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psx:substance/tianeptine/src/doi:10.1016/j.jad.2015.06.038

src2026-09-24recordconsumed

derived from · upstream

none recorded

feeds · downstream

Closure of psx:substance/tianeptine/src/doi:10.1016/j.jad.2015.06.038: 62 upstream, 118 downstream.

psx:substance/tianeptine/src/doi:10.1016/j.jad.2015.06.038
  ├─ used  src/doi:10.1038/tp.2014.30  The atypical antidepressant and neurorestorative agent tianeptine is a mu-opioid receptor agonist
  ├─ used  src/doi:10.1021/acschemneuro.4c00519  Classics in Chemical Neuroscience: Tianeptine
  ├─ used  src/doi:10.1038/s41386-021-01192-2  Mu opioid receptors on hippocampal GABAergic interneurons are critical for the antidepressant effects of tianeptine
  ├─ used  src/doi:10.1016/j.neuint.2011.10.008  Tianeptine potentiates AMPA receptors by activating CaMKII and PKA via the p38, p42/44 MAPK and JNK pathways
  ├─ used  src/doi:10.1080/15563650.2018.1476694  Poison control center experience with tianeptine: an unregulated pharmaceutical product with potential for abuse
  ├─ used  src/pmid:2306747  Lack of cardiovascular side effects of the new tricyclic antidepressant tianeptine
  ├─ used  src/pmid:17630235  Fatal intoxication with tianeptine (Stablon)
  ├─ used  src/doi:10.1097/ADM.0000000000000490
  ├─ used  src/url:99b14727ffb6e2ed  Tianeptine - Wikipedia
  ├─ used  src/pmid:11463130  Tianeptine: a review of its use in depressive disorders
  ├─ used  src/pmid:9405958  Prevention of stress-induced morphological and cognitive consequences
  ├─ used  src/pmid:10357248  Effects of antidepressants and benzodiazepine treatments on the dendritic structure of CA3 pyramidal neurons after chronic stress
  ├─ used  src/pmid:18072812  Neurobiological and clinical effects of the antidepressant tianeptine
  ├─ used  src/doi:10.1038/npp.2017.60  The Behavioral Effects of the Antidepressant Tianeptine Require the Mu-Opioid Receptor
  ├─ used  src/url:b75252f4d2854885  Tianeptine Crackdown Continues: New Legislative and Enforcement Efforts Target Tianeptine Products
  ├─ used  src/doi:10.1016/j.talanta.2025.128197  Tianeptine: enantiomeric separations, structural assignment, and biological interactions
  ├─ used  src/doi:10.1038/npp.2012.135  The same antidepressant elicits contrasting patterns of synaptic changes in the amygdala vs hippocampus
  ├─ used  src/pmid:2341111  The pharmacokinetics of the antidepressant tianeptine and its main metabolite in healthy humans--influence of alcohol co-administration
  ├─ used  src/pmid:3180120  Pharmacokinetic and metabolic parameters of tianeptine in healthy volunteers and in populations with risk factors
  ├─ used  src/doi:10.1016/0924-9338(96)82332-7  A double-blind comparison of tianeptine, imipramine and placebo in the treatment of major depressive episodes
  ├─ used  src/doi:10.1038/s41380-022-01824-z  Antidepressants for the treatment of adults with MDD in the maintenance phase: a systematic review and network meta-analysis
  ├─ used  src/doi:10.1097/JCP.0000000000000072
  ├─ used  src/doi:10.4088/JCP.17m11741
  ├─ used  src/doi:10.1177/0269881119826602  Adjunctive tianeptine treatment for bipolar disorder: A 24-week randomized, placebo-controlled, maintenance trial
  ├─ used  src/pmid:21963693  Tianeptine in the combined treatment of combat related posttraumatic stress disorder
  ├─ used  src/pmid:15964747  A comparative study of fluoxetine, moclobemide, and tianeptine in the treatment of posttraumatic stress disorder following an earthquake
  ├─ used  src/doi:10.1038/s41386-023-01645-w  Tianeptine promotes lasting antiallodynic effects in a mouse model of neuropathic pain
  ├─ used  src/pmid:1836619  Cardiovascular tolerance to tianeptine
  ├─ used  src/doi:10.1097/FBP.0b013e32833db7d4
  ├─ used  src/pmid:14766991  Chronic restraint stress up-regulates GLT-1 mRNA and protein expression in the rat hippocampus: reversal by tianeptine
  ├─ used  src/doi:10.1021/pr900799b  Neurotrophic effects of tianeptine on hippocampal neurons: a proteomic approach
  ├─ used  src/doi:10.1111/jnc.13452  Anti-inflammatory properties of tianeptine on lipopolysaccharide-induced changes in microglial cells involve toll-like receptor-related pathways
  ├─ used  src/doi:10.3390/ijms19071965  Targeting the NLRP3 Inflammasome-Related Pathways via Tianeptine Treatment--Suppressed Microglia Polarization to M1 Phenotype
  ├─ used  src/doi:10.1016/j.neulet.2014.09.022  The antiallodynic effect of intrathecal tianeptine is exerted by increased serotonin and norepinephrine in the spinal dorsal horn
  ├─ used  src/doi:10.1186/s12889-025-24666-0  Gas station heroin - tianeptine and its impact: a systematic review and exploratory analysis
  ├─ used  src/doi:10.1542/peds.2023-062382  Neonatal Opioid Withdrawal Syndrome Following Prenatal Use of Supplements Containing Tianeptine
  ├─ used  src/doi:10.1080/10550887.2023.2290139  Severe tianeptine withdrawal symptoms managed with medications for opioid use disorder: a case report
  ├─ used  src/doi:10.1155/crps/2981699  Tianeptine Misuse, Dependence, and Clinical Management: Three Case Reports and Literature Review
  ├─ used  src/doi:10.1097/ADM.0000000000001003
  ├─ used  src/doi:10.5055/jom.0851  Tianeptine as an opiate replacement in a patient on methadone treatment: A case report
  ├─ used  src/doi:10.9740/mhc.2022.12.356  Treatment of concurrent etizolam and tianeptine withdrawal following accidental overdose
  ├─ derived_from  gen/b0704ad7-7459-4c42-88cd-b3fe8c441aab  Generation — pipeline-v5
  ├─ generated_by  pub/1d2c099b-1e6b-4f62-a6dc-a48b48eb9bcc  Publication — backfill
    ├─ used  search/b204e3fb-5144-42b7-a860-a7d37e60b217  Searched PubChem for "tianeptine"
    ├─ used  search/39471f59-a06d-428a-a5d8-48350c473b5f  Searched PubMed for "tianeptine pharmacology mechanism action receptor"
    ├─ used  search/a902acba-a621-455a-b3f8-d7698c5d4300  Searched OpenAlex for "tianeptine antidepressant mechanism pharmacology"
    ├─ used  search/e01b0011-b9b2-41d4-8e10-e2a27349434b  Searched PubMed for "tianeptine pharmacokinetics bioavailability half-life metabolism"
