Acute effects of methadone on neural oscillations: an EEG study of theta, alpha, beta power, and frontal alpha asymmetry in opioid rehabilitation patients

Methadone is a synthetic opioid that commonly employed in opioid substitution therapy (OST) to reduce withdrawal symptoms and suppress cravings in individuals with opioid use disorder. While its pharmacological effects are well-documented, the neurophysiological changes it induces—especially during acute administration—remain underexplored. This study aims to address that gap by investigating methadone-induced alterations in brain oscillatory activity through electroencephalography (EEG). Specifically, it examines changes in theta (4–8 Hz), alpha (8–12 Hz), and beta (12–30 Hz) frequency bands, along with frontal alpha asymmetry (FAA) for F4-F3 and F8-F7, a biomarker associated with emotional and cognitive processing. EEG data were collected from patients enrolled in opioid rehabilitation programs both prior to and one hour following oral methadone intake. The results revealed a significant global decrease in theta power, notably within the frontal, temporal, and occipital cortices. This reduction may reflect changes in executive functioning, emotional regulation, and increased sedation. In contrast, alpha power showed a marked increase, particularly in the central, parietal, and occipital regions, suggesting reduced sensory processing and heightened sedation or attentional disengagement. Meanwhile, beta power was consistently reduced across cortical regions, pointing toward decreased cortical arousal and cognitive alertness. FAA analysis revealed high variability among participants, indicating that methadone's influence on emotional valence and approach-avoidance behavior may differ significantly across individuals. These findings underscore methadone’s sedative and stabilizing effects on neural activity and support its clinical role in managing opioid dependence. Further research into inter-individual differences in EEG responses may inform more personalized and effective OST protocols.