OPEN Foundation

MDMA-induced changes in within-network connectivity contradict the specificity of these alterations for the effects of serotonergic hallucinogens

Share This Post

Share on facebook
Share on linkedin
Share on twitter
Share on email


It has been reported that serotonergic hallucinogens like lysergic acid diethylamide (LSD) induce decreases in functional connectivity within various resting-state networks. These alterations were seen as reflecting specific neuronal effects of hallucinogens and it was speculated that these shifts in connectivity underlie the characteristic subjective drug effects. In this study, we test the hypothesis that these alterations are not specific for hallucinogens but that they can be induced by monoaminergic stimulation using the non-hallucinogenic serotonin-norepinephrine-dopamine releasing agent 3,4-methylenedioxymethamphetamine (MDMA). In a randomized, placebo-controlled, double-blind, crossover design, 45 healthy participants underwent functional magnetic resonance imaging (fMRI) following oral administration of 125 mg MDMA. The networks under question were identified using independent component analysis (ICA) and were tested with regard to within-network connectivity. Results revealed decreased connectivity within two visual networks, the default mode network (DMN), and the sensorimotor network. These findings were almost identical to the results previously reported for hallucinogenic drugs. Therefore, our results suggest that monoaminergic substances can induce widespread changes in within-network connectivity in the absence of marked subjective drug effects. This contradicts the notion that these alterations can be regarded as specific for serotonergic hallucinogens. However, changes within the DMN might explain antidepressants effects of some of these substances.

Müller, F., Holze, F., Dolder, P., Ley, L., Vizeli, P., Soltermann, A., Liechti, M. E., & Borgwardt, S. (2021). MDMA-induced changes in within-network connectivity contradict the specificity of these alterations for the effects of serotonergic hallucinogens. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 46(3), 545–553.

Link to full text

OPEN Foundation

Join ICPR 2022 Online!

ICPR features world-leading experts from many academic disciplines, including psychiatry, psychology, neuroscience, anthropology, ethnobotany, and philosophy who come together to give a scientific conference for academics, therapists, researchers, clinicians, policymakers, and members of the public. Get your ICPR 2022 livestream ticket today and use the code OPENLIVE30 at checkout for a €30 discount.

Learn More


Subscribe to our new OPEN-Minded newsletter to stay in the loop, hear about our events, and become a part of a community dedicated to advancing psychedelics.

By clicking subscribe, I confirm to receive emails from the OPEN Foundation and agree with its privacy policy.

22 May - Delivering Effective Psychedelic Clinical Trials