Using fMRI in nonhuman primates, this work compared how two different hallucinogens—psilocybin, a serotonergic psychedelic, and salvinorin-A, a kappa-opioid receptor agonist—alter resting-state functional connectivity. Both drugs acutely desynchronized the default mode network and affected a network involving the claustrum, prefrontal cortex, anterior cingulate cortices, and angular gyrus, supporting a cortico-claustro-cortical model for probing hallucinogen effects regardless of serotonergic activity. Thalamo-cortical changes appeared dependent on 5-HT2AR activation. The findings offer a framework for understanding mechanisms common across hallucinogenic drug classes.
Psilocybin, a serotonergic agonist, and Salvinorin-A, a kappa-opioid receptor agonist, both alter functional connectivity in the brains of non-human primates, but their effects overlap and differ in specific regions. Using fMRI, the study examined how these psychedelics influence connections within the default mode network and the claustrum. The findings suggest that each substance targets distinct receptor systems, leading to both shared and unique patterns of brain network activity, which may help explain their different mechanisms of action.