Table 1.
Main findings from human studies supporting the role of CB1r and CB2r as biomarkers in psychiatric disorders.
| CB1r | |||||
|---|---|---|---|---|---|
| Subjects/Diagnosis | Sample/Intervention | Method | Measurement | Results | References |
| Healthy controls | THC (10 mg) p.o. | [11C]MePPEP PET | CB1r availability in amygdala | ↑ CB1r | Bhattacharyya et al. (166) |
| Healthy controls | Rimonabant (90 mg) p.o. | Visual Analogue Mood Scale | Anxiety level | ↑ anxiety | Bergamaschi et al. (168) |
| AD/DD | Buccal mucosa cells | DNA Genotyping | CNR1 rs7766029 polymorphism | ↑ frequency financial-related anxiety and depression | Gonda et al. (170) |
| DD | PMBT – anterior cingulate cortex | Immunohistochemistry | Density of CB1r immunopositive glial cells | ↓ CB1r | Koethe et al. (223) |
| DD | PMBT – dorsolateral prefrontal cortex | Quantitative polymerase chain reaction (qPCR) | CB1r relative gene expression | ↑ CB1r | Choi et al. (224) |
| DD | Blood | DNA Genotyping | CNR1 rs1049353 (1359 G/A) polymorphism | ↑ frequency | Monteleone et al. (232) |
| DD/SCZ | Blood | DNA Genotyping | CNR1 rs1049353 (1359 G/A) polymorphism | ↑ depressive symptoms in G-allele carriers | Schennach et al. (233) |
| DD | Blood | DNA Genotyping | CNR1 rs1049353 (1359 G/A) polymorphism | ↑ treatment resistance in G-allele carriers | Domschke et al. (234) |
| DD | Blood | DNA Genotyping | CNR1 rs1049353 (1359 G/A) polymorphism | ↑ citalopram response in GG genotype male carriers | Mitjans et al. (235) |
| Missouri Adolescent Female Twin Study (MOAFTS) participants | Blood | DNA Genotyping | CNR1 rs1049353 (1359 G/A) polymorphism | ↓ risk for anhedonia/DD in A-allele carriers with childhood trauma | Agrawal et al. (236) |
| DD in Parkinson's disease | Blood | DNA Genotyping | CNR1 (AAT)n triplet polymorphism | ↓ risk for DD in 2 long alleles carriers | Barrero et al. (238) |
| DD in methadone-maintained patients | Blood | DNA Genotyping | CNR1 rs2023239 polymorphism | ↓ risk for DD in C-allele carriers | Icick et al. (239) |
| SCZ | PMBT – dorsolateral prefrontal cortex | In situ [3H]CP-55940 radioligand binding | CB1r binding | ↑ CB1r | Dean et al. (269) |
| SCZ | PMBT – dorsolateral prefrontal cortex | In situ [3H]MePPEP radioligand binding | CB1r binding | ↑ CB1r | Jenko et al. (270) |
| SCZ | PMBT – prefrontal cortex | In situ [3H]OMAR radioligand binding | CB1r binding | ↑ CB1r | Volk et al. (271) |
| SCZ | PMBT – anterior cingulate cortex | In situ [3H]SR141716A radioligand binding | CB1r binding | ↑ CB1r | Zavitsanou et al. (274) |
| SCZ | PMBT – posterior cingulate cortex | In situ [3H]CP-55,940 radioligand binding | CB1r binding | ↑ CB1r | Newell et al. (275) |
| SCZ | PMBT – posterior cingulate cortex | In situ hybridization Immunohistochemistry |
CB1r mRNA CB1r protein |
↓ CB1r ↓ CB1r |
Eggan et al. (277) |
| SCZ | PMBT – prefrontal cortex | Western Blot | CB1r protein | ↓ CB1r ↓ CB1r in antipsychotic-treated patients |
Urigüen et al. (278) |
| SCZ | PMBT – prefrontal cortex | Quantitative polymerase chain reaction (qPCR) | CB1r relative gene expression | ↓ CB1r | Muguruzaf et al. (273) |
| SCZ | In vivo neuroimaging (several brain regions) | [11C]-OMAR PET | CB1r binding | ↑ CB1r (only in the pons) | Wong et al. (279) |
| SCZ | In vivo neuroimaging (several brain regions) | [18F]-MK-9470 PET | CB1r binding | ↑ CB1r | Ceccarini et al. (280) |
| SCZ | In vivo neuroimaging (several brain regions) | [11C]-OMAR PET | CB1r binding | ↓ CB1r | Ranganathan et al. (281) |
| FEP | In vivo neuroimaging (several brain regions) | [18F]-FMPEP-d2 or [11C]-MePPEP PET | CB1r binding | ↓ CB1r ↔ severity | Borgan et al. (283) |
| SCZ | Blood | DNA genotyping | CNR1 rs1049353, rs7766029, rs806366 polymorphisms | Nominal association | Costa et al. (290) |
| SCZ | Blood | DNA genotyping | CNR1 (AAT)n triplet polymorphism | 9 and 17 repeat alleles ↔ ↑ susceptibility disorganized SCZ |
