Stefan Borgwardt


University Hospital Lübeck & Basel University

Distinct acute effects of LSD, MDMA, and D-amphetamine on brain connectivity


We used a double-blind, placebo-controlled, crossover design and administered lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), and d-amphetamine in healthy participants. We mapped substance-induced changes in functional and effective connectivity derived from a resting-state functional magnetic resonance imaging (fMRI) data. Due to the distinct pharmacological modes of action of the three substances, we were able to investigate specific effects mainly driven by different neurotransmitter systems on thalamocortical and corticothalamic interactions. Compared to placebo, all three 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, covering 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. Results from functional neuroimaging studies advance our knowledge concerning the specific action of different psychedelics on the brain and refine current models aiming to explain the underlying neurobiological processes.


Professor Stefan Borgwardt, MD, is a Professor and Chair of Psychiatry and Psychotherapy of the Universitätsklinikum Schleswig-Holstein at the University of Lübeck, Germany. He completed his MD at the Charite in Berlin, Germany and his psychiatric training at the University of Basel, Switzerland, where he also became Associate Professor. During his Habilitation he moved to the IoPPN, King’s College London, this relationship has continued as Visiting Professor. Since 2018, he has been listed by Clarivate/Web of Science as a ‚highly cited researcher‘ in the area of psychiatry. His research and clinical work focuses on the prediction, identification and treatment of mental disorders in young people at risk and in investigating the underlying neurofunctional mechanisms and efficacy of potential innovative treatments such as cannabinoids and psychedelics. He uses a variety of methods including structural and functional neuroimaging, neurocognitive and computational modeling as well as pharmacological and clinical studies.