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.  

Alteration in gene expression and immunomodulatory mechanisms as an explanation of psychedelic therapeutic effects

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.  

Alternative mechanisms of action for psychedelics 

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.

Alma College

Default Mode Network modulation has been a consistent approach to understanding the effects and mechanisms of different psychedelic drugs. It is a current hypothesis that the relation of DMN modulation has a relation with the therapeutic effects of these drugs. Nonetheless, the mechanisms of this relation are still unclear.  

DMN modulation by use of 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

Every psychedelic drug has its own mechanism of interaction with the Default Mode Network. Nevertheless, acute disruption in resting-state connectivity and increased functional connectivity between canonical resting-state networks seems to be a consistent finding in regard to modulation. 


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