Opioid Agonist Therapy and Neurocognitive Function: An Updated Literature Review

Authors

• Cindy L. Bird-Kue, University of LynchburgFollow

Specialty

Addiction Medicine

Abstract

ABSTRACT

Most clinicians in the United States will care for patients with opioid use disorder (OUD), and one in five of these patients will be on opioid agonist treatment (OAT).  Although pre-2020 literature attributed global neurocognitive impairment directly to methadone maintenance treatment (MMT), recent evidence indicates these historical conclusions were confounded by unaddressed baseline variables. To update current clinical understanding, a  comprehensive search and review of PubMed and Google Scholar databases was conducted, categorizing the literature across three distinct eras:1965-2000, 2002-2017 and 2020-present. Recent literature was critically evaluated to determine how OAT dosage, duration, concurrent substance use, and traumatic brain injury (TBI) influence cognitive performance. Post 2020 findings challenge historical findings, demonstrating no major differences in visual, logical, or numerical memory between OAT patients and illicit opioid naive controls. Importantly, up to 69% of individuals presenting for OAT have cognitive impairment, suggesting that the observed neurocognitive deficits preceded the treatment. Additionally, concurrent cannabis or cocaine use does not appear to compound cognitive deficits when compared to controls and are shown to have the benefits of preserved executive functioning and verbal fluency. Overall, evaluating the impact of OAT remains hampered by a lack of pre-treatment neurocognitive screenings, lack of untreated OUD control groups, and insufficient screening for history of TBI. Essentially, rather than concluding that OAT caused cognitive decline, clinicians and treatment programs must account for pre-existing factors. The OAT admission process needs to incorporate routine, baseline neurocognitive and TBI screenings, followed by periodic reassessments at standardized intervals established by governing agencies of opioid use disorder treatment programs. Lastly, researchers and clinicians must interpret cognitive test results within the framework of social determinants of health to ensure accurate clinical evaluation and patient care.

Recommended Citation

Bird-Kue CL. Opioid Agonist Therapy and Neurocognitive Function: An Updated Literature Review. University of Lynchburg Doctoral Project Assignment Repository. 2026; 8(3).