Spatial Correspondence of LSD-Induced Variations on Brain Functioning at Rest With Serotonin Receptor Expression.
Stefano Delli Pizzi, Piero Chiacchiaretta, Carlo Sestieri, Antonio Ferretti, Marco Onofrj, Stefania Della Penna, Leor Roseman, Christopher Timmermann, David Nutt, Robin Carhart-Harris, Stefano L. Sensi
Biological Psychiatry: Cognitive Neuroscience and Neuroimaging July 1, 2023 DOI: 10.1016/j.bpsc.2023.03.009 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 15 |
| Population | Healthy volunteers |
| Intervention | LSD |
| Topics | LSD Serotonin |
| Keywords | 5-ht2a Hallucinations Psychedelics LSD Acid Hallucinogens Brain Imaging FMRI Neuroimaging Serotonin receptors 5-ht1a |
| Citations | 18 |
| Key findings | LSD increases functional connectivity and local signal amplitude in cortical regions with high 5-HT2A receptor expression, correlating with visual hallucinations, while decreasing these measures in limbic areas with high 5-HT1A receptor expression. |
Abstract
Lysergic acid diethylamide (LSD) is an atypical psychedelic compound that exerts its effects through pleiotropic actions, mainly involving 1A/2A serotoninergic (5-HT) receptor subtypes. However, the mechanisms by which LSD promotes a reorganization of the brain's functional activity and connectivity are still partially unknown. Our study analyzed resting-state functional magnetic resonance imaging data acquired from 15 healthy volunteers undergoing LSD single-dose intake. A voxelwise analysis investigated the alterations of the brain's intrinsic functional connectivity and local signal amplitude induced by LSD or by a placebo. Quantitative comparisons assessed the spatial overlap between these 2 indices of functional reorganization and the topography of receptor expression obtained from a publicly available collection of in vivo, whole-brain atlases. Finally, linear regression models explored the relationships between changes in resting-state functional magnetic resonance imaging and behavioral aspects of the psychedelic experience. LSD elicited modifications of the cortical functional architecture that spatially overlapped with the distribution of serotoninergic receptors. Local signal amplitude and functional connectivity increased in regions belonging to the default mode and attention networks associated with high expression of 5-HT2A receptors. These functional changes correlate with the occurrence of simple and complex visual hallucinations. At the same time, a decrease in local signal amplitude and intrinsic connectivity was observed in limbic areas, which are dense with 5-HT1A receptors. This study provides new insights into the neural processes underlying the brain network reconfiguration induced by LSD. It also identifies a topographical relationship between opposite effects on brain functioning and the spatial distribution of different 5-HT receptors.
Comparable studies
Other observational and cohort studies on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Human participants | 2016 | Observational cohort | |
| Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Humans | 2017 | Observational study | |
| Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. USA adult respondents from the National Survey on Drug Use and Health (2008-2012) | 2015 | Observational cohort | n = 190,000 |
| Psychedelics not linked to mental health problems or suicidal behavior: A population study Randomly selected United States adults | 2015 | Observational cohort | n = 135,095 |
| Whole-Brain Multimodal Neuroimaging Model Using Serotonin Receptor Maps Explains Non-linear Functional Effects of LSD. Healthy human participants | 2018 | Observational study with computational modeling |
Citations in the library
Cited by 7
- A Comprehensive Review of the Current Status of the Cellular Neurobiology of Psychedelics Biology October 28, 2023
- 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
- Multimodal Neuroimaging of the Effect of Serotonergic Psychedelics on the Brain. AJNR. American journal of neuroradiology February 15, 2024
- What fMRI studies say about the nature of the psychedelic effect: a scoping review Frontiers in Neuroscience July 1, 2025
and 2 more in the library
Cites 28
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- 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
- Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors Science February 16, 2023
and 23 more in the library