Tianeptine
An atypical antidepressant with unique nootropic properties. Unlike SSRIs which increase serotonin, tianeptine is a mu-opioid receptor agonist and enhances serotonin reuptake. It reduces stress-induced neuronal damage in the hippocampus and amygdala, improving mood, cognition, and stress resilience simultaneously. Prescription medication in many countries but carries abuse potential at high doses.
Dosage
Prescription dose: 12.5 mg three times daily (Stablon). Extended-release: 25 mg once daily (Tianeurax). Do not exceed prescribed doses — abuse potential at higher doses due to opioid activity.
Dosages shown are for research reference only. Always consult a qualified healthcare provider.
Half-Life
2.5-3 hours (tianeptine), 7-8 hours (active metabolite MC5)
Administration
Oral (tablets). Immediate-release (12.5 mg TID) or extended-release (25 mg QD).
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Mechanism of Action
Tianeptine is a full agonist at mu-opioid (MOR) and delta-opioid (DOR) receptors, mediating both its antidepressant/anxiolytic effects and abuse potential at high doses. Paradoxically, it enhances serotonin reuptake via SERT—opposite to SSRIs—yet still produces antidepressant effects, possibly through opioid-mediated mood regulation. Tianeptine modulates glutamatergic signaling by reversing stress-induced downregulation of AMPA receptor subunits (GluA1/GluA2) and restoring synaptic plasticity. In the hippocampus and amygdala, it prevents stress-induced dendritic atrophy, spine loss, and CA3 pyramidal cell damage—likely through opioid receptor activation and downstream HPA axis effects. It increases BDNF levels and promotes neurogenesis. The combination of opioid agonism, glutamate normalization, and neuroplasticity enhancement underlies its unique profile.
Regulatory Status
Prescription antidepressant in France, Europe, Asia, and Latin America (Stablon, Coaxil). Not FDA-approved in the US. Banned or restricted as a supplement in several US states. Controlled substance in some jurisdictions.
Risks & Safety
Common
Nausea, constipation, abdominal pain, headache, dizziness, dry mouth.
Serious
Opioid-like effects at high doses (euphoria, dependence, respiratory depression). Withdrawal syndrome with abrupt cessation after chronic high-dose use. Abuse and overdose deaths reported.
Rare
Hepatotoxicity, skin reactions.
Compare Tianeptine With
Research Papers
10Published: November 5, 2024
AI Summary
Regardless of which neurotransmitter system is primarily responsible for the observed efficacy, the MOR agonist activity is problematic with respect to abuse liability. Increasing numbers of case reports have demonstrated that tianeptine is indeed being used recreationally at doses far beyond what are considered therapeutically relevant or safe,...
Published: January 2, 2019
AI Summary
These mechanisms support the hypothesis of the possible mechanism of action of this antidepressant. Tianeptine as a glutamatergic modulator, among other mechanisms, allows us to approach depression from a different point of view than other antidepressants.
Published: June 19, 2023
AI Summary
Tianeptine is associated with multiple side effects at high doses along with dependence, withdrawal symptoms, toxicity, respiratory depression, and even mortality. Tianeptine is often used by polysubstance drug abusers who may be unaware of the drug's dangers.
Published: October 14, 2023
AI Summary
Misuse of tianeptine can lead to euphoric, opioid-like highs with the potential for chronic users to develop dependence and tolerance. Overdose and use in suicide attempts have also been documented.
Published: February 28, 2018
AI Summary
The most prominent phenomena associated with tianeptine abuse and dependence were marked euphoria and withdrawal symptoms perpetuating further drug misuse. Caution should be taken when considering the prescription of tianeptine to patients with prior history of substance abuse, and close monitoring for drug misuse is needed during the treatment ...
Published: July 20, 2001
AI Summary
Comparison with maprotiline indicated superior efficacy for tianeptine but dothiepin appeared superior in another study. Tianeptine appears to be as effective as fluoxetine, sertraline, amitriptyline, clomipramine and mianserin and more effective than maprotiline in improving associated anxiety in patients with depressive disorders.
Published: November 18, 2018
AI Summary
Tianeptine (Stablon, Coaxil) abuse and dependence has become increasingly prominent worldwide with recent presence in the United States.
Published: May 14, 2008
AI Summary
Tianeptine, which has a mechanism of action opposite to that of SSRIs, necessitated a re-evaluation of the biochemical basis of depression and revealed that it cannot be explained by the monoamine hypothesis only.
Published: February 28, 1995
AI Summary
Preliminary evidence suggests that tianeptine may also be effective in patients with endogenous depression. The relative lack of sedative, anticholinergic and cardiovascular adverse effects with tianeptine makes it particularly suitable for use in the elderly and in patients following alcohol withdrawal; these patients are known to have increase...
Published: October 23, 1997
AI Summary
Final MADRS scores showed the efficacy of tianeptine in comparison with placebo (P = 0.007). In the intention-to-treat analysis, final MADRS scores showed a better efficacy of tianeptine and imipramine than placebo (P = 0.012 and P = 0.034, respectively).
Frequently Asked Questions
What is Tianeptine used for?
An atypical antidepressant with unique nootropic properties. Unlike SSRIs which increase serotonin, tianeptine is a mu-opioid receptor agonist and enhances serotonin reuptake. It reduces stress-induced neuronal damage in the hippocampus and amygdala, improving mood, cognition, and stress resilience simultaneously. Prescription medication in many countries but carries abuse potential at high doses.
What are the side effects of Tianeptine?
Common: Nausea, constipation, abdominal pain, headache, dizziness, dry mouth. Serious: Opioid-like effects at high doses (euphoria, dependence, respiratory depression). Withdrawal syndrome with abrupt cessation after chronic high-dose use. Abuse and overdose deaths reported. Rare: Hepatotoxicity, skin reactions.
How is Tianeptine administered?
Tianeptine is administered via oral (tablets). immediate-release (12.5 mg tid) or extended-release (25 mg qd)..
What is the half-life of Tianeptine?
The half-life of Tianeptine is 2.5-3 hours (tianeptine), 7-8 hours (active metabolite MC5).
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