Opiate addiction and cocaine addiction: underlying molecular neurobiology and genetics.
paper
Cited
Public
Unavailable
- Authors
- Kreek, Mary Jeanne; Levran, Orna; Reed, Brian; Schlussman, Stefan D; Zhou, Yan; Butelman, Eduardo R
- Year
- 2012
- Journal
- The Journal of clinical investigation
- PMID
- 23023708
- DOI
- 10.1172/JCI60390
- PMCID
- PMC3534165
Addictive diseases, including addiction to heroin, prescription opioids, or cocaine, pose massive personal and public health costs. Addictions are chronic relapsing diseases of the brain caused by drug-induced direct effects and persisting neuroadaptations at the epigenetic, mRNA, neuropeptide, neurotransmitter, or protein levels. These neuroadaptations, which can be specific to drug type, and their resultant behaviors are modified by various internal and external environmental factors, including stress responsivity, addict mindset, and social setting. Specific gene variants, including variants encoding pharmacological target proteins or genes mediating neuroadaptations, also modify vulnerability at particular stages of addiction. Greater understanding of these interacting factors through laboratory-based and translational studies have the potential to optimize early interventions for the therapy of chronic addictive diseases and to reduce the burden of relapse. Here, we review the molecular neurobiology and genetics of opiate addiction, including heroin and prescription opioids, and cocaine addiction.
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| Title | Year | PMID |
|---|---|---|
| Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond. | 2022 | 36207451 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| The Role of Clinical Pharmacogenetics and Opioid Interactions in Pain Management: Current Evidence and Future Perspectives. | Di Salvo C et al. | β | 2026 | β |
| Biochemical Diagnosis in Substance and Non-substance Addiction. | Shen W et al. | β | 2025 | β |
| Cocaine-Induced Remodeling of the Rat Brain Peptidome: Quantitative Mass Spectrometry Reveals Anatomically Specific Patterns of Cocaine-Regulated Peptide Changes. | Lu G et al. | β | 2025 | β |
| Honor Norms Predict Lower Support for Opioid Harm Reduction Policies in the U.S. | Foster S et al. | β | 2025 | β |
| Identification of Exercise-Related Signature Genes Potentially Associated with Cocaine Addiction by Integrating Bioinformatics and Mendelian Randomization Analysis. | He J et al. | β | 2025 | β |
| Non-canonical signaling initiated by hormone-responsive G protein-coupled receptors from subcellular compartments. | Yang LK et al. | β | 2025 | β |
| PET imaging of the opioid system using radioligands: Synthetic approaches and translational applications. | Reale C et al. | β | 2025 | β |
| Prophylactic administration of metformin alleviates withdrawal symptoms associated with heroin. | Liu M et al. | β | 2025 | β |
| Psychostimulant and opioid abuse: A perspective from Uruguay. | Richeri A et al. | β | 2025 | β |
| Research progress of DNA methylation on the regulation of substance use disorders and the mechanisms. | Liu Y et al. | β | 2025 | β |
| Endocannabinoids and related lipids linked to social exclusion in individuals with chronic non-medical prescription opioid use. | Kroll SL et al. | β | 2024 | β |
| Molecular and Environmental Determinants of Addictive Substances. | Lorek M et al. | β | 2024 | β |
| Opioid use disorder in pediatric populations: considerations for perioperative pain management and precision opioid analgesia. | Chen YH et al. | β | 2024 | β |
| Solving the Global Opioid Crisis: Incorporating Genetic Addiction Risk Assessment with Personalized Dopaminergic Homeostatic Therapy and Awareness Integration Therapy. | Zeine F et al. | β | 2024 | β |
