Neurobiological consequences of maternal cannabis on human fetal development and its neuropsychiatric outcome

  • Didier Jutras-Aswad
  • Jennifer A. DiNieri
  • Tibor Harkany
  • Yasmin L. Hurd
Special Issue

Abstract

Despite the high prevalence of marijuana use among pregnant women and adolescents, the impact of cannabis on the developing brain is still not well understood. However, growing evidence supports that the endocannabinoid system plays a major role in CNS patterning in structures relevant for mood, cognition, and reward, such as the mesocorticolimbic system. It is thus clear that exposure to cannabis during early ontogeny is not benign and potential compensatory mechanisms that might be expected to occur during neurodevelopment appear insufficient to eliminate vulnerability to neuropsychiatric disorders in certain individuals. Both human longitudinal cohort studies and animal models strongly emphasize the long-term influence of prenatal cannabinoid exposure on behavior and mental health. This review provides an overview of the endocannabinoid system and examines the neurobiological consequences of cannabis exposure in pregnancy and early life by addressing its impact on the development of neurotransmitters systems relevant to neuropsychiatric disorders and its association with these disorders later in life. It posits that studying in utero cannabis exposure in association with genetic mutations of neural systems that have strong relationships to endocannabinoid function, such as the dopamine, opioid, glutamate, and GABA, might help to identify individuals at risk. Such data could add to existing knowledge to guide public health platform in regard to the use of cannabis and its derivatives during pregnancy.

Keywords

Endocannabinoid Cannabinoid receptor Drug addiction Schizophrenia THC 

Abbreviations

2-AG

2-Arachidonoyl glycerol

5HT3

5-hydroxytryptamine 3 receptor

AAT

Adenosine-adenosine-thymine

ABHD4

Alpha/beta hydroxylase-4

AEA

Anandamide

AMPA

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

CB1R

Cannabinoid receptor type 1

CB2R

Cannabinoid receptor type 2

CNR1

Cannabinoid receptor type 1 gene

CNS

Central nervous system

COMT

Catechol-O-methyltransferase

D1

Dopamine receptor type 1

D2

Dopamine receptor type 2

DAGL

Diacylglycerol lipase

eCB

Endocannabinoid

FAAH

Fatty acid amide hydrolase

GABA

Gamma-aminobutyric acid

GABA-B

Gamma-aminobutyric acid type B receptor

GDE1

Glycerophosphodiester phosphodiesterase 1

GluR1

Glutamate receptor type 1

GluR2/3

Glutamate receptor type 2 and 3

GPCR

G protein-coupled receptor

GPR55

G-protein coupled receptor 55

GTPγS

Guanosine gamma thio-phosphate

IQ

Intelligence quotient

MAPK

Mitogen-activated protein kinase

Met

Methionine

MGL

Monoglyceride lipase

MHPCD

Maternal Health Practices and Child Development Project

mRNA

Messenger ribonucleic acid

NAPE-PLD

N-acyl-phosphatidylethanolamine-specific phospholipase D

NRG1

Neuregulin 1

OPPS

Ottawa Prenatal Prospective Study

THC

Δ9-tetrahydrocannabinol

TRPV1

Transient receptor potential vanilloid 1

Val

Valine

WIN55,212-2

R(+)-[2,3-Dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo [1,2,3-de]1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate

References

  1. 1.
    Akil H, Watson SJ, Young E, Lewis ME, Khachaturian H, Walker JM (1984) Endogenous opioids: biology and function. Annu Rev Neurosci 7:223–255PubMedCrossRefGoogle Scholar
  2. 2.
    Andreasson S, Allebeck P, Engstrom A, Rydberg U (1987) Cannabis and schizophrenia. A longitudinal study of Swedish conscripts. Lancet 2:1483–1486PubMedCrossRefGoogle Scholar
  3. 3.
    Antonelli T, Tanganelli S, Tomasini MC, Finetti S, Trabace L, Steardo L, Sabino V, Carratu MR, Cuomo V, Ferraro L (2004) Long-term effects on cortical glutamate release induced by prenatal exposure to the cannabinoid receptor agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinyl-methyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone: an in vivo microdialysis study in the awake rat. Neuroscience 124:367–375PubMedCrossRefGoogle Scholar
  4. 4.
    Antonelli T, Tomasini MC, Tattoli M, Cassano T, Tanganelli S, Finetti S, Mazzoni E, Trabace L, Steardo L, Cuomo V, Ferraro L (2005) Prenatal exposure to the CB1 receptor agonist WIN 55,212-2 causes learning disruption associated with impaired cortical NMDA receptor function and emotional reactivity changes in rat offspring. Cereb Cortex 15:2013–2020PubMedCrossRefGoogle Scholar
  5. 5.
    Arevalo-Martin A, Garcia-Ovejero D, Rubio-Araiz A, Gomez O, Molina-Holgado F, Molina-Holgado E (2007) Cannabinoids modulate Olig2 and polysialylated neural cell adhesion molecule expression in the subventricular zone of post-natal rats through cannabinoid receptor 1 and cannabinoid receptor 2. Eur J Neurosci 26:1548–1559PubMedCrossRefGoogle Scholar
  6. 6.
    Arseneault L, Cannon M, Poulton R, Murray R, Caspi A, Moffitt TE (2002) Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ 325:1212–1213PubMedCrossRefGoogle Scholar
  7. 7.
    Bals-Kubik R, Ableitner A, Herz A, Shippenberg TS (1993) Neuroanatomical sites mediating the motivational effects of opioids as mapped by the conditioned place preference paradigm in rats. J Pharmacol Exp Ther 264:489–495PubMedGoogle Scholar
  8. 8.
    Begbie J, Doherty P, Graham A (2004) Cannabinoid receptor, CB1, expression follows neuronal differentiation in the early chick embryo. J Anat 205:213–218PubMedCrossRefGoogle Scholar
  9. 9.
    Berghuis P, Dobszay MB, Wang X, Spano S, Ledda F, Sousa KM, Schulte G, Ernfors P, Mackie K, Paratcha G, Hurd YL, Harkany T (2005) Endocannabinoids regulate interneuron migration and morphogenesis by transactivating the TrkB receptor. Proc Natl Acad Sci USA 102:19115–19120PubMedCrossRefGoogle Scholar
  10. 10.
    Berghuis P, Rajnicek AM, Morozov YM, Ross RA, Mulder J, Urban GM, Monory K, Marsicano G, Matteoli M, Canty A, Irving AJ, Katona I, Yanagawa Y, Rakic P, Lutz B, Mackie K, Harkany T (2007) Hardwiring the brain: endocannabinoids shape neuronal connectivity. Science 316:1212–1216PubMedCrossRefGoogle Scholar
  11. 11.
    Bernard C, Milh M, Morozov YM, Ben-Ari Y, Freund TF, Gozlan H (2005) Altering cannabinoid signaling during development disrupts neuronal activity. Proc Natl Acad Sci USA 102:9388–9393PubMedCrossRefGoogle Scholar
  12. 12.
    Berrendero F, Garcia-Gil L, Hernandez ML, Romero J, Cebeira M, de Miguel R, Ramos JA, Fernandez-Ruiz JJ (1998) Localization of mRNA expression and activation of signal transduction mechanisms for cannabinoid receptor in rat brain during fetal development. Development 125:3179–3188PubMedGoogle Scholar
  13. 13.
    Berrendero F, Sepe N, Ramos JA, Di Marzo V, Fernandez-Ruiz JJ (1999) Analysis of cannabinoid receptor binding and mRNA expression and endogenous cannabinoid contents in the developing rat brain during late gestation and early postnatal period. Synapse 33:181–191PubMedCrossRefGoogle Scholar
  14. 14.
    Biegon A, Kerman IA (2001) Autoradiographic study of pre- and postnatal distribution of cannabinoid receptors in human brain. Neuroimage 14:1463–1468PubMedCrossRefGoogle Scholar
  15. 15.
    Biscaia M, Fernandez B, Higuera-Matas A, Miguens M, Viveros MP, Garcia-Lecumberri C, Ambrosio E (2008) Sex-dependent effects of periadolescent exposure to the cannabinoid agonist CP-55, 940 on morphine self-administration behaviour and the endogenous opioid system. Neuropharmacology 54:863–873PubMedCrossRefGoogle Scholar
  16. 16.
    Bisogno T, Hanus L, De Petrocellis L, Tchilibon S, Ponde DE, Brandi I, Moriello AS, Davis JB, Mechoulam R, Di Marzo V (2001) Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol 134:845–852PubMedCrossRefGoogle Scholar
  17. 17.
    Bonnin A, de Miguel R, Castro JG, Ramos JA, Fernandez-Ruiz JJ (1996) Effects of perinatal exposure to delta 9-tetrahydrocannabinol on the fetal and early postnatal development of tyrosine hydroxylase-containing neurons in rat brain. J Mol Neurosci 7:291–308PubMedCrossRefGoogle Scholar
  18. 18.
    Bossong MG, van Berckel BN, Boellaard R, Zuurman L, Schuit RC, Windhorst AD, van Gerven JM, Ramsey NF, Lammertsma AA, Kahn RS (2009) Delta9-tetrahydrocannabinol induces dopamine release in the human striatum. Neuropsychopharmacology 34:759–766PubMedCrossRefGoogle Scholar
  19. 19.
    Boucher AA, Arnold JC, Duffy L, Schofield PR, Micheau J, Karl T (2007) Heterozygous neuregulin 1 mice are more sensitive to the behavioural effects of Delta9-tetrahydrocannabinol. Psychopharmacology (Berl) 192:325–336CrossRefGoogle Scholar
  20. 20.
    Brana C, Charron G, Aubert I, Carles D, Martin-Negrier ML, Trouette H, Fournier MC, Vital C, Bloch B (1995) Ontogeny of the striatal neurons expressing neuropeptide genes in the human fetus and neonate. J Comp Neurol 360:488–505PubMedCrossRefGoogle Scholar
  21. 21.
    Breivogel CS, Childers SR, Deadwyler SA, Hampson RE, Vogt LJ, Sim-Selley LJ (1999) Chronic delta9-tetrahydrocannabinol treatment produces a time-dependent loss of cannabinoid receptors and cannabinoid receptor-activated G proteins in rat brain. J Neurochem 73:2447–2459PubMedCrossRefGoogle Scholar
  22. 22.
    Buckley NE, Hansson S, Harta G, Mezey E (1998) Expression of the CB1 and CB2 receptor messenger RNAs during embryonic development in the rat. Neuroscience 82:1131–1149PubMedCrossRefGoogle Scholar
  23. 23.
    Campolongo P, Trezza V, Cassano T, Gaetani S, Morgese MG, Ubaldi M, Soverchia L, Antonelli T, Ferraro L, Massi M, Ciccocioppo R, Cuomo V (2007) Perinatal exposure to delta-9-tetrahydrocannabinol causes enduring cognitive deficits associated with alteration of cortical gene expression and neurotransmission in rats. Addict Biol 12:485–495PubMedCrossRefGoogle Scholar
  24. 24.
    Caspi A, Moffitt TE, Cannon M, McClay J, Murray R, Harrington H, Taylor A, Arseneault L, Williams B, Braithwaite A, Poulton R, Craig IW (2005) Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. Biol Psychiatry 57:1117–1127PubMedCrossRefGoogle Scholar
  25. 25.
