A review of the kappa opioid receptor system in opioid use.
Level 5 - mechanism / opinion, no new human data
Systematic scoping review synthesizing predominantly preclinical animal experiments alongside limited human observational and clinical data.
PubMed 38733895 · doi:10.1016/j.neubiorev.2024.105713
What was done
Authors conducted a systematic scoping review following PRISMA guidelines across MEDLINE, Embase, PsycINFO, Web of Science, Scopus, and Cochrane. They included preclinical animal and clinical human studies that tested kappa opioid receptor (KOR) agonists, KOR antagonists, or dynorphin, or that measured dynorphin levels or KOR expression during opioid intoxication or withdrawal. A total of 100 studies were included in the final analysis.
What was found
The abstract reports qualitative directions without numerical effect estimates or confidence intervals. Preclinical administration of KOR agonists decreased drug-seeking or drug-taking behaviors and reduced opioid withdrawal symptoms. KOR antagonists showed mixed findings depending on the specific agent or withdrawal symptom evaluated. Administration of dynorphins attenuated opioid withdrawal symptoms in both preclinical and clinical studies. In a limited number of human studies, dynorphin levels increased in the cerebrospinal fluid and peripheral blood lymphocytes of patients with opioid use disorder. In animal models, dynorphin levels and KOR expression showed mixed changes during opioid use.
Why it matters
This review highlights that the KOR and dynorphin system possesses multifaceted biological actions rather than functioning solely as an aversive anti-reward pathway during opioid withdrawal. Clarifying these complex mechanisms is necessary to guide therapeutic development targeting KOR modulation for opioid use disorder.
Limits
The abstract reports no quantitative metrics, effect sizes, or statistical significance tests. The evidence base is predominantly preclinical with sparse human clinical data, and findings were heterogeneous across different pharmacological agents and withdrawal symptom categories.
Cited by
- supports Dynorphin is an endogenous opioid that binds to kappa-opioid receptors and produces dysphoria.