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Cited by 1,234Cannabis and Cannabinoid ResearchNeuroscience and Neuropharmacology ResearchSchizophrenia research and treatment

An Introduction to the Endogenous Cannabinoid System

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Lu, Hui-Chen, Mackie, Ken·2016·Biological Psychiatry
DOI 10.1016/j.biopsych.2015.07.028PMC PMC4789136
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Abstract

The endocannabinoid system (ECS) is a widespread neuromodulatory system that plays important roles in central nervous system development, synaptic plasticity, and the response to endogenous and environmental insults. The ECS comprises cannabinoid receptors, endogenous cannabinoids (endocannabinoids), and the enzymes responsible for the synthesis and degradation of the endocannabinoids. The most abundant cannabinoid receptors are the CB1 cannabinoid receptors; however, CB2 cannabinoid receptors, transient receptor potential channels, and peroxisome proliferator activated receptors are also engaged by some cannabinoids. Exogenous cannabinoids, such as tetrahydrocannabinol, produce their biological effects through their interactions with cannabinoid receptors. The best-studied endogenous cannabinoids are 2-arachidonoyl glycerol and arachidonoyl ethanolamide (anandamide). Despite similarities in chemical structure, 2-arachidonoyl glycerol and anandamide are synthesized and degraded by distinct enzymatic pathways, which impart fundamentally different physiologic and pathophysiologic roles to these two endocannabinoids. As a result of the pervasive social use of cannabis and the involvement of endocannabinoids in a multitude of biological processes, much has been learned about the physiologic and pathophysiologic roles of the ECS. This review provides an introduction to the ECS with an emphasis on its role in synaptic plasticity and how the ECS is perturbed in schizophrenia.

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  • Growing evidence indicates that dysregulation of the endocannabinoid system may contribute to brain dysfunction, psychopathology, neurodevelopmental problems, neurodegenerative diseases, and neuroinflammation.

    “Growing evidence indicates that dysregulation of ECS may contribute to brain dysfunction, psychopathology, neurodevelopmental problems, neurodegenerative diseases, neuroinflammation, among other physiological functions [9, 10].”

    From Cannabis, cannabinoids and health: a review of evidence on risks and medical benefits (2025) · cites this paper as [9]

    The Introduction links ECS perturbations to psychiatric disorders, and the LTD section suggests that disrupted cannabinoid signaling could contribute to developmental abnormalities. The Endocannabinoid degradation section links loss of an enzyme involved in endocannabinoid metabolism to a neurodegenerative syndrome. The Cannabinoid receptors section describes changes in CB2 expression during inflammation, but does not establish that ECS dysregulation contributes to neuroinflammation. Page numbers were not available in our copy. (LLM, conf=0.84)

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Authors
Lu, H.-C., & Mackie, K.
Affiliations
Indiana University Bloomington (US)
Corresponding author
Mackie, Ken
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2016-04
Volume
79
Issue
7
Pages
516-525
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2015.07.028
PMC
PMC4789136
OpenAlex
W1886084954
Cited by
1,234
References
12
Citations by year
2026: 109 · 2025: 135 · 2024: 188 · 2023: 161 · 2022: 136 · 2021: 143 · 2020: 108 · 2019: 102 · 2018: 62 · 2017: 53 · 2016: 32 · 2015: 3
FWCI
6.28
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • HCL (NS086794, NS048884)
  • KM (DA021696, DA011322)
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords
endocannabinoid system, cannabinoid receptors, CB1 receptor, CB2 receptor, TRP channels, peroxisome proliferator-activated receptors, tetrahydrocannabinol, 2-arachidonoylglycerol, anandamide, synaptic plasticity, central nervous system development, schizophrenia, cannabis use
MeSH terms
Arachidonic Acids, Glycerides, Humans, Neuronal Plasticity, Schizophrenia, Dronabinol, Receptor, Cannabinoid, CB1, Receptor, Cannabinoid, CB2, Polyunsaturated Alkamides, Cannabinoid Receptor Agonists, Endocannabinoids

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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