Evidence map›Paper›PMID 40247807›Full record

ArticleCurrent pharmaceutical biotechnology2025

A Comprehensive 4-layered

Alireza Sharafshah, Kai-Uwe Lewandrowski, Igor Elman, David Baron, Panayotis K Thanos, Colin Hanna, Mark S Gold, Rajendra D Badgaiyan, Jean Lud Cadet, Edward J Modestino and 15 more

Abstract read
PubMed Publisher
In one paragraph

Article in Current pharmaceutical biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Alireza SharafshahCellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
Kai-Uwe LewandrowskiDepartment of Orthopaedics, Fundación Universitaria Sanitas, Bogotá D.C., Colombia.
Igor ElmanCambridge Health Alliance, Harvard Medical School, Cambridge, MA, USA.
David BaronDivision of Addiction Research & Education, Center for Sports, Exercise, and Mental Health, Western University of Health Sciences, Pomona, CA, USA.
Panayotis K ThanosBehavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, and Department of Psychology, University at Buffalo, Buffalo, NY, USA.
Colin HannaBehavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, and Department of Psychology, University at Buffalo, Buffalo, NY, USA.
Mark S GoldDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Rajendra D BadgaiyanDepartment of Psychiatry, Case Western Reserve University, School of Medicine, Cleveland, OH., USA.
Jean Lud CadetMolecular Neuropsychiatry Research Branch, NIH National Institute on Drug Abuse, Bethesda, MD, USA.
Edward J ModestinoDepartment of Psychology, Curry College, Milton, MA, USA.
Eric R BravermanDivision of Clinical Neurology, The Kenneth Blum Institute of Neurogenetics and Behavior, LLC, Austin, Tx., USA.
Catherine A DennenDepartment of Family Medicine, Jefferson Health Northeast, Philadelphia, PA, USA.
Milan MakaleDepartment of Radiation Medicine and Applied Sciences, UC San Diego, La Jolla, CA., USA.
Keerthy SunderDepartment of Medicine, University of California, Riverside School of Medicine, Riverside, CA, USA.
Kevin T MurphyDepartment of Radiation Oncology, University of California San Diego, La Jolla, CA, USA.
Abdalla BowirratDepartment of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel, Israel.
Albert PinhasovDepartment of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel, Israel.
Marjorie Gondre-LewisMolecular Neuropsychiatry Research Branch, NIH National Institute on Drug Abuse, Bethesda, MD, 20892, USA.
Eliot GardnerNeuropsychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Daniel SipplePhysical Medicine and Rehabilitation, Midwest Brain & Spine Institute, Roseville, MN, USA.
Nicole JafariDepartment of Health Science, California State University at Long Beach, Long Beach, CA., 90804, USA.
Foojan ZeineDepartment of Applied Clinical Psychology, The Chicago School of Professional Psychology, Los Angeles, CA., 90017, USA.
Jag KhalsaDivision of Therapeutics and Medical Consequences, Medical Consequences of Drug Abuse and Infections Branch, National Institute on Drug Abuse, NIH, Special Volunteer, 16071 Industrial Drive, Gaithersburg, MD 20877 USA.
Rossano Kepler Alvim FiorelliDepartment of General and Specialized Surgery, Gaffrée e Guinle Universitary Hospital, Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro, Brazil.
Kenneth BlumDivision of Addiction Research & Education, Center for Sports, Exercise, and Mental Health, Western University of Health Sciences, Pomona, CA, USA.

Funding

National Institute on Minority Health and Health Disparities (NIMHD) of the National Institutes of Health (NIH) R41 MD012318/MD/NIMHDNIH HHS/United States
6 · The paper itself

Abstract

backgroundOverdose involving opioids is the black heart of the addiction crisis. "Pre-addiction," as an encouraging concept by NIDA and NIAAA, seems best captured with the construct of dopamine dysregulation. Referring to the abundant publications on "Reward Deficiency Syndrome" (RDS), Genetic Addiction Risk Score (GARS) test, RDSQ29, and KB220, Pre-addiction can be referred to as "reward dysregulation" as a suitable suggestion. The hypothesis is that the true phenotype is RDS, and other behavioral disorders are endophenotypes where the genetic variants play important roles, specifically in the Brain Reward Cascade (BRC).

methodsThis study tested the pharmacogenomics of the GARS panel by a multi-model in silico investigation in four layers: 1) Protein-Protein Interactions (PPIs); 2) Gene Regulatory Networks (GRNs); 3) Disease, drugs and chemicals (DDCs); and 4) Gene Coexpression Networks (GCNs).

resultsAll in silico findings were combined in an Enrichment Analysis for 59 refined genes, which represented highly significant associations of dopamine pathways in the BRC and supported our hypothesis.

conclusionThis paper provides scientific evidence for the importance of incorporating GARS as a predictive test to identify Pre-addiction, introduce unique therapeutic targets assisting in the treatment of pain, drug dosing of prescription pharmaceuticals, and identify the risk for subsequent addiction early in -life.

Indexed as

Behavior, AddictiveOpioid-Related DisordersPharmacogeneticsAnalgesics, OpioidComputer SimulationGene Regulatory NetworksGenetic Predisposition to DiseaseHumansPrecision MedicineProtein Interaction MapsAnalgesics, Opioiddopamine dysregulationGenetic Addiction Risk Score (GARS)in silico.pharmacogenomicsPre-addictionReward Deficiency Syndrome (RDS)

Identifiers

PMID40247807

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.