ReviewScience advances2021
Cues conditioned to withdrawal and negative reinforcement: Neglected but key motivational elements driving opioid addiction.
Review in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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.
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
38 citing papers in PubMed, 69 citations in OpenAlex.
- Effects of suvorexant on diurnal cortisol and patient-reported stress during opioid withdrawal in a randomized trial.Psychoneuroendocrinology · 2025Trial
- The relationship of pain intensity and opioid craving with delayed methadone dose: A preliminary study of individuals with opioid use disorder.British journal of clinical pharmacology · 2024Trial
- Decoding the Neural Circuit Underlying Context-Cue Association in Retrieval of Morphine Reward Memory.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Can the incentive-sensitization theory of addiction incorporate addiction to opioid drugs?Psychopharmacology · 2026Review
- Incentive salience, not psychomotor sensitization or tolerance, drives escalation of cocaine self-administration in heterogeneous stock rats.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
- "It's like scratching at the door": Experiences of outpatient buprenorphine low dose initiation among people using fentanyl.Journal of substance use and addiction treatment · 2026Article
- The analgesic effect of neuropeptide S (NPS) in alcohol-dependent male and female rats.Alcohol (Fayetteville, N.Y.) · 2026Article
- Propranolol Administration During Morphine Addiction Attenuates Reinstatement of Drug-Aversive Memories Caused by Exposure to Stressful Stimuli.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Chemogenetic Inhibition and Optogenetic Depotentiation of the Prelimbic Cortex to Paraventricular Thalamus Pathway Attenuate Abstinence-Induced Plasticity and Heroin Seeking in Rats.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Incentive Salience, not Psychomotor Sensitization or Tolerance, Drives Escalation of Cocaine Self-Administration in Heterogeneous Stock Rats.bioRxiv : the preprint server for biology · 2025Article
- A Challenge To The Assumption That Short- versus Long-Access Groups of Opioid Users Represent Distinct Phenotypes.bioRxiv : the preprint server for biology · 2025Article
- Integrating maintaining theories for addiction and binge-eating pathology: A review of affective and reward-based theories.Clinical psychology review · 2025Review
- Presynaptic Mu Opioid Receptors Suppress the Functional Connectivity of Ventral Tegmental Area Dopaminergic Neurons with Aversion-Related Brain Regions.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Hyperbaric oxygen treatment attenuates naloxone-precipitated opioid withdrawal behaviors and alters microglial activity in male and female mice.Scientific reports · 2025Article
- Xenon gas as a potential treatment for opioid use disorder, alcohol use disorder, and related disorders.Medical gas research · 2025Review
- Negative affectivity drivers of impulsivity in opioid use disorder.Nature reviews. Psychology · 2025Article
- Theoretical Frameworks and Mechanistic Aspects of Alcohol Addiction: Alcohol Addiction as a Reward Deficit/Stress Surfeit Disorder.Current topics in behavioral neurosciences · 2025Review
- Oral fentanyl consumption and withdrawal impairs fear extinction learning and enhances basolateral amygdala principal neuron excitatory-inhibitory balance in male and female mice.Addiction neuroscience · 2024Article
- Modulating reward and aversion: Insights into addiction from the paraventricular nucleus.CNS neuroscience & therapeutics · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Opioid use disorder (OUD) is a debilitating disorder that affects millions of people. Neutral cues can acquire motivational properties when paired with the positive emotional effects of drug intoxication to stimulate relapse. However, much less research has been devoted to cues that become conditioned to the aversive effects of opioid withdrawal. We argue that environmental stimuli promote motivation for opioids when cues are paired with withdrawal (conditioned withdrawal) and generate opioid consumption to terminate conditioned withdrawal (conditioned negative reinforcement). We review evidence that cues associated with pain drive opioid consumption, as patients with chronic pain may misuse opioids to escape physical and emotional pain. We highlight sex differences in withdrawal-induced stress reactivity and withdrawal cue processing and discuss neurocircuitry that may underlie withdrawal cue processing in dependent individuals. These studies highlight the importance of studying cues associated with withdrawal in dependent individuals and point to areas for exploration in OUD research.
Indexed as
Identifiers
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.