MDMA-induced changes in within-network connectivity contradict the specificity of these alterations for the effects of serotonergic hallucinogens
Neuropsychopharmacology – November 20, 2020
Source: OpenAlex
Summary
Serotonergic hallucinogens like LSD significantly alter brain connectivity, but this study reveals that non-hallucinogenic substances such as MDMA can induce similar effects. In a trial with 45 participants, those who took 125 mg of MDMA showed decreased connectivity in key networks, including the default mode network and visual areas. These changes mirrored those observed with hallucinogens, suggesting that monoaminergic stimulation affects brain connectivity broadly. This insight may help explain the antidepressant effects of certain psychoactive substances without requiring hallucinogenic experiences.
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.