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N,N-dimethyltryptamine effects on connectome harmonics, subjective experience and comparative psychedelic experiences

Summary

Researchers studied how DMT, a powerful psychedelic drug, changes brain activity patterns and how these changes relate to what people experience. Using advanced brain imaging and network analysis, they found that DMT shifts brain activity away from large-scale network patterns toward smaller, more diverse patterns. Importantly, these brain changes directly tracked with how intensely participants reported experiencing the drug’s effects moment-to-moment.

Background

Psychedelic substances offer unique insights into how specific neurotransmitter systems influence perception, cognition, and consciousness. Understanding how brain structure and function relate to subjective experience requires examining how psychedelics alter functional activity across the structural connectome network.

Objective

To investigate how N,N-dimethyltryptamine (DMT) alters connectome harmonics and relate these neural changes to subjective experience intensity using connectome harmonic decomposition analysis.

Results

DMT suppressed low-frequency connectome harmonics and increased high-frequency harmonics, consistent with other psychedelics (psilocybin, LSD, ketamine). Connectome harmonic repertoire entropy increased significantly under DMT. Time-resolved analysis demonstrated that both energy spectrum difference and repertoire entropy correlated with subjective experience intensity ratings in a dynamic manner.

Conclusion

DMT reshapes the connectome harmonic landscape in consistent ways with other psychedelics and demonstrates for the first time a tight temporal coupling between connectome harmonic signatures and subjective experience intensity, supporting the entropic brain hypothesis of psychedelic action.
  • Published in:Neuropsychopharmacology,
  • Study Type:Clinical Trial,
  • Source: 10.1038/s41386-025-02190-4, PMID: 40940591
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