    Cha YM, White AM, Kuhn CM, Wilson WA, Swartzwelder HS (2006) Differential effects of delta9-THC on learning in adolescent and adult rats. Pharmacol Biochem Behav 83:448–455PubMedCrossRefGoogle Scholar
  26. 26.
    Cossu G, Ledent C, Fattore L, Imperato A, Bohme GA, Parmentier M, Fratta W (2001) Cannabinoid CB1 receptor knockout mice fail to self-administer morphine but not other drugs of abuse. Behav Brain Res 118:61–65PubMedCrossRefGoogle Scholar
  27. 27.
    Cristino L, de Petrocellis L, Pryce G, Baker D, Guglielmotti V, Di Marzo V (2006) Immunohistochemical localization of cannabinoid type 1 and vanilloid transient receptor potential vanilloid type 1 receptors in the mouse brain. Neuroscience 139:1405–1415PubMedCrossRefGoogle Scholar
  28. 28.
    Day NL, Richardson GA, Geva D, Robles N (1994) Alcohol, marijuana, and tobacco: effects of prenatal exposure on offspring growth and morphology at age six. Alcohol Clin Exp Res 18:786–794PubMedCrossRefGoogle Scholar
  29. 29.
    Day NL, Richardson GA, Goldschmidt L, Robles N, Taylor PM, Stoffer DS, Cornelius MD, Geva D (1994) Effect of prenatal marijuana exposure on the cognitive development of offspring at age three. Neurotoxicol Teratol 16:169–175PubMedCrossRefGoogle Scholar
  30. 30.
    Day NL, Goldschmidt L, Thomas CA (2006) Prenatal marijuana exposure contributes to the prediction of marijuana use at age 14. Addiction 101:1313–1322PubMedCrossRefGoogle Scholar
  31. 31.
    Dean B, Sundram S, Bradbury R, Scarr E, Copolov D (2001) Studies on [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 103:9–15PubMedCrossRefGoogle Scholar
  32. 32.
    Derbenev AV, Stuart TC, Smith BN (2004) Cannabinoids suppress synaptic input to neurones of the rat dorsal motor nucleus of the vagus nerve. J Physiol 559:923–938PubMedGoogle Scholar
  33. 33.
    Diamond A (2000) Close interrelation of motor development and cognitive development and of the cerebellum and prefrontal cortex. Child Dev 71:44–56PubMedCrossRefGoogle Scholar
  34. 34.
    Dow-Edwards DL, Benveniste H, Behnke M, Bandstra ES, Singer LT, Hurd YL, Stanford LR (2006) Neuroimaging of prenatal drug exposure. Neurotoxicol Teratol 28:386–402PubMedCrossRefGoogle Scholar
  35. 35.
    Egertova M, Giang DK, Cravatt BF, Elphick MR (1998) A new perspective on cannabinoid signalling: complementary localization of fatty acid amide hydrolase and the CB1 receptor in rat brain. Proc Biol Sci 265:2081–2085PubMedCrossRefGoogle Scholar
  36. 36.
    Egertova M, Cravatt BF, Elphick MR (2003) Comparative analysis of fatty acid amide hydrolase and cb(1) cannabinoid receptor expression in the mouse brain: evidence of a widespread role for fatty acid amide hydrolase in regulation of endocannabinoid signaling. Neuroscience 119:481–496PubMedCrossRefGoogle Scholar
  37. 37.
    Ehrenreich H, Rinn T, Kunert HJ, Moeller MR, Poser W, Schilling L, Gigerenzer G, Hoehe MR (1999) Specific attentional dysfunction in adults following early start of cannabis use. Psychopharmacology (Berl) 142:295–301CrossRefGoogle Scholar
  38. 38.
    El Marroun H, Tiemeier H, Jaddoe VW, Hofman A, Mackenbach JP, Steegers EA, Verhulst FC, van den Brink W, Huizink AC (2008) Demographic, emotional and social determinants of cannabis use in early pregnancy: the Generation R study. Drug Alcohol Depend 98:218–226PubMedCrossRefGoogle Scholar
  39. 39.
    Ellgren M, Spano SM, Hurd YL (2007) Adolescent cannabis exposure alters opiate intake and opioid limbic neuronal populations in adult rats. Neuropsychopharmacology 32:607–615PubMedCrossRefGoogle Scholar
  40. 40.
    Ellgren M, Artmann A, Tkalych O, Gupta A, Hansen HS, Hansen SH, Devi LA, Hurd YL (2008) Dynamic changes of the endogenous cannabinoid and opioid mesocorticolimbic systems during adolescence: THC effects. Eur Neuropsychopharmacol 18:826–834PubMedCrossRefGoogle Scholar
  41. 41.
    Fadda P, Scherma M, Spano MS, Salis P, Melis V, Fattore L, Fratta W (2006) Cannabinoid self-administration increases dopamine release in the nucleus accumbens. Neuroreport 17:1629–1632PubMedCrossRefGoogle Scholar
  42. 42.
    Faden VB, Graubard BI (2000) Maternal substance use during pregnancy and developmental outcome at age three. J Subst Abuse 12:329–340PubMedCrossRefGoogle Scholar
  43. 43.
    Fergusson DM, Horwood LJ, Northstone K (2002) Maternal use of cannabis and pregnancy outcome. BJOG 109:21–27PubMedCrossRefGoogle Scholar
  44. 44.
    Fergusson DM, Horwood LJ, Swain-Campbell N (2002) Cannabis use and psychosocial adjustment in adolescence and young adulthood. Addiction 97:1123–1135PubMedCrossRefGoogle Scholar
  45. 45.
    Fernandez-Ruiz J, Berrendero F, Hernandez ML, Ramos JA (2000) The endogenous cannabinoid system and brain development. Trends Neurosci 23:14–20PubMedCrossRefGoogle Scholar
  46. 46.
    Flanagan JM, Gerber AL, Cadet JL, Beutler E, Sipe JC (2006) The fatty acid amide hydrolase 385 A/A (P129T) variant: haplotype analysis of an ancient missense mutation and validation of risk for drug addiction. Hum Genet 120:581–588PubMedCrossRefGoogle Scholar
  47. 47.
    Forcelli PA, Heinrichs SC (2008) Teratogenic effects of maternal antidepressant exposure on neural substrates of drug-seeking behavior in offspring. Addict Biol 13:52–62PubMedCrossRefGoogle Scholar
  48. 48.
    Frank MJ, Moustafa AA, Haughey HM, Curran T, Hutchison KE (2007) Genetic triple dissociation reveals multiple roles for dopamine in reinforcement learning. Proc Natl Acad Sci USA 104:16311–16316PubMedCrossRefGoogle Scholar
  49. 49.
    Fried PA (1982) Marihuana use by pregnant women and effects on offspring: an update. Neurobehav Toxicol Teratol 4:451–454PubMedGoogle Scholar
  50. 50.
    Fried PA (1995) Prenatal exposure to marihuana and tobacco during infancy, early and middle childhood: effects and an attempt at synthesis. Arch Toxicol Suppl 17:233–260PubMedGoogle Scholar
  51. 51.
    Fried PA (2002) Adolescents prenatally exposed to marijuana: examination of facets of complex behaviors and comparisons with the influence of in utero cigarettes. J Clin Pharmacol 42:97S–102SPubMedGoogle Scholar
  52. 52.
    Fried PA (2002) Conceptual issues in behavioral teratology and their application in determining long-term sequelae of prenatal marihuana exposure. J Child Psychol Psychiatry 43:81–102PubMedCrossRefGoogle Scholar
  53. 53.
    Fried PA, Makin JE (1987) Neonatal behavioural correlates of prenatal exposure to marihuana, cigarettes and alcohol in a low risk population. Neurotoxicol Teratol 9:1–7PubMedCrossRefGoogle Scholar
  54. 54.
    Fried PA, Smith AM (2001) A literature review of the consequences of prenatal marihuana exposure. An emerging theme of a deficiency in aspects of executive function. Neurotoxicol Teratol 23:1–11PubMedCrossRefGoogle Scholar
  55. 55.
