A preliminary study of endocannabinoid system regulation in psychosis: Distinct alterations of CNR1 promoter DNA methylation in patients with schizophrenia

Schizophrenia Research

Volumn 188, Issue , 2017, Pages 132-140

  D'Addario, Claudio ^a,b   Micale, Vincenzo ^c,d   Di Bartolomeo, Martina ^a   Stark, Tibor ^c   Pucci, Mariangela ^a   Sulcova, Alexandra ^c   Palazzo, Mariacarlotta ^e   Babinska, Zuzana ^c   Cremaschi, Laura ^f   Drago, Filippo ^d   Carlo Altamura, A ^f   Maccarrone, Mauro ^g,h   Dell'Osso, Bernardo ^f,i  

^a UNIVERSITY OF TERAMO   (Italy)

^b KAROLINSKA INSTITUTE   (Sweden)

^c MASARYK UNIVERSITY   (Czech Republic)

^d UNIVERSITY OF CATANIA   (Italy)

^e Centro Sant'Ambrogio   (Italy)

^f UNIVERSITY OF MILAN   (Italy)

^g UNIVERSITY CAMPUS BIO MEDICO   (Italy)

^h IRCCS FONDAZIONE SANTA LUCIA   (Italy)

ⁱ STANFORD UNIVERSITY   (United States)

Author keywords

Cannabinoid receptor type 1; DNA methylation; Endocannabinoid system (ECS); Methylazoxymethanol (MAM) rat model; Schizophrenia

Indexed keywords

ANTICONVULSIVE AGENT; ANTIDEPRESSANT AGENT; ANXIOLYTIC AGENT; BENZODIAZEPINE; CANNABINOID 1 RECEPTOR; CHLORPROMAZINE; DIAZEPAM; ENDOCANNABINOID; LITHIUM; METHYLAZOXYMETHANOL ACETATE; NEUROLEPTIC AGENT; CNR1 PROTEIN, HUMAN; CNR1 PROTEIN, RAT;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIPOLAR I DISORDER; BIPOLAR II DISORDER; CNR1 GENE; CONTROLLED STUDY; CPG ISLAND; DISEASE MARKER; DISEASE MODEL; DNA DETERMINATION; DNA METHYLATION; FEMALE; GENE CONTROL; GENE EXPRESSION; HUMAN; HUMAN CELL; MAJOR CLINICAL STUDY; MAJOR DEPRESSION; MALE; NONHUMAN; PERIPHERAL BLOOD MONONUCLEAR CELL; PREFRONTAL CORTEX; PRENATAL EXPOSURE; PRIORITY JOURNAL; PROMOTER REGION; PSYCHOSIS; RAT; REGULATORY MECHANISM; SCHIZOPHRENIA; TRANSCRIPTION REGULATION; ANIMAL; BIPOLAR DISORDER; COHORT ANALYSIS; COMPARATIVE STUDY; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MIDDLE AGED; MONONUCLEAR CELL; SPRAGUE DAWLEY RAT;

ANIMALS; BIPOLAR DISORDER; COHORT STUDIES; CPG ISLANDS; DEPRESSIVE DISORDER, MAJOR; DISEASE MODELS, ANIMAL; DNA METHYLATION; ENDOCANNABINOIDS; FEMALE; GENE EXPRESSION REGULATION; HUMANS; LEUKOCYTES, MONONUCLEAR; MALE; METHYLAZOXYMETHANOL ACETATE; MIDDLE AGED; PREFRONTAL CORTEX; PROMOTER REGIONS, GENETIC; RATS, SPRAGUE-DAWLEY; RECEPTOR, CANNABINOID, CB1; SCHIZOPHRENIA;

EID: 85009775090     PISSN: 09209964     EISSN: 15732509     Source Type: Journal    
DOI: 10.1016/j.schres.2017.01.022     Document Type: Article

References (92)

1. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders. fifth ed., 2013 (Washington, DC).
2. Arguello, P.A., Jentsch, J.D., Cannabinoid CB1 receptor-mediated impairment of visuospatial attention in the rat. Psychopharmacology 177:1–2 (2004), 141–150.
3. Arosio, B., D'Addario, C., Gussago, C., Casati, M., Tedone, E., Ferri, E., Nicolini, P., Rossi, P.D., Maccarrone, M., Mari, D., Peripheral blood mononuclear cells as a laboratory to study dementia in the elderly. Biomed. Res. Int., 2014, 2014, 169203.
4. Ashton, C.H., Moore, P.B., Endocannabinoid system dysfunction in mood and related disorders. Acta Psychiatr. Scand. 124:4 (2011), 250–261.
5. Ashton, C.H., Moore, P.B., Gallagher, P., Young, A.H., Cannabinoids in bipolar affective disorder a review and discussion of their therapeutic potential. J. Psychopharmacol. 19:3 (2005), 293–300.
6. Bambico, F.R., Gobbi, G., The cannabinoid CB1 receptor and the endocannabinoid anandamide possible antidepressant targets. Expert Opin. Ther. Targets 12:11 (2008), 1347–1366.
7. Bell, J.T., Pai, A.A., Pickrell, J.K., Gaffney, D.J., Pique-Regi, R., Degner, J.F., et al. DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines. Genome Biol., 12(1), 2011, R10.
8. Bosker, F.J., Gladkevich, A.V., Pietersen, C.Y., Kooi, K.A., Bakker, P.L., Gerbens, F., den Boers, J.A., Korf, J., te Meerman, G., Comparison of brain and blood gene expression in an animal model of negative symptoms in schizophrenia. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 38:2 (2012), 142–148.
9. Bossong, M.G., Jager, G., Bhattacharyya, S., Allen, P., Acute and non-acute effects of cannabis on human memory function: a critical review of neuroimaging studies. Curr. Pharm. Des. 20:13 (2014), 2114–2125.
10. Cao, Q., Martinez, M., Zhang, J., Sanders, A.R., Badner, J.A., Cravchik, A., Markey, C.J., Beshah, E., Guroff, J.J., Maxwell, M.E., Kazuba, D.M., Whiten, R., Goldin, L.R., Gershon, E.S., Gejman, P.V., Suggestive evidence for a schizophrenia susceptibility locus on chromosome 6q and a confirmation in an independent series of pedigrees. Genomics 43:1 (1997), 1–8.
11. Ceccarini, J., De Hert, M., Van Winkel, R., Peuskens, J., Bormans, G., Kranaster, L., et al. Increased ventral striatal CB1 receptor binding is related to negative symptoms in drug-free patients with schizophrenia. NeuroImage 79 (2013), 304–312.
12. Centonze, D., Battistini, L., Maccarrone, M., The endocannabinoid system in peripheral lymphocytes as a mirror of neuroinflammatory diseases. Curr. Pharm. Des. 14:23 (2008), 2370–2382.
13. Chase, K.A., Rosen, C., Gin, H., Bjorkquist, O., Feiner, B., Marvin, R., Conrin, S., Sharma, R.P., Metabolic and inflammatory genes in schizophrenia. Psychiatry Res. 225:1–2 (2015), 208–211.
14. Chase, K.A., Feiner, B., Rosen, C., Gavin, D.P., Sharma, R.P., Characterization of peripheral cannabinoid receptor expression and clinical correlates in schizophrenia. Psychiatry Res. 245 (2016), 346–353.
15. Chomczynski, P., Sacchi, N., The single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction: twenty-something years on. Nat. Protoc. 1:2 (2006), 581–585.
16. Cross, S.H., Bird, A.P., CPG islands and genes. Curr. Opin. Genet. Dev. 5:3 (1995), 309–314.
17. D'Addario, C., Dell'Osso, B., Palazzo, M.C., Benatti, B., Lietti, L., Cattaneo, E., et al. Selective DNA methylation of BDNF promoter in bipolar disorder: differences among patients with BDI and BDII. Neuropsychopharmacology 37:7 (2012), 1647–1655.
18. D'Addario, C., Di Francesco, A., Pucci, M., Finazzi Agro, A., Maccarrone, M., Epigenetic mechanisms and endocannabinoid signalling. FEBS J. 280 (2013), 1905–1917.
