LSD-induced changes in the functional connectivity of distinct thalamic nuclei.
Stefano Delli Pizzi, Piero Chiacchiaretta, Carlo Sestieri, Antonio Ferretti, Maria Giulia Tullo, Stefania Della Penna, Giovanni Martinotti, Marco Onofrj, Leor Roseman, Christopher Timmermann, David Nutt, Robin Carhart-Harris, Stefano L. Sensi
Neuroimage December 1, 2023 DOI: 10.1016/j.neuroimage.2023.120414 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Placebo-controlled study Peer reviewed |
|---|---|
| Population | Healthy volunteers |
| Intervention | Lysergic acid diethylamide (LSD) |
| Topics | LSD Psilocybin |
| Keywords | Striatum Thalamo-cortical connectivity Thalamus Psychedelics LSD Hallucinogens Entheogens Neural pathways Neural circuits Consciousness awareness Cognition Perception Mental |
| Citations | 27 |
| Key points | LSD selectively increases thalamocortical functional connectivity of the ventral complex, pulvinar, and non-specific nuclei with sensory and associative cortices while decreasing striatal-thalamic connectivity. |
Abstract
The role of the thalamus in mediating the effects of lysergic acid diethylamide (LSD) was recently proposed in a model of communication and corroborated by imaging studies. However, a detailed analysis of LSD effects on nuclei-resolved thalamocortical connectivity is still missing. Here, in a group of healthy volunteers, we evaluated whether LSD intake alters the thalamocortical coupling in a nucleus-specific manner. Structural and resting-state functional Magnetic Resonance Imaging (MRI) data were acquired in a placebo-controlled study on subjects exposed to acute LSD administration. Structural MRI was used to parcel the thalamus into its constituent nuclei based on individual anatomy. Nucleus-specific changes of resting-state functional MRI (rs-fMRI) connectivity were mapped using a seed-based approach. LSD intake selectively increased the thalamocortical functional connectivity (FC) of the ventral complex, pulvinar, and non-specific nuclei. Functional coupling was increased between these nuclei and sensory cortices that include the somatosensory and auditory networks. The ventral and pulvinar nuclei also exhibited increased FC with parts of the associative cortex that are dense in serotonin type 2A receptors. These areas are hyperactive and hyper-connected upon LSD intake. At subcortical levels, LSD increased the functional coupling among the thalamus's ventral, pulvinar, and non-specific nuclei, but decreased the striatal-thalamic connectivity. These findings unravel some LSD effects on the modulation of subcortical-cortical circuits and associated behavioral outputs.
Comparable studies
Other randomized controlled trials on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases Patients with anxiety associated with life-threatening diseases | 2014 | Randomized controlled trial | n = 12 |
| Dose-Response Study of N,N-Dimethyltryptamine in Humans Experienced hallucinogen users | 1994 | Double-blind, saline placebo-controlled, randomized study | n = 12 |
| Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Healthy subjects (8 women, 8 men) | 2014 | Double-blind, randomized, placebo-controlled, crossover study | n = 16 |
| Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Healthy human participants | 2018 | Double-blind, randomized, counterbalanced, cross-over study | n = 24 |
| LSD-induced entropic brain activity predicts subsequent personality change. Healthy adults | 2016 | Balanced-order, placebo-controlled study | n = 19 |
Citations in the library
Cited by 23
- Psychedelics for the Treatment of Obsessive–Compulsive Disorder: Efficacy and Proposed Mechanisms The International Journal of Neuropsychopharmacology November 29, 2024
- Dose-dependent LSD effects on cortical/thalamic and cerebellar activity: brain oxygen level-dependent fMRI study in awake rats. Brain Communications 2024
- Psilocybin in pharmacotherapy of obsessive-compulsive disorder Pharmacological Reports August 1, 2024
- Psychedelics, entactogens and psychoplastogens for depression and related disorders British Journal of Pharmacology June 15, 2025
- The Clinical Potential of Dimethyltryptamine: Breakthroughs into the Other Side of Mental Illness, Neurodegeneration, and Consciousness Psychoactives February 26, 2024
and 18 more in the library
Cites 13
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
- Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Current Biology April 13, 2016
- Increased global integration in the brain after psilocybin therapy for depression. Nature Medicine April 11, 2022
- Psychedelic Psychiatry's Brave New World. Cell April 1, 2020
and 8 more in the library