Effective Connectivity of Thalamocortical Interactions Following d-Amphetamine, LSD, and MDMA Administration.
Mihai Avram, Felix Müller, Katrin H. Preller, Adeel Razi, Helena Rogg, Alexandra Korda, Friederike Holze, Patrick Vizeli, Laura Ley, Matthias E. Liechti, Stefan Borgwardt
Biological Psychiatry: Cognitive Neuroscience and Neuroimaging May 1, 2024 DOI: 10.1016/j.bpsc.2023.07.010 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, placebo-controlled, crossover design Peer reviewed |
|---|---|
| Sample size | 25 |
| Population | Healthy participants |
| Interventions | LSD MDMA d-amphetamine |
| Topics | LSD MDMA |
| Keywords | Dynamic causal modeling Effective connectivity Psychedelics Transmodal cortex Unimodal cortex D-amphetamine Psychopharmacology Brain connectivity Psychedelic research Drug effects |
| Citations | 13 |
| Key points | LSD increased effective connectivity from the thalamus to both unimodal and transmodal cortices, indicating a breach in hierarchical brain organization, whereas amphetamines showed opposite effects for transmodal cortices. |
Abstract
While the exploration of serotonergic psychedelics as psychiatric medicines deepens, so does the pressure to better understand how these compounds act on the brain. We used a double-blind, placebo-controlled, crossover design and administered lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), and d-amphetamine in 25 healthy participants. By using spectral dynamic causal modeling, we mapped substance-induced changes in effective connectivity between the thalamus and different cortex types (unimodal vs. transmodal) derived from a previous study with resting-state functional magnetic resonance imaging data. Due to the distinct pharmacological modes of action of the 3 substances, we were able to investigate specific effects mainly driven by different neurotransmitter systems on thalamocortical and corticothalamic interactions. Compared with placebo, all 3 substances increased the effective connectivity from the thalamus to specific unimodal cortices, whereas the influence of these cortices on the thalamus was reduced. These results indicate increased bottom-up and decreased top-down information flow between the thalamus and some unimodal cortices. However, for the amphetamines, we found the opposite effects when examining the effective connectivity with transmodal cortices, including parts of the salience network. Intriguingly, LSD increased the effective connectivity from the thalamus to both unimodal and transmodal cortices, indicating a breach in the hierarchical organization of ongoing brain activity. The results advance our knowledge about the action of psychedelics on the brain and refine current models aiming to explain the underlying neurobiological processes.
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 11
- The central role of the Thalamus in psychosis, lessons from neurodegenerative diseases and psychedelics. Translational Psychiatry December 13, 2023
- Large-scale brain connectivity changes following the administration of lysergic acid diethylamide, d-amphetamine, and 3,4-methylenedioxyamphetamine. Molecular Psychiatry April 1, 2025
- Classification schemes of altered states of consciousness. Neuroscience & Biobehavioral Reviews August 1, 2025
- Dose-dependent LSD effects on cortical/thalamic and cerebellar activity: brain oxygen level-dependent fMRI study in awake rats. Brain Communications 2024
- Neurobiological Correlates of Psychedelic Experiences and Psychedelic-Associated Adverse Effects. Current Topics in Behavioral Neurosciences July 31, 2024
and 6 more in the library
Cites 29
- 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
- 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
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
and 24 more in the library