19. D'Souza, D.C., Perry, E., Mc Dougall, L., Ammerman, Y., Cooper, T., Wu, Y.T., Braley, G., Gueorguieva, R., Krystal, J.H., The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology 29:8 (2004), 1558–1572.
20. D'Addario, C., Micioni Di Bonaventura, M.V., Pucci, M., Romano, A., Gaetani, S., Ciccocioppo, R., Cifani, C., Maccarrone, M., Endocannabinoid signaling and food addiction. Neurosci. Biobehav. Rev. 47 (2014), 203–224.
21. Dalton, V.S., Long, L.E., Weickert, C.S., Zavitsanou, K., Paranoid schizophrenia is characterized by increased CB1 receptor binding in the dorsolateral prefrontal cortex. Neuropsychopharmacology 36:8 (2011), 1620–1630.
22. 3H]CP-55940 binding in the human central nervous system: regional specific changes in density of cannabinoid-1 receptors associated with schizophrenia and cannabis use. Neuroscience 103:1 (2001), 9–15.
23. Debey, S., Schoenbeck, U., Hellmich, M., Gathof, B.S., Pillai, R., Zander, T., Schultze, J.L., Comparison of different isolation techniques prior gene expression profiling of blood derived cells: impact on physiological responses, on overall expression and the role of different cell types. Pharm. J. 4:3 (2004), 193–207.
24. Dell'Osso, B., D'Addario, C., Carlotta Palazzo, M., Benatti, B., Camuri, G., Galimberti, D., Fenoglio, C., Scarpini, E., Di Francesco, A., Carlo Altamura, A., Epigenetic modulation of BDNF gene: differences in DNA methylation between unipolar and bipolar patients. J. Affect. Disord. 166 (2014), 330–333.
25. Dissanayake, D.W., Mason, R., Marsden, C.A., Sensory gating, cannabinoids and schizophrenia. Neuropharmacology 67 (2013), 66–77.
26. Eggan, S.M., Hashimoto, T., Lewis, D.A., Reduced cortical cannabinoid 1 receptor messenger RNA and protein expression in schizophrenia. Arch. Gen. Psychiatry 65:7 (2008), 772–784.
27. Emrich, H.M., Leweke, F.M., Schneider, U., Towards a cannabinoid hypothesis of schizophrenia: cognitive impairments due to a dysregulation of the endogenous cannabinoid system Pharmacol. Biochem. Behav. 56:4 (1997), 803–807.
28. European Network of Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI), Identifying gene–environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations. Schizophr. Bull. 40 (2014), 729–736.
29. Fervaha, G., Zakzanis, K.K., Foussias, G., Graff-Guerrero, A., Agid, O., Remington, G., Motivational deficits and cognitive test performance in schizophrenia. JAMA Psychiatry 71:9 (2014), 1058–1065.
30. First, M.B., Gibbon, M., Spitzer, R.L., Williams, J.B.W., Benjamin, L.S., Structured Clinical Interview for DSM-IV Axis II Personality Disorders, (SCID-II). 1997, American Psychiatric Press, Inc., Washington, D.C.
31. First, M.B., Spitzer, R.L., Miriam, G., Williams, J.B.W., Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition. (SCID-I/P) New York: Biometrics Research. 2002, New York State Psychiatric Institute.
32. First, M.B., Spitzer, R.L., Miriam, G., Williams, J.B.W., Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Non-patient Edition. (SCID-I/NP) New York: Biometrics Research. 2002, State Psychiatric Institute, New York.
33. Gage, S.H., Zammit, S., Hickman, M., Stronger evidence is needed before accepting that cannabis plays an important role in the aetiology of schizophrenia in the population. F1000 Med. Rep. 5, 2, 2013.
34. Giuffrida, A., Leweke, F.M., Gerth, C.W., Schreiber, D., Koethe, D., Faulhaber, J., et al. Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms. Neuropsychopharmacology 29:11 (2004), 2108–2114.
35. Gladkevich, A., Kauffman, H.F., Korf, J., Lymphocytes as a neural probe: potential for studying psychiatric disorders. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 28:3 (2004), 559–576.