    Fried PA, Watkinson B (1988) 12- and 24-month neurobehavioural follow-up of children prenatally exposed to marihuana, cigarettes and alcohol. Neurotoxicol Teratol 10:305–313PubMedCrossRefGoogle Scholar
  56. 56.
    Fried PA, Watkinson B (1990) 36- and 48-month neurobehavioral follow-up of children prenatally exposed to marijuana, cigarettes, and alcohol. J Dev Behav Pediatr 11:49–58PubMedCrossRefGoogle Scholar
  57. 57.
    Fried PA, Watkinson B (2001) Differential effects on facets of attention in adolescents prenatally exposed to cigarettes and marihuana. Neurotoxicol Teratol 23:421–430PubMedCrossRefGoogle Scholar
  58. 58.
    Fried PA, Watkinson B, Dillon RF, Dulberg CS (1987) Neonatal neurological status in a low-risk population after prenatal exposure to cigarettes, marijuana, and alcohol. J Dev Behav Pediatr 8:318–326PubMedCrossRefGoogle Scholar
  59. 59.
    Fried PA, O’Connell CM, Watkinson B (1992) 60- and 72-month follow-up of children prenatally exposed to marijuana, cigarettes, and alcohol: cognitive and language assessment. J Dev Behav Pediatr 13:383–391PubMedCrossRefGoogle Scholar
  60. 60.
    Fried PA, Watkinson B, Gray R (1998) Differential effects on cognitive functioning in 9- to 12-year olds prenatally exposed to cigarettes and marihuana. Neurotoxicol Teratol 20:293–306PubMedCrossRefGoogle Scholar
  61. 61.
    Fried P, Watkinson B, James D, Gray R (2002) Current and former marijuana use: preliminary findings of a longitudinal study of effects on IQ in young adults. CMAJ 166:887–891PubMedGoogle Scholar
  62. 62.
    Fried PA, Watkinson B, Gray R (2003) Differential effects on cognitive functioning in 13- to 16-year-olds prenatally exposed to cigarettes and marihuana. Neurotoxicol Teratol 25:427–436PubMedCrossRefGoogle Scholar
  63. 63.
    Fried PA, Watkinson B, Gray R (2005) Neurocognitive consequences of marihuana–a comparison with pre-drug performance. Neurotoxicol Teratol 27:231–239PubMedCrossRefGoogle Scholar
  64. 64.
    Galve-Roperh I, Aguado T, Palazuelos J, Guzman M (2007) The endocannabinoid system and neurogenesis in health and disease. Neuroscientist 13:109–114PubMedCrossRefGoogle Scholar
  65. 65.
    Garcia-Gil L, Ramos JA, Rubino T, Parolaro D, Fernandez-Ruiz JJ (1998) Perinatal delta9-tetrahydrocannabinol exposure did not alter dopamine transporter and tyrosine hydroxylase mRNA levels in midbrain dopaminergic neurons of adult male and female rats. Neurotoxicol Teratol 20:549–553PubMedCrossRefGoogle Scholar
  66. 66.
    Garcia-Gil L, de Miguel R, Romero J, Perez A, Ramos JA, Fernandez-Ruiz JJ (1999) Perinatal delta9-tetrahydrocannabinol exposure augmented the magnitude of motor inhibition caused by GABA(B), but not GABA(A), receptor agonists in adult rats. Neurotoxicol Teratol 21:277–283PubMedCrossRefGoogle Scholar
  67. 67.
    Garcia-Gil L, Romero J, Ramos JA, Fernandez-Ruiz JJ (1999) Cannabinoid receptor binding and mRNA levels in several brain regions of adult male and female rats perinatally exposed to delta9-tetrahydrocannabinol. Drug Alcohol Depend 55:127–136PubMedCrossRefGoogle Scholar
  68. 68.
    Garon N, Bryson SE, Smith IM (2008) Executive function in preschoolers: a review using an integrative framework. Psychol Bull 134:31–60PubMedCrossRefGoogle Scholar
  69. 69.
    Gerard CM, Mollereau C, Vassart G, Parmentier M (1991) Molecular cloning of a human cannabinoid receptor which is also expressed in testis. Biochem J 279(Pt 1):129–134PubMedGoogle Scholar
  70. 70.
    Ghozland S, Matthes HW, Simonin F, Filliol D, Kieffer BL, Maldonado R (2002) Motivational effects of cannabinoids are mediated by mu-opioid and kappa-opioid receptors. J Neurosci 22:1146–1154PubMedGoogle Scholar
  71. 71.
    Giuffrida A, Parsons LH, Kerr TM, Rodriguez de Fonseca F, Navarro M, Piomelli D (1999) Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nat Neurosci 2:358–363PubMedCrossRefGoogle Scholar
  72. 72.
    Glass M, Dragnunow M, Faull RL (1997) Cannabinoid receptors in the human brain: a detailed anatomical quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neurosci 77:299–318CrossRefGoogle Scholar
  73. 73.
    Goldschmidt L, Day NL, Richardson GA (2000) Effects of prenatal marijuana exposure on child behavior problems at age 10. Neurotoxicol Teratol 22:325–336PubMedCrossRefGoogle Scholar
  74. 74.
    Goldschmidt L, Richardson GA, Willford J, Day NL (2008) Prenatal marijuana exposure and intelligence test performance at age 6. J Am Acad Child Adolesc Psychiatry 47:254–263PubMedCrossRefGoogle Scholar
  75. 75.
    Gordon N (2007) The cerebellum and cognition. Eur J Paediatr Neurol 11:232–234PubMedCrossRefGoogle Scholar
  76. 76.
    Gray KA, Day NL, Leech S, Richardson GA (2005) Prenatal marijuana exposure: effect on child depressive symptoms at ten years of age. Neurotoxicol Teratol 27:439–448PubMedCrossRefGoogle Scholar
  77. 77.
    Griffin G, Tao Q, Abood ME (2000) Cloning and pharmacological characterization of the rat CB(2) cannabinoid receptor. J Pharmacol Exp Ther 292:886–894PubMedGoogle Scholar
  78. 78.
    Griffith DR, Azuma SD, Chasnoff IJ (1994) Three-year outcome of children exposed prenatally to drugs. J Am Acad Child Adolesc Psychiatry 33:20–27PubMedCrossRefGoogle Scholar
  79. 79.
    Groenewegen HJ, Uylings HB (2000) The prefrontal cortex and the integration of sensory, limbic and autonomic information. Prog Brain Res 126:3–28PubMedCrossRefGoogle Scholar
  80. 80.
    Haber SN (2003) The primate basal ganglia: parallel and integrative networks. J Chem Neuroanat 26:317–330PubMedCrossRefGoogle Scholar
  81. 81.
    Hall W, Degenhardt L (2008) Cannabis use and the risk of developing a psychotic disorder. World Psychiatry 7:68–71PubMedGoogle Scholar
  82. 82.
    Harder VS, Stuart EA, Anthony JC (2008) Adolescent cannabis problems and young adult depression: male-female stratified propensity score analyses. Am J Epidemiol 168:592–601PubMedCrossRefGoogle Scholar
  83. 83.
    Harkany T, Guzman M, Galve-Roperh I, Berghuis P, Devi LA, Mackie K (2007) The emerging functions of endocannabinoid signaling during CNS development. Trends Pharmacol Sci 28:83–92PubMedCrossRefGoogle Scholar
  84. 84.
    Harkany T, Keimpema E, Barabas K, Mulder J (2008) Endocannabinoid functions controlling neuronal specification during brain development. Mol Cell Endocrinol 286:S84–S90PubMedCrossRefGoogle Scholar
  85. 85.
    Harkany T, Mackie K, Doherty P (2008) Wiring and firing neuronal networks: endocannabinoids take center stage. Curr Opin Neurobiol 18:338–345PubMedCrossRefGoogle Scholar
  86. 86.
    Harvey MA, Sellman JD, Porter RJ, Frampton CM (2007) The relationship between non-acute adolescent cannabis use and cognition. Drug Alcohol Rev 26:309–319PubMedCrossRefGoogle Scholar
  87. 87.
    Hayatbakhsh MR, Najman JM, Jamrozik K, Mamun AA, Alati R, Bor W (2007) Cannabis and anxiety and depression in young adults: a large prospective study. J Am Acad Child Adolesc Psychiatry 46:408–417PubMedCrossRefGoogle Scholar