| AKAP150 from nucleus accumbens dopamine D1 and D2 receptor-expressing medium spiny neurons regulates morphine withdrawal. | Bai X et al. | β | 2023 | β |
| Evaluation of the Anti-Inflammatory Pain Effect of Ginsenoside-Conjugated O-Carboxymethyl Chitosan Particles. | Lu HJ et al. | β | 2023 | β |
| Neurogenetics and Epigenetics of Loneliness. | Bowirrat A et al. | β | 2023 | β |
| Neuroplasticity of the extended amygdala in opioid withdrawal and prolonged opioid abstinence. | Kaplan GB et al. | β | 2023 | β |
| Plasma Lysophosphatidic Acid Concentrations in Sex Differences and Psychiatric Comorbidity in Patients with Cocaine Use Disorder. | Requena-OcaΓ±a N et al. | β | 2023 | β |
| Repeated dosing with cocaine produces strain-dependent effects on responding for conditioned reinforcement in Collaborative Cross mice. | Bailey LS et al. | β | 2023 | β |
| Topical Cocaine Hydrochloride Nasal Solution: Anesthetic and Surgical Considerations. | Lutfallah SC et al. | β | 2023 | β |
| Elevation of Extracellular Glutamate by Blockade of Astrocyte Glutamate Transporters Inhibits Cocaine Reinforcement in Rats via a NMDA-GluN2B Receptor Mechanism. | Yang HJ et al. | β | 2022 | β |
| Endogenous Opioids and Their Role in Stem Cell Biology and Tissue Rescue. | Petrocelli G et al. | β | 2022 | β |
| Establishment of a biomarker of peripheral stress in opioid addicts based on the hypothalamic-pituitary-adrenal axis-The improvement effect of exercise. | Wang J et al. | β | 2022 | β |
| Experimental considerations for the assessment of in vivo and in vitro opioid pharmacology. | Hill R et al. | β | 2022 | β |
| GABRB2, a key player in neuropsychiatric disorders and beyond. | Barki M et al. | β | 2022 | β |
| Heroin Addiction Induces Axonal Transport Dysfunction in the Brain Detected by In Vivo MRI. | Luo Y et al. | β | 2022 | β |
| Historical Pathways for Opioid Addiction, Withdrawal with Traditional and Alternative Treatment Options with Ketamine, Cannabinoids, and Noribogaine: A Narrative Review. | Edinoff AN et al. | β | 2022 | β |
| Iatrogenic opioid withdrawal syndromes in adults in intensive care units: a narrative review. | Lamey PS et al. | β | 2022 | β |
| Molecular genetics of cocaine use disorders in humans. | FernΓ ndez-Castillo N et al. | β | 2022 | β |
| Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond. | Gaddis N et al. | β | 2022 | β |
| Neurodevelopmental origins of substance use disorders: Evidence from animal models of early-life adversity and addiction. | Levis SC et al. | β | 2022 | β |
| Why haven't we solved the addiction crisis? | Blum K et al. | β | 2022 | β |
| A Review of DNA Risk Alleles to Determine Epigenetic Repair of mRNA Expression to Prove Therapeutic Effectiveness in Reward Deficiency Syndrome (RDS): Embracing "Precision Behavioral Management". | Blum K et al. | β | 2021 | β |
| A vicious cycle of neuropathological, cognitive and behavioural sequelae of repeated opioid overdose. | Voronkov M et al. | β | 2021 | β |
| Blockade of 5-Hydroxytryptamine 2A Receptor Attenuates Precipitation of Naloxone-Induced Withdrawal Symptoms in Opioid-Exposed Mice. | Li B et al. | β | 2021 | β |
| Development of a novel computational model for the Balloon Analogue Risk Task: The Exponential-Weight Mean-Variance Model. | Park H et al. | β | 2021 | β |
| Evidence for Modulation of Substance Use Disorders by the Gut Microbiome: Hidden in Plain Sight. | Angoa-PΓ©rez M et al. | β | 2021 | β |
| Investigating the CYP2B6 rs3745274 and rs3211371 polymorphisms in Methadone-Responder and Non-Responder Addicts in Iran. | Sadat Aghabozorg Afjeh S et al. | β | 2021 | β |
