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"Large-Scale and Local Functional Connectivity Changes Following Psilocybin Administration in Methamphetamine Use

Joga Chaganti1, Krista J Siefried1, Veda S Vyakaranam1

  • 1From the Thomas Jefferson University (J.C.); St. Vincent's Hospital Alcohol and Drug Service (K.J.S., L.A.), Sydney, Australia; National Drug and Alcohol Research Centre (NDARC) (K.J.S., L.A.), The University of New South Wales, Randwick, Australia; New South Wales Drug and Alcohol Clinical Research and Improvement Network (DACRIN) (K.J.S., L.A.), c/o the Ministry of Health, Sydney, Australia; Jefferson Integrated Magnetic Resonance Imaging Center (JIMRIC) (V.S.V.), Thomas Jefferson University, Philadelphia-19107, USA and St. Vincent's Clinical School (J.B), University of New South Wales, Sydney, Australia.

AJNR. American Journal of Neuroradiology
|April 24, 2026
PubMed
Summary
This summary is machine-generated.

Psilocybin treatment, combined with psychotherapy, reorganized brain networks in individuals with methamphetamine use disorder. This intervention improved functional connectivity and was linked to reduced drug use and psychological distress.

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Addiction Research

Background:

  • Methamphetamine (MA) use disorder disrupts brain networks crucial for cognitive control, attention, and salience.
  • Resting-state functional MRI (rs-fMRI) can identify these disruptions, but network recovery after treatment is understudied.

Purpose of the Study:

  • To investigate changes in large-scale and local functional connectivity after psilocybin administration in individuals with MA use disorder.

Main Methods:

  • Prospective longitudinal study using rs-fMRI before and after psilocybin and psychotherapy.
  • Assessed large-scale connectivity in default mode, salience, dorsal attention, and executive control networks.
  • Evaluated local connectivity using regional homogeneity (ReHo) and correlated changes with clinical outcomes.

Main Results:

  • Psilocybin administration led to significant reorganization within and between attentional, default mode, and salience networks.
  • Increased network integration correlated with increased ReHo in frontal and sensorimotor regions.
  • Reduced MA use linked to restored frontostriatal and attentional connectivity; reduced distress linked to strengthened attentional and prefrontal-striatal circuits.

Conclusions:

  • Psilocybin administration induced measurable reorganization of brain connectivity and local coherence in MA use disorder.
  • Findings suggest psilocybin may promote network plasticity, offering potential as an imaging biomarker for stimulant addiction treatment.