cbd-two-pathway-model/CITATION.cff at main · templetwo/cbd-two-pathway-model · GitHub

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cff-version: 1.2.0
message: "If you use this work, please cite it as below."
authors:
  - family-names: "Vasquez"
    given-names: "Anthony J."
    name-suffix: "Sr."
    affiliation: "Delaware Valley University"
title: "Context-Dependent Pharmacology of Cannabidiol: A Two-Pathway Model Linking Mitochondrial Status to Divergent Cellular Outcomes"
version: 1.2.0
date-released: 2026-02-13
url: "https://github.com/templetwo/cbd-two-pathway-model"
repository-code: "https://github.com/templetwo/cbd-two-pathway-model"
license: CC-BY-4.0
type: article
keywords:
  - cannabidiol
  - CBD
  - VDAC1
  - mitochondria
  - context-dependent pharmacology
  - neuroprotection
  - apoptosis
  - glioblastoma
  - dose-response
  - multi-model convergence
  - IRIS Gate Evo
  - Monte Carlo simulation
abstract: >-
  Cannabidiol (CBD) exhibits paradoxical effects across cell types,
  inducing apoptosis in glioma and cancer models while conferring
  neuroprotection under excitotoxic stress. We propose that CBD acts
  as a mitochondrial stress test, with outcomes determined by
  pre-existing cellular metabolic status. A two-pathway framework
  explains the paradox: (1) at therapeutic concentrations (1-5 μM),
  CBD engages TRPV1, 5-HT1A, PPARγ, and GPR55, producing neuroprotective
  effects; (2) at higher concentrations (>10 μM), CBD binds VDAC1 on
  the outer mitochondrial membrane, triggering apoptosis in metabolically
  vulnerable cells. Literature analysis of 70+ papers yielded 90%
  concordance with model predictions. Computational validation via
  IRIS Gate Evo (five independent AI models) confirmed convergence
  on the two-pathway mechanism with large predicted effect sizes
  (Cohen's d 0.81-0.95).
references:
  - type: article
    authors:
      - family-names: "Rimmerman"
        given-names: "N."
    title: "Direct modulation of VDAC1 by cannabidiol"
    journal: "Cell Death & Disease"
    year: 2013
    volume: 4
    pages: "e949"
  - type: article
    authors:
      - family-names: "Devinsky"
        given-names: "O."
    title: "Trial of cannabidiol for drug-resistant seizures in Dravet syndrome"
    journal: "New England Journal of Medicine"
    year: 2017
    volume: 376
    issue: 21
    pages: "2011-2020"