Evidence map›Paper›PMID 31400808›Full record

ReviewBiological psychiatry2020

Neurobiology of Opioid Addiction: Opponent Process, Hyperkatifeia, and Negative Reinforcement.

George F Koob

Abstract readReview
PubMed Publisher
In one paragraph

Review in Biological psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 242 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
242citing papers in PubMed, 4 pooled it
–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

242 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Opioid conversion in adults with cancer: MASCC-ASCO-AAHPM-HPNA-NICSO guideline.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025
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  13. Pain-contingent opioid use and addiction risk in cancer pain: a reappraisal of around-the-clock dosing.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026
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182 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

1 author.

George F KoobNational Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland. Electronic address: george.koob@nih.gov.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Opioids are powerful drugs that usurp and overpower the reward function of endogenous opioids and engage dramatic tolerance and withdrawal via molecular and neurocircuitry neuroadaptations within the same reward system. However, they also engage the brain systems for stress and pain (somatic and emotional) while producing hyperalgesia and hyperkatifeia, which drive pronounced drug-seeking behavior via processes of negative reinforcement. Hyperkatifeia (derived from the Greek "katifeia" for dejection or negative emotional state) is defined as an increase in intensity of the constellation of negative emotional or motivational signs and symptoms of withdrawal from drugs of abuse. In animal models, repeated extended access to drugs or opioids results in negative emotion-like states, reflected by the elevation of reward thresholds, lower pain thresholds, anxiety-like behavior, and dysphoric-like responses. Such negative emotional states that drive negative reinforcement are hypothesized to derive from the within-system dysregulation of key neurochemical circuits that mediate incentive-salience and/or reward systems (dopamine, opioid peptides) in the ventral striatum and from the between-system recruitment of brain stress systems (corticotropin-releasing factor, dynorphin, norepinephrine, hypocretin, vasopressin, glucocorticoids, and neuroimmune factors) in the extended amygdala. Hyperkatifeia can extend into protracted abstinence and interact with learning processes in the form of conditioned withdrawal to facilitate relapse to compulsive-like drug seeking. Compelling evidence indicates that plasticity in the brain pain emotional systems is triggered by acute excessive drug intake and becomes sensitized during the development of compulsive drug taking with repeated withdrawal. It then persists into protracted abstinence and contributes to the development and persistence of compulsive opioid-seeking behavior.

Indexed as

Opioid-Related DisordersSubstance-Related DisordersSubstance Withdrawal SyndromeAnimalsBrainMotivationNeurobiologyReinforcement, PsychologyRewardAddictionDysphoriaHyperkatifeiaNegative reinforcementOpioidsStress

Identifiers

PMID31400808

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.