ArticleProceedings of the National Academy of Sciences of the United States of America2015
Endocannabinoids are conserved inhibitors of the Hedgehog pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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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.
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Who cites it
54 citing papers in PubMed, 79 citations in OpenAlex.
- The Role of the Hedgehog Pathway in Alcohol-Induced Birth Defects.Advances in experimental medicine and biology · 2026Review
- Article
- Cannabidiol exerts teratogenic effects on developing zebrafish through the sonic hedgehog signaling pathway.Scientific reports · 2025Article
- Is hemp (Translational animal science · 2025Article
- Long term exposure to dietary cannabinoids inhibits rapid functional tolerance to ethanol inmicroPublication biology · 2025Article
- Efcab7 deletion sensitizes mice to the teratogenic effects of gastrulation-stage alcohol exposure.Reproductive toxicology (Elmsford, N.Y.) · 2024Article
- Review
- Combined exposure to alcohol and cannabis during development: Mechanisms and outcomes.Alcohol (Fayetteville, N.Y.) · 2023Review
- Article
- Hepatocyte Smoothened Activity Controls Susceptibility to Insulin Resistance and Nonalcoholic Fatty Liver Disease.Cellular and molecular gastroenterology and hepatology · 2023Article
- Perturbation of 3D nuclear architecture, epigenomic dysregulation and aging, and cannabinoid synaptopathy reconfigures conceptualization of cannabinoid pathophysiology: part 1-aging and epigenomics.Frontiers in psychiatry · 2023Review
- The emerging roles of Hedgehog signaling in tumor immune microenvironment.Frontiers in oncology · 2023Review
- Gene-environment interactions in birth defect etiology: Challenges and opportunities.Current topics in developmental biology · 2023Review
- Promoting Oligodendrocyte Differentiation from Human Induced Pluripotent Stem Cells by Activating Endocannabinoid Signaling for Treating Spinal Cord Injury.Stem cell reviews and reports · 2022Article
- Cannabinoid receptor 2 (Cb2r) mediates cannabinol (CBN) induced developmental defects in zebrafish.Scientific reports · 2022Article
- Fusion protein strategies for cryo-EM study of G protein-coupled receptors.Nature communications · 2022Article
- Brain Organization and Human Diseases.Cells · 2022Review
- Δ9-Tetrahydrocannabinol inhibits Hedgehog-dependent patterning during development.Development (Cambridge, England) · 2021Article
- Cannabinoids modulate food preference and consumption in Drosophila melanogaster.Scientific reports · 2021Article
- Examining the developmental toxicity of piperonyl butoxide as a Sonic hedgehog pathway inhibitor.Chemosphere · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hedgehog ligands control tissue development and homeostasis by alleviating repression of Smoothened, a seven-pass transmembrane protein. The Hedgehog receptor, Patched, is thought to regulate the availability of small lipophilic Smoothened repressors whose identity is unknown. Lipoproteins contain lipids required to repress Smoothened signaling in vivo. Here, using biochemical fractionation and lipid mass spectrometry, we identify these repressors as endocannabinoids. Endocannabinoids circulate in human and Drosophila lipoproteins and act directly on Smoothened at physiological concentrations to repress signaling in Drosophila and mammalian assays. Phytocannabinoids are also potent Smo inhibitors. These findings link organismal metabolism to local Hedgehog signaling and suggest previously unsuspected mechanisms for the physiological activities of cannabinoids.
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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.