Methadone maintenance treatment is an established approach for the management of opioid use disorder and can play an important role in reducing illicit opioid use and supporting treatment retention. However, long-term opioid exposure and treatment-related factors may also be associated with differences in cognitive performance. Previous research has examined domains including memory, attention, executive functioning and psychomotor performance.
The review presented in this article evaluated studies published between 2020 and 2025 and focused on three major cognitive domains: working memory, attention and executive control, and reaction time.
According to the summary presented in the source material, 15 studies involving 658 patients receiving methadone maintenance treatment and 572 healthy control participants were included. The participants represented several countries, and the reported mean age was approximately 38.4 years.
The reported meta-analytic results indicated differences between methadone-maintained participants and healthy controls in all three evaluated domains:
- Working memory: g = 1.12
- Attention and executive control: g = 0.98
- Reaction time: g = 1.24
Among these domains, reaction time showed the largest reported effect size. The findings suggest that cognitive and psychomotor performance may deserve attention during the assessment and rehabilitation of individuals receiving methadone maintenance treatment.
Importantly, cognitive findings in this area should be interpreted carefully. Research indicates that cognitive performance can be influenced by several factors, including previous opioid exposure, duration of treatment, methadone dose, co-occurring substance use, psychiatric symptoms and other clinical characteristics. Earlier systematic reviews have also emphasized methodological limitations and heterogeneity among studies.
For example, experimental research has reported differences in psychomotor speed, divided attention and working memory depending on the timing of cognitive testing relative to methadone dosing. Other research has reported poorer prospective memory, sustained attention and response inhibition among individuals receiving methadone maintenance treatment compared with drug-free controls.
From a clinical perspective, the findings support the value of brief cognitive screening when appropriate, particularly when patients report difficulties with concentration, memory, planning or reaction speed. Cognitive rehabilitation strategies, individualized treatment planning and attention to safety-sensitive activities may also be considered as part of comprehensive care.
The purpose of such assessment is not to stigmatize patients receiving methadone treatment. Rather, understanding individual cognitive strengths and difficulties can help clinicians provide more appropriate rehabilitation and support.
