ArticleNature medicine2013
Targeting the endocannabinoid system in the treatment of fragile X syndrome.
Article in Nature medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 2 of them syntheses that pooled 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.
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.
Who cites it
120 citing papers in PubMed, 2 syntheses or guidelines pooled it, 236 citations in OpenAlex.
- Efficacy of cannabinoids in neurodevelopmental and neuropsychiatric disorders among children and adolescents: a systematic review.European child & adolescent psychiatry · 2024Pooled it
- Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases.International journal of molecular sciences · 2020Pooled it
- A randomized, controlled trial of ZYN002 cannabidiol transdermal gel in children and adolescents with fragile X syndrome (CONNECT-FX).Journal of neurodevelopmental disorders · 2022Trial
- CB1 receptor inhibition restores synaptoneurosomal alternative splicing landscape in fragile X syndrome mice.iScience · 2026Article
- Enhanced CB1 receptor function in GABAergic neurons mediates hyperexcitability and impaired sensory-driven synchrony of cortical circuits in Fragile X Syndrome model mice.Molecular psychiatry · 2026Article
- Endocannabinoid Enhancement via MAGL Inhibition in CDKL5 Deficiency: Selective Cellular Benefits and Domain-Specific Functional Effects in AdultInternational journal of molecular sciences · 2026Article
- Autophagy controls the hippocampal postsynaptic organization and affects cognition in a mouse model of Fragile X syndrome.Molecular psychiatry · 2026Article
- Blarcamesine improves EEG biomarkers of cortical dysfunction in a mouse model of fragile X syndrome.Frontiers in pharmacology · 2026Article
- Naringin Alleviates Autistic-Like Behaviors in BTBR Mice Through Cannabinoid Receptor Type 1-Mediated Restoration of Hippocampal Neurogenesis.CNS neuroscience & therapeutics · 2025Article
- Targeting dysregulated CB1 receptors in a Down syndrome mouse model improves neurological outcomes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Autophagy controls the hippocampal postsynaptic organization and affects cognition in a mouse model of Fragile X syndrome.Research square · 2025Article
- The endocannabinoidome-gut microbiome-brain axis as a novel therapeutic target for autism spectrum disorder.Journal of biomedical science · 2025Review
- Synthesis and Pharmacological Characterization of a Novel Cannabinoid Receptor 1 Antagonist.ACS omega · 2025Article
- From Discovery to Innovative Translational Approaches in 80 Years of Fragile X Syndrome Research.Biomedicines · 2025Review
- Article
- Potential mechanism of Qinggong Shoutao pill alleviating age-associated memory decline based on integration strategy.Pharmaceutical biology · 2024Article
- Article
- Unraveling the Endocannabinoid System: Exploring Its Therapeutic Potential in Autism Spectrum Disorder.Neuromolecular medicine · 2024Review
- The CBEMBO molecular medicine · 2024Article
- Hyperactive mTORC1 in striatum dysregulates dopamine receptor expression and odor preference behavior.Frontiers in neuroscience · 2024Article
60 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fragile X syndrome (FXS), the most common monogenic cause of inherited intellectual disability and autism, is caused by the silencing of the FMR1 gene, leading to the loss of fragile X mental retardation protein (FMRP), a synaptically expressed RNA-binding protein regulating translation. The Fmr1 knockout model recapitulates the main traits of the disease. Uncontrolled activity of metabotropic glutamate receptor 5 (mGluR5) and mammalian target of rapamycin (mTOR) signaling seem crucial in the pathology of this disease. The endocannabinoid system (ECS) is a key modulator of synaptic plasticity, cognitive performance, anxiety, nociception and seizure susceptibility, all of which are affected in FXS. The cannabinoid receptors CB1 (CB1R) and CB2 (CB2R) are activated by phospholipid-derived endocannabinoids, and CB1R-driven long-term regulation of synaptic strength, as a consequence of mGluR5 activation, is altered in several brain areas of Fmr1 knockout mice. We found that CB1R blockade in male Fmr1 knockout (Fmr1(-/y)) mice through pharmacological and genetic approaches normalized cognitive impairment, nociceptive desensitization, susceptibility to audiogenic seizures, overactivated mTOR signaling and altered spine morphology, whereas pharmacological blockade of CB2R normalized anxiolytic-like behavior. Some of these traits were also reversed by pharmacological inhibition of mTOR or mGluR5. Thus, blockade of ECS is a potential therapeutic approach to normalize specific alterations in FXS.
Indexed as
Identifiers
What OpenQuestion holds
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.