| Mind-body approaches targeting the psychological aspects of opioid use problems in patients with chronic pain: evidence and opportunities. | Martel MO et al. | β | 2021 | β |
| Neurochemical mechanisms and neurocircuitry underlying the contribution of stress to cocaine seeking. | Caccamise A et al. | β | 2021 | β |
| OPRD1 SNPs associated with opioid addiction are cis-eQTLs for the phosphatase and actin regulator 4 gene, PHACTR4, a mediator of cytoskeletal dynamics. | Levran O et al. | β | 2021 | β |
| Population-specific genetic background for the OPRM1 variant rs1799971 (118A>G): implications for genomic medicine and functional analysis. | Levran O et al. | β | 2021 | β |
| The Developmental Origins of Opioid Use Disorder and Its Comorbidities. | Levis SC et al. | β | 2021 | β |
| A functional polymorphism in the ATP-Binding Cassette B1 transporter predicts pharmacologic response to combination of nortriptyline and morphine in neuropathic pain patients. | Benavides R et al. | β | 2020 | β |
| Chronic Exposure to Morphine Leads to a Reduced Affective Pain Response in the Presence of Hyperalgesia in an Animal Model of Empathy. | Nazeri-Rezaabad M et al. | β | 2020 | β |
| Further evidence for the association of <i>GAL</i>, <i>GALR1</i>Β and <i>NPY1R</i>Β variants with opioid dependence. | Randesi M et al. | β | 2020 | β |
| Haplotype-Based Association and In Silico Studies of OPRM1 Gene Variants with Susceptibility to Opioid Dependence Among Addicted Iranians Undergoing Methadone Treatment. | Tolami HF et al. | β | 2020 | β |
| Modelling Differential Vulnerability to Substance Use Disorder in Rodents: Neurobiological Mechanisms. | Jupp B et al. | β | 2020 | β |
| Newly Emerging Drugs of Abuse. | Tamama K et al. | β | 2020 | β |
| Opioid use disorder. | Strang J et al. | β | 2020 | β |
| Receptors and Channels Possibly Mediating the Effects of Phytocannabinoids on Seizures and Epilepsy. | Senn L et al. | β | 2020 | β |
| Regulators of G Protein Signaling in Analgesia and Addiction. | Sakloth F et al. | β | 2020 | β |
| The Influence of Co-Occurring Substance Use on the Effectiveness of Opiate Treatment Programs According to Intervention Type. | Blondino CT et al. | β | 2020 | β |
| The pharmacogenetics of opioid treatment for pain management. | Singh A et al. | β | 2020 | β |
| A 3' UTR SNP rs885863, a cis-eQTL for the circadian gene VIPR2 and lincRNA 689, is associated with opioid addiction. | Levran O et al. | β | 2019 | β |
| Developmental Trajectories of Opioid Use Among Juvenile Offenders: An Epidemiological Examination of Group Characteristics and Criminological Risk Factors. | Wojciechowski TW | β | 2019 | β |
| Four single nucleotide polymorphisms in genes involved in neuronal signaling are associated with Opioid Use Disorder in West Virginia. | Kaski SW et al. | β | 2019 | β |
| Identifying epigenetic targets underlying the effects of prenatal exposure to opioids. | Ehringer MA | β | 2019 | β |
| Liposome-Encapsulated Morphine Affords a Prolonged Analgesia While Facilitating Extinction of Reward and Aversive Memories. | GΓ³mez-Murcia V et al. | β | 2019 | β |
| Structure and dynamics of dynorphin peptide and its receptor. | FerrΓ© G et al. | β | 2019 | β |
| The epigenetic legacy of illicit drugs: developmental exposures and late-life phenotypes. | Wanner NM et al. | β | 2019 | β |
| The polymorphism of dopamine D2 receptor TaqIA gene is associated with brain response to drug cues in male heroin-dependent individuals during methadone maintenance treatment. | Li Y et al. | β | 2019 | β |
| Trace amine-associated receptor gene polymorphism increases drug craving | Loftis JM et al. | β | 2019 | β |
| Trace amine-associated receptor gene polymorphism increases drug craving in individuals with methamphetamine dependence. | Loftis JM et al. | β | 2019 | β |