    ├─ used  search/5597d597-078e-4291-b3de-f8324e367829  Searched PubMed for "tianeptine dependence withdrawal opioid abuse case report"
    ├─ used  search/97338c6c-5544-4c69-a3a1-2c0a315e66ad  Searched ClinicalTrials.gov for "tianeptine"
    ├─ used  search/a7cc5cf4-57ea-4182-a7b6-18522ca2882f  Searched PubMed for "tianeptine dependence withdrawal syndrome opioid treatment"
    ├─ used  search/397fd5ef-1c88-4af3-a035-fde0e31f3974  Searched PubMed for "tianeptine neuroprotection neuroplasticity stress hippocampus"
    ├─ used  search/c74b56d4-3668-4285-840f-39a617b3a0ca  Searched WebSearch for "tianeptine legal status scheduling DEA FDA banned states 2024"
    ├─ used  search/31625ec2-1d3c-4cf3-b3b2-7542df854f99  Searched PubMed for "tianeptine clinical efficacy depression randomized controlled trial"
    ├─ used  search/e5ba0cba-e3ff-4c92-8b25-823a18bafe6a  Searched PubMed for "tianeptine withdrawal buprenorphine treatment opioid use disorder"
    ├─ used  search/e900957a-8fd0-4704-b51c-b91498d0d507  Searched PubMed for "tianeptine hippocampus dendritic atrophy stress prevention McEwen"
    ├─ used  search/b42127a0-4da8-4533-bdb8-b744adc6d557  Searched PubMed for "PMID 39382192 full text"
    ├─ used  search/5c9331a8-00eb-42c8-b0fe-64868ab73909  Searched WebSearch for "tianeptine approved countries Europe France 1989 Stablon Servier regulatory UK Australia Canada"
    ├─ used  search/cd51a427-193d-4087-a315-0ef34985f628  Searched PubMed for "tianeptine PTSD treatment outcome"
    ├─ used  search/91f8c176-982a-4d3f-a61b-7171b79e070c  Searched PubMed for "tianeptine review depressive disorders pharmacokinetics"
    ├─ used  search/30952f69-37d6-4265-9f91-429920c46c6b  Searched PubMed for "tianeptine cardiovascular effects safety"
    ├─ used  search/ac8e39f5-ec73-4a40-81b6-6039edbe641a  Searched PubChem + PubMed for "tianeptine chemical class verification"
    └─ used  search/45fda60c-3095-49aa-a37e-f920e66daffd  Searched PubMed for "tianeptine systematic review gas station heroin misuse"
├─ used  version/1  Revision 1
├─ used  claim/2c36e933-775d-4e3b-a1e8-19ffd7bdf24b  Claim in clinical-evidence — inconclusive  working
  ├─ derived_from  issue/notice@4485cfdd7f5b  Issued notice
  ├─ derived_from  issue/info_card@99fa2e4a68a8  Issued info_card
  ├─ derived_from  issue/emergency@f85b2d2362c9  Issued emergency
  ├─ derived_from  issue/info_card@7d35c4956b0d  Issued info_card
  ├─ informed_by  section/clinical-evidence.full@1
    ├─ used  claim/5cdacba9-beea-453c-87f8-7cc4507582b2  Claim in summary — supported
    ├─ used  claim/d1c0f86c-f939-40eb-9cf9-54858044e90a  Claim in summary — supported
    ├─ used  claim/776172aa-6c43-44d0-914a-25907f679b40  Claim in pharmacology — supported
    ├─ used  claim/40315085-b5ec-4e8b-8b30-e5d02186b728  Claim in pharmacology — supported
    ├─ used  claim/5c69da62-0fa6-45a7-a455-e4f4930a090f  Claim in pharmacology — inconclusive  working
    ├─ used  claim/02646a9b-cc07-45cc-99ee-deba9f957f7d  Claim in history — supported
    ├─ used  claim/630343de-53af-40b0-bbda-c8802235c7c8  Claim in effects-overview — supported
    ├─ used  claim/7878d4a7-6ce1-47d4-bcd9-ffd1c43c643f  Claim in summary — inconclusive  working
    ├─ used  claim/221fe2f6-9ec3-4fb3-95f2-d3eccb92728e  Claim in summary — inconclusive  working
    ├─ used  claim/efd3e878-9a5f-462b-81f3-8224911072e1  Claim in pharmacology — inconclusive  working
    ├─ used  claim/ea8d7100-18a7-48ab-a113-fef8518f3acc  Claim in chemistry — inconclusive  working
    ├─ used  claim/a1c61350-69bc-4e03-a6ed-95864616d417  Claim in receptor-pharmacology — inconclusive  working
    ├─ used  claim/ef8904d3-89b5-4d79-894d-690d48457532  Claim in summary — supported
    ├─ used  claim/8d7c862d-f5c7-4e8b-838f-726ac190fdea  Claim in pharmacology — supported
    ├─ used  claim/1f129c02-7787-4673-9066-c9accc7caf13  Claim in pharmacology — supported
    ├─ used  claim/239d7330-3c5c-4cc9-a224-2a6784f6bc07  Claim in history — supported
    ├─ used  claim/133b0843-13a1-48b8-b5c3-43e7e69fee36  Claim in neuroscience — partially_supported
    ├─ used  claim/7b8fa4e2-f2d5-41b5-a9ae-a13aedd53acb  Claim in neuroscience — supported
    ├─ used  claim/9c9132c3-bd97-4ed0-b1ff-fd92af5feb9a  Claim in summary — supported
    ├─ used  claim/330f3c4e-8b94-47e4-b12c-d6a912523996  Claim in pharmacology — supported
    ├─ used  claim/157dbff0-eddf-4f40-a4fd-f49bd39b5c11  Claim in receptor-pharmacology — supported
    ├─ used  claim/bed9dde7-2d01-4d05-8047-97f4e0be9bba  Claim in summary — inconclusive  working
    ├─ used  claim/bea904ef-9ca2-417f-a056-f10d2d511d32  Claim in summary — partially_supported
    ├─ used  claim/bc92edb7-18c7-455a-8108-89ba4e2bc1a3  Claim in history — supported
    ├─ used  claim/a5604650-fb7f-4ceb-9fec-b58c619df7e7  Claim in safety — inconclusive  working
    ├─ used  claim/883f6a22-94c7-4a2e-944c-b4b03e663409  Claim in safety — supported
    ├─ used  claim/d75199ab-6f81-4864-a595-a26809c2c3b5  Claim in safety — inconclusive  working
    ├─ used  claim/a6f84600-47e4-41c3-8504-9db22505b552  Claim in summary — supported
    ├─ used  claim/f541063f-e301-46bf-8e8b-5b4b27cd4583  Claim in safety — supported
    ├─ used  claim/bc639ed2-0d3b-4439-9171-afa8641c2aab  Claim in summary — supported
    ├─ used  claim/350b3774-dccf-4e54-9619-6d228a74eb18  Claim in pharmacokinetic-detail — supported
    ├─ used  claim/b0019988-efcb-4f0a-a93b-a2c2572569d8  Claim in safety — supported
    ├─ used  claim/5b5d9a60-1432-4699-919a-c6fe757b7bae  Claim in safety — supported
    ├─ used  claim/9e832548-5614-45c1-8aae-eaed2cafc9ba  Claim in safety — supported
    ├─ used  claim/d75464be-e67f-4746-9e30-b0be1f92bb71  Claim in safety — supported
    ├─ used  claim/b985c508-01d2-4aab-8fdf-f9c49e515363  Claim in safety — supported
    ├─ used  claim/6219f1c2-65f4-4616-b7aa-f5597ebd03df  Claim in safety — inconclusive  working
    ├─ used  claim/72f58891-a2db-4f49-b518-0ecfe4c0878c  Claim in safety — supported
    ├─ used  claim/bbcf0534-620c-4636-b44b-9ab875f22ba0  Claim in safety — supported
    ├─ used  claim/19985a33-60e4-419e-9afa-f1cfd465d120  Claim in pharmacology — inconclusive  working
    ├─ used  claim/f448d0db-c54e-476d-aea5-d2b58ac11514  Claim in pharmacology — supported
