2026-09-19T16:27:04Zhttps://ecommons.cornell.edu/server/oai/requestoai:ecommons.cornell.edu:1813/1141462026-07-07T15:02:19Zcom_1813_35col_1813_47
Singleton, Stephen
Kuceyeski, Amy
Sabuncu, Mert
Gonzalez Caraballo, Marlen
2024-01-31T21:19:55Z
2024-01-31T21:19:55Z
2023-05
ProQuest Submission ID: 13535
ProQuest Publication ID: 30420106
https://hdl.handle.net/1813/114146
https://doi.org/10.7298/99m6-4878
16176546
Psychedelic and entactogenic drugs, once prohibited, are now being decriminalized at the local level and are poised to soon be regulated as medicines by the FDA. With nearly 100 pharmaceutical and biotech companies developing novel therapeutics from these compounds, it is essential to understand their mechanisms and impacts on the human brain. In this dissertation, we first explore the acute effects of psychedelic drugs on human brain dynamics using a computational framework called network control theory. We reveal that LSD and psilocybin decrease the barriers required for state-transitions in the brain, and this effect covaries with more dynamic brain activity. Incorporating anatomical receptor densities, we find that the serotonin 2a receptor is optimally positioned throughout the brain to facilitate this effect. We then show that time-resolved network control analysis can accurately map and simulate the rapidly-evolving dynamics of DMT, a powerful but short-acting psychedelic. Finally, we investigate brain changes associated with MDMA-assisted therapy for PTSD. We find that MDMA-assisted therapy alters brain response to traumatic memories, highlighting several regions of interest in the salience and default mode networks. Overall, this work provides a framework for understanding the acute impacts of psychedelic drugs on human brain dynamics and could potentially be used to harness or predict these effects for future clinical applications.
en
Attribution-NonCommercial-ShareAlike 4.0 International
https://creativecommons.org/licenses/by-nc-sa/4.0/
computational neuroscience
fMRI
MDMA
network control theory
psychedelics
THIS IS YOUR BRAIN ON DRUGS: A MULTIMODAL NEUROIMAGING AND COMPUTATIONAL INVESTIGATION INTO THE EFFECTS OF PSYCHEDELIC TRYPTAMINES AND MDMA ON HUMAN BRAIN DYNAMICS
dissertation or thesis
https://newcatalog.library.cornell.edu/catalog/16176546
application/pdf
Computational Biology
Cornell University
Doctor of Philosophy
Ph. D., Computational Biology
https://hdl.handle.net/1813/59810.2
Publication
Cornell Theses and Dissertations
Singleton, Stephen
5893a6ea-7af3-41d7-abc6-04bcd26ab5df
COMPLETE
open.access
open.access
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<Abstract>Psychedelic and entactogenic drugs, once prohibited, are now being decriminalized at the local level and are poised to soon be regulated as medicines by the FDA. With nearly 100 pharmaceutical and biotech companies developing novel therapeutics from these compounds, it is essential to understand their mechanisms and impacts on the human brain. In this dissertation, we first explore the acute effects of psychedelic drugs on human brain dynamics using a computational framework called network control theory. We reveal that LSD and psilocybin decrease the barriers required for state-transitions in the brain, and this effect covaries with more dynamic brain activity. Incorporating anatomical receptor densities, we find that the serotonin 2a receptor is optimally positioned throughout the brain to facilitate this effect. We then show that time-resolved network control analysis can accurately map and simulate the rapidly-evolving dynamics of DMT, a powerful but short-acting psychedelic. Finally, we investigate brain changes associated with MDMA-assisted therapy for PTSD. We find that MDMA-assisted therapy alters brain response to traumatic memories, highlighting several regions of interest in the salience and default mode networks. Overall, this work provides a framework for understanding the acute impacts of psychedelic drugs on human brain dynamics and could potentially be used to harness or predict these effects for future clinical applications.</Abstract>
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