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50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CNR1
cannabinoid receptor 1
Chromosome 6 · 6q15
NCBI Gene: 1268Ensembl: ENSG00000118432.14HGNC: HGNC:2159UniProt: P21554
528PubMed Papers
21Diseases
12Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
RESEARCH IMPACT
Highly Studied
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
plasma membranecannabinoid receptor activityadenylate cyclase-modulating G protein-coupled receptor signaling pathwaycannabinoid signaling pathwayobesityLennox-Gastaut syndromeepilepsycancer
✦AI Summary

CNR1 encodes cannabinoid receptor 1 (CB1R), a G protein-coupled receptor that binds endocannabinoid ligands with high affinity and modulates adenylate cyclase signaling 1. CNR1 is expressed throughout the brain at presynaptic and postsynaptic sites, including GABAergic and glutamatergic synapses, where it regulates neurotransmitter release 2. CNR1 mRNA expression shows moderate-to-strong correlation with CB1R protein levels in human brain tissue 1. Clinically, CNR1 dysregulation associates with multiple neuropsychiatric and metabolic disorders. In schizophrenia, CNR1 is downregulated in subcortical brain regions and positively correlates with GABAergic gene expression, suggesting involvement in negative symptoms 3. Astrocytic CB1R in the nucleus accumbens promotes stress resilience by stabilizing blood-brain barrier function and reducing inflammation 2. CB1R also functions as an upstream regulator of NLRP3 inflammasome-mediated pyroptosis in cardiomyocytes, contributing to antipsychotic cardiotoxicity 4. CNR1 polymorphisms associate with diabetic nephropathy risk in type 2 diabetes 5 and show minor associations with substance dependence vulnerability, particularly the AAT repeat in Caucasian populations 6. CNR1 participates in lipid metabolism disruption linked to hepatic steatosis through interactions with metabolic pathways 7.

Sources cited
1
CNR1 mRNA expression shows moderate-to-strong correlation with CB1R protein levels measured by PET imaging and receptor autoradiography in human brain
PMID: 36440544
2
Astrocytic CB1R in nucleus accumbens promotes stress resilience by stabilizing blood-brain barrier and reducing inflammation
PMID: 40016352
3
CB1R regulates NLRP3 inflammasome-mediated pyroptosis in cardiomyocytes, contributing to antipsychotic-induced cardiotoxicity
PMID: 35739093
4
CNR1 is downregulated in subcortical brain regions of schizophrenia patients and positively correlates with GABAergic receptor genes
PMID: 37611908
5
CNR1 rs1776966256 and rs1243008337 polymorphisms are associated with increased risk of diabetic nephropathy in type 2 diabetes
PMID: 38406790
6
CNR1 AAT polymorphism shows minor association with illicit substance dependence vulnerability, particularly in Caucasian populations
PMID: 20192949
7
CNR1 interacts with organophosphate flame retardants and participates in lipid metabolism disruption linked to hepatic steatosis
PMID: 40540538
Disease Associationsⓘ21
obesityOpen Targets
0.64Moderate
Lennox-Gastaut syndromeOpen Targets
0.56Moderate
epilepsyOpen Targets
0.55Moderate
cancerOpen Targets
0.52Moderate
Nausea and vomitingOpen Targets
0.50Moderate
SeizureOpen Targets
0.49Moderate
NauseaOpen Targets
0.46Moderate
insomniaOpen Targets
0.45Moderate
type 2 diabetes mellitusOpen Targets
0.41Moderate
PainOpen Targets
0.39Weak
AnorexiaOpen Targets
0.39Weak
smoking cessationOpen Targets
0.38Weak
Dravet syndromeOpen Targets
0.38Weak
osteoarthritis, kneeOpen Targets
0.37Weak
hamartomaOpen Targets
0.37Weak
bipolar disorderOpen Targets
0.36Weak
Chronic painOpen Targets
0.36Weak
infantile spasmsOpen Targets
0.36Weak
Disorder of lipid metabolismOpen Targets
0.35Weak
Hepatic steatosisOpen Targets
0.34Weak
ObesityUniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets12
AZD2207Phase II
Cannabinoid CB1 receptor antagonist
CANNABIDIOLApproved
Cannabinoid CB1 receptor negative allosteric modulator
hamartoma
DRINABANTPhase II
Cannabinoid CB1 receptor antagonist
psychosis
DRONABINOLApproved
Cannabinoid CB1 receptor agonist
Nausea and vomiting
IBIPINABANTPhase II/III
Cannabinoid CB1 receptor antagonist
type 2 diabetes mellitus
NABILONEApproved
Cannabinoid CB1 receptor agonist
Nausea and vomiting
NIMACIMABPhase II
Cannabinoid CB1 receptor negative allosteric modulator
diabetic nephropathy
OTENABANTPhase III
Cannabinoid CB1 receptor antagonist
obesity
RIMONABANTApproved
Cannabinoid CB1 receptor antagonist
obesity
SAD448Phase I
Cannabinoid CB1 receptor agonist
ocular hypertension
SURINABANTPhase II
Cannabinoid CB1 receptor antagonist
obesity
TARANABANTPhase III
Cannabinoid CB1 receptor inverse agonist
obesity
Related Genes
GNG4Protein interaction100%GNG2Protein interaction100%BDNFProtein interaction100%GNG3Protein interaction100%HTR2AProtein interaction99%MGLLProtein interaction97%
Tissue Expression6 tissues
Brain
100%
Lung
31%
Ovary
20%
Bone Marrow
12%
Heart
9%
Liver
1%
Gene Interaction Network
Click a node to explore
CNR1GNG4GNG2BDNFGNG3HTR2AMGLL
PROTEIN STRUCTURE
Preparing viewer…
PDB5U09 · 2.60 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.69LoF Tolerant
pLIⓘ
0.32Tolerant
Observed/Expected LoF0.41 [0.25–0.69]
RankingsWhere CNR1 stands among ~20K protein-coding genes
  • #483of 20,598
    Most Researched528 · top 5%
  • #360of 1,025
    FDA-Approved Drug Targets4
  • #5,249of 17,882
    Most Constrained (LOEUF)0.69
Genes detectedCNR1
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
Association of CNR1 gene and cannabinoid 1 receptor protein in the human brain.
PMID: 36440544
J Neurosci Res · 2023
1.00
2
CB1R-stabilized NLRP3 inflammasome drives antipsychotics cardiotoxicity.
PMID: 35739093
Signal Transduct Target Ther · 2022
0.90
3
The potent BECN2-ATG14 coiled-coil interaction is selectively critical for endolysosomal degradation of GPRASP1/GASP1-associated GPCRs.
PMID: 37409929
Autophagy · 2023
0.84
4
Variations in the human cannabinoid receptor (CNR1) gene modulate striatal responses to happy faces.
PMID: 16623851
Eur J Neurosci · 2006
0.82
5
Astrocytic cannabinoid receptor 1 promotes resilience by dampening stress-induced blood-brain barrier alterations.
PMID: 40016352
Nat Neurosci · 2025
0.80