severe withdrawal.
02 Mechanism
Modulates glutamatergic AMPA/NMDA signalling and synaptic plasticity; also a full mu-opioid receptor agonist, which mediates its euphoric and dependence-producing effects at high doses.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Therapeutic | 12–37 mg/day | Oral | Approved antidepressant dosing, ~12.5 mg three times daily. |
| Supratherapeutic (misuse) | 100–1000 mg/day | Oral | Doses used for opioid-like effect; associated with dependence, toxicity and overdose. Not a recommendation. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Antidepressant effectImprovement in depressive symptoms at therapeutic doses, supported by clinical trials in approving countries. | Clinical | ||
| Opioid-like euphoriaAt high doses, mu-opioid agonism produces euphoria and sedation — the basis of its misuse. | Observational | ||
| Anxiolytic effectReduction in comorbid anxiety reported in trials at therapeutic doses. | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Hepatic and other therapeutic-dose effectsNausea, constipation, dry mouth, dizziness and, rarely, hepatic reactions at therapeutic doses. | Mild | Common | Clinical | |
| Dependence and opioid-type withdrawalCompulsive use, tolerance and an opioid-like withdrawal syndrome (anxiety, sweating, GI distress, craving) on cessation. | Severe | Common at high doses | Observational | |
| Respiratory depression / overdoseHigh doses can cause sedation and opioid-type respiratory depression, especially combined with other CNS depressants. | Life-threatening | Uncommon | Observational |