Influence of DRD2 polymorphisms on the clinical outcomes of opioiddependent patients on methadone maintenance therapy

Zahari, Zalina; Lee, Chee Siong; Ibrahim, Muslih Abdulkarim; Musa, Nurfadhlina; Yasin, Mohd Azhar Mohd; Lee, Yeong Yeh; Tan, Soo Choon; Mohamad, Nasir; Ismail, Rusli

doi:10.4103/jpbs.jpbs_248_19

Cited by 3 publications

(2 citation statements)

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“…According to Moreira and Dalley, partial agonists of the D2R could be effective in treating various addictions to different classes of abused drugs 9 . Additionally, previous studies have investigated the link between genetic variants in the DRD2 gene and treatment outcomes for patients with opioid dependence undergoing MMT, potentially influencing changes in DRD2 expression 10,11 . The dysfunction of D2R, especially in relation to genetic factors, has been extensively studied and implicated in various addiction‐related behaviors 12 .…”

Section: Introductionmentioning

confidence: 99%

“…9 Additionally, previous studies have investigated the link between genetic variants in the DRD2 gene and treatment outcomes for patients with opioid dependence undergoing MMT, potentially influencing changes in DRD2 expression. 10,11 The dysfunction of D2R, especially in relation to genetic factors, has been extensively studied and implicated in various addiction-related behaviors. 12 Therefore, exploring treatments that specifically target D2R, such as agonists, could potentially be beneficial in addressing addiction.…”

Section: Introductionmentioning

confidence: 99%

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Exploring neuroadaptive cellular pathways in chronic morphine exposure: An in‐vitro analysis of cabergoline and Mdivi‐1 co‐treatment effects on the autophagy–apoptosis axis

Makvand,

Mirtorabi,

Campbell

et al. 2024

J of Cellular Biochemistry

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The complex impacts of prolonged morphine exposure continue to be a significant focus in the expanding area of addiction studies. This research investigates the effectiveness of a combined treatment using Cabergoline and Mdivi‐1 to counteract the neuroadaptive changes caused by in vitro morphine treatment. The impact of Methadone, Cabergoline, and a combination of Cabergoline and Mdivi‐1 on the cellular and molecular responses associated with Morphine‐induced changes was studied in human Neuroblastoma (SK‐N‐MC) and Glioblastoma (U87‐MG) cell lines that were exposed to prolong Morphine treatment. Cabergoline and Mdivi‐1 combined treatment effectively influenced the molecular alterations associated with neuroadaptation in chronic morphine‐exposed neural cells. This combination therapy normalized autophagy and reduced oxidative stress by enhancing total‐antioxidant capacity, mitigating apoptosis, restoring BDNF expression, and balancing apoptotic elements. Our research outlines morphine's dual role in modulating mitochondrial dynamics via the dysregulation of the autophagy–apoptosis axis. This emphasizes the significant involvement of DRP1 activity in neurological adaptation processes, as well as disturbances in the dopaminergic pathway during in vitro chronic exposure to morphine in neural cells. This study proposes a novel approach by recommending the potential effectiveness of combining Cabergoline and Mdivi‐1 to modulate the neuroadaptations caused by morphine. Additionally, we identified BDNF and PCNA in neural cells as potential neuroprotective markers for assessing the effectiveness of drugs against opioid toxicity, emphasizing the need for further validation. The study uncovers diverse effects observed in pretreated morphine glioblastoma cells under treatment with Cabergoline and methadone. This highlights the potential for new treatments in the DRD2 pathway and underscores the importance of investigating the interplay between autophagy and apoptosis to advance research in managing cancer‐related pain. The study necessitates an in‐depth investigation into the relationship between autophagy and apoptosis, with a specific emphasis on protein interactions and the dynamics of cell signaling.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exploring neuroadaptive cellular pathways in chronic morphine exposure: An in‐vitro analysis of cabergoline and Mdivi‐1 co‐treatment effects on the autophagy–apoptosis axis

Makvand,

Mirtorabi,

Campbell

et al. 2024

J of Cellular Biochemistry

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Hyperalgesia in Patients With a History of Opioid Use Disorder

Trøstheim,

Eikemo

2024

JAMA Psychiatry

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ImportanceShort-term and long-term opioid treatment have been associated with increased pain sensitivity (ie, opioid-induced hyperalgesia). Treatment of opioid use disorder (OUD) mainly involves maintenance with methadone and buprenorphine, and observations of heightened cold pain sensitivity among patients are often considered evidence of opioid-induced hyperalgesia.ObjectiveTo critically examine the evidence that hyperalgesia in patients with OUD is related to opioid use.Data SourcesWeb of Science, PubMed, and Embase between March 1, 2023, and April 12, 2024, were searched.Study SelectionStudies assessing cold pressor test (CPT) pain responses during treatment seeking, pharmacological treatment, or abstinence in patients with OUD history were included.Data Extraction and SynthesisMultilevel random-effects models with robust variance estimation were used for all analyses. Study quality was rated with the JBI checklist. Funnel plots and Egger regression tests were used to assess reporting bias.Main Outcomes and MeasuresMain outcomes were pain threshold, tolerance, and intensity in patients and healthy controls, and unstandardized, standardized (Hedges g), and percentage differences (%Δ) in these measures between patients and controls. The association between pain sensitivity and opioid tolerance, withdrawal, and abstinence indices was tested with meta-regression.ResultsThirty-nine studies (1385 patients, 741 controls) met the inclusion criteria. Most studies reported CPT data on patients undergoing opioid agonist treatment. These patients had a mean 2- to 3-seconds lower pain threshold (95% CI, −4 to −1; t test P = .01; %Δ, −22%; g = −0.5) and 29-seconds lower pain tolerance (95% CI, −39 to −18; t test P &lt; .001; %Δ, −52%; g = −0.9) than controls. Egger tests suggested that these differences may be overestimated. There were some concerns of bias due to inadequate sample matching and participant dropout. Meta-regressions yielded no clear support for hyperalgesia being opioid related.Conclusion and RelevancePatients receiving opioid agonist treatment for OUD are hypersensitive to cold pain. It remains unclear whether hyperalgesia develops prior to, independent of, or as a result of long-term opioid treatment. Regardless, future studies should investigate the impact of hyperalgesia on patients’ well-being and treatment outcomes.

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