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Age-Dependent Effects of Cannabinoids on Neurophysiological, Emotional, and Motivational States

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Book cover Cannabinoid Modulation of Emotion, Memory, and Motivation

Abstract

Cannabis sativa preparations are among the illicit drugs most commonly used by young people, including pregnant women. The endocannabinoid (eCB) system, which is involved in the regulation of emotional and motivational homeostasis, synaptic plasticity and cognitive functions, also plays a critical role in diverse phases of brain development. Both perinatal and periadolescent periods are critical for brain eCB system development. Thus, interference of endocannabinoid signalling by cannabis exposure may contribute to explain the enduring negative impact of cannabis on neurodevelopmental processes and the resulting psycho-physio-pathological consequences. In the present chapter we describe and discuss published data dealing with the long-term neurobehavioural effects of cannabis exposure during the prenatal and adolescent periods. Human studies have demonstrated that marijuana consumption by pregnant women critically affects the neurobehavioural development of their children. Investigations using animal models provide useful information for a better understanding of the long-lasting deleterious consequences of cannabis exposure during pregnancy and lactation. Increasing use of cannabis among adolescents is a matter of great public concern that has led to a parallel increase in research on appropriate animal models. Chronic administration of cannabinoid agonists during the periadolescent period causes persistent behavioural alterations related to cognitive deficits, increased risk of psychosis, mood disorders and addiction to cannabis and other drugs of abuse. The underlying mechanisms by which cannabis use may lead to these disorders, including genetic vulnerability and the increasing content of the main psychoactive ingredient in cannabis preparations, delta-9-tetrahydrocannabinol (THC), will be discussed. To conclude, prevention and therapeutic strategies based on scientific knowledge will be proposed.

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References

  1. Marco EM, Romero-Zerbo SY, Viveros MP, Bermudez-Silva FJ. The role of the endocannabinoid system in eating disorders: pharmacological implications. Behav Pharmacol. 2012;23(5–6):526–36.

    Article  CAS  PubMed  Google Scholar 

  2. Bermudez-Silva FJ, Viveros MP, McPartland JM, Rodriguez de Fonseca F. The endocannabinoid system, eating behavior and energy homeostasis: the end or a new beginning? Pharmacol Biochem Behav. 2010;95(4):375–82.

    Article  CAS  PubMed  Google Scholar 

  3. Marco EM, Viveros MP. The critical role of the endocannabinoid system in emotional homeostasis: avoiding excess and deficiencies. Mini Rev Med Chem. 2009;9(12):1407–15.

    Article  CAS  PubMed  Google Scholar 

  4. Castillo PE, Younts TJ, Chavez AE, Hashimotodani Y. Endocannabinoid signaling and synaptic function. Neuron. 2012;76(1):70–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Katona I, Freund TF. Multiple functions of endocannabinoid signaling in the brain. Annu Rev Neurosci. 2012;35:529–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Oleson EB, Cheer JF. A brain on cannabinoids: the role of dopamine release in reward seeking. Cold Spring Harb Perspect Med. 2012;2(8).

    Google Scholar 

  7. Gardner EL. Addiction and brain reward and antireward pathways. Adv Psychosom Med. 2011;30:22–60.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Harkany T, Guzman M, Galve-Roperh I, Berghuis P, Devi LA, Mackie K. The emerging functions of endocannabinoid signaling during CNS development. Trends Pharmacol Sci. 2007;28(2):83–92.

    Article  CAS  PubMed  Google Scholar 

  9. Galve-Roperh I, Palazuelos J, Aguado T, Guzman M. The endocannabinoid system and the regulation of neural development: potential implications in psychiatric disorders. Eur Arch Psychiatry Clin Neurosci. 2009;259(7):371–82.

    Article  PubMed  Google Scholar 

  10. Keimpema E, Alpar A, Howell F, Malenczyk K, Hobbs C, Hurd YL, et al. Diacylglycerol lipase alpha manipulation reveals developmental roles for intercellular endocannabinoid signaling. Sci Rep. 2013;3:2093.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Keimpema E, Mackie K, Harkany T. Molecular model of cannabis sensitivity in developing neuronal circuits. Trends Pharmacol Sci. 2011;32(9):551–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wu CS, Jew CP, Lu HC. Lasting impacts of prenatal cannabis exposure and the role of endogenous cannabinoids in the developing brain. Future Neurol. 2011;6(4):459–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Burns JK. Pathways from cannabis to psychosis: a review of the Evidence. Front Psychiatry. 2013;4:128.

    PubMed  PubMed Central  Google Scholar 

  14. Fernandez-Espejo E, Viveros MP, Nunez L, Ellenbroek BA, Rodriguez de Fonseca F. Role of cannabis and endocannabinoids in the genesis of schizophrenia. Psychopharmacology (Berl). 2009;206(4):531–49.

