Context-Dependent Pharmacology of Cannabidiol: A Two-Pathway Model Linking Mitochondrial Status to Divergent Cellular Outcomes
Anthony J. Vasquez Sr.
Delaware Valley University, Doylestown, PA
This repository contains a hypothesis and theory article proposing a mechanistic framework to explain CBD's paradoxical effects—neuroprotection in some cellular contexts, cytotoxicity in others.
How does the same molecule protect neurons while killing cancer cells?
CBD's effects are determined by dose-dependent target engagement and pre-existing mitochondrial status:
| Pathway | Concentration | Targets | Outcome |
|---|---|---|---|
| Therapeutic | 1-5 μM | TRPV1, 5-HT1A, PPARγ, GPR55 | Neuroprotection |
| Cytotoxic | >10 μM | VDAC1 → Mitochondrial disruption | Apoptosis |
CBD functions as a mitochondrial stress test—amplifying the pre-existing state of cellular bioenergetics rather than selectively targeting pathology.
cbd-two-pathway-model/
├── README.md # This file
├── LICENSE # CC BY 4.0 License
├── CITATION.cff # Citation metadata
├── paper/
│ └── CBD_TwoPathway_Hypothesis_Paper.pdf # Full manuscript (9 pages)
└── figures/
├── diagram1_dual_pathway.png # Two-pathway mechanism schematic
├── diagram2_stress_test.png # Stress test model visualization
├── diagram3_dose_affinity.png # Target engagement by concentration
└── diagram4_proposed_experiment.png # VDAC1 neuroprotection test design
- 90% concordance (18/20 predictions confirmed) with published literature
- Analysis of 70+ papers on CBD cellular mechanisms
- Temporal primacy: Mitochondrial effects occur within minutes, preceding receptor signaling
- Pre-stress sensitization: Metabolically compromised cells show 3-5× greater CBD sensitivity
- VDAC1 dependence: VDAC1 inhibitors attenuate CBD-induced cytotoxicity
- Measurable changes: Consistent alterations in ΔΨm, ROS, Ca²⁺ flux across studies
No published study tests whether VDAC1 blockade eliminates CBD's neuroprotective effects. This represents a critical experiment that could validate or refute the two-pathway model.
If validated, this model suggests:
- Therapeutic selectivity can exploit metabolic vulnerability rather than molecular uniqueness
- Biomarker-guided dosing using mtDNA status, CYP450 variants, tumor metabolic phenotype
- Combination therapy rationale for metabolic sensitization strategies
Claude (Anthropic) was used as a research and writing assistant for literature synthesis, hypothesis refinement, and figure generation. The IRIS Gate protocol was used for cross-architecture validation of the experimental gap identification.
The author maintains full responsibility for scientific content and accuracy.
@article{vasquez2025cbd,
title={Context-Dependent Pharmacology of Cannabidiol: A Two-Pathway Model
Linking Mitochondrial Status to Divergent Cellular Outcomes},
author={Vasquez, Anthony J., Sr.},
journal={Hypothesis and Theory Article},
year={2025},
institution={Delaware Valley University},
note={Preprint}
}- IRIS Gate Protocol - Cross-architecture phenomenological convergence research framework
This work is licensed under CC BY 4.0 - you are free to share and adapt with attribution.
This paper presents a mechanistic synthesis and hypothesis, not clinical recommendations. CBD-related cancer treatment decisions belong within oncology trials and clinical teams.
Contact: Anthony J. Vasquez Sr. | Delaware Valley University
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