Evidence mapPaperPMID 42576458Full record

ReviewJournal of neuroscience research2026

The Endoterpenoid System: A Membrane-Based Logic Framework for Integrating Cannabinoid, Olfactory, and Lipid-Sensitive Receptor Crosstalk.

Erhan Yarar, Aytug Altundag, Christopher E Mason, Michael Aschner, Emirhan Harbi

Abstract readReview
In one paragraph

Review in Journal of neuroscience research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Erhan YararInstitute for Cannabinoid Research and Translational Medicine (ICR), Amsterdam, the Netherlands.ORCID https://orcid.org/0000-0002-9164-3639
Aytug AltundagDepartment of Otorhinolaryngology, Biruni University School of Medicine, Istanbul, Turkey.ORCID https://orcid.org/0000-0003-0794-5050
Christopher E MasonDepartment of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY, USA.ORCID https://orcid.org/0000-0002-1850-1642
Michael AschnerDepartment of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA.ORCID https://orcid.org/0000-0002-2619-1656
Emirhan HarbiBiruni Scientific Research Center (B@MER), Faculty of Medicine, Biruni University, Istanbul, Turkey.ORCID https://orcid.org/0009-0005-9260-8316

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Endoterpenoid System (ETS) is a proposed new membrane-based framework that ensembles classical endocannabinoid signaling (ECS) with ectopically expressed olfactory GPCRs, ion channels, and microbially derived terpenoids. Integrated with this model is the proposed endoterpenoidome (eTBome) machine: a chemically diverse pool of endogenous cannabinoids, dietary terpenoids, and microbial metabolites whose lipophilicity drives partitioning into cholesterol-rich lipid rafts. Within these nanoscale microdomains, ETS components undergo co-localization and co-expression, enabling receptor heteromerization and β-arrestin-scaffolded signalosomes that facilitate dynamic crosstalk and emergent responses such as bistable apoptotic switches and context specific modulation of Gᵢ/o, Gₛ/olf, and Gq pathways. We detail molecular mechanisms underpinning ETS behavior, including lipid mediated allostery, scaffold protein recruitment, and lateral diffusion effects, and highlight the gut microbiota as pivotal architects of the eTBome through terpene synthase-driven production of bioactive ligands. Germ free and antibiotic treated animal models underscore the dependence of ETS ligand pools and receptor distributions on microbial colonization. This article proposes key avenues for experimental validation, including high resolution structural studies of CB-OR heteromers, quantitative lipidomic mapping of eTBome distributions, live cell super resolution imaging of receptor nanoclusters, and gnotobiotic manipulations of microbial terpene synthesis. By introducing them as proposals to the scientific community and by integrating ECS/eCBome biology with olfactory receptor (OR) and microbial metabolite research, the ETS/eTBome concept offers a cohesive hypothesis for lipid-driven GPCR crosstalk and indicated non-standard targets for therapeutic modulation in cancer, neuroinflammation, and metabolic disorders.

Indexed as

CannabinoidsEndocannabinoidsReceptor Cross-TalkReceptors, CannabinoidReceptors, OdorantTerpenesAnimalsHumansMembrane MicrodomainsSignal TransductionCannabinoidsEndocannabinoidsReceptors, CannabinoidReceptors, OdorantTerpenesco‐expressionendoterpenoidomeendoterpenoid systemGPCR heteromerizationlipid raftsreceptor crosstalk

Identifiers

PMID42576458
PMCPMC13458236

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.