    Article  CAS  Google Scholar 

  15. Marco EM, Garcia-Gutierrez MS, Bermudez-Silva FJ, Moreira FA, Guimaraes F, Manzanares J, et al. Endocannabinoid system and psychiatry: in search of a neurobiological basis for detrimental and potential therapeutic effects. Front Behav Neurosci. 2011;5:63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Huizink AC. Prenatal cannabis exposure and infant outcomes: overview of studies. Prog Neuropsychopharmacol Biol Psychiatry. 2013.

    Google Scholar 

  17. Hurd YL, Michaelides M, Miller ML, Jutras-Aswad D. Trajectory of adolescent cannabis use on addiction vulnerability. Neuropharmacology 2014;76 Pt B:416–24.

    Google Scholar 

  18. Viveros MP, Llorente R, Suarez J, Llorente-Berzal A, Lopez-Gallardo M, de Fonseca FR. The endocannabinoid system in critical neurodevelopmental periods: sex differences and neuropsychiatric implications. J Psychopharmacol. 2012;26(1):164–76.

    Article  CAS  PubMed  Google Scholar 

  19. Viveros MP, Marco EM, Lopez-Gallardo M, Garcia-Segura LM, Wagner EJ. Framework for sex differences in adolescent neurobiology: a focus on cannabinoids. Neurosci Biobehav Rev. 2011;35(8):1740–51.

    Article  PubMed  Google Scholar 

  20. Crippa JA, Zuardi AW, Martin-Santos R, Bhattacharyya S, Atakan Z, McGuire P, et al. Cannabis and anxiety: a critical review of the evidence. Hum Psychopharmacol. 2009;24(7):515–23.

    Article  CAS  PubMed  Google Scholar 

  21. Budney AJ, Hughes JR. The cannabis withdrawal syndrome. Curr Opin Psychiatry. 2006;19(3):233–8.

    Article  PubMed  Google Scholar 

  22. Fattore L, Fadda P, Spano MS, Pistis M, Fratta W. Neurobiological mechanisms of cannabinoid addiction. Mol Cell Endocrinol. 2008;286(1–2 Suppl 1):S97–S107.

    Article  CAS  PubMed  Google Scholar 

  23. Hasin DS, O’Brien CP, Auriacombe M, Borges G, Bucholz K, Budney A, et al. DSM-5 criteria for substance use disorders: recommendations and rationale. Am J Psychiatry. 2013;170(8):834–51.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Hesse M, Thylstrup B. Time-course of the DSM-5 cannabis withdrawal symptoms in poly-substance abusers. BMC Psychiatry. 2013;13:258.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Gorelick DA, Levin KH, Copersino ML, Heishman SJ, Liu F, Boggs DL, et al. Diagnostic criteria for cannabis withdrawal syndrome. Drug Alcohol Depend. 2012;123(1–3):141–7.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Solowij N, Pesa N. Cannabis and cognition: short and long-term effects. In: Castle D, Murray R, D’Souza DC, editors. Marijuana and madness. 2nd ed. Cambridge: Cambridge University Press; 2012. p. 91–102.

    Google Scholar 

  27. Meier MH, Caspi A, Ambler A, Harrington H, Houts R, Keefe RS, et al. Persistent cannabis users show neuropsychological decline from childhood to midlife. Proc Natl Acad Sci U S A. 2012;109(40):E2657–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Casadio P, Fernandes C, Murray RM, Di Forti M. Cannabis use in young people: the risk for schizophrenia. Neurosci Biobehav Rev. 2011;35(8):1779–87.

    Article  PubMed  Google Scholar 

  29. Hurd YL, Michaelides M, Miller ML, Jutras-Aswad D. Trajectory of adolescent cannabis use on addiction vulnerability. Neuropharmacology. 2014;76PB:416–24.

    Article  CAS  Google Scholar 

  30. Copeland J, Rooke S, Swift W. Changes in cannabis use among young people: impact on mental health. Curr Opin Psychiatry. 2013;26(4):325–9.

    Article  PubMed  Google Scholar 

  31. Trezza V, Campolongo P, Manduca A, Morena M, Palmery M, Vanderschuren LJ, et al. Altering endocannabinoid neurotransmission at critical developmental ages: impact on rodent emotionality and cognitive performance. Front Behav Neurosci. 2012;6:2.

    Article  PubMed  Google Scholar 

  32. Passey ME, Sanson-Fisher RW, D’Este CA, Stirling JM. Tobacco, alcohol and cannabis use during pregnancy: Clustering of risks. Drug Alcohol Depend. 2013.