    ├─ used  claim/63fbbe79-00a6-4e56-8e4d-58a25b9ebd16  Claim in comparative-pharmacology — inconclusive  working
    ├─ used  claim/8c8ab958-fe21-4c1a-94ff-54821e82f398  Claim in safety — inconclusive  working
    ├─ used  claim/abeb5e63-7a95-4962-a632-7be9ae6a4a16  Claim in safety — inconclusive  working
    ├─ used  claim/8ffe8ea4-8d52-4f5f-a8a0-ed0ba70879ed  Claim in safety — inconclusive  working
    ├─ used  claim/4953c59e-c31e-493b-9d14-731013bf8fd6  Claim in safety — inconclusive  working
    ├─ used  claim/fdab4c15-adbf-4b48-a2e4-4226de011656  Claim in safety — supported
    ├─ used  claim/456e61d5-0abe-434f-86f3-a8c2a4fe7269  Claim in history — inconclusive  working
    ├─ used  claim/502327bb-ca5c-4cfb-ab7a-c76002d3f50e  Claim in pharmacokinetic-detail — supported
    ├─ used  claim/7b02d6cd-8da9-439a-8ac7-449116d5f88e  Claim in comparative-pharmacology — supported
    ├─ used  claim/aef2d985-fdc7-4c7e-8295-30ab1c48711f  Claim in pharmacology — supported
    ├─ used  claim/00620f87-52cc-422c-8b73-3812a7bd8e41  Claim in neuroscience — partially_supported
    ├─ used  claim/ed423806-d619-4cfd-b232-468f01fabb32  Claim in history — supported
    ├─ used  claim/6843d985-0374-4961-8309-8a0bcbba4840  Claim in comparative-pharmacology — supported
    ├─ used  claim/614bcd99-453b-49b3-b0a1-4ae961d9de1f  Claim in neuroscience — supported
    ├─ used  claim/70d12a51-9872-4280-865f-5c08cb8e681f  Claim in pharmacology — supported
    ├─ used  claim/6e902b4d-bf44-4986-a35b-ac7907719b4e  Claim in neuroscience — supported
    ├─ used  claim/87946a87-9e6d-4f64-a0ca-ef26d792fd14  Claim in history — supported
    ├─ used  claim/c261d45a-5032-4d22-a9af-b87d76853703  Claim in pharmacology — supported
    ├─ used  claim/c4112dd4-30bd-4684-8f56-edcb277dc580  Claim in pharmacology — inconclusive  working
    ├─ used  claim/459c88ca-8bb1-47f4-9696-034b7be886c1  Claim in pharmacology — supported
    ├─ used  claim/13a5f26a-8684-4212-9905-e1681ee819b9  Claim in neuroscience — inconclusive  working
    ├─ used  claim/1c37ecdc-c7b9-4d78-ac7a-cbc27def75f1  Claim in chemistry — supported
    ├─ used  claim/b93d88e6-60eb-4106-a70e-772b3ce5e186  Claim in neuroscience — supported
    ├─ used  claim/a083713c-15e9-426a-a6e6-f21004edf9c4  Claim in pharmacology — supported
    ├─ used  claim/a599f24f-4b2f-451a-a460-23b16d281a9b  Claim in pharmacology — supported
    ├─ used  claim/31c74656-62b1-4f02-bfe2-f8b697c87433  Claim in safety — supported
    ├─ used  claim/f989c999-ad00-4a87-95ae-30815ad65d62  Claim in pharmacology — supported
    ├─ used  claim/7d517abc-8a3e-408d-acc1-b9db48ef9195  Claim in pharmacokinetic-detail — inconclusive  working
    ├─ used  claim/0a68750f-e3fa-401e-af5f-4676326c6b7f  Claim in safety — supported
    ├─ used  claim/39edab28-722a-47aa-9b14-c8e992870d43  Claim in pharmacokinetic-detail — inconclusive  working
    ├─ used  claim/36d08d7e-2b51-4a77-a5c0-7de6f82d0c96  Claim in safety — supported
    ├─ used  claim/fdbf0eb2-ba95-4c70-ba95-e01caaa0510a  Claim in clinical-evidence — supported
    ├─ used  claim/9a82856b-bbef-46cb-b9dd-f6b96fb79a78  Claim in clinical-evidence — supported
    ├─ used  claim/8e6e9688-7b5a-4c1e-9f7d-dd22179a49a5  Claim in comparative-pharmacology — supported
    ├─ used  claim/a25aabf3-8624-4fb4-95fb-5291853ec103  Claim in clinical-evidence — supported
    ├─ used  claim/0a3eb3bb-279a-4aa8-a571-549d0f5bfcc5  Claim in clinical-evidence — supported
    ├─ used  claim/76e4e041-3a9f-42ca-a51e-2d29f2e8c0be  Claim in clinical-evidence — supported
    ├─ used  claim/730f993c-9db6-45b9-aecb-ee40f97160e1  Claim in safety — supported
    ├─ used  claim/38714bf6-720e-40fe-b6e1-85254b6f1047  Claim in safety — supported
    ├─ used  claim/241f77e7-7585-4630-a27d-426da223a2d2  Claim in comparative-pharmacology — supported
    ├─ used  claim/adf1b51a-ffce-4c9e-b581-6315f91664bf  Claim in neuroscience — supported
    ├─ used  claim/e5694b85-f3ac-4242-8107-02518a9aeb56  Claim in neuroscience — partially_supported
    ├─ used  claim/95f144dd-6317-4967-bcec-3bc434b7779b  Claim in neuroscience — supported
    ├─ used  claim/6915ecf8-37da-4925-ab50-232eab074629  Claim in neuroscience — partially_supported
    ├─ used  claim/3a539464-ddda-49e6-adc5-b9fe79d24b95  Claim in neuroscience — supported
    ├─ used  claim/c690855c-13e2-4970-81ee-74b65ac3136b  Claim in neuroscience — supported
    ├─ used  claim/47f0379b-b13a-498f-99ad-625b5d85fb9a  Claim in safety — supported
    ├─ used  claim/18e46712-928b-4973-9902-924d58a3108f  Claim in safety — supported
    ├─ used  claim/3998355e-58eb-4f81-b486-18f633c9cd0e  Claim in safety — supported
    ├─ used  claim/1b82a7ae-5ef5-455d-b35b-8bdac794d349  Claim in safety — supported
    ├─ used  claim/db0848b4-2a86-4287-bd8b-89a6d0e7086d  Claim in safety — not_supported  working
    ├─ used  claim/a5c67eb3-22d5-45b7-b285-a61f110cd95a  Claim in safety — inconclusive  working
    ├─ used  claim/5a3fa9a6-edae-4e98-9363-983ce1133c58  Claim in safety — inconclusive  working
    ├─ used  claim/703704f5-0c16-47d2-82ba-c2a6bd8f2770  Claim in safety — supported
    ├─ used  claim/e7ae59a0-e867-4f68-a87d-822f2c4fc0ec  Claim in safety — inconclusive  working
    ├─ used  claim/9724707e-d959-4c20-9746-bebd8aca6025  Claim in safety — supported
    ├─ used  claim/f40aa913-ed12-495a-83ee-d79d171b5c12  Claim in safety — supported
    ├─ used  claim/158c4e94-7974-473b-bef0-ba4e84f68cb1  Claim in safety — supported
    ├─ used  claim/8bd5c0d0-cfab-4ca5-9abc-071e4f68cafd  Claim in safety — supported
    ├─ used  claim/7f432a84-13f8-434f-b741-c1f87aaeb75b  Claim in safety — supported
      ├─ informed_by  section/summary.full@1
      ├─ informed_by  section/pharmacology.full@1
      ├─ informed_by  section/history.full@1
      ├─ informed_by  section/effects-overview.full@1
      ├─ informed_by  section/chemistry.full@1
      ├─ informed_by  section/receptor-pharmacology.full@1
      ├─ informed_by  section/neuroscience.full@1
      ├─ informed_by  section/safety.full@1
      ├─ informed_by  section/pharmacokinetic-detail.full@1
      └─ informed_by  section/comparative-pharmacology.full@1