Ujike et al. (285) |
| SCZ | Blood | DNA genotyping | CNR1 rs1049353 (1359 G/A) polymorphism | ↑ treatment response in G-allele carriers | Hamdani et al. (290) |
| SCZ | Blood | DNA genotyping | CNR1 rs2023239 polymorphism | ↑ better improvement in TT genotype carriers | Suárez-Pinilla et al. (292) |
| FEP | Blood | DNA genotyping | CNR1 rs7766029, rs12720071 polymorphisms | ↑ better improvement in rs7766029 CC genotype or rs12720071 AG genotype | Kuzman, R. et al. (293) |
| SCZ | Blood | DNA genotyping | CNR1 rs6928499, rs1535255, rs2023239 polymorphisms | ↓ risk metabolic syndrome in minor alleles carriers | Yu et al. (294) |
| SCZ | Blood | DNA genotyping | CB1r relative gene expression | ↑ treatment response in G-allele carriers | Schennach et al. (233) |
| SCZ | Blood – PBMCs | Flow cytometry | CNR1 rs1049353 (1359 G/A) polymorphism | ↑ CB1r | De Campos-Carli et al. (297) |
| SCZ | Blood - PBMCs | Quantitative polymerase chain reaction (qPCR) | CB1r expression | ↑ CB1r | Chase et al. (298) |
| BD | Blood | DNA genotyping | CNR1 rs6454674 polymorphism | ↑ severity in T/G heterozygotes | Alpak et al. (314) |
| Detroit Neighborhood Health Study (DNHS) participants | Blood | DNA genotyping | CNR1 rs1049353 polymorphism | ↑ risk for PTSD-related symptoms in A-allele carriers with childhood abuse | Mota et al. (339) |
| PTSD | In vivo neuroimaging (several brain regions) | [11C]-OMAR PET | CB1r binding | ↑ CB1r | Neumeister, A. et al. (342) |
| ADHD | Blood | DNA genotyping | SNP variants at the CNR1 gene | ↑ frequency SNP haplotype (C-G) | Lu et al. (340) |
| ADHD (alcoholic patients) |
Blood | DNA genotyping | CNR1 (AAT)n triplet polymorphism | ↑ frequency longer form of alleles | Ponce et al. (358) |
| AN/BN | In vivo neuroimaging (several brain regions) | [18F]-MK-9470 PET | CB1r binding | ↑ CB1r | Gérard et al. (371) |
| AN/BN | Blood | Quantitative polymerase chain reaction (qPCR) | CB1r relative gene expression | ↓ CB1r in AN/BN women with self-injurious behavior | Schroeder et al. (372) |
| CB2r | |||||
| Subjects/Diagnosis | Sample | Method | Measurement | Results | References |
| General population | Buccal mucosa | DNA genotyping | CNR2 rs2501432 (R63Q) polymorphism | ↑ risk for AD/DD in rs2501432 R-allele carriers with childhood trauma | Lazary et al. (176) |
| DD | Blood | DNA genotyping | CNR2 rs2501431 polymorphism | ↑ depressive symptoms in G-allele carriers | Mitjans et al. (235) |
| DD | Blood | DNA genotyping | CNR2 rs2501432 (R63Q) polymorphism | ↑ frequency R63Q polymorphism | Onaivi et al. (249, 241) |
| SCZ | Blood – PBMCs | Quantitative polymerase chain reaction (qPCR) | CB2r relative gene expression | ↓ CB2r with clinical remission | De Marchi et al. (295) |
| SCZ | Blood – PBMCs | Quantitative polymerase chain reaction (qPCR) | CB2r relative gene expression | ↑ CB2r | Chase et al. (298) |
| SCZ | Blood – PBMCs | Flow cytometry | CB2r expression | ↑ CB2r | De Campos-Carli et al. (297) |
| SCZ | Blood – PBMCs | Western Blot | CB2r expression | ↓ CB2r | Bioque et al. (310) |
| SCZ | Blood | DNA genotyping | CNR2 rs2501432 (R63Q), rs12744386 polymorphism | ↑ frequency in rs2501432 R63 and rs12744386 C alleles | Ishiguro et al. (265) |
| SCZ | Blood | DNA genotyping | CNR2 rs2501432C/T polymorphism | ↑ risk for SCZ in T-allele carriers | Tong et al. (311) |
| BD | Blood | DNA genotyping | CNR2 rs41311993 (524C/A) polymorphism | ↑ frequency 524C/A polymorphism | Minocci et al. (317) |
AD, anxiety disorder; DD, depressive disorder; SCZ, schizophrenia; FEP, first episode psychosis; BD, bipolar disorder; PTSD, post-traumatic stress disorder; ADHD, attention-deficit hyperactivity disorder; AN, anorexia nervosa; BN, bulimia nervosa; PMBT, post-mortem brain tissue; PET, positron emission tomography; PBMCs, peripheral blood mononuclear cells.
↓: decrease and ↑: increase.