  88. 88.
    Henquet C, Rosa A, Krabbendam L, Papiol S, Fananas L, Drukker M, Ramaekers JG, van Os J (2006) An experimental study of catechol-o-methyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology 31:2748–2757PubMedCrossRefGoogle Scholar
  89. 89.
    Henquet C, Rosa A, Delespaul P, Papiol S, Fananas L, van Os J, Myin-Germeys I (2008) COMT Val(158)Met moderation of cannabis-induced psychosis: a momentary assessment study of ‘switching on’ hallucinations in the flow of daily life. Acta Psychiatr Scand 119(2):156–160PubMedCrossRefGoogle Scholar
  90. 90.
    Herkenham M, Lynn A, Little M, Johnson M, Melvin L, De Costa B, Rice K (1990) Cannabinoid receptor localization in brain. Proc Natl Acad Sci USA 87:1932PubMedCrossRefGoogle Scholar
  91. 91.
    Herkenham M, Lynn AB, de Costa BR, Richfield EK (1991) Neuronal localization of cannabinoid receptors in the basal ganglia of the rat. Brain Res 547:267–274PubMedCrossRefGoogle Scholar
  92. 92.
    Herkenham M, Lynn AB, Johnson MR, Melvin LS, de Costa BR, Rice KC (1991) Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J Neurosci 11:563–583PubMedGoogle Scholar
  93. 93.
    Hernandez ML, Garcia-Gil L, Berrendero F, Ramos JA, Fernandez-Ruiz JJ (1997) Delta 9-Tetrahydrocannabinol increases activity of tyrosine hydroxylase in cultured fetal mesencephalic neurons. J Mol Neurosci 8:83–91PubMedCrossRefGoogle Scholar
  94. 94.
    Hernandez M, Berrendero F, Suarez I, Garcia-Gil L, Cebeira M, Mackie K, Ramos JA, Fernandez-Ruiz J (2000) Cannabinoid CB(1) receptors colocalize with tyrosine hydroxylase in cultured fetal mesencephalic neurons and their activation increases the levels of this enzyme. Brain Res 857:56–65PubMedCrossRefGoogle Scholar
  95. 95.
    Higuera-Matas A, Soto-Montenegro ML, del Olmo N, Miguens M, Torres I, Vaquero JJ, Sanchez J, Garcia-Lecumberri C, Desco M, Ambrosio E (2008) Augmented acquisition of cocaine self-administration and altered brain glucose metabolism in adult female but not male rats exposed to a cannabinoid agonist during adolescence. Neuropsychopharmacology 33:806–813PubMedCrossRefGoogle Scholar
  96. 96.
    Hollis C, Groom MJ, Das D, Calton T, Bates AT, Andrews HK, Jackson GM, Liddle PF (2008) Different psychological effects of cannabis use in adolescents at genetic high risk for schizophrenia and with attention deficit/hyperactivity disorder (ADHD). Schizophr Res 105:216–223PubMedCrossRefGoogle Scholar
  97. 97.
    Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, Devane WA, Felder CC, Herkenham M, Mackie K, Martin BR, Mechoulam R, Pertwee RG (2002) International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 54:161–202PubMedCrossRefGoogle Scholar
  98. 98.
    Huizink AC, Mulder EJ (2006) Maternal smoking, drinking or cannabis use during pregnancy and neurobehavioral and cognitive functioning in human offspring. Neurosci Biobehav Rev 30:24–41PubMedCrossRefGoogle Scholar
  99. 99.
    Hurd Y, Hall H (2005) Human forebrain dopamine systems: characterization of the normal brain and in relation to psychiatric disorders. In: Dunnett SB, Bentivoglio M (eds) Handbook of chemical neuroanatomy. Elsevier B.V., Amsterdam, pp 525–571Google Scholar
  100. 100.
    Hurd YL, Wang X, Anderson V, Beck O, Minkoff H, Dow-Edwards D (2005) Marijuana impairs growth in mid-gestation fetuses. Neurotoxicol Teratol 27:221–229PubMedCrossRefGoogle Scholar
  101. 101.
    Kandel DB (2003) Does marijuana use cause the use of other drugs? JAMA 289:482–483PubMedCrossRefGoogle Scholar
  102. 102.
    Kearn CS, Blake-Palmer K, Daniel E, Mackie K, Glass M (2005) Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors enhances heterodimer formation: a mechanism for receptor cross-talk? Mol Pharmacol 67:1697–1704PubMedCrossRefGoogle Scholar
  103. 103.
    Kempel P, Lampe K, Parnefjord R, Hennig J, Kunert HJ (2003) Auditory-evoked potentials and selective attention: different ways of information processing in cannabis users and controls. Neuropsychobiology 48:95–101PubMedCrossRefGoogle Scholar
  104. 104.
    Klimek V, Schenck JE, Han H, Stockmeier CA, Ordway GA (2002) Dopaminergic abnormalities in amygdaloid nuclei in major depression: a postmortem study. Biol Psychiatry 52:740–748PubMedCrossRefGoogle Scholar
  105. 105.
    Lauckner JE, Jensen JB, Chen HY, Lu HC, Hille B, Mackie K (2008) GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc Natl Acad Sci USA 105:2699–2704PubMedCrossRefGoogle Scholar
  106. 106.
    Leech SL, Richardson GA, Goldschmidt L, Day NL (1999) Prenatal substance exposure: effects on attention and impulsivity of 6-year-olds. Neurotoxicol Teratol 21:109–118PubMedCrossRefGoogle Scholar
  107. 107.
    Leech SL, Larkby CA, Day R, Day NL (2006) Predictors and correlates of high levels of depression and anxiety symptoms among children at age 10. J Am Acad Child Adolesc Psychiatry 45:223–230PubMedCrossRefGoogle Scholar
  108. 108.
    Leinekugel X, Khalilov I, McLean H, Caillard O, Gaiarsa JL, Ben-Ari Y, Khazipov R (1999) GABA is the principal fast-acting excitatory transmitter in the neonatal brain. Adv Neurol 79:189–201PubMedGoogle Scholar
  109. 109.
    Leroy S, Griffon N, Bourdel MC, Olie JP, Poirier MF, Krebs MO (2001) Schizophrenia and the cannabinoid receptor type 1 (CB1): association study using a single-base polymorphism in coding exon 1. Am J Med Genet 105:749–752PubMedCrossRefGoogle Scholar
  110. 110.
    Levin HS, Culhane KA, Hartman J, Evankovich K, Mattson AJ, Harward H, Ringholtz G, Ewing-Cobbs L, Fletcher JM (1991) Developmental changes in performance on tests of purported frontal lobe functioning. Dev Neuropsychol 7:377–395Google Scholar
  111. 111.
    Lopez-Bendito G, Cautinat A, Sanchez JA, Bielle F, Flames N, Garratt AN, Talmage DA, Role LW, Charnay P, Marin O, Garel S (2006) Tangential neuronal migration controls axon guidance: a role for neuregulin-1 in thalamocortical axon navigation. Cell 125:127–142PubMedCrossRefGoogle Scholar
  112. 112.
    Lozano J, Garcia-Algar O, Marchei E, Vall O, Monleon T, Giovannandrea RD, Pichini S (2007) Prevalence of gestational exposure to cannabis in a Mediterranean city by meconium analysis. Acta Paediatr 96:1734–1737PubMedCrossRefGoogle Scholar
  113. 113.
    Lundqvist T (2005) Cognitive consequences of cannabis use: comparison with abuse of stimulants and heroin with regard to attention, memory and executive functions. Pharmacol Biochem Behav 81:319–330PubMedCrossRefGoogle Scholar
  114. 114.
    Lupica CR, Riegel AC (2005) Endocannabinoid release from midbrain dopamine neurons: a potential substrate for cannabinoid receptor antagonist treatment of addiction. Neuropharmacology 48:1105–1116PubMedCrossRefGoogle Scholar
  115. 115.