indented by distance from this node, not by parentage

1Provenance card

the boundary, as counts

Sources

4228 with DOI

11 strong · 20 moderate · 11 weak

Compilations

12026-04-26T02:50:59.475Z

pipeline-v5 · prompt hash not recorded — run predates 2026-09

Decisions

31last ruled 2026-06-04

1 awaiting a ruling

Issued documents

42026-10-19T20:34:19.733Z

notice · info card · emergency

Searches

190 with no results

queries and counts on the build

Claims checked

10276 supported

76 supported · 26 not

Correspondence

0received

consent field ships in Phase 4

Edges

308

derivations recorded for this entity

Complete over 42 sources, 1 compilation, and 31 decisions.Not here: the private journal (never); 1 proposal awaiting a ruling (listed as pending only).Working material — drafts, discards, unsupported claims — is listed below and readable on the working page.Cite: psychedex.org/substances/tianeptine/archive

2Build

one panel per compilation run

generation run 2026-04-26

63 min completedmodel pipeline-v5plan not recordedrun/afa7027a…

Selection

results seen100
selected by the model55
consumed as sources42

Verification

claims checked102
supported71
partially supported5
not supported1
inconclusive25
  • record
  • seen / partial
  • working

The model's own caveats

  • evidence_basis_case_reports
  • dose_context_bifurcation
  • not_a_gradual_taper

Reproduce

inputs
42 source keys (listed under Sources)
plan
not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
model
pipeline-v5
streams
none — agent transcripts are persisted from 2026-09 onward
19 searches — query, source, results, what was kept and why
19 searches for this run
#sourcequeryseenkeptrationale
1PubMedtianeptine clinical efficacy depression randomized controlled trial124Clinical efficacy trials specific to tianeptine
2PubMedtianeptine pharmacology mechanism action receptor157Core pharmacology papers selected; general papers discarded
3PubMedtianeptine neuroprotection neuroplasticity stress hippocampus43Mechanistic neuroplasticity papers
4PubMedtianeptine dependence withdrawal opioid abuse case report11Direct abuse/dependence case report
5ClinicalTrials.govtianeptine96All tianeptine trials selected
6PubMedtianeptine dependence withdrawal syndrome opioid treatment33Safety/toxicity and dependence papers
7OpenAlextianeptine antidepressant mechanism pharmacology101Tianeptine-specific paper confirmed as landmark; other papers not tianeptine-specific
8PubChemtianeptine11Primary chemical identity verification
9WebSearchtianeptine legal status scheduling DEA FDA banned states 2024103Legal status information from authoritative sources
10PubMedtianeptine pharmacokinetics bioavailability half-life metabolism22Primary human PK studies
11PubMedtianeptine cardiovascular effects safety33Cardiovascular safety evidence
12PubMedtianeptine systematic review gas station heroin misuse11Most comprehensive recent epidemiological review
13WebSearchtianeptine approved countries Europe France 1989 Stablon Servier regulatory UK Australia Canada103Regulatory status by jurisdiction
14PubMedtianeptine review depressive disorders pharmacokinetics11Comprehensive clinical review with PK/metabolism details
15PubChem + PubMedtianeptine chemical class verification10FLAG: Chemical class discrepancy identified
16PubMedPMID 39382192 full text11Comprehensive recent review
17PubMedtianeptine PTSD treatment outcome22PTSD clinical evidence
18PubMedtianeptine withdrawal buprenorphine treatment opioid use disorder76All selected as treatment guidance
19PubMedtianeptine hippocampus dendritic atrophy stress prevention McEwen77Core stress/neuroplasticity papers all selected
102 claims by section — every cited sentence, checked against its source
safety36 · 25 ok
  • The pivotal RCT confirmed no difference between tianeptine and placebo for heart rate or blood pressuresupported

    No cardiovascular effects. 0924-9338(96)82332-7

  • Buprenorphine-naloxone is first-line treatment for tianeptine use disordersupported

    Case report: buprenorphine/naloxone successfully used to treat tianeptine use disorder; tianeptine use disorder can follow clinical course consistent with OUD. adm.0000000000000490

  • Claim in safety — inconclusiveinconclusiveworking →

  • Naloxone partially or fully reverses these effects.supported

    Naloxone partially effective. 15563650.2018.1476694

  • Death was attributed to combined tianeptine–alcohol intoxicationsupported

    Death ruled as intoxication from suicidal tianeptine + alcohol ingestion. pmid:17630235

  • A 2025 systematic review notes increasing fatal toxicities associated with tianeptine misuse.supported

    Systematic review of tianeptine misuse patterns, overdose risk factors with co-administration, and treatment efficacy including naloxone; MOR activity drives opioid crisis contribution. s12889-025-24666-0

  • A double-blind, placebo-controlled study in 21 healthy volunteers demonstrated no ECG changes and no orthostatic hypotensionsupported

    Double-blind, placebo-controlled, crossover study in 21 healthy volunteers; no orthostatic hypotension, no ECG changes, no change in cardiac output or conduction time. pmid:2306747

  • In clinical populations exceeding 3,300 patients, cardiovascular safety was maintained over up to 1 year of treatment, with fewer cases of orthostatic hypotension than comparator antidepressantssupported

    >3,300 patients; no cardiovascular deaths from overdose; fewer cases of orthostatic hypotension vs other antidepressants. pmid:1836619

  • Claim in safety — inconclusiveinconclusiveworking →

  • A case of severe neonatal opioid withdrawal syndrome (NOWS) was documented following chronic prenatal maternal tianeptine supplement use; the infant required oral morphine after phenobarbital failuresupported

    Case report: severe neonatal withdrawal after maternal tianeptine supplement use; refractory to phenobarbital, responded to oral morphine. peds.2023-062382

  • Tianeptine is not detected by standard opioid immunoassay urine drug screenssupported

    Tianeptine not detected by routine urine screens. peds.2023-062382

  • Published case reports describe a clinical course consistent with opioid use disorder: compulsive use despite negative consequences, preoccupation with obtaining the substance, and continued use despite physical and psychological deteriorationsupported

    Tianeptine use disorder can follow clinical course consistent with OUD. adm.0000000000000490

  • Claim in safety — not_supportednot supportedworking →

  • Claim in safety — inconclusiveinconclusiveworking →

  • Claim in safety — inconclusiveinconclusiveworking →

  • Animal models demonstrate no analgesic tolerance or withdrawal at clinically relevant doses.supported

    No analgesic tolerance or withdrawal at clinical doses. s41386-023-01645-w

  • Claim in safety — inconclusiveinconclusiveworking →

  • Claim in safety — inconclusiveinconclusiveworking →

  • Claim in safety — inconclusiveinconclusiveworking →

  • Withdrawal symptoms: Anxiety, agitation, nausea, vomiting, diarrhea, diaphoresis, myalgia, and cravings — identical in character to opioid withdrawalsupported

    Withdrawal includes anxiety, agitation, GI distress. 2981699

  • Clinical course: Consistent with opioid use disordersupported

    Tianeptine use disorder can follow clinical course consistent with OUD. adm.0000000000000490

  • Buprenorphine-naloxone is established as first-line treatment for tianeptine withdrawal and maintenance, with efficacy documented across multiple case reportssupported

    Buprenorphine/naloxone successfully used to treat tianeptine use disorder. adm.0000000000000490

  • Claim in safety — inconclusiveinconclusiveworking →

  • Buprenorphine-naloxone is established as first-line treatment for tianeptine withdrawal and maintenance, with efficacy documented across multiple case reportssupported

    Microdose buprenorphine induction in a tianeptine user; describes low-dose buprenorphine approach to manage tianeptine dependence. adm.0000000000001003

  • Microdose buprenorphine induction has been describedsupported

    Microdose buprenorphine induction in a tianeptine user; describes low-dose buprenorphine approach to manage tianeptine dependence. adm.0000000000001003

  • Claim in safety — inconclusiveinconclusiveworking →

  • Methadone has been used in complex casessupported

    Case report showing tianeptine used as OTC opiate replacement; buprenorphine-naloxone successfully used to manage tianeptine use disorder alongside methadone treatment. jom.0851

  • Alcohol reduces tianeptine absorption (~30% lower Cmax and AUC) but the combination is pharmacodynamically potentiating in overdosesupported

    Alcohol co-admin decreases absorption ~30%. pmid:2341111

  • The only confirmed fatal case involved tianeptine plus alcohol (ethanol 0.53 g/L).supported

    Fatal case in 26-year-old male; blood tianeptine 5.1 ug/mL with ethanol 0.53 g/L; death ruled as intoxication from suicidal tianeptine + alcohol ingestion. pmid:17630235

  • A complex case of concurrent methadone and tianeptine use has been documented.supported