| A 35.8 kilobases haplotype spanning ANKK1 and DRD2 is associated with heroin dependence in Han Chinese males. | Zhang J et al. | β | 2018 | β |
| A case of heroin linear track hyperpigmentation: histopathology and treatment with Q-switched Nd:YAG 1064nm laser. | Kazlouskaya V et al. | β | 2018 | β |
| Discriminative Stimulus Properties of Opioid Ligands: Progress and Future Directions. | Butelman ER et al. | β | 2018 | β |
| DNA methylation signatures: Biomarkers of drug and alcohol abuse. | Mahna D et al. | β | 2018 | β |
| Downregulation of the neuronal opioid gene expression concomitantly with neuronal decline in dorsolateral prefrontal cortex of human alcoholics. | Bazov I et al. | β | 2018 | β |
| Dynorphin and ΞΊ-Opioid Receptor Dysregulation in the Dopaminergic Reward System of Human Alcoholics. | Bazov I et al. | β | 2018 | β |
| Effects of cytochrome P450 single nucleotide polymorphisms on methadone metabolism and pharmacodynamics. | Ahmad T et al. | β | 2018 | β |
| Elevated levels of DNA methylation at the OPRM1 promoter region in men with opioid use disorder. | Ebrahimi G et al. | β | 2018 | β |
| Genetic variations in genes of the stress response pathway are associated with prolonged abstinence from heroin. | Levran O et al. | β | 2018 | β |
| Heroin Abuse Results in Shifted RNA Expression to Neurodegenerative Diseases and Attenuation of TNFΞ± Signaling Pathway. | Zhu M et al. | β | 2018 | β |
| Macrophage migration inhibitory factor mediates peripheral nerve injury-induced hypersensitivity by curbing dopaminergic descending inhibition. | Wang X et al. | β | 2018 | β |
| Methadone Dosage and Plasma Levels, SNPs of OPRM1 Gene and Age of First Drug Use Were Associated With Outcomes of Methadone Maintenance Treatment. | Peng S et al. | β | 2018 | β |
| Oprm1 A112G, a single nucleotide polymorphism, alters expression of stress-responsive genes in multiple brain regions in male and female mice. | Collins D et al. | β | 2018 | β |
| Pexacerfont as a CRF1 antagonist for the treatment of withdrawal symptoms in men with heroin/methamphetamine dependence: a randomized, double-blind, placebo-controlled clinical trial. | Morabbi MJ et al. | β | 2018 | β |
| Pharmacogenetics of Methadone Response. | Fonseca F et al. | β | 2018 | β |
| Suppression of RGSz1 function optimizes the actions of opioid analgesics by mechanisms that involve the Wnt/Ξ²-catenin pathway. | Gaspari S et al. | β | 2018 | β |
| The role of neuronal nitric oxide synthase in cocaine place preference and mu opioid receptor expression in the nucleus accumbens. | ThΓ©riault RK et al. | β | 2018 | β |
| Anesthetic implications of recreational drug use. | Beaulieu P | β | 2017 | β |
| Association of Variants of Arginine Vasopressin and ArginineΒ Vasopressin Receptor 1A With Severe AcetaminophenΒ Liver Injury. | Randesi M et al. | β | 2017 | β |
| Biochemical Diagnosis in Substance and Non-substance Addiction. | Shen W et al. | β | 2017 | β |
| Learning and generalization from reward and punishment in opioid addiction. | Myers CE et al. | β | 2017 | β |
| Medications for substance use disorders (SUD): emerging approaches. | Butelman ER et al. | β | 2017 | β |
| Peripheral levels of BDNF and opiate-use disorder: literature review and update. | Palma-Γlvarez RF et al. | β | 2017 | β |
| The ΞΌ-opioid receptor nonsynonymous variant 118A>G is associated with prolonged abstinence from heroin without agonist treatment. | Levran O et al. | β | 2017 | β |
| African-specific variability in the acetylcholine muscarinic receptor M4: association with cocaine and heroin addiction. | Levran O et al. | β | 2016 | β |
