A sweeping international analysis suggests psychedelics do not just alter perception, they reconfigure how major brain networks communicate, offering one of the clearest maps yet of their large-scale effects on the human brain.
Study: An international mega-analysis of psychedelic drug effects on brain circuit function. Image Credit: Lightspring / Shutterstock
In a recent study published in the journal Nature Medicine, researchers analyzed the effects of psychedelic drugs on brain circuit function.
Psychedelic drugs like psilocybin, lysergic acid diethylamide (LSD), N, N-dimethyltryptamine (DMT), and mescaline have reemerged as drivers of clinical innovation and scientific insight in mental health. They are characterized by their ability to induce changes in conscious experience, and have shown strong therapeutic potential in treating depression, generalized anxiety disorder, alcoholism, end-of-life distress, and tobacco addiction.
The rise of psychedelic-assisted therapies necessitates a better understanding of the underlying mechanisms. Research on psychedelics has rapidly evolved over the past decade, ranging from cellular or molecular analyses of neuronal plasticity and morphology to investigations of functional networks in humans primarily using resting-state functional magnetic resonance imaging (rsfMRI). However, rsfMRI studies on psychedelic effects have yielded inconsistent or fragmented findings.
Psychedelic Brain Network Study Design
In the present study, researchers performed a mega-analysis incorporating intrinsic functional coupling data across various drugs and studies to characterize how brain circuits are affected by psychedelic drugs. They used 11 independent rsfMRI datasets from five countries in Europe, North America, and South America, encompassing 267 participants and over 500 brain scanning sessions.
First, the team examined drug-placebo differences across datasets to characterize the overall nature of psychedelic-induced changes in functional connectivity (FC). They noted the strongest increases in between-network FC between transmodal association networks, such as the frontoparietal (FPN) and default networks (DN), and unimodal/heteromodal sensory networks, such as the visual (VIS), somatomotor (SMN), and dorsal attention networks (DAN).
FC increases with sensorimotor networks were found for subcortical regions, especially the putamen, caudate, thalamus, and cerebellum. Reductions in between-network FC were predominantly observed between the SMN and VIS networks. Further, descriptive analyses indicated that all networks showed decreases in within-network FC, with VIS and SMN networks exhibiting the largest reductions. Subcortical data revealed reduced integration within all regions.
Drug-Specific Functional Connectivity Changes
Next, the team investigated drug-induced changes in between- and within-network FC for each drug. Psilocybin and LSD had highly similar FC changes, comparable to the results of all drugs. Both drugs increased between-network FC, particularly between unimodal/heteromodal sensorimotor networks and transmodal association networks. Elevated FC between sensorimotor networks and subcortical regions was particularly prominent for LSD.
Reductions in FC were observed between sensorimotor regions for both LSD and psilocybin. Further, DMT showed the largest apparent effect among drugs, featuring a pattern that resembled an amplified version of all drugs, LSD, and psilocybin, although these estimates were accompanied by greater uncertainty. In particular, FPN and DN networks, as well as the thalamus, putamen, and caudate, showed pronounced FC increases with unimodal/heteromodal sensorimotor networks.
Strong decreases in FC were also noted for DMT within and between VIS and SMN networks, as well as between the putamen, caudate, thalamus, globus pallidus, and cerebellum. Mescaline showed a pattern moderately resembling that of all drugs, LSD, psilocybin, and DMT; there were increases in between-network FC, particularly between FPN, DN, limbic (LIM), salience (SAL), and sensorimotor networks (DAN, SMN, and VIS).
Ayahuasca showed a relatively idiosyncratic pattern of changes in FC. Prominent decreases in FC were evident between unimodal/heteromodal sensorimotor networks and between LIM, DN, hippocampus, and amygdala and sensorimotor networks. Next, the team used Bayesian hierarchical inference to quantify the uncertainty and strength of these effects.
Bayesian Analysis of Psychedelic Brain Effects
Bayesian models were developed for each network and network pair. Across network pairs, there was a consistent pattern of elevated between-network coupling, with variability in effect magnitude and uncertainty by drug and network pair. Distributions for LSD, psilocybin, and mescaline were commonly overlapping and also had the least dispersion. DMT and ayahuasca showed the least certainty in effects, likely reflecting their smaller sample sizes.
The strongest positive posterior shifts were noted for caudate coupling with unimodal networks, including caudate-VIS and caudate-SMN networks. Positive posterior shifts were observed for cross-network coupling between transmodal and VIS subnetworks. Further, weak-to-moderate decreases in within-network FC were evident across networks, with variability in effect magnitude and uncertainty across drugs.
Several networks had consistent posterior shifts towards reduced within-network FC. LSD and psilocybin had the most reliable drug response effects, with relatively narrow posterior distributions across networks. Mescaline had broadly similar but variable effects, while ayahuasca and DMT had wider, more dispersed posteriors, reflecting greater uncertainty.
Psychedelic Brain Organization Conclusions
Psychedelics robustly increased functional integration between select pairs of transmodal and unimodal subnetworks, as well as between key subcortical regions and both unimodal and transmodal cortical regions. Notably, a core brain signature of elevated functional coupling was identified between transmodal association circuits and unimodal/heteromodal sensorimotor circuits. Overall, the study offered a probabilistic map of how psychedelics alter brain organization, providing a foundation for future research.
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