    Case report showing tianeptine used as OTC opiate replacement; buprenorphine-naloxone successfully used to manage tianeptine use disorder alongside methadone treatment. jom.0851

  • Concurrent etizolam and tianeptine withdrawal has been documented, highlighting polysubstance complexity.supported

    Case of concurrent etizolam and tianeptine withdrawal; highlights polysubstance abuse risk with tianeptine. mhc.2022.12.356

  • Claim in safety — inconclusiveinconclusiveworking →

  • CYP450-metabolized drugs: Tianeptine's beta-oxidation metabolism confers lower drug interaction risk than most antidepressantssupported

    Tianeptine not primarily CYP450 metabolized (beta-oxidation pathway). pmid:11463130

  • Tianeptine crosses the placenta and produces severe neonatal opioid withdrawal syndrome requiring opioid-based treatment.supported

    Case report: severe neonatal withdrawal after maternal tianeptine supplement use; refractory to phenobarbital, responded to oral morphine. peds.2023-062382

  • While the pharmacokinetic interaction reduces tianeptine absorption, pharmacodynamic potentiation in overdose and the documented fatality elevate risk, particularly in patients with supratherapeutic use patterns.supported

    Fatal case in 26-year-old male; blood tianeptine 5.1 ug/mL with ethanol 0.53 g/L; death ruled as intoxication from suicidal tianeptine + alcohol ingestion. pmid:17630235

  • Severe renal impairment requires dose reduction due to prolonged t₁/₂supported

    Dose adjustment needed in elderly and renal failure. pmid:3180120

pharmacology17 · 13 ok
  • Gassaway et al. established this mechanism using radioligand binding assays and BRET-based G-protein activation assays, reporting Ki = 383 ± 183 nM and EC₅₀ = 194 ± 70 nM at human MORsupported

    Identified tianeptine as MOR agonist (Ki 383+/-183 nM, EC50 194+/-70 nM). Landmark pharmacology paper. tp.2014.30

  • Tianeptine is approximately 200-fold less potent at the delta-opioid receptor (DOR; EC₅₀ = 37.4 ± 11.2 µM at human DOR) and is inactive at the kappa-opioid receptor.supported

    DOR agonist (EC50 37.4 uM), inactive at KOR. tp.2014.30

  • Behavioral studies in MOR-knockout mice demonstrate complete loss of antidepressant-like activitysupported

    Demonstrated tianeptine antidepressant effects require MOR. npp.2017.60

  • Cell-type-specific knockout studies localized this requirement to MOR expression on somatostatin-positive GABAergic interneurons in the ventral hippocampus; deletion of MOR from these neurons abolished both acute and chronic antidepressant responsessupported

    MOR on somatostatin-positive hippocampal GABAergic neurons required for antidepressant effect; ventral hippocampus implicated. s41386-021-01192-2

  • Tianeptine does not promote hippocampal neurogenesis — unlike fluoxetine — indicating a mechanistically distinct antidepressant circuit.supported

    Different mechanism from fluoxetine; no hippocampal neurogenesis requirement. s41386-021-01192-2

  • Claim in pharmacology — inconclusiveinconclusiveworking →

  • The potentiation operates through postsynaptic kinase signaling: activation of CaMKII and PKA via the p38, p42/44 MAPK, and JNK pathways leads to increased GluA1 phosphorylation at Ser831 (CaMKII site) and Ser845 (PKA site), enhancing AMPA receptor conductancesupported

    Tianeptine increases AMPA receptor-mediated responses via CaMKII and PKA; increases GluA1 phosphorylation at Ser831 and Ser845; potentiates synaptic plasticity. Postsynaptic site of action. j.neuint.2011.10.008

  • Tianeptine enhances both AMPA and NMDA currents in hippocampal CA1 pyramidal neurons while paradoxically reducing NMDA currents in the lateral amygdalasupported

    Tianeptine reduces NMDA-mediated currents in lateral amygdala but enhances both NMDA and AMPA currents in hippocampal CA1. npp.2012.135

  • Claim in pharmacology — inconclusiveinconclusiveworking →

  • Multiple animal studies operated within this frameworksupported

    Tianeptine (10 mg/kg/day) prevented stress-induced atrophy of CA3 dendrites and spatial memory impairment; fluoxetine and desipramine failed. pmid:9405958

  • Multiple animal studies operated within this frameworksupported

    Tianeptine (labeled as 5-HT reuptake enhancer) prevented CA3 dendritic atrophy; fluoxetine and fluvoxamine failed. pmid:10357248

  • Claim in pharmacology — inconclusiveinconclusiveworking →

  • Claim in pharmacology — inconclusiveinconclusiveworking →

  • Tianeptine displays near-complete oral bioavailability (~99%) with no significant first-pass hepatic metabolismsupported

    Bioavailability ~99%, Tmax 0.94h. pmid:2341111

  • Tianeptine displays near-complete oral bioavailability (~99%) with no significant first-pass hepatic metabolismsupported

    Oral absorption rapid and complete; bioavailability 99%. pmid:3180120

  • The primary metabolic pathway is mitochondrial beta-oxidation of the heptanoic acid side chain — analogous to fatty acid metabolism — rather than hepatic CYP450 oxidationsupported

    Tianeptine not primarily CYP450 metabolized (beta-oxidation pathway). pmid:11463130

  • The principal active metabolite MC5 (a C5 beta-oxidation product) has a longer half-life of approximately 7.2 ± 5.7 hours and demonstrates behavioral effects in a MOR-dependent fashionsupported

    Demonstrated tianeptine antidepressant effects require MOR; metabolite MC5 has longer half-life. npp.2017.60

neuroscience13 · 12 ok
  • Chronic restraint stress (21 days) produces measurable CA3 apical dendritic retraction in rodent models; tianeptine at 10 mg/kg/day prevents this atrophy when co-administered with the stressor and reverses already-established atrophy caused by chronic corticosterone treatmentpartially supported

    Tianeptine (10 mg/kg/day) prevented stress-induced atrophy of CA3 dendrites and spatial memory impairment; fluoxetine and desipramine failed. pmid:9405958

  • Chronic restraint stress (21 days) produces measurable CA3 apical dendritic retraction in rodent models; tianeptine at 10 mg/kg/day prevents this atrophy when co-administered with the stressor and reverses already-established atrophy caused by chronic corticosterone treatmentsupported

    Tianeptine (labeled as 5-HT reuptake enhancer) prevented CA3 dendritic atrophy; tianeptine reversed established corticosterone-induced atrophy. pmid:10357248

  • Paradoxically, tianeptine reduces morphine antinociceptive tolerance and physical dependence in animal models, suggesting it modulates opioid receptor signaling cascades in a manner distinct from simple additive agonism.supported

    Tianeptine (1-5mg/kg) reduces morphine tolerance development and naloxone-precipitated withdrawal in mice; no antinociception alone. fbp.0b013e32833db7d4

  • MOR expression on somatostatin-positive GABAergic interneurons in the ventral hippocampus is both necessary and sufficient for antidepressant behavioral effects; cell-type-specific MOR knockout from these neurons abolishes acute and chronic antidepressant-like responses in micepartially supported

    MOR on somatostatin-positive hippocampal GABAergic neurons required for antidepressant effect. s41386-021-01192-2

  • Claim in neuroscience — inconclusiveinconclusiveworking →

  • The neuroprotective mechanism involves glutamate transporter regulation — tianeptine prevents upregulation of GLT-1 mRNA and protein in hippocampal CA3 under chronic restraint stress, likely reducing excitotoxic glutamate exposurepartially supported

    Tianeptine reverses stress-induced GLT-1 upregulation in hippocampus CA3. pmid:14766991

  • It inhibits TLR4 expression and ERK1/2 phosphorylation, reducing production of IL-1β, IL-18, IL-6, TNF-α, nitric oxide, and reactive oxygen species in LPS-stimulated microgliapartially supported