36. 1 receptor antagonism prevents neurochemical and behavioural deficits induced by chronic phencyclidine. Int. J. Neuropsychopharmacol. 14 (2011), 17–28.
37. Hamilton, M., A rating scale for depression. J. Neurol. Neurosurg. Psychiatry 23:1 (1960), 56–62.
38. Henikoff, S., Matzke, M.A., Exploring and explaining epigenetic effects. Trends Genet. 13:8 (1997), 293–295.
39. Hill, M.N., Gorzalka, B.B., Is there a role for the endocannabinoid system in the etiology and treatment of melancholic depression?. Behav. Pharmacol. 16:5–6 (2005), 333–352.
40. Ishiguro, H., Horiuchi, Y., Ishikawa, M., Koga, M., Imai, K., Suzuki, Y., et al. Brain cannabinoid CB2 receptor in schizophrenia. Biol. Psychiatry 67:10 (2010), 974–982.
41. Iversen, L., Cannabis and the brain. Brain 126:Pt6 (2003), 1252–1270.
42. Jaffe, A.E., Irizarry, R.A., Accounting for cellular heterogeneity is critical in epigenome-wide association studies. Genome Biol., 15(2), 2014, R31.
43. Jaffe, A.E., Gao, Y., Deep-Soboslay, A., Tao, R., Hyde, T.M., Weinberger, D.R., Kleinman, J.E., Mapping DNA methylation across development, genotype and schizophrenia in the human frontal cortex. Nat. Neurosci. 19:1 (2015), 40–47.
44. Kucerova, J., Tabiova, K., Drago, F., Micale, V., Therapeutic potential of cannabinoids in schizophrenia. Recent Pat. CNS Drug Discov. 9:1 (2014), 13–25.
45. Laprairie, R.B., Kelly, M.E., Denovan-Wright, E.M., The dynamic nature of type 1 cannabinoid receptor (CB (1)) gene transcription. Br. J. Pharmacol. 167:8 (2012), 1583–1590.
46. Lee, K.S., Asgar, J., Zhang, Y., Chung, M.K., Ro, J.Y., The role of androgen receptor in transcriptional modulation of cannabinoid receptor type 1 gene in rat trigeminal ganglia. Neuroscience 254 (2013), 395–403.
47. Leroy, S., Griffon, N., Bourdel, M.C., Olie, J.P., Poirier, M.F., Krebs, M.O., Schizophrenia and the cannabinoid receptor type 1 (CB1): association study using a single-base polymorphism in coding exon 1. Am. J. Med. Genet. 105:8 (2001), 749–752.
48. Levenson, J.M., Sweatt, J.D., Epigenetic mechanisms: a common theme in vertebrate and invertebrate memory formation. Cell. Mol. Life Sci. 63:9 (2006), 1009–1016.
49. Leweke, F.M., Koethe, D., Cannabis and psychiatric disorders: it is not only addiction. Addict. Biol. 13:2 (2008), 264–275.
50. Liew, C.C., Ma, J., Tang, H.C., Zheng, R., Dempsey, A.A., The peripheral blood transcriptome dynamically reflects system wide biology: a potential diagnostic tool. J. Lab. Clin. Med. 147:3 (2006), 126–132.
51. Livak, K.J., Schmittgen, T.D., Analysis of relative gene expression data using real-time quantitative PCR and the 2(deltadelta C(T)) method. Methods 25:4 (2001), 402–408.
52. Llorente-Berzal, A., Assis, M.A., Rubino, T., Zamberletti, E., Marco, E.M., Parolaro, D., Ambrosio, E., Viveros, M.P., Sex-dependent changes in brain CB1R expression and functionality and immune CB2R expression as a consequence of maternal deprivation and adolescent cocaine exposure. Pharmacol. Res. 74 (2013), 23–33.
53. Lodge, D.J., Grace, A.A., Gestational methylazoxymethanol acetate administration: a developmental disruption model of schizophrenia. Behav. Brain Res. 204:2 (2009), 306–312.
54. Lupski, J.R., Belmont, J.W., Boerwinkle, E., Gibbs, R.A., Clan genomics and the complex architecture of human disease. Cell 147:1 (2011), 32–43.
55. Lyon, E., Millson, A., Lowery, M.C., Woods, R., Wittwer, C.T., Quantification of HER2/neu gene amplification by competitive PCR using fluorescent melting curve analysis. Clin. Chem. 47:5 (2001), 844–851.
56. Maccarrone, M., Gasperi, V., Catani, M.V., Diep, T.A., Dainese, E., Hansen, H.S., Avigliano, L., The endocannabinoid system and its relevance for nutrition. Annu. Rev. Nutr. 30 (2010), 423–440.
