Acute Effects of Hallucinogens on Functional Connectivity: Psilocybin and Salvinorin-A
ACS Chemical Neuroscience – June 25, 2024
Source: OpenAlex
Summary
A compelling finding in **Drug Studies** reveals that **Hallucinogens**, including **Psilocybin** and Salvinorin-A, dramatically reshape brain connectivity. Despite their distinct **Neurotransmitter Receptor Influence on Behavior**—one a classical **Psychedelic**, the other a kappa-opioid agonist—both acutely desynchronize the brain's default mode network. Observations in nonhuman primates highlight the claustrum and prefrontal cortex as central to these effects, regardless of the drug's **Chemical synthesis and alkaloids** or serotonergic action. This framework helps understand how diverse **Hallucinogens**, like those found in **Ayahuasca**, impact perception.
Abstract
The extent of changes in functional connectivity (FC) within functional networks as a common feature across hallucinogenic drug classes is under-explored. This work utilized fMRI to assess the dissociative hallucinogens Psilocybin, a classical serotonergic psychedelic, and Salvinorin-A, a kappa-opioid receptor (KOR) agonist, on resting-state FC in nonhuman primates. We highlight overlapping and differing influence of these substances on FC relative to the thalamus, claustrum, prefrontal cortex (PFC), default mode network (DMN), and DMN subcomponents. Analysis was conducted on a within-subject basis. Findings support the cortico-claustro-cortical network model for probing functional effects of hallucinogens regardless of serotonergic potential, with a potential key paradigm centered around the claustrum, PFC, anterior cingulate cortices (ACC), and angular gyrus relationship. Thalamo-cortical networks are implicated but appear dependent on 5-HT2AR activation. Acute desynchronization relative to the DMN for both drugs was also shown. Our findings provide a framework to understand broader mechanisms at which hallucinogens in differing classes may impact subjects regardless of the target receptor.