In this section
@article{Ali:2026:10.1038/s44220-026-00626-4,
author = {Ali, SS and Carhart-Harris, RL and Sieg, KG},
doi = {10.1038/s44220-026-00626-4},
journal = {Nature Mental Health},
title = {Classic psychedelics in obsessive–compulsive disorder: a circuit-based framework},
url = {http://dx.doi.org/10.1038/s44220-026-00626-4},
year = {2026}
}
TY - JOUR
AB - Obsessive–compulsive disorder (OCD) is a psychiatric condition with high rates of treatment resistance. Emerging neuroimaging evidence implicates dysfunction in large-scale brain networks, particularly the cortico–striatal–thalamo–cortical (CSTC) circuit, default mode network (DMN) and salience network (SN). Lysergic acid diethylamide (LSD) and psilocybin induce acute dysregulation of the DMN and increase connectivity across normally segregated networks, potentially disrupting maladaptive rumination and self-referential loops. Furthermore, psychedelics may improve aberrant DMN–SN connectivity in OCD, improving functioning under the triple network model. Simultaneously, both LSD and psilocybin modulate CSTC function, particularly by modulating activity in the subthalamic nucleus and striatum, regions implicated in compulsive behavior. Beyond network disruption, psychedelics rapidly enhance neuroplasticity via 5-HT<inf>2A</inf>-receptor-mediated pathways, promoting dendritic spine formation (rodents). These dual mechanisms may ‘reset’ pathological patterns and support long-term restructuring of maladaptive circuits. Future clinical trials with specific neuroimaging endpoints are needed to validate the presented framework for psychedelic action in OCD.
AU - Ali,SS
AU - Carhart-Harris,RL
AU - Sieg,KG
DO - 10.1038/s44220-026-00626-4
PY - 2026///
TI - Classic psychedelics in obsessive–compulsive disorder: a circuit-based framework
T2 - Nature Mental Health
UR - http://dx.doi.org/10.1038/s44220-026-00626-4
ER -