| A Mixed-Method Analysis of Reports on 100 Cases of Improper Prescribing of Controlled Substances. | DuBois JM et al. | β | 2016 | β |
| A Population-Based Study of Four Genes Associated with Heroin Addiction in Han Chinese. | Li Y et al. | β | 2016 | β |
| Commentary: A Gene-Based Association Method for Mapping Traits Using Reference Transcriptome Data. | Ghitza UE | β | 2016 | β |
| CYP gene family variants as potential protective factors in drug addiction in Han Chinese. | Zhang H et al. | β | 2016 | β |
| Glutamatergic and GABAergic susceptibility loci for heroin and cocaine addiction in subjects of African and European ancestry. | Levran O et al. | β | 2016 | β |
| Influence of the Novelty-Seeking Endophenotype on the Rewarding Effects of Psychostimulant Drugs in Animal Models. | Arenas MC et al. | β | 2016 | β |
| In search of predictive endophenotypes in addiction: insights from preclinical research. | Belin D et al. | β | 2016 | β |
| Machine-learning identifies substance-specific behavioral markers for opiate and stimulant dependence. | Ahn WY et al. | β | 2016 | β |
| Opioid Use Disorders. | Sharma B et al. | β | 2016 | β |
| Proposed Mode of Binding and Action of Positive Allosteric Modulators at Opioid Receptors. | Shang Y et al. | β | 2016 | β |
| The effects of morphine treatment on the NCAM and its signaling in the MLDS of rats. | Cao JP et al. | β | 2016 | β |
| Towards a 'Sociorelational' Approach to Conceptualizing and Managing Addiction. | van der Eijk Y et al. | β | 2016 | β |
| Activation of serotonin 5-HT(2C) receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice. | Wu X et al. | β | 2015 | β |
| Agonist Medications for the Treatment of Cocaine Use Disorder. | Negus SS et al. | β | 2015 | β |
| Association between DRD2/ANKK1 TaqIA polymorphism and common illicit drug dependence: evidence from a meta-analysis. | Deng XD et al. | β | 2015 | β |
| Behavioural, biochemical and molecular changes induced by chronic crack-cocaine inhalation in mice: The role of dopaminergic and endocannabinoid systems in the prefrontal cortex. | Areal LB et al. | β | 2015 | β |
| Butyrylcholinesterase levels and subjective effects of smoked cocaine in healthy cocaine users. | Askalsky P et al. | β | 2015 | β |
| Emergence of sex differences in the development of substance use and abuse during adolescence. | Kuhn C | β | 2015 | β |
| Increased functional connectivity in the resting-state basal ganglia network after acute heroin substitution. | Schmidt A et al. | β | 2015 | β |
| Initial locomotor sensitivity to cocaine varies widely among inbred mouse strains. | Wiltshire T et al. | β | 2015 | β |
| Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies. | Befort K | β | 2015 | β |
| Neuropsychological Performance in Polyconsumer Men Under Treatment. Influence of Age of Onset of Substance Use. | Capella Mdel M et al. | β | 2015 | β |
| Opioid receptors: Structural and mechanistic insights into pharmacology and signaling. | Shang Y et al. | β | 2015 | β |
| Overlapping dopaminergic pathway genetic susceptibility to heroin and cocaine addictions in African Americans. | Levran O et al. | β | 2015 | β |
| Psychostimulant-Induced Testicular Toxicity in Mice: Evidence of Cocaine and Caffeine Effects on the Local Dopaminergic System. | GonzΓ‘lez CR et al. | β | 2015 | β |
| Susceptibility loci for heroin and cocaine addiction in the serotonergic and adrenergic pathways in populations of different ancestry. | Levran O et al. | β | 2015 | β |
| Synaptic Plasticity and Signal Transduction Gene Polymorphisms and Vulnerability to Drug Addictions in Populations of European or African Ancestry. | Levran O et al. | β | 2015 | β |
| Translating the human genome to manage pediatric postoperative pain. | Manworren RC et al. | β | 2015 | β |
