Speciociliatine: Evidence and Caveats

What is well supported

  • Binds MOR and KOR (sub-100 nM MOR; low-hundreds nM KOR) and shows partial MOR agonism in multiple G-protein–biased assays.
  • Human PK (product study): Speciociliatine can be the dominant circulating alkaloid post-ingestion (AUC₀-inf ≈ 5120 nM·h vs 420 nM·h for mitragynine in the same product).
  • Metabolism: CYP3A4-dominant, with no human-specific disproportionate metabolite seen in HLM.

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    What remains uncertain / conflicting

  • Efficacy is assay-dependent: BRET-based work observed weak antagonism/no agonism for speciociliatine, in contrast to HTRF/other G-protein assays and in-vivo antinociception; always report the assay modality next to EC₅₀/Emax.
  • Human clinical efficacy & safety: No controlled efficacy trials; zebrafish embryo toxicity occurs at very high in-vitro concentrations (≫ human Cmax after kratom), so translate cautiously.

    • How to phrase your on-site disclaimers

    Human data for speciociliatine are limited. Binding/activity depend on the assay used (G-protein vs β-arrestin). Exposure and effects may vary by product and metabolism. Sources are linked below.

    References (primary, open or stable)

  • Obeng S. et al., 2020, J. Med. Chem. (PMC) — Full MOR/KOR Kᵢ table and functional discussion (assay-dependence noted).
  • Berthold E.C. et al., 2021, J. Pharm. Biomed. Anal. (PubMed abstract) — Rat PK: Vz, CL, F with dosing paradigm (2.5 mg/kg i.v., 20 mg/kg p.o.).
  • Kamble S.H. et al., 2022, AAPS J (PMC author ms.) — Metabolism (pathways, CYP3A4≫2D6), cross-species hepatocyte t½, and human AUC dominance of speciociliatine.
  • Frontiers in Pharmacology review, 2022 — Consolidated tables and discussion of mitragynine diastereomers; useful for context but defer to primary data above.
  • PubChem — Identity, structure, IDs for link-outs and infobox