ReviewNeuropharmacology2009
Neurobiological substrates for the dark side of compulsivity in addiction.
Review in Neuropharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 224 papers, 4 of them syntheses that pooled it.
What it found
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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.
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.
Who cites it
224 citing papers in PubMed, 4 syntheses or guidelines pooled it, 451 citations in OpenAlex.
- Naltrexone effects on subjective responses to alcohol in the human laboratory: A systematic review and meta-analysis.Addiction biology · 2019Pooled it
- The effect of laboratory manipulations of negative affect on alcohol craving and use: A meta-analysis.Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors · 2018Pooled it
- Cigarette smoking and depression comorbidity: systematic review and proposed theoretical model.Addiction (Abingdon, England) · 2017Pooled it
- Efficacy of psychostimulant drugs for amphetamine abuse or dependence.The Cochrane database of systematic reviews · 2013Pooled it
- Effects of suvorexant on diurnal cortisol and patient-reported stress during opioid withdrawal in a randomized trial.Psychoneuroendocrinology · 2025Trial
- The effects of nalmefene on the impulsive and reflective system in alcohol use disorder: A resting-state fMRI study.Psychopharmacology · 2022Trial
- Smoking relapse risk is increased among individuals in recovery.Drug and alcohol dependence · 2019Trial
- Development of the Neuroimmune Modulator Ibudilast for the Treatment of Alcoholism: A Randomized, Placebo-Controlled, Human Laboratory Trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Trial
- Exaggerated acquisition and resistance to extinction of avoidance behavior in treated heroin-dependent men.The Journal of clinical psychiatry · 2016Trial
- A selective reversible monoamine oxidase B inhibitor in smoking cessation: effects on its own and in association with transdermal nicotine patch.Psychopharmacology · 2012Trial
- Guanfacine effects on stress, drug craving and prefrontal activation in cocaine dependent individuals: preliminary findings.Journal of psychopharmacology (Oxford, England) · 2012Trial
- An ethical defense of safer supply.Theoretical medicine and bioethics · 2026Article
- BLA kappa opioid receptor inputs to the BNST mediate social stress-induced increases in alcohol drinking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Local control of dopamine release in nucleus accumbens gates opioid withdrawal aversion.bioRxiv : the preprint server for biology · 2026Article
- Spironolactone and clinical outcomes in patients with alcohol use disorder and comorbid hypertension: a target trial emulation study.Psychopharmacology · 2026Article
- The pituitary adenylate cyclase-activating polypeptide receptor and its splice variants: Unique roles in affective and motivated behavior.Journal of neuroendocrinology · 2026Review
- From Synaptic Plasticity to Neurotoxicity: Endocannabinoid Influence on Addiction and Neurodegeneration.International journal of molecular sciences · 2025Review
- Dihydrotestosterone regulation of stress-related behaviors in mice exposed to subchronic variable stress.Psychoneuroendocrinology · 2025Article
- 5-HT 2A receptor inverse agonist attenuates morphine withdrawal syndrome and its aversiveness in rats.Behavioural pharmacology · 2025Article
- Calcium imaging of central amygdala activity after escalation of fentanyl self-administration.Neuropharmacology · 2025Article
164 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
Drug addiction can be defined by a compulsion to seek and take drug, loss of control in limiting intake, and the emergence of a negative emotional state when access to the drug is prevented. Drug addiction impacts multiple motivational mechanisms and can be conceptualized as a disorder that progresses from impulsivity (positive reinforcement) to compulsivity (negative reinforcement). The construct of negative reinforcement is defined as drug taking that alleviates a negative emotional state. The negative emotional state that drives such negative reinforcement is hypothesized to derive from dysregulation of key neurochemical elements involved in reward and stress within the basal forebrain structures involving the ventral striatum and extended amygdala. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission, such as decreases in dopamine and opioid peptide function in the ventral striatum, but also recruitment of brain stress systems, such as corticotropin-releasing factor (CRF), in the extended amygdala. Acute withdrawal from all major drugs of abuse produces increases in reward thresholds, increases in anxiety-like responses, and increases in extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists also block excessive drug intake produced by dependence. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence, and to contribute to the compulsivity of addiction. Other components of brain stress systems in the extended amygdala that interact with CRF and may contribute to the negative motivational state of withdrawal include norepinephrine, dynorphin, and neuropeptide Y. The combination of loss of reward function and recruitment of brain stress systems provides a powerful neurochemical basis for a negative emotional state that is responsible for the negative reinforcement driving, at least in part, the compulsivity of addiction.
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What OpenQuestion holds
Registered trials
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.