| Behavioral endophenotypes of drug addiction: Etiological insights from neuroimaging studies. | Jupp B et al. | β | 2014 | β |
| Buprenorphine maintenance and mu-opioid receptor availability in the treatment of opioid use disorder: implications for clinical use and policy. | Greenwald MK et al. | β | 2014 | β |
| Changes in endocannabinoid and N-acylethanolamine levels in rat brain structures following cocaine self-administration and extinction training. | Bystrowska B et al. | β | 2014 | β |
| Decision-making in stimulant and opiate addicts in protracted abstinence: evidence from computational modeling with pure users. | Ahn WY et al. | β | 2014 | β |
| Disruption of dopamine D1 receptor phosphorylation at serine 421 attenuates cocaine-induced behaviors in mice. | Zhang Y et al. | β | 2014 | β |
| Drug addiction and stress-response genetic variability: association study in African Americans. | Levran O et al. | β | 2014 | β |
| Effects of topiramate on ethanol-cocaine interactions and DNA methyltransferase gene expression in the rat prefrontal cortex. | Echeverry-Alzate V et al. | β | 2014 | β |
| Fate of systemically administered cocaine in nonhuman primates treated with the dAd5GNE anticocaine vaccine. | Hicks MJ et al. | β | 2014 | β |
| Genetic factors in exercise adoption, adherence and obesity. | Herring MP et al. | β | 2014 | β |
| Increased densities of nitric oxide synthase expressing neurons in the temporal cortex and the hypothalamic paraventricular nucleus of polytoxicomanic heroin overdose victims: possible implications for heroin neurotoxicity. | Bernstein HG et al. | β | 2014 | β |
| Interactions of HIV and drugs of abuse: the importance of glia, neural progenitors, and host genetic factors. | Hauser KF et al. | β | 2014 | β |
| Mixed ΞΊ/ΞΌ partial opioid agonists as potential treatments for cocaine dependence. | Bidlack JM | β | 2014 | β |
| Polymorphisms of COMT Val158Met and DAT1 3'-UTR VNTR in illicit drug use and drug-related psychiatric disorders. | Chen CK et al. | β | 2014 | β |
| Role of ALDH5A1 in methadone treatment. | Torrens M et al. | β | 2014 | β |
| Stress-related genes and heroin addiction: a role for a functional FKBP5 haplotype. | Levran O et al. | β | 2014 | β |
| The role of D-serine as co-agonist of NMDA receptors in the nucleus accumbens: relevance to cocaine addiction. | D'Ascenzo M et al. | β | 2014 | β |
| Acupuncture therapy for psychiatric illness. | Pilkington K | β | 2013 | β |
| Assessing addiction vulnerability with different rat strains and place preference procedures: the role of the cocaine and amphetamine-regulated transcript. | Salas E et al. | β | 2013 | β |
| Circulating cell-free microRNA as biomarkers for screening, diagnosis and monitoring of neurodegenerative diseases and other neurologic pathologies. | Sheinerman KS et al. | β | 2013 | β |
| Design, synthesis, and biological evaluation of 14-heteroaromatic-substituted naltrexone derivatives: pharmacological profile switch from mu opioid receptor selectivity to mu/kappa opioid receptor dual selectivity. | Yuan Y et al. | β | 2013 | β |
| Harm reduction: compassionate care of persons with addictions. | Bartlett R et al. | β | 2013 | β |
| Kappa-opioid receptor signaling in the striatum as a potential modulator of dopamine transmission in cocaine dependence. | Trifilieff P et al. | β | 2013 | β |
| Long-term effects of cocaine experience on neuroplasticity in the nucleus accumbens core of addiction-prone rats. | Waselus M et al. | β | 2013 | β |
| Mu opioid receptors on primary afferent nav1.8 neurons contribute to opiate-induced analgesia: insight from conditional knockout mice. | Weibel R et al. | β | 2013 | β |