    Google Scholar 

  33. Hutchings DE, Martin BR, Gamagaris Z, Miller N, Fico T. Plasma concentrations of delta-9-tetrahydrocannabinol in dams and fetuses following acute or multiple prenatal dosing in rats. Life Sci. 1989;44(11):697–701.

    Article  CAS  PubMed  Google Scholar 

  34. Gomez M, Hernandez M, Johansson B, de Miguel R, Ramos JA, Fernandez-Ruiz J. Prenatal cannabinoid and gene expression for neural adhesion molecule L1 in the fetal rat brain. Brain Res Dev Brain Res. 2003;147(1–2):201–7.

    Article  CAS  PubMed  Google Scholar 

  35. Perez-Reyes M, Wall ME. Presence of delta9-tetrahydrocannabinol in human milk. N Engl J Med. 1982;307(13):819–20.

    Article  CAS  PubMed  Google Scholar 

  36. DiNieri JA, Hurd YL. Rat Models of prenatal and adolescent cannabis exposure. In: Kobeissy FH, editor. Psychiatric disorders: methods and protocols: Springer protocols. USA: Humana Press; 2012. p. 231–42.

    Google Scholar 

  37. Viveros MP, Llorente R, Moreno E, Marco EM. Behavioural and neuroendocrine effects of cannabinoids in critical developmental periods. Behav Pharmacol. 2005 Sep;16(5–6):353–62.

    Article  CAS  PubMed  Google Scholar 

  38. Schneider M. Cannabis use in pregnancy and early life and its consequences: animal models. Eur Arch Psychiatry Clin Neurosci. 2009;259(7):383–93.

    Article  PubMed  Google Scholar 

  39. Rubino T, Parolaro D. Cannabis abuse in adolescence and the risk of psychosis: a brief review of the preclinical evidence. Prog Neuropsychopharmacol Biol Psychiatry. 2014;52:41–4.

    Article  CAS  PubMed  Google Scholar 

  40. Lisdahl KM, Gilbart ER, Wright NE, Shollenbarger S. Dare to delay? The impacts of adolescent alcohol and marijuana use onset on cognition, brain structure, and function. Front Psychiatry. 2013;4:53.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Adriani W, Laviola G. Windows of vulnerability to psychopathology and therapeutic strategy in the adolescent rodent model. Behav Pharmacol. 2004;15(5–6):341–52.

    Article  CAS  PubMed  Google Scholar 

  42. Schneider M. Adolescence as a vulnerable period to alter rodent behavior. Cell Tissue Res. 2013;354(1):99–106.

    Article  CAS  PubMed  Google Scholar 

  43. Viveros MP, Marco EM, File SE. Endocannabinoid system and stress and anxiety responses. Pharmacol Biochem Behav. 2005;81(2):331–42.

    Article  CAS  PubMed  Google Scholar 

  44. Gaffuri AL, Ladarre D, Lenkei Z. Type-1 cannabinoid receptor signaling in neuronal development. Pharmacology 2012;90(1–2):19–39.

    Article  CAS  PubMed  Google Scholar 

  45. Belue RC, Howlett AC, Westlake TM, Hutchings DE. The ontogeny of cannabinoid receptors in the brain of postnatal and aging rats. Neurotoxicol Teratol. 1995;17(1):25–30.

    Article  CAS  PubMed  Google Scholar 

  46. Rodriguez de Fonseca F Ramos JA Bonnin A Fernandez-Ruiz JJ. Presence of cannabinoid binding sites in the brain from early postnatal ages. Neuroreport. 1993;4(2):135–8.

    Article  CAS  PubMed  Google Scholar 

  47. Mato S, Del Olmo E, Pazos A. Ontogenetic development of cannabinoid receptor expression and signal transduction functionality in the human brain. Eur J Neurosci. 2003;17(9):1747–54.

    Article  PubMed  Google Scholar 

  48. Berrendero F, Garcia-Gil L, Hernandez ML, Romero J, Cebeira M, de Miguel R, et al. Localization of mRNA expression and activation of signal transduction mechanisms for cannabinoid receptor in rat brain during fetal development. Development. 1998;125(16):3179–88.

    CAS  PubMed  Google Scholar 

  49. Reisenberg M, Singh PK, Williams G, Doherty P. The diacylglycerol lipases: structure, regulation and roles in and beyond endocannabinoid signalling. Philos Trans R Soc Lond B Biol Sci. 2012;367(1607):3264–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Mulder J, Aguado T, Keimpema E, Barabas K, Ballester Rosado CJ, Nguyen L, et al. Endocannabinoid signaling controls pyramidal cell specification and long-range axon patterning. Proc Natl Acad Sci U S A. 2008;105(25):8760–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Berghuis P, Dobszay MB, Wang X, Spano S, Ledda F, Sousa KM, et al. Endocannabinoids regulate interneuron migration and morphogenesis by transactivating the TrkB receptor. Proc Natl Acad Sci U S A. 2005;102(52):19115–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Wenger T, Gerendai I, Fezza F, Gonzalez S, Bisogno T, Fernandez-Ruiz J, et al. The hypothalamic levels of the endocannabinoid, anandamide, peak immediately before the onset of puberty in female rats. Life Sci. 2002;70(12):1407–14.

