Anesthetic alterations of collective terahertz oscillations in tubulin correlate with clinical potency: implications for anesthetic action and post-operative cognitive dysfunction
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Anesthesia blocks consciousness and memory while sparing non-conscious brain activities. While the exact mechanisms of anesthetic action are unknown, the Meyer-Overton correlation provides a link between anesthetic potency and solubility in a lipid-like, non-polar medium. Anesthetic action is also related to an anesthetic’s hydrophobicity, permanent dipole, and polarizability, and is accepted to occur in lipid-like, non-polar regions within brain proteins. Generally the protein target for anesthetics is assumed to be neuronal membrane receptors and ion channels, however new evidence points to critical effects on intra-neuronal microtubules, a target of interest due to their potential role in post-operative cognitive dysfunction (POCD). Here we use binding site predictions on tubulin, the protein subunit of microtubules, with molecular docking simulations, quantum chemistry calculations, and theoretical modeling of collective dipole interactions in tubulin to investigate the effect of a group of gases including anesthetics, non-anesthetics, and anesthetic/convulsants on tubulin dynamics. We found that these gases alter collective terahertz dipole oscillations in a manner that is correlated with their anesthetic potency. Understanding anesthetic action may help reveal brain mechanisms underlying consciousness, and minimize POCD in the choice and development of anesthetics used during surgeries for patients suffering from neurodegenerative conditions with compromised cytoskeletal microtubules.
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A detailed quantum chemical modeling study found that potencies of several volatile anesthetics were predicted by their binding affinity to delocalized electron sites within tubulin subunits.
“Remarkably, a detailed quantum chemical modeling study found that the potencies of several volatile anesthetics were predicted by their binding affinity to delocalized electron sites within the tubulin subunits that make up MTs (Craddock et al. 2015, 2017).”
From A quantum microtubule substrate of consciousness is experimentally supported and solves the binding and epiphenomenalism problems (2025) · cites this paper as Craddock et al. 2017
The Methods and Results describe docking several anesthetics at sites on tubulin and using quantum-chemical modeling. But the Results link clinical potency (MAC) to modeled collective dipole-oscillation frequencies, not to binding affinity at delocalized-electron sites. The claimed basis for predicting potency is therefore unsupported. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThese theoretical results essentially reproduce the Meyer-Overton correlation by assuming that anesthesia is primarily mediated by MTs.
“These theoretical results essentially reproduce the Meyer–Overton correlation by assuming that anesthesia is primarily mediated by MTs.”
From A quantum microtubule substrate of consciousness is experimentally supported and solves the binding and epiphenomenalism problems (2025) · cites this paper as Craddock et al. 2017
The Results (Quantum Chemical Estimate of Polarizability and MAC; page unavailable) report a strong correlation between modeled tubulin oscillations and anesthetic potency, slightly stronger than the Meyer–Overton correlation for the anesthetics studied. But the Discussion (page unavailable) calls microtubules a potential site of anesthetic action and says other candidate sites need testing; it does not assume anesthesia is primarily mediated by microtubules. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSeveral theories incorporate anesthetic effects on microtubule dynamics as fundamental for loss of awareness.
“Moreover, several theories now incorporate anesthetic effects on microtubule dynamics as being fundamental for loss of awareness [88].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [88]
Detailed quantum chemical modeling studies support that anesthetic potency is predicted by the modeled disruption or failure to disrupt high-frequency vibrational states of MT proteins.
“As we noted above, detailed quantum chemical modeling studies support that anesthetic potency is predicted by the modeled disruption or failure to disrupt high-frequency vibrational states of MT proteins (Craddock et al., 2015, 2017).”
From Microtubule-stabilizer epothilone B delays anesthetic-induced unconsciousness in rats (2024) · cites this paper as Craddock et al., 2017
Another class of quantum model understands consciousness in terms of physical vibrational states of MTs in neurons.
“In contrast, another class of quantum model understands consciousness in terms of physical vibrational states of MTs in neurons (S. Hameroff and Penrose, 1996, 2014; Craddock et al., 2017; S. Hameroff, 2022).”
From Microtubule-stabilizer epothilone B delays anesthetic-induced unconsciousness in rats (2024) · cites this paper as Craddock et al., 2017
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“Computer modeling shows collective terahertz oscillations among tubulin’s 86 pi electron resonance rings are specifically dampened by anesthetics (Craddock et al., 2017).”
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Self-citation
- Authors
- Craddock, T. J. A., Kurian, P., Preto, J., Sahu, K., Hameroff, S. R., Klobukowski, M., & Tuszynski, J. A.
- Affiliations
- Nova Southeastern University (US)
- Howard University (US)
- Cross Cancer Institute (CA)
- University of Alberta (CA)
- University of Arizona (US)
- Corresponding author
- Craddock, Travis J. A.
- Venue
- Scientific Reports
- Published
- 2017-08-29
- Volume
- 7
- Issue
- 1
- Pages
- 9877-9877
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5575257
- OpenAlex
- W2749658452
- Cited by
- 109
- References
- 96
- Citations by year
- 2026: 16 · 2025: 12 · 2024: 12 · 2023: 25 · 2022: 7 · 2021: 9 · 2020: 6 · 2019: 13 · 2018: 7 · 2017: 2
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UA Campus Repository (The University of Arizona) (acceptedVersion, cc-by)
- PORTO@Iris (submittedVersion, cc-by)
- NSUWorks (Nova Southeastern University) (submittedVersion)
- Funders
- Nova Southeastern University (PFRDG 335426)
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Keywords
- anesthetic activity, tubulin, microtubules, anesthetic potency, anesthetic binding sites, consciousness, cytoskeleton, inhalational anesthetics, convulsants, molecular docking, quantum chemical calculations
- MeSH terms
- Anesthetics, Humans, Molecular Conformation, Postoperative Complications, Protein Binding, Structure-Activity Relationship, Tubulin, Cognitive Dysfunction
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