A randomized trial found changes in brain activation and connectivity after active stimulation, but no significant advantage over sham stimulation in self-reported methamphetamine craving. The imaging findings should not be presented as proof of a clinical craving benefit.
Ekhtiari and colleagues randomized 60 people with methamphetamine use disorder to active or sham transcranial direct current stimulation. Active treatment used 2 mA for 20 minutes with an anode over F4 and cathode over Fp1. Participants underwent a drug-cue functional MRI task before and after stimulation. Participants, the staff delivering and assessing treatment, and data analysts were blinded to allocation.
Self-reported craving fell after stimulation, but the time-by-group interaction was not significant. A before-and-after reduction within a treatment group does not show superiority over the control group when both experience the study procedures. The result supports the narrower conclusion that this single active session did not demonstrate an additional craving reduction over sham.
Brain responses to drug cues declined more broadly after sham than active stimulation. Significant group-by-time differences appeared in selected frontal, insular, parietal and precuneus regions, with relatively higher activation after active treatment. Task-related connectivity also differed. Higher activation is a measurement result; whether it represents beneficial engagement, sustained cue reactivity or another process requires additional evidence.
This trial investigated immediate responses to one specific stimulation arrangement. It does not resolve whether repeated sessions, another electrode placement or a different patient population would produce clinical benefit. Individual variation and possible nonlinear relationships between delivered current, imaging signals and craving complicate mechanistic interpretation. Neither the MRI signal nor stimulation exposure was a measure of methamphetamine concentration. For evaluating treatment claims, the controlled clinical outcome should remain visible alongside the mechanistic findings, even when the latter are statistically significant.
See also a different stimulation study examining visual-memory outcomes.