Maxwell B. Madden

2 papers in the library · 200 citations · publishing 2021-2025

Papers

Models of psychedelic drug action: modulation of cortical-subcortical circuits

Brain October 22, 2021 Manoj K. Doss, Maxwell B. Madden, Andrew Gaddis et al. 196 citations

Classic psychedelic drugs like psilocybin and LSD may help treat psychiatric disorders by altering brain circuits. Two existing models—the cortico-striatal thalamo-cortical (CSTC) model and the relaxed beliefs under psychedelics (REBUS) model—highlight different subcortical structures in mediating these effects. This paper introduces a third circuit-level model, the cortico-claustro-cortical (CCC) model, focusing on the claustrum, a thin strip of grey matter that densely expresses serotonin 2A receptors. The CCC model proposes that the claustrum entrains canonical cortical network states, and psychedelic drugs disrupt 5-HT2A-mediated coupling between claustrum and cortex, attenuating these networks. Together, the three models may explain many phenomena of the psychedelic experience.

DOI: 10.1093/brain/awab406 Full text Default mode network Psilocybin Circuit models Claustrum +9

Serotonin and psilocybin activate 5-HT1B receptors to suppress cortical signaling through the claustrum

Nature Communications August 19, 2025 Maxwell B. Madden, Chloe Schaefgen, Binita Vedak et al. 4 citations

Serotonin activates 5-HT1B receptors on anterior cingulate cortex inputs to the claustrum, suppressing signaling to parietal association cortex-projecting claustrum neurons. Psilocybin, metabolized to the serotonin receptor agonist psilocin, similarly activates these presynaptic 5-HT1B receptors, reducing cortical signaling through the claustrum. This gain-control mechanism may be directly targeted by psilocybin to modulate downstream cortical network states, offering insight into how the classic psychedelic disrupts widespread brain activity.

DOI: 10.1038/s41467-025-62980-8 Full text Psilocybin Serotonin Claustrum Neuroscience +4