    Suppresses IL-1beta, IL-18, IL-6, TNF-alpha, NO; inhibits TLR4 expression and ERK1/2 phosphorylation. jnc.13452

  • Tianeptine produces antinociception via increased spinal serotonin and norepinephrine releasesupported

    Intrathecal tianeptine shows antiallodynic effect via increased 5-HT and NE in spinal dorsal horn. j.neulet.2014.09.022

  • The cell-type-specific MOR knockout data establish that MOR activation on somatostatin interneurons gates antidepressant-relevant hippocampal outputsupported

    MOR on somatostatin-positive hippocampal GABAergic neurons required for antidepressant effect; ventral hippocampus implicated. s41386-021-01192-2

  • Tianeptine's prevention of stress-induced dendritic atrophy and promotion of synaptogenesis align with the broader neuroplasticity hypothesis of antidepressant actionsupported

    Tianeptine (10 mg/kg/day) prevented stress-induced atrophy of CA3 dendrites and spatial memory impairment. pmid:9405958

  • Tianeptine's prevention of stress-induced dendritic atrophy and promotion of synaptogenesis align with the broader neuroplasticity hypothesis of antidepressant actionsupported

    Tianeptine augments neurite growth and promotes synaptic contacts in cultured hippocampal neurons. pr900799b

  • The anti-inflammatory effects on microglial polarization position tianeptine within the neuroimmune hypothesis of depression, where chronic neuroinflammation contributes to depressive pathophysiologysupported

    Attenuates M1 polarization; decreases CD40, MHC II; reduces IL-1beta, IL-18, IL-6, TNF-alpha, NO, ROS; inhibits NLRP3. ijms19071965

  • Enantiomeric pharmacology: Differential in vivo effects of R- and S-tianeptine remain uncharacterized beyond albumin binding. This is a significant gap given the potential for enantioselective MOR activity.supported

    Chiral separation methods developed; absolute configurations determined by VCD spectroscopy; S-enantiomer has higher affinity for human serum albumin. j.talanta.2025.128197

summary10 · 7 ok
  • In 2014, Gassaway, Javitch, and Sames identified it as a full MOR agonist, fundamentally revising the mechanistic understanding and prompting re-evaluation of its abuse liabilitysupported

    Identified tianeptine as MOR agonist (Ki 383+/-183 nM, EC50 194+/-70 nM). Landmark pharmacology paper. tp.2014.30

  • Claim in summary — inconclusiveinconclusiveworking →

  • Tianeptine binds MOR with moderate affinity (Ki = 383 ± 183 nM; EC₅₀ = 194 ± 70 nM) and is inactive at the kappa-opioid receptorsupported

    Identified tianeptine as MOR agonist (Ki 383+/-183 nM, EC50 194+/-70 nM), DOR agonist (EC50 37.4 uM), inactive at KOR. tp.2014.30

  • Antidepressant effects require MOR expression on somatostatin-positive GABAergic interneurons in the ventral hippocampussupported

    MOR on somatostatin-positive hippocampal GABAergic neurons required for antidepressant effect; ventral hippocampus implicated. s41386-021-01192-2

  • AMPA receptor currents are potentiated indirectly through CaMKII and PKA kinase cascades.supported

    Tianeptine increases AMPA receptor-mediated responses via CaMKII and PKA; potentiates synaptic plasticity. j.neuint.2011.10.008

  • Claim in summary — inconclusiveinconclusiveworking →

  • Cardiovascular safety at therapeutic doses is well-establishedsupported

    No orthostatic hypotension, no ECG changes, no change in cardiac output or conduction time. pmid:2306747

  • The critical risk is dose-dependent: supratherapeutic use produces rapid opioid-type tolerance, severe physical dependence with withdrawal onset within hours, and respiratory depression reversible by naloxonepartially supported

    Opioid withdrawal symptoms; naloxone partially effective; outcomes minor to major. 15563650.2018.1476694

  • One confirmed fatality involved tianeptine combined with alcoholsupported

    Fatal case in 26-year-old male; blood tianeptine 5.1 ug/mL with ethanol 0.53 g/L; death ruled as intoxication from suicidal tianeptine + alcohol ingestion. pmid:17630235

  • Claim in summary — inconclusiveinconclusiveworking →

clinical-evidence6 · 5 ok
  • Emsley et al. evaluated tianeptine 25–50 mg/day in elderly patients with recurrent major depressive disorder, establishing efficacy and providing dose-finding data for this population.supported

    8-week placebo- and escitalopram-controlled study in elderly MDD patients; tianeptine 25-50mg/d evaluated for efficacy and safety. jcp.17m11741

  • Tianeptine demonstrated antidepressant efficacy significantly superior to placebo, with a safety profile markedly better than imipramine — no difference between tianeptine and placebo was observed for heart rate or blood pressure.supported

    Both active drugs superior to placebo on MADRS; tianeptine had significantly fewer anticholinergic side effects; no cardiovascular effects. 0924-9338(96)82332-7

  • Tianeptine efficacy in maintenance treatment was confirmed in a systematic review and network meta-analysis of antidepressants for MDD.supported

    Tianeptine outperformed placebo on 6-month relapse rate in maintenance phase; network meta-analysis of 20 antidepressants. s41380-022-01824-z

  • Claim in clinical-evidence — inconclusiveinconclusiveworking →

  • Kauer-Sant'Anna et al. conducted a 24-week randomized, placebo-controlled maintenance trial of adjunctive tianeptine in bipolar disorder (NCT00879372), supporting efficacy as adjunctive treatment.supported

    24-week RCT of adjunctive tianeptine for bipolar depression; efficacy and tolerability assessed. 0269881119826602

  • Onder et al. compared tianeptine, fluoxetine, and moclobemide for PTSD following an earthquake, providing comparative efficacy data across antidepressant classes.supported

    Open-label study; fluoxetine, moclobemide, tianeptine compared for PTSD post-earthquake; CAPS and CGI-S outcomes measured. pmid:15964747

history6 · 5 ok
  • The colloquial designation "gas station heroin" emerged by the 2010s as poison control centers documented increasing reports of opioid-like intoxication and withdrawalsupported

    9 cases reported to NY PCCs; 5 intentional abuse; abuse doses 5-10g daily; opioid withdrawal symptoms; naloxone partially effective. 15563650.2018.1476694

  • Claim in history — inconclusiveinconclusiveworking →

  • Bruce McEwen's group at Rockefeller University demonstrated that tianeptine prevents and reverses stress-induced dendritic atrophy in hippocampal CA3 neurons — effects that fluoxetine and desipramine failed to replicate in the same modelssupported

    Tianeptine (10 mg/kg/day) prevented stress-induced atrophy of CA3 dendrites and spatial memory impairment; fluoxetine and desipramine failed. pmid:9405958

  • The Kasper and McEwen 2008 review synthesized a decade of neurobiological findings, positioning tianeptine as the exemplar compound for stress-related hippocampal plasticity and arguing that its mechanism transcended simple monoamine modulation.supported

    Comprehensive review: tianeptine prevents/reverses stress-induced dendritic atrophy in hippocampus, improves neurogenesis, normalizes glutamatergic transmission; effective for mild-to-severe MDD and anxiety. pmid:18072812

  • In 2014, Gassaway, Javitch, and Sames at Columbia University published the landmark finding that tianeptine is a full agonist at the mu-opioid receptor, with Ki = 383 nM and EC₅₀ = 194 nM at human MORsupported

    Identified tianeptine as MOR agonist (Ki 383+/-183 nM, EC50 194+/-70 nM). Landmark pharmacology paper. tp.2014.30

  • Subsequent cell-type-specific studies refined the circuit mechanism, demonstrating that MOR expression on somatostatin-positive GABAergic interneurons in the ventral hippocampus is required for the antidepressant effect.supported

    MOR on somatostatin-positive hippocampal GABAergic neurons required for antidepressant effect; ventral hippocampus implicated. s41386-021-01192-2

comparative-pharmacology5 · 4 ok
  • Claim in comparative-pharmacology — inconclusiveinconclusiveworking →

