Acute Effects of Hallucinogens on Functional Connectivity: Psilocybin and Salvinorin-A
Jingyuan Chen, Frederick A. Bagdasarian, Hanne D. Hansen, Chi‐hyeon Yoo, Michael S. Placzek, Jacob M Hooker, Hsiao‐ying Wey
ACS Chemical Neuroscience June 25, 2024 DOI: 10.1021/acschemneuro.4c00245 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Within-subject fMRI study Peer reviewed |
|---|---|
| Population | Nonhuman primates |
| Interventions | Psilocybin Salvinorin-A |
| Topics | Ayahuasca Psilocybin Salvia divinorum |
| Keywords | Hallucinogen |
| Citations | 11 |
| Key points | Both psilocybin and salvinorin-A acutely desynchronized the default mode network and affected a cortico-claustro-cortical network, while thalamo-cortical changes depended on 5-HT2AR activation. |
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.
Comparable studies
Other preclinical and animal studies on salvia divinorum, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Effects of the plant-derived hallucinogen salvinorin A on basal dopamine levels in the caudate putamen and in a conditioned place aversion assay in mice: agonist actions at kappa opioid receptors. Mice | 2005 | Experimental study | |
| Potential anxiolytic‐ and antidepressant‐like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents Male Sprague-Dawley rats and male Albino Swiss mice | 2009 | Experimental study | |
| Involvement of kappa-opioid and endocannabinoid system on Salvinorin A-induced reward. Wistar rats | 2008 | Experimental study | |
| Role of kappa-opioid receptors in the effects of salvinorin A and ketamine on attention in rats. Rats | 2010 | Experimental study | |
| The plant-derived hallucinogen, salvinorin A, produces kappa-opioid agonist-like discriminative effects in rhesus monkeys. Rhesus monkeys | 2004 | Experimental study | n = 3 |
Citations in the library
Cited by 9
- Psychedelics and Eating Disorders: Exploring the Therapeutic Potential for Anorexia Nervosa and Beyond ACS Pharmacology & Translational Science March 7, 2025
- What fMRI studies say about the nature of the psychedelic effect: a scoping review Frontiers in Neuroscience July 1, 2025
- Salvinorin A and Salvia divinorum: Toxicology, Pharmacological Profile, and Therapeutic Potential. International Journal of Molecular Sciences June 11, 2025
- Psychedelic experiences elicited by serotonergic psychedelics: Molecular mechanisms and functional connectivity changes in the brain Neuroscience & Biobehavioral Reviews December 16, 2025
- Psychedelics Reverse the Polarity of Long-Term Synaptic Plasticity in Cortical-Projecting Claustrum Neurons eNeuro October 1, 2025
and 4 more in the library
Cites 41
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine June 1, 2021
- The Psychedelic State Induced by Ayahuasca Modulates the Activity and Connectivity of the Default Mode Network PLoS One February 18, 2015
and 36 more in the library