Evidence map›Paper›PMID 26068727›Full record

ReviewNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2016

Neurobiological Interactions Between Stress and the Endocannabinoid System.

Maria Morena, Sachin Patel, Jaideep S Bains, Matthew N Hill

Registry-linked trialOpen access · bronzeAbstract readReview
In one paragraph

Review in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05142267 (Stress and Opioid Misuse Risk), which is not on this map. Cited by 317 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
317citing papers in PubMed, 3 pooled it
36.6field-weighted citation impact, top 1% of its field
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.

NCT05142267 narecruitingnot on this mapstarted 2022, after this paper: background citation

Stress and Opioid Misuse Risk: The Role of Endogenous Opioid and Endocannabinoid Mechanisms

TypeinterventionalSponsorVanderbilt University Medical CenterRan2022 to 2026Enrolled120ConditionsOpioid Use Disorder, Back Pain, StressArmsPlacebo, Oxycodone, Naloxone
3 · Its place in the literature

Who cites it

317 citing papers in PubMed, 3 syntheses or guidelines pooled it, 636 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Trial
  7. Circulating endocannabinoids in children and adolescents: associations with anxiety and the impact of selective serotonin reuptake inhibitors.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
    Trial
  8. Trial
  9. Endocannabinoid contributions to the perception of socially relevant, affective touch in humans.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
    Trial
  10. Trial
  11. Trial
  12. The effects of FAAH inhibition on the neural basis of anxiety-related processing in healthy male subjects: a randomized clinical trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021
    Trial
  13. Cannabinoid CBBritish journal of pharmacology · 2026
    Article
  14. The neuroimmune-glutamate hypothesis of addiction.Neuroscience and biobehavioral reviews · 2026
    Review
  15. Article
  16. Article
  17. Glucocorticoid-endocannabinoid crosstalk in the ventrolateral periaqueductal gray (vlPAG) promotes pain resolution.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  18. Article
  19. Article
  20. Review

257 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 2 countries.

Maria MorenaHotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.ORCID http://orcid.org/0000-0001-6590-8130
Sachin PatelDepartment of Molecular Physiology and Biophysics and Psychiatry, Vanderbilt Brain Institute, Vanderbilt-Kennedy Center for Research on Human Development, Vanderbilt University Medical Center, Nashville, TN, USA.
Jaideep S BainsHotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
Matthew N HillHotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
University of Calgary · CAVanderbilt University Medical Center · US

Funding

Research Project: Sensory and Multisensory Contributions to AutismU54HD083211 · NICHD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DYKENS, ELISABETH MAY · 2015 to 2019
$7.1M
Substrate-selective inhibition of COX-2 to target affective disordersR01MH100096 · NIMH · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PATEL, SACHIN · 2013 to 2018
$2.4M
Stress adaptations in endocannabinoid signaling in the amygdalaK08MH090412 · NIMH · VANDERBILT UNIVERSITY · PI PATEL, SACHIN · 2010 to 2014
$842k
Afferent-specific Endocannabinoid Signaling in the Central AmygdalaR21MH103515 · NIMH · VANDERBILT UNIVERSITY · PI PATEL, SACHIN · 2014 to 2015
$412k
CIHRNICHD NIH HHS U54 HD083211NIMH NIH HHS K08 MH090412NIMH NIH HHS MH090412NIMH NIH HHS R01 MH100096NIMH NIH HHS R21 MH103515
6 · The paper itself

Abstract

Stress affects a constellation of physiological systems in the body and evokes a rapid shift in many neurobehavioral processes. A growing body of work indicates that the endocannabinoid (eCB) system is an integral regulator of the stress response. In the current review, we discuss the evidence to date that demonstrates stress-induced regulation of eCB signaling and the consequential role changes in eCB signaling have with respect to many of the effects of stress. Across a wide array of stress paradigms, studies have generally shown that stress evokes bidirectional changes in the two eCB molecules, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), with stress exposure reducing AEA levels and increasing 2-AG levels. Additionally, in almost every brain region examined, exposure to chronic stress reliably causes a downregulation or loss of cannabinoid type 1 (CB1) receptors. With respect to the functional role of changes in eCB signaling during stress, studies have demonstrated that the decline in AEA appears to contribute to the manifestation of the stress response, including activation of the hypothalamic-pituitary-adrenal (HPA) axis and increases in anxiety behavior, while the increased 2-AG signaling contributes to termination and adaptation of the HPA axis, as well as potentially contributing to changes in pain perception, memory and synaptic plasticity. More so, translational studies have shown that eCB signaling in humans regulates many of the same domains and appears to be a critical component of stress regulation, and impairments in this system may be involved in the vulnerability to stress-related psychiatric conditions, such as depression and posttraumatic stress disorder. Collectively, these data create a compelling argument that eCB signaling is an important regulatory system in the brain that largely functions to buffer against many of the effects of stress and that dynamic changes in this system contribute to different aspects of the stress response.

Indexed as

AnimalsArachidonic AcidsCannabinoid Receptor ModulatorsEndocannabinoidsGlyceridesHumansHypothalamo-Hypophyseal SystemPituitary-Adrenal SystemPolyunsaturated AlkamidesReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2Stress, PsychologicalanandamideArachidonic AcidsCannabinoid Receptor ModulatorsEndocannabinoidsGlyceridesglyceryl 2-arachidonatePolyunsaturated AlkamidesReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2

Identifiers

PMID26068727
PMCPMC4677118
OpenAlexW2257383498

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.