    Magnan J, Tiberi M (1989) Evidence for the presence of mu- and kappa- but not of delta-opioid sites in the human fetal brain. Brain Res Dev Brain Res 45:275–281PubMedCrossRefGoogle Scholar
  116. 116.
    Mailleux P, Vanderhaeghen JJ (1992) Localization of cannabinoid receptor in the human developing and adult basal ganglia. Higher levels in the striatonigral neurons. Neurosci Lett 148:173–176PubMedCrossRefGoogle Scholar
  117. 117.
    Mailleux P, Parmentier M, Vanderhaeghen JJ (1992) Distribution of cannabinoid receptor messenger RNA in the human brain: an in situ hybridization histochemistry with oligonucleotides. Neurosci Lett 143:200–204PubMedCrossRefGoogle Scholar
  118. 118.
    Malone DT, Taylor DA (1999) Modulation by fluoxetine of striatal dopamine release following Delta9-tetrahydrocannabinol: a microdialysis study in conscious rats. Br J Pharmacol 128:21–26PubMedCrossRefGoogle Scholar
  119. 119.
    Mato S, Del Olmo E, Pazos A (2003) Ontogenetic development of cannabinoid receptor expression and signal transduction functionality in the human brain. Eur J Neurosci 17:1747–1754PubMedCrossRefGoogle Scholar
  120. 120.
    Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564PubMedCrossRefGoogle Scholar
  121. 121.
    McPartland JM (2004) Phylogenomic and chemotaxonomic analysis of the endocannabinoid system. Brain Res Brain Res Rev 45:18–29PubMedCrossRefGoogle Scholar
  122. 122.
    Medina KL, Hanson KL, Schweinsburg AD, Cohen-Zion M, Nagel BJ, Tapert SF (2007) Neuropsychological functioning in adolescent marijuana users: subtle deficits detectable after a month of abstinence. J Int Neuropsychol Soc 13:807–820PubMedCrossRefGoogle Scholar
  123. 123.
    Mereu G, Fa M, Ferraro L, Cagiano R, Antonelli T, Tattoli M, Ghiglieri V, Tanganelli S, Gessa GL, Cuomo V (2003) Prenatal exposure to a cannabinoid agonist produces memory deficits linked to dysfunction in hippocampal long-term potentiation and glutamate release. Proc Natl Acad Sci USA 100:4915–4920PubMedCrossRefGoogle Scholar
  124. 124.
    Mezey E, Toth ZE, Cortright DN, Arzubi MK, Krause JE, Elde R, Guo A, Blumberg PM, Szallasi A (2000) Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human. Proc Natl Acad Sci USA 97:3655–3660PubMedCrossRefGoogle Scholar
  125. 125.
    Michelsen KA, Schmitz C, Steinbusch HW (2007) The dorsal raphe nucleus—from silver stainings to a role in depression. Brain Res Rev 55:329–342PubMedCrossRefGoogle Scholar
  126. 126.
    Middleton FA, Strick PL (2001) Cerebellar projections to the prefrontal cortex of the primate. J Neurosci 21:700–712PubMedGoogle Scholar
  127. 127.
    Moldrich G, Wenger T (2000) Localization of the CB1 cannabinoid receptor in the rat brain. An immunohistochemical study. Peptides 21:1735–1742PubMedCrossRefGoogle Scholar
  128. 128.
    Molina-Holgado F, Amaro A, Gonzalez MI, Alvarez FJ, Leret ML (1996) Effect of maternal delta 9-tetrahydrocannabinol on developing serotonergic system. Eur J Pharmacol 316:39–42PubMedCrossRefGoogle Scholar
  129. 129.
    Molina-Holgado F, Alvarez FJ, Gonzalez I, Antonio MT, Leret ML (1997) Maternal exposure to delta 9-tetrahydrocannabinol (delta 9-THC) alters indolamine levels and turnover in adult male and female rat brain regions. Brain Res Bull 43:173–178PubMedCrossRefGoogle Scholar
  130. 130.
    Morita Y, Ujike H, Tanaka Y, Uchida N, Nomura A, Ohtani K, Kishimoto M, Morio A, Imamura T, Sakai A, Inada T, Harano M, Komiyama T, Yamada M, Sekine Y, Iwata N, Iyo M, Sora I, Ozaki N, Kuroda S (2005) A nonsynonymous polymorphism in the human fatty acid amide hydrolase gene did not associate with either methamphetamine dependence or schizophrenia. Neurosci Lett 376:182–187PubMedCrossRefGoogle Scholar
  131. 131.
    Mulder J, Aguado T, Keimpema E, Barabas K, Ballester Rosado CJ, Nguyen L, Monory K, Marsicano G, Di Marzo V, Hurd YL, Guillemot F, Mackie K, Lutz B, Guzman M, Lu HC, Galve-Roperh I, Harkany T (2008) Endocannabinoid signaling controls pyramidal cell specification and long-range axon patterning. Proc Natl Acad Sci USA 105:8760–8765PubMedCrossRefGoogle Scholar
  132. 132.
    Munro S, Thomas KL, Abu-Shaar M (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature 365:61–65PubMedCrossRefGoogle Scholar
  133. 133.
    Nader MA, Czoty PW (2005) PET imaging of dopamine D2 receptors in monkey models of cocaine abuse: genetic predisposition versus environmental modulation. Am J Psychiatry 162:1473–1482PubMedCrossRefGoogle Scholar
  134. 134.
    Neumeister A, Young T, Stastny J (2004) Implications of genetic research on the role of the serotonin in depression: emphasis on the serotonin type 1A receptor and the serotonin transporter. Psychopharmacology (Berl) 174:512–524CrossRefGoogle Scholar
  135. 135.
    Noorlander CW, Ververs FF, Nikkels PG, van Echteld CJ, Visser GH, Smidt MP (2008) Modulation of serotonin transporter function during fetal development causes dilated heart cardiomyopathy and lifelong behavioral abnormalities. PLoS ONE 3:e2782PubMedCrossRefGoogle Scholar
  136. 136.
    O’Shea M, Singh ME, McGregor IS, Mallet PE (2004) Chronic cannabinoid exposure produces lasting memory impairment and increased anxiety in adolescent but not adult rats. J Psychopharmacol 18:502–508PubMedCrossRefGoogle Scholar
  137. 137.
    Onaivi ES, Ishiguro H, Gong JP, Patel S, Meozzi PA, Myers L, Perchuk A, Mora Z, Tagliaferro PA, Gardner E, Brusco A, Akinshola BE, Hope B, Lujilde J, Inada T, Iwasaki S, Macharia D, Teasenfitz L, Arinami T, Uhl GR (2008) Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects. PLoS ONE 3:e1640PubMedCrossRefGoogle Scholar
  138. 138.
    Padula CB, Schweinsburg AD, Tapert SF (2007) Spatial working memory performance and fMRI activation interaction in abstinent adolescent marijuana users. Psychol Addict Behav 21:478–487PubMedCrossRefGoogle Scholar
  139. 139.
    Patton GC, Coffey C, Carlin JB, Degenhardt L, Lynskey M, Hall W (2002) Cannabis use and mental health in young people: cohort study. BMJ 325:1195–1198PubMedCrossRefGoogle Scholar
  140. 140.
    Pedersen W (2008) Does cannabis use lead to depression and suicidal behaviours? A population-based longitudinal study. Acta Psychiatr Scand 118:395–403PubMedCrossRefGoogle Scholar
  141. 141.
    Perez-Rosado A, Manzanares J, Fernandez-Ruiz J, Ramos JA (2000) Prenatal Delta(9)-tetrahydrocannabinol exposure modifies proenkephalin gene expression in the fetal rat brain: sex-dependent differences. Dev Brain Res 120:77–81CrossRefGoogle Scholar
  142. 142.
    Perez-Rosado A, Gomez M, Manzanares J, Ramos JA, Fernandez-Ruiz J (2002) Changes in prodynorphin and POMC gene expression in several brain regions of rat fetuses prenatally exposed to Delta(9)-tetrahydrocannabinol. Neurotox Res 4:211–218PubMedCrossRefGoogle Scholar
  143. 143.
