Dissociable effects of LSD and MDMA on striato-cortical connectivity in healthy subjects.
Natalie Ertl, Imran Ashraf, Lisa Azizi, Leor Roseman, David Erritzøe, David Nutt, Robin Carhart-Harris, Matthew B. Wall
Neuropsychopharmacology October 31, 2025 DOI: 10.1038/s41386-025-02270-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort (re-analysis of two previous studies) Peer reviewed |
|---|---|
| Interventions | LSD MDMA |
| Topics | MDMA LSD |
| Keywords | Psychedelics: LSD Compounds Areas controlling thought Connections Pathways Brain networks Brain imaging Crucial discovery Insights Emotional processing Social bonding Distinct psychological effects |
| Citations | 1 |
| Key findings | Neither MDMA nor LSD significantly altered within-network striatal connectivity, but both drugs changed striatal connectivity with other brain regions: MDMA reduced limbic striatum-amygdala connectivity, and LSD increased associative striatum connectivity with frontal, sensorimotor, and visual cortices. |
Abstract
Lysergic acid diethylamide (LSD) and 3,4-Methylenedioxymethamphetamine (MDMA) are widely used psychoactive drugs and their potential use in psychiatric medicine is currently generating interest. The mechanism by which these drugs may assist recovery in various disorders such as addiction and post-traumatic stress disorder (PTSD) is still not well understood. Most investigations of the effects of these drugs on brain activity have focused on cortical resting-state networks, however the striatum is a key reward and motivation hub of the brain and aberrant striatal processing may be part of the pathophysiology of these disorders. Consequently, we investigated striatal connectivity following acute MDMA and LSD administration. Resting-state fMRI (rs-fMRI) data were acquired from two separate previous studies, and seed-voxel functional connectivity analyses were used with the striatum subdivided into three seed regions: the associative, limbic, and sensorimotor striatum. Within-network connectivity was measured using group mean network maps and whole-brain connectivity (seed-to-voxel) was also examined. Neither MDMA nor LSD significantly changed within-network connectivity of any of the three striatal seed regions. However, striatal connectivity with other brain regions was significantly altered with both MDMA and LSD. Most notably, MDMA reduced connectivity between the limbic striatum and the amygdala, while LSD increased connectivity between the associative striatum and the frontal, sensorimotor, and visual cortices. Changes in connectivity were mostly observed outside the standard striatal networks, consistent with previous findings that psychedelics reduce network modularity or between-network segregation and increase connectivity across standard networks.
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
Cites 56
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
- Homological scaffolds of brain functional networks Journal of the Royal Society, Interface October 29, 2014
- Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Current Biology April 13, 2016
- Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. Pharmacology & Therapeutics May 1, 2019
- Increased global integration in the brain after psilocybin therapy for depression. Nature Medicine April 11, 2022
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