Comparison of executive function indices, inflammatory factors, and oxidative stress in individuals undergoing maintenance treatment with methadone and buprenorphine

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Arezoomandan Mohammad; Zhiani Rahele; Mehrzad Jamshid; Motavalizadehkakhky Alireza; Arezoomandan Reza

Title

Comparison of executive function indices, inflammatory factors, and oxidative stress in individuals undergoing maintenance treatment with methadone and buprenorphine

Author(s)

Keywords

BuprenorphineQ4

MethadoneQ4

Executive functionsQ4

Oxidative stressQ4

inflammationQ4

Abstract

Introduction Addiction is recognized as a serious societal problem with potentially severe and undesirable consequences, including social and health problems. Individuals addicted to drugs such as opioids experience impaired natural brain function, leading to compromised Executive functions, ultimately affecting their quality of life and interpersonal and occupational capabilities. In addition, ample evidence indicates that opioid consumption induces changes in Oxidative stress levels, typically resulting in negative alterations and an exacerbation of Oxidative stress in the body. Methadone and Buprenorphine are widely used as maintenance treatments for opioids in treatment centers. Methadone, a full μ-opioid receptor agonist, is the most widely used substitution treatment in Europe and the United States, as well as in Iran, and its effectiveness in the reduction of drug-associated harm and improvement of abstinence rate is clearly proven. Buprenorphine, a partial μ-receptor agonist and k-receptor antagonist, compared to Methadone, causes less analgesia due to being a partial agonist of μ receptor. Several lines of evidence have shown the impact of Methadone and Buprenorphine on Oxidative stress levels. In addition, long-term use of opioids can affect neuronal functions and neural connectivity and subsequently affect normal brain functioning and cognitive functions, including Executive functions, learning, memory, and attention. Impairment in cognitive function can significantly affect the routine daily life of individuals. Accordingly, this study aimed to investigate Executive functions and inflammatory factors, including malondialdehyde (MDA) levels, total antioxidant capacity (TAC), and ferritin patients undergoing maintenance treatment with Methadone and Buprenorphine, and compare them with healthy individuals. Methods This cross-sectional study investigated oxidative/antioxidant activity, inflammatory factors, and cognitive ‎functions in patients under maintenance treatment and healthy control participants. The participants were selected from individuals actively pursuing addiction treatment in South Khorasan, Iran. Participants were categorized into three distinct groups, each comprising 30 members. The groups included the Buprenorphine treatment group, the Methadone treatment group, and a control group consisting of healthy, demographically matched individuals. All groups were matched based on age, sex, and education level. The Methadone and Buprenorphine groups had been under treatment for at least 12 months, and healthy subjects ‎had no history of drug use. Executive function was measured using the Wisconsin Card Sorting Test (WCST). The WCST is a gold standard instrument used to assess Executive functions. The test requires respondents to match a total of 128 response cards to one of four key cards representing different perceptual sorting dimensions. Once respondents find the correct sorting rule, they need to ignore other sorting dimensions and follow this rule across other changing stimuli. After correctly matching ten cards in a row, the sorting criterion shifts to a new dimension without warning, prompting participants to adapt by devising a fresh sorting strategy. Furthermore, to delve into the biochemical aspects associated with addiction treatment, blood samples were systematically collected for the comprehensive evaluation of serum levels. In brief, for each participant, a 10 ml blood sample was collected from a forearm vein. Each blood sample was drawn after neuropsychological assessments. The serum samples were immediately separated by centrifugation at 3000 g for 10 min and were stored at -80 °C for further analysis. The concentrations of MDA, an indicator of Oxidative stress, and TAC were measured. Additionally, the study examined the serum levels of ferritin, a marker of inflammatory processes. The thorough analysis of these biochemical markers aimed to provide insights into the potential impact of Buprenorphine and Methadone treatments on Oxidative stress and inflammatory pathways. Results The WCST results reveal that healthy participants significantly outperformed the other groups in numerous executive function subscales. Additionally, individuals under Buprenorphine treatment demonstrated better performance compared to those under Methadone treatment, although these improvements were not statistically significant in some cases. The Methadone treatment group exhibited the weakest performance on all subscales compared to healthy and Buprenorphine groups. The analysis of inflammatory factors showed variations in serum ferritin levels among the three groups, with higher levels in the healthy and Methadone groups compared to the Buprenorphine treatment group. The assessment of Oxidative stress factors (MDA and TAC) also revealed differences among the study groups. Serum MDA levels were significantly higher in the Buprenorphine treatment group compared to both the healthy and Methadone treatment groups. Furthermore, serum MDA levels in the Methadone treatment group were significantly higher than in the healthy group. Serum TAC levels were significantly higher in Methadone treatment groups compared to the Buprenorphine treatment group. Additionally, the healthy group exhibited significantly higher serum TAC levels than the Buprenorphine treatment group. Conclusion The current research suggests that although both Methadone and Buprenorphine are associated with heightened Oxidative stress, inflammation, compromised antioxidant defenses, and cognitive impairments, these adverse effects are significantly less severe than those linked to morphine and heroin use. Considering the obtained results and comparing them, it can be generally stated that long-term Methadone use elevates inflammation in the body. Moreover, the measurement of lipid oxidation indicates that individuals receiving Buprenorphine alternative treatment exhibit higher oxidation levels, and the measurement of TAC, representing antioxidant capacity, is significantly lower in the Buprenorphine group compared to Methadone. However, Oxidative stress levels in all patients were worse than those in healthy individuals. Additionally, the WCST and Executive functions results revealed that both patient groups performed poorly compared to healthy individuals. Among the Methadone and Buprenorphine groups, individuals under Buprenorphine treatment exhibited better performance in comparison to those under Methadone treatment. However, notably, due to the higher cost of Buprenorphine, individuals under Buprenorphine treatment likely had a higher quality of life, which could impact their Executive functions. It is suggested that Oxidative stress can affect normal brain activity and, consequently, cognitive functions. However, concomitant antioxidant administration with Buprenorphine or Methadone can potentially enhance their beneficial action by regulating blood redox status. Ethical considerations Compliance with ethical guidelines Participants entered the study with informed consent and were assured that all information would remain confidential and only be used for research purposes. Ethical principles were rigorously adhered to throughout all stages of the research, and the study received ethical approval from the Ethics Committee of the Islamic Azad University under the code IR.IAU.PS.REC.1397.387. Authors’ contributions Rahele Zhiani: selecting the topic, defining concepts, and designing the study. Alireza Motavalizadehkakhky: conducted source search and database review. Reza Arezoomandan: gathering information. Jamshid Mehrzad: carried out data analysis. Mohammad Arezoomandan: writing and preparation of the initial draft. All authors reviewed the obtained results and contributed to editing the article’s final version. Funding This manuscript did not receive any funding. Acknowledgments The article’s authors consider it necessary to express their sincere appreciation to all the staff and personnel of addiction treatment centers in Qaen City and precious patients for helping to carry out this project. Conflict of interest This article has no conflict of interest.

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Scientific Information Database

ISSN: 2588-4824

Journal Paper

Comparison of executive function indices, inflammatory factors, and oxidative stress in individuals undergoing maintenance treatment with methadone and buprenorphine