    Pertwee RG (2008) The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol 153:199–215PubMedCrossRefGoogle Scholar
  144. 144.
    Pettit DA, Harrison MP, Olson JM, Spencer RF, Cabral GA (1998) Immunohistochemical localization of the neural cannabinoid receptor in rat brain. J Neurosci Res 51:391–402PubMedCrossRefGoogle Scholar
  145. 145.
    Pfeiffer A, Brandt V, Herz A (1986) Psychotomimesis mediated by kappa opiate receptors. Science 233:774–776PubMedCrossRefGoogle Scholar
  146. 146.
    Pope HG Jr, Yurgelun-Todd D (1996) The residual cognitive effects of heavy marijuana use in college students. JAMA 275:521–527PubMedCrossRefGoogle Scholar
  147. 147.
    Pope HG Jr, Gruber AJ, Hudson JI, Huestis MA, Yurgelun-Todd D (2001) Neuropsychological performance in long-term cannabis users. Arch Gen Psychiatry 58:909–915PubMedCrossRefGoogle Scholar
  148. 148.
    Pope HG Jr, Gruber AJ, Yurgelun-Todd D (2001) Residual neuropsychologic effects of cannabis. Curr Psychiatry Rep 3:507–512PubMedCrossRefGoogle Scholar
  149. 149.
    Pope HG Jr, Gruber AJ, Hudson JI, Cohane G, Huestis MA, Yurgelun-Todd D (2003) Early-onset cannabis use and cognitive deficits: what is the nature of the association? Drug Alcohol Depend 69:303–310PubMedCrossRefGoogle Scholar
  150. 150.
    Porath AJ, Fried PA (2005) Effects of prenatal cigarette and marijuana exposure on drug use among offspring. Neurotoxicol Teratol 27:267–277PubMedCrossRefGoogle Scholar
  151. 151.
    Quinn HR, Matsumoto I, Callaghan PD, Long LE, Arnold JC, Gunasekaran N, Thompson MR, Dawson B, Mallet PE, Kashem MA, Matsuda-Matsumoto H, Iwazaki T, McGregor IS (2008) Adolescent rats find repeated Delta(9)-THC less aversive than adult rats but display greater residual cognitive deficits and changes in hippocampal protein expression following exposure. Neuropsychopharmacology 33:1113–1126PubMedCrossRefGoogle Scholar
  152. 152.
    Remington G (2008) Alterations of dopamine and serotonin transmission in schizophrenia. Prog Brain Res 172:117–140PubMedCrossRefGoogle Scholar
  153. 153.
    Richardson GA, Day NL, Goldschmidt L (1995) Prenatal alcohol, marijuana, and tobacco use: infant mental and motor development. Neurotoxicol Teratol 17:479–487PubMedCrossRefGoogle Scholar
  154. 154.
    Richardson GA, Ryan C, Willford J, Day NL, Goldschmidt L (2002) Prenatal alcohol and marijuana exposure. Effects on neuropsychological outcomes at 10 years. Neurotoxicol Teratol 24:309–320PubMedCrossRefGoogle Scholar
  155. 155.
    Riedel G, Platt B, Micheau J (2003) Glutamate receptor function in learning and memory. Behav Brain Res 140:1–47PubMedCrossRefGoogle Scholar
  156. 156.
    Riegel AC, Lupica CR (2004) Independent presynaptic and postsynaptic mechanisms regulate endocannabinoid signaling at multiple synapses in the ventral tegmental area. J Neurosci 24:11070–11078PubMedCrossRefGoogle Scholar
  157. 157.
    Rodriguez de Fonseca F, Cebeira M, Fernandez-Ruiz JJ, Navarro M, Ramos JA (1991) Effects of pre- and perinatal exposure to hashish extracts on the ontogeny of brain dopaminergic neurons. Neuroscience 43:713–723PubMedCrossRefGoogle Scholar
  158. 158.
    Romero J, Garcia-Palomero E, Berrendero F, Garcia-Gil L, Hernandez ML, Ramos JA, Fernandez-Ruiz JJ (1997) Atypical location of cannabinoid receptors in white matter areas during rat brain development. Synapse 26:317–323PubMedCrossRefGoogle Scholar
  159. 159.
    Romero J, Garcia-Palomero E, Castro JG, Garcia-Gil L, Ramos JA, Fernandez-Ruiz JJ (1997) Effects of chronic exposure to delta9-tetrahydrocannabinol on cannabinoid receptor binding and mRNA levels in several rat brain regions. Brain Res Mol Brain Res 46:100–108PubMedCrossRefGoogle Scholar
  160. 160.
    Ross RA (2003) Anandamide and vanilloid TRPV1 receptors. Br J Pharmacol 140:790–801PubMedCrossRefGoogle Scholar
  161. 161.
    Ryberg E, Larsson N, Sjogren S, Hjorth S, Hermansson NO, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ (2007) The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol 152:1092–1101PubMedCrossRefGoogle Scholar
  162. 162.
    Saha S, Chant D, Welham J, McGrath J (2005) A systematic review of the prevalence of schizophrenia. PLoS Med 2:e141PubMedCrossRefGoogle Scholar
  163. 163.
    SAMHSA SAaMHSA (2006) Results from the 2005 National Survey on Drug Use and Health: Detailed Tables. In:SAMHSA Office of Applied Studies, Rockville, MDGoogle Scholar
  164. 164.
    SAMHSA SAaMHSA (2006) Results from the 2005 National Survey on Drug Use and Health: National Findings. In:SAMHSA Office of Applied Studies, Rockville, MDGoogle Scholar
  165. 165.
    Sawzdargo M, Nguyen T, Lee DK, Lynch KR, Cheng R, Heng HH, George SR, O’Dowd BF (1999) Identification and cloning of three novel human G protein-coupled receptor genes GPR52, PsiGPR53 and GPR55: GPR55 is extensively expressed in human brain. Mol Brain Res 64:193–198PubMedCrossRefGoogle Scholar
  166. 166.
    Schweinsburg AD, Nagel BJ, Schweinsburg BC, Park A, Theilmann RJ, Tapert SF (2008) Abstinent adolescent marijuana users show altered fMRI response during spatial working memory. Psychiatry Res 163:40–51PubMedCrossRefGoogle Scholar
  167. 167.
    Seeman P (2006) Targeting the dopamine D2 receptor in schizophrenia. Expert Opin Ther Targets 10:515–531PubMedCrossRefGoogle Scholar
  168. 168.
    Shippenberg TS, Bals-Kubik R, Herz A (1987) Motivational properties of opioids: evidence that an activation of delta-receptors mediates reinforcement processes. Brain Res 436:234–239PubMedCrossRefGoogle Scholar
  169. 169.
    Sipe JC, Chiang K, Gerber AL, Beutler E, Cravatt BF (2002) A missense mutation in human fatty acid amide hydrolase associated with problem drug use. Proc Natl Acad Sci USA 99:8394–8399PubMedCrossRefGoogle Scholar
  170. 170.
    Smith DM, Mizumori SJ (2006) Hippocampal place cells, context, and episodic memory. Hippocampus 16:716–729PubMedCrossRefGoogle Scholar
  171. 171.
    Smith AM, Fried PA, Hogan MJ, Cameron I (2004) Effects of prenatal marijuana on response inhibition: an fMRI study of young adults. Neurotoxicol Teratol 26:533–542PubMedCrossRefGoogle Scholar
  172. 172.
    Smith AM, Fried PA, Hogan MJ, Cameron I (2006) Effects of prenatal marijuana on visuospatial working memory: an fMRI study in young adults. Neurotoxicol Teratol 28:286–295PubMedCrossRefGoogle Scholar
  173. 173.
    Spano MS, Ellgren M, Wang X, Hurd YL (2007) Prenatal cannabis exposure increases heroin seeking with allostatic changes in limbic enkephalin systems in adulthood. Biol Psychiatry 61:554–563PubMedCrossRefGoogle Scholar
  174. 174.
    Starowicz K, Nigam S, Di Marzo V (2007) Biochemistry and pharmacology of endovanilloids. Pharmacol Ther 114:13–33PubMedCrossRefGoogle Scholar
  175. 175.
