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

Felix Müller, Friederike Holze, Patrick C. Dolder, Laura Ley, Patrick Vizeli, Alain Soltermann, Matthias E. Liechti, Stefan Borgwardt

Neuropsychopharmacology November 20, 2020 DOI: 10.1038/s41386-020-00906-2 via OpenAlex

Summary

AI-generated from the abstract

The non-hallucinogenic drug MDMA reduces functional connectivity within several resting-state brain networks, including the default mode network, visual networks, and the sensorimotor network. These decreases closely match those previously reported for hallucinogenic drugs like LSD. The findings suggest that such connectivity changes are not specific to serotonergic hallucinogens but can be induced by monoaminergic stimulation without marked subjective drug effects. However, alterations within the default mode network may help explain the antidepressant effects of some of these substances.

Study at a glance

Characteristics Randomized controlled trial Placebo-controlled Double-blind Peer reviewed
Sample size 45
Population Healthy participants
Topics Default mode network LSD MDMA Psilocybin Serotonin
Keywords Hallucinogen Monoaminergic Psychology
Citations 43
Key finding MDMA induces decreases in within-network connectivity in visual networks, the default mode network, and the sensorimotor network, similar to those seen with hallucinogenic drugs.

Abstract

Abstract 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.

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