  • Paradoxically, tianeptine reduces morphine antinociceptive tolerance and physical dependence in animal models, suggesting a complex interaction at the MOR signaling level rather than simple additive agonism.supported

    Tianeptine (1-5mg/kg) reduces morphine tolerance development and naloxone-precipitated withdrawal in mice; no antinociception alone; comedication may benefit long-term opioid users. fbp.0b013e32833db7d4

  • Fluoxetine and desipramine failed to prevent CA3 dendritic remodeling in chronic restraint stress models where tianeptine was effective.supported

    Tianeptine (10 mg/kg/day) prevented stress-induced atrophy of CA3 dendrites; fluoxetine and desipramine failed. pmid:9405958

  • Antidepressant efficacy is broadly comparable between tianeptine and SSRIs in clinical trialssupported

    Equivalent efficacy to SSRIs and TCAs. pmid:11463130

  • Tianeptine demonstrated superior neurocognitive outcomes versus escitalopram in the CAMPION trialsupported

    Tianeptine 37.5mg/d vs escitalopram 10mg/d for 12 weeks (n=164); tianeptine superior for commission errors and verbal immediate memory. jcp.0000000000000072

pharmacokinetic-detail4 · 2 ok
  • Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

  • This pharmacokinetic interaction is paradoxically relevant in overdose contexts, where the tianeptine–alcohol combination appears pharmacodynamically potentiating despite reduced tianeptine absorption — the only confirmed fatal case involved concurrent alcohol (ethanol 0.53 g/L).supported

    Fatal case in 26-year-old male; blood tianeptine 5.1 ug/mL with ethanol 0.53 g/L; death ruled as intoxication from suicidal tianeptine + alcohol ingestion. pmid:17630235

  • Tianeptine is metabolized primarily via mitochondrial beta-oxidation of the heptanoic acid side chain, producing sequential two-carbon truncations analogous to fatty acid catabolismsupported

    Tianeptine not primarily CYP450 metabolized (beta-oxidation pathway). pmid:11463130

  • Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

chemistry2 · 1 ok
  • Claim in chemistry — inconclusiveinconclusiveworking →

  • Enantiomeric separation has been achieved using WhelkoShell and NicoShell chiral HPLC columns, and absolute configurations were assigned by vibrational circular dichroism spectroscopysupported

    Chiral separation methods developed; absolute configurations determined by VCD spectroscopy. j.talanta.2025.128197

receptor-pharmacology2 · 1 ok
  • Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

  • These kinases phosphorylate the GluA1 AMPA receptor subunit at Ser831 (CaMKII) and Ser845 (PKA), increasing receptor conductance and surface expression.supported

    Increases GluA1 phosphorylation at Ser831 and Ser845; potentiates synaptic plasticity. j.neuint.2011.10.008

effects-overview1 · 1 ok
  • The opioid phenomenology only emerges at doses substantially above the therapeutic range, where the compound's moderate MOR affinity (Ki = 383 nM) produces sufficient receptor occupancy to generate classical opioid effectssupported

    Identified tianeptine as MOR agonist (Ki 383+/-183 nM, EC50 194+/-70 nM). Landmark pharmacology paper. tp.2014.30