57. Maccarrone, M., Guzmán, M., Mackie, K., Doherty, P., Harkany, T., Programming of neural cells by (endo)cannabinoids: from physiological rules to emerging therapies. Nat. Rev. Neurosci. 15:12 (2014), 786–801.
58. Maccarrone, M., Bab, I., Bíró, T., Cabral, G.A., Dey, S.K., Di Marzo, V., Konje, J.C., Kunos, G., Mechoulam, R., Pacher, P., Sharkey, K.A., Zimmer, A., Endocannabinoid signaling at the periphery: 50 years after THC. Trends Pharmacol. Sci. 36:5 (2015), 277–296.
59. Marco, E.M., Echeverry-Alzate, V., López-Moreno, J.A., Giné, E., Peñasco, S., Viveros, M.P., Consequences of Early Life Stress on the Expression of Endocannabinoid-related Genes in the Rat Brain. 2014.
60. McLaughlin, R.J., Hill, M.N., Gorzalka, B.B., A critical role for prefrontocortical endocannabinoid signaling in the regulation of stress and emotional behavior. Neurosci. Biobehav. Rev. 42 (2014), 116–131.
61. Micale, V., Di Marzo, V., Sulcova, A., Wotjak, C.T., Drago, F., Endocannabinoid system and mood disorders: priming a target for new therapies. Pharmacol. Ther. 138:1 (2013), 18–37.
62. Micale, V., Kucerova, J., Sulcova, A., Leading compounds for the validation of animal models of psychopathology. Cell Tissue Res. 354:1 (2013), 309–330.
63. Micale, V., Tabiová, K., Kučerová, J., Drago, F., Role of the endocannabinoid system in depression: from preclinical to clinical evidence. Campolongo, P., Fattore, L., (eds.) Cannabinoid Modulation of Emotion, Memory, and Motivation, 2015, Springer, New York, 97–129.
64. Modinos, G., Allen, P., Grace, A.A., McGuire, P., Translating the MAM model of psychosis to humans. Trends Neurosci. 38:3 (2015), 129–138.
65. Mukhopadhyay, B., Liu, J., Osei-Hyiaman, D., Godlewski, G., Mukhopadhyay, P., Wang, L., et al. Transcriptional regulation of cannabinoid receptor-1 expression in the liver by retinoic acid acting via retinoic acid receptor-gamma. J. Biol. Chem. 285:25 (2010), 19002–19011.
66. Nagre, N.N., Subbanna, S., Shivakumar, M., Psychoyos, D., Basavarajappa, B.S., CB1-receptor knockout neonatal mice are protected against ethanol-induced impairments of DNMT1, DNMT3A, and DNA methylation. J. Neurochem. 132:4 (2015), 429–442.
67. Newell, K.A., Deng, C., Huang, X.F., Increased endocannabinoid receptor density in the posterior cingulate cortex in schizophrenia. Exp. Brain Res. 172:4 (2006), 556–560.
68. Pistis, M., Perra, S., Pillola, G., Melis, M., Muntoni, A.L., Gessa, G.L., Adolescent exposure to cannabinoids induces long-lasting changes in the response to drugs of abuse of rat midbrain dopamine neurons. Biol. Psychiatry 56:2 (2004), 86–94.
69. Pratt, J.A., Winchester, C., Egerton, A., Cochran, S.M., Morris, B.J., Modelling prefrontal cortex deficits in schizophrenia: implications for treatment. Br. J. Pharmacol. 153:S1 (2008), S465–S470.
70. Ranganathan, M., Cortes-Briones, J., Radhakrishnan, R., Thurnauer, H., Planeta, B., Skosnik, P., et al. Reduced brain cannabinoid receptor availability in schizophrenia. Biol. Psychiatry 79:12 (2016), 997–1005.
71. Razin, A., Riggs, A.D., DNA methylation and gene function. Science 210:4470 (1980), 604–610.
72. Robinson, S.A., Loiacono, R.E., Christopoulos, A., Sexton, P.M., Malone, D.T., The effect of social isolation on rat brain expression of genes associated with endocannabinoid signaling. Brain Res. 1343 (2010), 153–167.
73. Robson, P.J., Guy, G.W., Di Marzo, V., Cannabinoids and schizophrenia: therapeutic prospects. Curr. Pharm. Des. 20:13 (2014), 2194–2204.
74. Rotter, A., Bayerlein, K., Hansbauer, M., Weiland, J., Sperling, W., Kornhuber, J., Biermann, T., CB1 and CB2 receptor expression and promoter methylation in patients with cannabis dependence. Eur. Addict. Res. 19:1 (2013), 13–20.
