Evidence map›Paper›PMID 27031992›Full record

ArticlePloS one2016

Endocannabinoid Signaling Regulates Sleep Stability.

Matthew J Pava, Alexandros Makriyannis, David M Lovinger

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 3 pooled it
6.1field-weighted citation impact, top 4% 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.

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

40 citing papers in PubMed, 3 syntheses or guidelines pooled it, 71 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Trial
  7. Trial
  8. FAAH and MAGL inhibition: Evolving approaches to treating substance use disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
  9. A sleepy cannabis constituent: cannabinol and its active metabolite influence sleep architecture in rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Changes in striatal dopamine release, sleep, and behavior during spontaneous Δ-9-tetrahydrocannabinol abstinence in male and female mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022
    Article
  19. Review
  20. The current understanding of the benefits, safety, and regulation of cannabidiol in consumer products.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2021
    Review
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

3 authors at 2 institutions in 1 country.

Matthew J PavaSection on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, Division of Intramural Biological and Clinical Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, United States of America.
Alexandros MakriyannisCenter for Drug Discovery and Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts, United States of America.
David M LovingerSection on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, Division of Intramural Biological and Clinical Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, United States of America.
National Institute on Alcohol Abuse and Alcoholism · USNortheastern University · US

Funding

Corticostriatal mechanisms of action learning and habit formationZIAAA000416 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI LOVINGER, DAVID M · 2009 to 2025
$25.2M
MOLECULAR BASIS OF CANNABINOID ACITIVITYR37DA003801 · NIDA · UNIVERSITY OF CONNECTICUT STORRS · PI MAKRIYANNIS, ALEXANDROS · 1997 to 2006
$3.7M
MOLECULAR BASIS OF CANNABINOID ACTIVITYR01DA003801 · NIDA · UNIVERSITY OF CONNECTICUT STORRS · PI MAKRIYANNIS, ALEXANDROS · 1985 to 2017
$2.5M
Intramural NIH HHS ZIA AA000416NIDA NIH HHS DA003801NIDA NIH HHS R01 DA003801NIDA NIH HHS R37 DA003801
6 · The paper itself

Abstract

The hypnogenic properties of cannabis have been recognized for centuries, but endogenous cannabinoid (endocannabinoid) regulation of vigilance states is poorly characterized. We report findings from a series of experiments in mice measuring sleep with polysomnography after various systemic pharmacological manipulations of the endocannabinoid system. Rapid, unbiased scoring of vigilance states was achieved using an automated algorithm that we devised and validated. Increasing endocannabinoid tone with a selective inhibitor of monoacyglycerol lipase (JZL184) or fatty acid amide hydrolase (AM3506) produced a transient increase in non-rapid eye movement (NREM) sleep due to an augmentation of the length of NREM bouts (NREM stability). Similarly, direct activation of type 1 cannabinoid (CB1) receptors with CP47,497 increased NREM stability, but both CP47,497 and JZL184 had a secondary effect that reduced NREM sleep time and stability. This secondary response to these drugs was similar to the early effect of CB1 blockade with the antagonist/inverse agonist AM281, which fragmented NREM sleep. The magnitude of the effects produced by JZL184 and AM281 were dependent on the time of day this drug was administered. While activation of CB1 resulted in only a slight reduction in gamma power, CB1 blockade had dramatic effects on broadband power in the EEG, particularly at low frequencies. However, CB1 blockade did not significantly reduce the rebound in NREM sleep following total sleep deprivation. These results support the hypothesis that endocannabinoid signaling through CB1 is necessary for NREM stability but it is not necessary for sleep homeostasis.

Indexed as

Signal TransductionAlgorithmsAmidohydrolasesAnimalsBenzodioxolesDrug Inverse AgonismElectrodes, ImplantedElectroencephalographyFatty Acid Amide HydrolasesMaleMiceMice, Inbred C57BLMonoacylglycerol LipasesMorpholinesPiperidinesPyrazolesAM 281AmidohydrolasesBenzodioxolesFatty Acid Amide HydrolasesJZL 184Monoacylglycerol LipasesMorpholinesPiperidinesPyrazolesReceptor, Cannabinoid, CB1

Identifiers

PMID27031992
PMCPMC4816426
OpenAlexW2323017067

What OpenQuestion holds

Textmetadata
LicenceCC0
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.