3Sources

42 consumed · sorted by year · feeds = sections resting on it

Sources 1 to 30
yearsourcetierstatusfeeds
2026Tianeptine Misuse, Dependence, and Clinical Management: Three Case Reports and Literature ReviewSaldana VA, Earley PH, Silverstein DS, Tang YL · Case Reports in Psychiatrydoi:10.1155/crps/2981699weakconsumed1 section
2025Gas station heroin - tianeptine and its impact: a systematic review and exploratory analysisParnia S, Jain L, Ali M, Sarfraz Z, Nasir MJ, et al. · BMC Public Healthdoi:10.1186/s12889-025-24666-0strongconsumed1 section
2025Severe tianeptine withdrawal symptoms managed with medications for opioid use disorder: a case reportRawal VY, Gallardo M, Henderson K, Hall OT, et al. · Journal of Addictive Diseasesdoi:10.1080/10550887.2023.2290139weakconsumed1 section
2025Tianeptine: enantiomeric separations, structural assignment, and biological interactionsAslani S, Nafie J, Wahab MF, Armstrong DW · Talantadoi:10.1016/j.talanta.2025.128197moderateconsumed2 sections
2024Classics in Chemical Neuroscience: TianeptineNishio Y, Lindsley CW, Bender AM · ACS Chemical Neurosciencedoi:10.1021/acschemneuro.4c00519moderateconsumed4 sections
2024Neonatal Opioid Withdrawal Syndrome Following Prenatal Use of Supplements Containing TianeptineIkeri K, Anderson A, Eyal F, Whitehurst R · Pediatricsdoi:10.1542/peds.2023-062382weakconsumed1 section
2024Tianeptine - WikipediaWikipedia contributorsurl:99b14727ffb6e2edweakconsumedcited only
2024Tianeptine as an opiate replacement in a patient on methadone treatment: A case reportVelagapudi V, Calabrese J, Sethi R · Journal of Opioid Managementdoi:10.5055/jom.0851weakconsumed1 section
2024Tianeptine Crackdown Continues: New Legislative and Enforcement Efforts Target Tianeptine ProductsBuchanan Ingersoll & Rooney PCurl:b75252f4d2854885weakconsumedcited only
2023Antidepressants for the treatment of adults with MDD in the maintenance phase: a systematic review and network meta-analysisKishi T, Ikuta T, Sakuma K, et al. · Molecular Psychiatrydoi:10.1038/s41380-022-01824-zstrongconsumed1 section
2023Tianeptine promotes lasting antiallodynic effects in a mouse model of neuropathic painSerafini RA, Estill M, Pekarskaya EA, Sakloth F, Shen L, Javitch JA, et al. · Neuropsychopharmacologydoi:10.1038/s41386-023-01645-wmoderateconsumed1 section
2022Microdose Induction of Buprenorphine in a Patient Using TianeptineSzczesniak L, Sullivan R · Journal of Addiction Medicinedoi:10.1097/adm.0000000000001003weakconsumedcited only
2022Mu opioid receptors on hippocampal GABAergic interneurons are critical for the antidepressant effects of tianeptineHan J, Andreu V, Langreck C, Pekarskaya EA, Grinnell SG, et al. · Neuropsychopharmacologydoi:10.1038/s41386-021-01192-2moderateconsumed4 sections
2022Treatment of concurrent etizolam and tianeptine withdrawal following accidental overdoseMarkovic M, Niwash D · Mental Health Cliniciandoi:10.9740/mhc.2022.12.356weakconsumed1 section
2019Adjunctive tianeptine treatment for bipolar disorder: A 24-week randomized, placebo-controlled, maintenance trialKauer-Sant'Anna M, Frey BN, Fijtman A, et al. · Journal of Psychopharmacologydoi:10.1177/0269881119826602strongconsumed1 section
2019Use of Buprenorphine-Naloxone in the Treatment of Tianeptine Use DisorderTrowbridge P, Walley AY · Journal of Addiction Medicinedoi:10.1097/adm.0000000000000490weakconsumedcited only
2018Efficacy of Tianeptine 25-50 mg in Elderly Patients With Recurrent Major Depressive DisorderEmsley R, Ahokas A, Suarez A, Marinescu D, et al. · Journal of Clinical Psychiatrydoi:10.4088/jcp.17m11741strongconsumedcited only
2018Poison control center experience with tianeptine: an unregulated pharmaceutical product with potential for abuseMarraffa JM, Stork CM, Hoffman RS, Su MK · Clinical Toxicologydoi:10.1080/15563650.2018.1476694weakconsumed3 sections
2018Targeting the NLRP3 Inflammasome-Related Pathways via Tianeptine Treatment--Suppressed Microglia Polarization to M1 PhenotypeSlusarczyk J, Trojan E, Glombik K, Piotrowska A, et al. · International Journal of Molecular Sciencesdoi:10.3390/ijms19071965moderateconsumed1 section
2017The Behavioral Effects of the Antidepressant Tianeptine Require the Mu-Opioid ReceptorSamuels BA, Nautiyal KM, Kruegel AC, Levinstein MR, Magalong VM, Gassaway MM, et al. · Neuropsychopharmacologydoi:10.1038/npp.2017.60moderateconsumed2 sections
2016Anti-inflammatory properties of tianeptine on lipopolysaccharide-induced changes in microglial cells involve toll-like receptor-related pathwaysSlusarczyk J, Trojan E, Glombik K, Piotrowska A, Budziszewska B, et al. · Journal of Neurochemistrydoi:10.1111/jnc.13452moderateconsumed1 section
2015Influence of anxiety symptoms on improvement of neurocognitive functions in patients with MDD: CAMPION studyYoo I, Woo JM, Lee SH, Fava M, Mischoulon D, et al. · Journal of Affective Disordersdoi:10.1016/j.jad.2015.06.038strongconsumed1 section
2014Improvement in subjective and objective neurocognitive functions in patients with MDD: the CAMPION studyJeon HJ, Woo JM, Lee SH, Kim EJ, Chung S, Ha JH, et al. · Journal of Clinical Psychopharmacologydoi:10.1097/jcp.0000000000000072strongconsumedcited only
2014The antiallodynic effect of intrathecal tianeptine is exerted by increased serotonin and norepinephrine in the spinal dorsal hornLee HG, Choi JI, Yoon MH, Obata H, Saito S, Kim WM · Neuroscience Lettersdoi:10.1016/j.neulet.2014.09.022moderateconsumed1 section
2014The atypical antidepressant and neurorestorative agent tianeptine is a mu-opioid receptor agonistGassaway MM, Rives ML, Kruegel AC, Javitch JA, Sames D · Translational Psychiatrydoi:10.1038/tp.2014.30strongconsumed4 sections
2012The same antidepressant elicits contrasting patterns of synaptic changes in the amygdala vs hippocampusPillai AG, Anilkumar S, Chattarji S · Neuropsychopharmacologydoi:10.1038/npp.2012.135moderateconsumed1 section
2011Tianeptine in the combined treatment of combat related posttraumatic stress disorderFranciskovic T, Sukovic Z, Janovic S, Stevanovic A, et al. · Psychiatria Danubinapmid:21963693moderateconsumedcited only
2011Tianeptine potentiates AMPA receptors by activating CaMKII and PKA via the p38, p42/44 MAPK and JNK pathwaysSzegedi V, Juhasz G, Zhang X, Barkoczi B, Qi H, Madeira A, et al. · Neurochemistry Internationaldoi:10.1016/j.neuint.2011.10.008moderateconsumed3 sections
2010Neurotrophic effects of tianeptine on hippocampal neurons: a proteomic approachChu CC, Wang JJ, Chen KT, Shieh JP, Wang LK, Shui HA, et al. · Journal of Proteome Researchdoi:10.1021/pr900799bmoderateconsumed1 section
2010Tianeptine reduces morphine antinociceptive tolerance and physical dependenceChu CC, Shieh JP, Shui HA, Chen JY, Hsing CH, et al. · Behavioural Pharmacologydoi:10.1097/fbp.0b013e32833db7d4moderateconsumedcited only
Show all 42 sources — 12 more
Sources 31 to 42
yearsourcetierstatusfeeds
2008Neurobiological and clinical effects of the antidepressant tianeptineKasper S, McEwen BS · CNS Drugspmid:18072812moderateconsumed1 section
2007Fatal intoxication with tianeptine (Stablon)Proenca P, Teixeira H, Pinheiro J, Monsanto PV, Vieira DN · Forensic Science Internationalpmid:17630235weakconsumed3 sections
2006A comparative study of fluoxetine, moclobemide, and tianeptine in the treatment of posttraumatic stress disorder following an earthquakeOnder E, Tural U, Aker T · European Psychiatrypmid:15964747moderateconsumed1 section
2004Chronic restraint stress up-regulates GLT-1 mRNA and protein expression in the rat hippocampus: reversal by tianeptineReagan LP, Rosell DR, Wood GE, Spedding M, Munoz C, Rothstein J, McEwen BS · PNASpmid:14766991moderateconsumed1 section
2001Tianeptine: a review of its use in depressive disordersWagstaff AJ, Ormrod D, Spencer CM · CNS Drugspmid:11463130moderateconsumed5 sections
1999Effects of antidepressants and benzodiazepine treatments on the dendritic structure of CA3 pyramidal neurons after chronic stressMagarinos AM, Deslandes A, McEwen BS · European Journal of Pharmacologypmid:10357248moderateconsumed2 sections
1997Prevention of stress-induced morphological and cognitive consequencesMcEwen BS, Conrad CD, Kuroda Y, Frankfurt M, Magarinos AM, McKittrick C · European Neuropsychopharmacologypmid:9405958moderateconsumed4 sections
1996A double-blind comparison of tianeptine, imipramine and placebo in the treatment of major depressive episodesCassano GB, Heinze G, Loo H, Mendlewicz J, Sousa MP · European Psychiatrydoi:10.1016/0924-9338(96)82332-7strongconsumed2 sections
1991Cardiovascular tolerance to tianeptineLasnier C, Marey C, Lapeyre G, Delalleau B, Ganry H · Presse Medicalepmid:1836619moderateconsumed1 section
1990Lack of cardiovascular side effects of the new tricyclic antidepressant tianeptineJuvent M, Douchamps J, Delcourt E, Kostucki W, Dulcire C, et al. · Clinical Neuropharmacologypmid:2306747strongconsumed2 sections
1990The pharmacokinetics of the antidepressant tianeptine and its main metabolite in healthy humans--influence of alcohol co-administrationSalvadori C, Ward C, Defrance R, Hopkins R · Fundamental & Clinical Pharmacologypmid:2341111strongconsumed2 sections
1988Pharmacokinetic and metabolic parameters of tianeptine in healthy volunteers and in populations with risk factorsRoyer RJ, Albin H, Barrucand D, Salvadori-Failler C, Kamoun A · Clinical Neuropharmacologypmid:3180120strongconsumed3 sections

4Docket

one filing per activity — decisions, correspondence, reports

awaiting ruling — 1

  • dependence · tapercited2026-07-03
  1. 0012026-04-26revisionRevision 1

    Initial LLM generation (v5 pipeline, wiki)

    psx:substance/tianeptine/version/1
  2. 0022026-06-04proposal28 value proposals approved together

    one review action inferred from a shared reviewer and instant — the graph records one activity per proposal

    28 items in this filing

    • dose_tier · light
    • dose_tier · common
    • dose_tier · strong
    • dose_tier · heavy
    • timeline · oral · onset
    • timeline · oral · come_up
    • timeline · oral · peak
    • timeline · oral · resolution
    • timeline · oral · afterglow
    • toxicity
    • dependence · full
    • withdrawal
    • tolerance
    • dosage · oral
    • duration · oral · onset
    • duration · oral · come_up
    • duration · oral · peak
    • duration · oral · offset
    • duration · oral · total
    • duration · oral · aftereffects
    • contraindication · pregnancy_breastfeeding
    • contraindication · respiratory
    • contraindication · other
    • contraindication · other
    • contraindication · renal
    • contraindication · age
    • contraindication · other
    psx:substance/tianeptine/proposal/dose_tier/c9de0763-8e04-41a6-a89d-19f2c49b1cf7
  3. 0032026-06-04publicationPublication — backfill

5Issued documents

what the notice, info card and emergency page said, by hash

Issued documents
documentcontent hashissuedfrom versionsuperseded
info_card7d35c4956b0d92ec9113a64e…2026-10-19 20:34Revision 1current
emergencyf85b2d2362c98030e2585598…2026-09-04 04:32Revision 1current
info_card99fa2e4a68a8f35ae3b29134…2026-09-04 04:32Revision 1superseded2026-10-19
notice4485cfdd7f5b64e4fc89ee3f…2026-09-04 04:32Revision 1current