    Suarez I, Bodega G, Fernandez-Ruiz JJ, Ramos JA, Rubio M, Fernandez B (2002) Reduced glial fibrillary acidic protein and glutamine synthetase expression in astrocytes and Bergmann glial cells in the rat cerebellum caused by delta(9)-tetrahydrocannabinol administration during development. Dev Neurosci 24:300–312PubMedCrossRefGoogle Scholar
  176. 176.
    Suarez I, Bodega G, Fernandez-Ruiz J, Ramos JA, Rubio M, Fernandez B (2004) Down-regulation of the AMPA glutamate receptor subunits GluR1 and GluR2/3 in the rat cerebellum following pre- and perinatal delta9-tetrahydrocannabinol exposure. Cerebellum 3:66–74PubMedCrossRefGoogle Scholar
  177. 177.
    Suarez I, Bodega G, Rubio M, Fernandez-Ruiz JJ, Ramos JA, Fernandez B (2004) Prenatal cannabinoid exposure down- regulates glutamate transporter expressions (GLAST and EAAC1) in the rat cerebellum. Dev Neurosci 26:45–53PubMedCrossRefGoogle Scholar
  178. 178.
    Tapert SF, Schweinsburg AD, Drummond SP, Paulus MP, Brown SA, Yang TT, Frank LR (2007) Functional MRI of inhibitory processing in abstinent adolescent marijuana users. Psychopharmacology (Berl) 194:173–183CrossRefGoogle Scholar
  179. 179.
    Tripathi A, Khurshid N, Kumar P, Iyengar S (2008) Expression of delta- and mu-opioid receptors in the ventricular and subventricular zones of the developing human neocortex. Neurosci Res 61:257–270PubMedCrossRefGoogle Scholar
  180. 180.
    Ujike H, Takaki M, Nakata K, Tanaka Y, Takeda T, Kodama M, Fujiwara Y, Sakai A, Kuroda S (2002) CNR1, central cannabinoid receptor gene, associated with susceptibility to hebephrenic schizophrenia. Mol Psychiatry 7:515–518PubMedCrossRefGoogle Scholar
  181. 181.
    Valverde O, Noble F, Beslot F, Dauge V, Fournie-Zaluski MC, Roques BP (2001) Delta9-tetrahydrocannabinol releases and facilitates the effects of endogenous enkephalins: reduction in morphine withdrawal syndrome without change in rewarding effect. Eur J Neurosci 13:1816–1824PubMedCrossRefGoogle Scholar
  182. 182.
    van der Stelt M, Di Marzo V (2003) The endocannabinoid system in the basal ganglia and in the mesolimbic reward system: implications for neurological and psychiatric disorders. Eur J Pharmacol 480:133–150PubMedCrossRefGoogle Scholar
  183. 183.
    Van Sickle MD, Duncan M, Kingsley PJ, Mouihate A, Urbani P, Mackie K, Stella N, Makriyannis A, Piomelli D, Davison JS, Marnett LJ, Di Marzo V, Pittman QJ, Patel KD, Sharkey KA (2005) Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 310:329–332PubMedCrossRefGoogle Scholar
  184. 184.
    Vataeva LA, Kudrin VS, Vershinina EA, Mosin VM, Tiul’kova EI, Otellin VA (2008) Maternal para-chlorophenylalanine exposure modifies central monoamines and behaviors in the adult offspring. Brain Res 1234:1–7PubMedCrossRefGoogle Scholar
  185. 185.
    Vela G, Martin S, Garcia-Gil L, Crespo JA, Ruiz-Gayo M, Javier Fernandez-Ruiz J, Garcia-Lecumberri C, Pelaprat D, Fuentes JA, Ramos JA, Ambrosio E (1998) Maternal exposure to delta9-tetrahydrocannabinol facilitates morphine self-administration behavior and changes regional binding to central mu opioid receptors in adult offspring female rats. Brain Res 807:101–109PubMedCrossRefGoogle Scholar
  186. 186.
    Verney C, Zecevic N, Nikolic B, Alvarez C, Berger B (1991) Early evidence of catecholaminergic cell groups in 5- and 6-week-old human embryos using tyrosine hydroxylase and dopamine-b-hydroxylase immunocytochemistry. Neurosci Lett 131:121–124PubMedCrossRefGoogle Scholar
  187. 187.
    Vitalis T, Laine J, Simon A, Roland A, Leterrier C, Lenkei Z (2008) The type 1 cannabinoid receptor is highly expressed in embryonic cortical projection neurons and negatively regulates neurite growth in vitro. Eur J Neurosci 28:1705–1718PubMedCrossRefGoogle Scholar
  188. 188.
    Volkow ND, Fowler JS, Wang GJ, Swanson JM (2004) Dopamine in drug abuse and addiction: results from imaging studies and treatment implications. Mol Psychiatry 9:557–569PubMedCrossRefGoogle Scholar
  189. 189.
    Walter L, Franklin A, Witting A, Wade C, Xie Y, Kunos G, Mackie K, Stella N (2003) Nonpsychotropic cannabinoid receptors regulate microglial cell migration. J Neurosci 23:1398–1405PubMedGoogle Scholar
  190. 190.
    Walters DE, Carr LA (1986) Changes in brain catecholamine mechanisms following perinatal exposure to marihuana. Pharmacol Biochem Behav 25:763–768PubMedCrossRefGoogle Scholar
  191. 191.
    Wang X, Dow-Edwards D, Keller E, Hurd YL (2003) Preferential limbic expression of the cannabinoid receptor mRNA in the human fetal brain. Neuroscience 118:681–694PubMedCrossRefGoogle Scholar
  192. 192.
    Wang X, Dow-Edwards D, Anderson V, Minkoff H, Hurd YL (2004) In utero marijuana exposure associated with abnormal amygdala dopamine D2 gene expression in the human fetus. Biol Psychiatry 56:909–915PubMedCrossRefGoogle Scholar
  193. 193.
    Wang X, Dow-Edwards D, Anderson V, Minkoff H, Hurd YL (2006) Discrete opioid gene expression impairment in the human fetal brain associated with maternal marijuana use. Pharmacogenomics J 6:255–264PubMedCrossRefGoogle Scholar
  194. 194.
    Watson S, Chambers D, Hobbs C, Doherty P, Graham A (2008) The endocannabinoid receptor, CB1, is required for normal axonal growth and fasciculation. Mol Cell Neurosci 38:89–97PubMedCrossRefGoogle Scholar
  195. 195.
    Welsh MC, Pennington BF, Groisser DB (1991) A normative-developmental study of executive function: A window on prefrontal function in children. Dev Neuropsychol 7:131–149CrossRefGoogle Scholar
  196. 196.
    Williamson S, Jackson L, Skeoch C, Azzim G, Anderson R (2006) Determination of the prevalence of drug misuse by meconium analysis. Arch Dis Child Fetal Neonatal Ed 91:F291–F292PubMedCrossRefGoogle Scholar
  197. 197.
    Zammit S, Spurlock G, Williams H, Norton N, Williams N, O’Donovan MC, Owen MJ (2007) Genotype effects of CHRNA7, CNR1 and COMT in schizophrenia: interactions with tobacco and cannabis use. Br J Psychiatry 191:402–407PubMedCrossRefGoogle Scholar
  198. 198.
    Zhuang S, Kittler J, Grigorenko EV, Kirby MT, Sim LJ, Hampson RE, Childers SR, Deadwyler SA (1998) Effects of long-term exposure to delta9-THC on expression of cannabinoid receptor (CB1) mRNA in different rat brain regions. Brain Res Mol Brain Res 62:141–149PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Didier Jutras-Aswad
    • 1
    • 2
  • Jennifer A. DiNieri
    • 1
  • Tibor Harkany
    • 3
    • 4
  • Yasmin L. Hurd
    • 1
  1. 1.Departments of Psychiatry, Pharmacology and Systems Therapeutics and NeuroscienceMount Sinai School of MedicineNew YorkUSA
  2. 2.Department of PsychiatryCentre Hospitalier de l’Université de MontréalMontrealCanada
  3. 3.Institute of Medical Sciences, School of Medical SciencesUniversity of AberdeenAberdeenUK
  4. 4.Division of Molecular Neurobiology, Department of Medical Biochemistry and BiophysicsKarolinska InstituteStockholmSweden

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