LSD alters brain network connectivity. In a double-blind, randomized, crossover study, 20 healthy participants received 100 μg LSD or placebo, and resting-state brain activity was measured with fMRI. LSD decreased functional connectivity within visual, sensorimotor, auditory, and default mode networks, while increasing connectivity between networks and subcortical (thalamus, striatum) and cortical (precuneus, anterior cingulate cortex) hub structures. These hub changes resemble patterns seen in psychosis and may relate to therapeutic effects of hallucinogens.
Chronic MDMA users show increased fractional anisotropy in white matter tracts, particularly the corpus callosum and corticospinal tracts, with some links to usage intensity. However, blood neurofilament light chain levels did not differ from controls. The absence of reduced fractional anisotropy and elevated NfL—typically seen in conditions with white matter lesions, such as stimulant and ketamine use disorders—suggests MDMA use is not associated with significant white matter damage. Thus, axonal degradation observed in animal models was not replicated in this human sample of 39 chronic users and 39 matched controls.