ArticlePloS one2017
Rare genetic variants in the endocannabinoid system genes CNR1 and DAGLA are associated with neurological phenotypes in humans.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 77 citations in OpenAlex.
- The Endocannabinoid System in Neuropsychiatric Disorders: Mechanisms, Dysregulation and Therapeutic Potential.Biomedicines · 2026Review
- Autism spectrum disorder trios from consanguineous populations are enriched for rare homozygous variants, identifying 32 new candidate genes.Scientific reports · 2026Article
- Article
- Research Review: What we have learned about the endocannabinoid system in developmental psychopathology.Journal of child psychology and psychiatry, and allied disciplines · 2025Review
- Ppp2r1a haploinsufficiency increases excitatory synaptic transmission and decreases spatial learning by impairing endocannabinoid signaling.The Journal of clinical investigation · 2025Article
- Article
- Treatment of Migraine With Phytocannabinoids, the Involvement of Endocannabinoids in Migraine, and Potential Mechanisms of Action.Pain research & management · 2025Review
- Genetic crosstalk of autism spectrum disorders and epilepsy: an insight into the presynapse.Frontiers in neurology · 2025Article
- Cannabinoids: Role in Neurological Diseases and Psychiatric Disorders.International journal of molecular sciences · 2024Review
- Article
- Resting State Brain Networks under Inverse Agonist versus Complete Knockout of the Cannabinoid Receptor 1.ACS chemical neuroscience · 2024Article
- Anandamide and 2-arachidonoylglycerol differentially modulate autistic-like traits in a genetic model of autism based on FMR1 deletion in rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Role of the endocannabinoid system in fragile X syndrome: potential mechanisms for benefit from cannabidiol treatment.Journal of neurodevelopmental disorders · 2023Review
- Endocannabinoid dysfunction in neurological disease: neuro-ocular DAGLA-related syndrome.Brain : a journal of neurology · 2022Article
- Article
- Blood RNA Sequencing Indicates UpregulatedInternational journal of molecular sciences · 2022Article
- Roles and mechanisms of ankyrin-G in neuropsychiatric disorders.Experimental & molecular medicine · 2022Review
- Molecular Alterations of the Endocannabinoid System in Psychiatric Disorders.International journal of molecular sciences · 2022Review
- A fluorescence recovery after photobleaching protocol to measure surface diffusion of DAGLα in primary cultured cortical mouse neurons.STAR protocols · 2022Article
- Variability in cannabinoid receptor genes is associated with psychiatric comorbidities in anorexia nervosa.Eating and weight disorders : EWD · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Rare genetic variants in the core endocannabinoid system genes CNR1, CNR2, DAGLA, MGLL and FAAH were identified in molecular testing data from 6,032 patients with a broad spectrum of neurological disorders. The variants were evaluated for association with phenotypes similar to those observed in the orthologous gene knockouts in mice. Heterozygous rare coding variants in CNR1, which encodes the type 1 cannabinoid receptor (CB1), were found to be significantly associated with pain sensitivity (especially migraine), sleep and memory disorders-alone or in combination with anxiety-compared to a set of controls without such CNR1 variants. Similarly, heterozygous rare variants in DAGLA, which encodes diacylglycerol lipase alpha, were found to be significantly associated with seizures and neurodevelopmental disorders, including autism and abnormalities of brain morphology, compared to controls. Rare variants in MGLL, FAAH and CNR2 were not associated with any neurological phenotypes in the patients tested. Diacylglycerol lipase alpha synthesizes the endocannabinoid 2-AG in the brain, which interacts with CB1 receptors. The phenotypes associated with rare CNR1 variants are reminiscent of those implicated in the theory of clinical endocannabinoid deficiency syndrome. The severe phenotypes associated with rare DAGLA variants underscore the critical role of rapid 2-AG synthesis and the endocannabinoid system in regulating neurological function and development. Mapping of the variants to the 3D structure of the type 1 cannabinoid receptor, or primary structure of diacylglycerol lipase alpha, reveals clustering of variants in certain structural regions and is consistent with impacts to function.
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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.