Relaxed Beliefs Under Psychedelics and Brain Entropy or (REBUS), Cortico-Striatal-Thalamo-Cortical Model (CSTC), and  Cortico-Claustro-Cortical (CCC) model are all different hypotheses that propose alternative mechanisms of action of psychedelics that are not supportive of the DMN mechanism.  

Alma College

Currently, DMN modulation in terms of therapeutic effects is a theory and causality is hard to address in terms of internal validity. Furthermore, there are still discrepancies in the psychedelic mechanism of action which can obscure the origin of the therapeutic effects.

Limitations of DMN modulation with Psychedelics 

Gattuso, J. J., Perkins, D., Ruffell, S., Lawrence, A. J., Hoyer, D., Jacobson, L. H., Timmermann, C., Castle, D., Rossell, S. L., Downey, L. A., Pagni, B. A., Galvão-Coelho, N. L., Nutt, D., &amp; Sarris, J. (2022). Default mode network modulation by psychedelics: A systematic review. International Journal of Neuropsychopharmacology, 26(3), 155–188. https://doi.org/10.1093/ijnp/pyac074 

Default Mode Network Modulation by Psychedelics: A
Systematic Review

Studies suggest that therapeutic changes can be due to evidence that suggests that psychedelics can induce marked neuronal structural and functional changes via neurotrophic signaling and neuroplasticity. 

Neuronal structural and functional change as an explanation of psychedelic therapeutic effects 

Alterations in gene expression and immunomodulatory mechanisms are suggested to rewire pathological cortical networks which are related to a reduction of neuronal inflammation that can help with addiction, neurodegeneration, and depression.  

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