75. Rubino, T., Zamberletti, E., Parolaro, D., Endocannabinoids and mental disorders. Handb. Exp. Pharmacol. 231 (2015), 261–283.
76. Ruda-Kucerova, J., Babinska, Z., Amchova, P., Stark, T., Drago, F., Sulcova, A., Micale, V., Reactivity to addictive drugs in the methylazoxymethanol (MAM) model of schizophrenia in male and female rats. World J. Biol. Psychiatry 21 (2016), 1–14.
77. Saito, A., Ballinger, M.D., Pletnikov, M.V., Wong, D.F., Kamiya, A., Endocannabinoid system: potential novel targets for treatment of schizophrenia. Neurobiol. Dis. 53 (2013), 10–17.
78. Seillier, A., Advani, T., Cassano, T., Hensler, J.G., Giuffrida, A., Inhibition of fatty-acid amide hydrolase and CB1 receptor antagonism differentially affect behavioural responses in normal and PCP-treated rats. Int. J. Neuropsychopharmacol. 13:3 (2010), 373–386.
79. Shapiro, G.K., Buckley-Hunter, L., What every adolescent needs to know: cannabis can cause psychosis. J. Psychosom. Res. 69 (2010), 533–539.
80. Sullivan, P.F., Kendler, K.S., Neale, M.C., Schizophrenia as a complex trait – evidence from a meta-analysis of twin studies. Arch. Gen. Psychiatry 60:12 (2003), 1187–1192.
81. Tsankova, N., Renthal, W., Kumar, A., Nestler, E.J., Epigenetic regulation in psychiatric disorders. Nat. Rev. Neurosci. 8:5 (2007), 355–367.
82. Urigüen, L., García-Fuster, M.J., Callado, L.F., Morentin, B., La Harpe, R., Casadó, V., Lluis, C., Franco, R., García-Sevilla, J.A., Meana, J.J., Immunodensity and mRNA expression of A2A adenosine, D2 dopamine, and CB1 cannabinoid receptors in postmortem frontal cortex of subjects with schizophrenia: effect of antipsychotic treatment. Psychopharmacology 206:2 (2009), 313–324.
83. Vigano, D., Guidali, C., Petrosino, S., Realini, N., Rubino, T., Di Marzo, V., Parolaro, D., Involvement of the endocannabinoid system in phencyclidine-induced cognitive deficits modelling schizophrenia. Int. J. Neuropsychopharmacol. 12:5 (2009), 599–614.
84. Volk, D.W., Lewis, D.A., The role of endocannabinoid signaling in cortical inhibitory neuron dysfunction in schizophrenia. Biol. Psychiatry 79:7 (2015), 595–603.
85. Volk, D.V., Eggan, M.S., Horti, A., Wong, D.F., Lewis, D.A., Reciprocal alterations in cortical cannabinoid receptor 1 binding relative to protein immunoreactivity and transcript levels in schizophrenia. Schizophr. Res. 159:1 (2014), 124–129.
86. Ware, M.A., Adams, H., Guy, G.W., The medicinal use of cannabis in the UK: results of a nationwide survey. Int. J. Clin. Pract. 59:3 (2005), 291–295.
87. Whitney, A.R., Diehn, M., Popper, S.J., Alizadeh, A.A., Boldrick, J.C., Relman, D.A., Brown, P.O., Individuality and variation in gene expression patterns in human blood. Proc. Natl. Acad. Sci. U. S. A. 100:4 (2003), 1896–1901.
88. Woelk, C.H., Singhania, A., Pérez-Santiago, J., Glatt, S.J., Tsuang, M.T., The utility of gene expression in blood cells for diagnosing neuropsychiatric disorders. Int. Rev. Neurobiol. 101 (2011), 41–63.
89. 11C]OMAR. NeuroImage 52:4 (2010), 1505–1513.
90. Young, R.C., Biggs, J.T., Ziegler, V.E., Meyer, D.A., A rating scale for mania: reliability, validity and sensitivity. Br. J. Psychiatry 133:5 (1978), 429–435.
91. Zamberletti, E., Viganò, D., Guidali, C., Rubino, T., Parolaro, D., Long-lasting recovery of psychotic-like symptoms in isolation-reared rats after chronic but not acute treatment with the cannabinoid antagonist AM251. Int. J. Neuropsychopharmacol. 15:2 (2012), 267–280.
92. 3H]SR141716A binding to cannabinoid CB1 receptors is increased in the anterior cingulate cortex in schizophrenia. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 28:2 (2004), 355–360.