What is it about?
Individuals with cocaine use disorder underwent a brain imaging task designed to weaken drug memories by extinguishing reactivity to images that were previously associated with drug use. When methylphenidate was administered before a memory reactivation session (i.e., memory reconsolidation), activity in the ventromedial prefrontal cortex (a brain region critical for regulating emotional and motivational responses) shifted toward a more adaptive pattern.
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Why is it important?
For the first time, we demonstrated that, when paired with a memory-modulating behavioral intervention, a single dose of orally administered methylphenidate (a dopamine-enhancing medication commonly used to treat ADHD), can normalize disrupted prefrontal brain function in people with cocaine addiction. The findings point to a neuroscience-informed treatment approach that simultaneously targets memory and dopamine systems to reduce the power of drug cues that may trigger relapse.
Perspectives
We are thrilled to publish these results illustrating that a well-timed dose of methylphenidate, paired with a behavioral intervention that targets memory updating, restores balance in brain circuits that support learning and emotional regulation. We think this is especially important for the fight against the addiction epidemic, as the ability to modify deeply ingrained drug memories in a precise and biologically informed way opens a new frontier for addiction treatment.
Ahmet Ceceli
Icahn School of Medicine at Mount Sinai
These findings support the previous use of methylphenidate (orally administered) to enhance cognitive and emotional function, and underlying neural substrates, in people with stimulant use disorders. Beyond its previously demonstrated use to normalize salience processing, inhibitory control and resting-state functional connectivity, we now show methylphenidate’s benefit when combined with memory reconsolidation. When paired with this memory modulation approach, this simple pharmacological boost (which does not cause craving or a high, nor is it subjectively perceived by the participants) normalized prefrontal function. By improving the brain substrates underlying targeted neuropsychological functions, these results move us closer to developing interventions that reduce drug seeking, and enhance brain recovery, in people with addiction.
Rita Z Goldstein
Icahn School of Medicine at Mount Sinai
Read the Original
This page is a summary of: The synergy of methylphenidate- and reconsolidation-based extinction normalizes ventromedial prefrontal function in drug addiction, Proceedings of the National Academy of Sciences, November 2025, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2512310122.
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