    Article  CAS  PubMed  Google Scholar 

  53. Ellgren M, Artmann A, Tkalych O, Gupta A, Hansen HS, Hansen SH, et al. Dynamic changes of the endogenous cannabinoid and opioid mesocorticolimbic systems during adolescence: THC effects. Eur Neuropsychopharmacol. 2008;18(11):826–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lee TT, Hill MN, Hillard CJ, Gorzalka BB. Temporal changes in N-acylethanolamine content and metabolism throughout the peri-adolescent period. Synapse. 2013;67(1):4–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Marco EM, Adriani W, Canese R, Podo F, Viveros MP, Laviola G. Enhancement of endocannabinoid signalling during adolescence: Modulation of impulsivity and long-term consequences on metabolic brain parameters in early maternally deprived rats. Pharmacol Biochem Behav. 2007;86(2):334–45.

    Article  CAS  PubMed  Google Scholar 

  56. Reich CG, Taylor ME, McCarthy MM. Differential effects of chronic unpredictable stress on hippocampal CB1 receptors in male and female rats. Behav Brain Res. 2009;203(2):264–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Mateos B, Borcel E, Loriga R, Luesu W, Bini V, Llorente R, et al. Adolescent exposure to nicotine and/or the cannabinoid agonist CP 55,940 induces gender-dependent long-lasting memory impairments and changes in brain nicotinic and CB(1) cannabinoid receptors. J Psychopharmacol. 2011;25(12):1676–90.

    Article  CAS  PubMed  Google Scholar 

  58. Suarez J, Llorente R, Romero-Zerbo SY, Mateos B, Bermudez-Silva FJ, de Fonseca FR, et al. Early maternal deprivation induces gender-dependent changes on the expression of hippocampal CB(1) and CB(2) cannabinoid receptors of neonatal rats. Hippocampus. 2009;19(7):623–32.

    Article  CAS  PubMed  Google Scholar 

  59. Duff G, Argaw A, Cecyre B, Cherif H, Tea N, Zabouri N, et al. Cannabinoid receptor CB2 modulates axon guidance. PLoS ONE. 2013;8(8):e70849.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Palazuelos J, Ortega Z, Diaz-Alonso J, Guzman M, Galve-Roperh I. CB2 cannabinoid receptors promote neural progenitor cell proliferation via mTORC1 signaling. J Biol Chem. 2012;287(2):1198–209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Fried PA, Watkinson B. Differential effects on facets of attention in adolescents prenatally exposed to cigarettes and marihuana. Neurotoxicol Teratol. 2001;23(5):421–30.

    Article  CAS  PubMed  Google Scholar 

  62. Fried PA, Watkinson B, Gray R. A follow-up study of attentional behavior in 6-year-old children exposed prenatally to marihuana, cigarettes, and alcohol. Neurotoxicol Teratol. 1992;14(5):299–311.

    Article  CAS  PubMed  Google Scholar 

  63. Fried PA, Watkinson B, Gray R. Differential effects on cognitive functioning in 9–12-year olds prenatally exposed to cigarettes and marihuana. Neurotoxicol Teratol. 1998;20(3):293–306.

    Article  CAS  PubMed  Google Scholar 

  64. Fried PA, Watkinson B, Gray R. Differential effects on cognitive functioning in 13–16-year-olds prenatally exposed to cigarettes and marihuana. Neurotoxicol Teratol. 2003;25(4):427–36.

    Article  CAS  PubMed  Google Scholar 

  65. Smith AM, Fried PA, Hogan MJ, Cameron I. Effects of prenatal marijuana on visuospatial working memory: an fMRI study in young adults. Neurotoxicol Teratol. 2006;28(2):286–95.

    Article  CAS  PubMed  Google Scholar 

  66. Mereu G, Fa M, Ferraro L, Cagiano R, Antonelli T, Tattoli M, et al. Prenatal exposure to a cannabinoid agonist produces memory deficits linked to dysfunction in hippocampal long-term potentiation and glutamate release. Proc Natl Acad Sci U S A. 2003;100(8):4915–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Antonelli T, Tomasini MC, Tattoli M, Cassano T, Tanganelli S, Finetti S, et al. 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. 2005;15(12):2013–20.

    Article  PubMed  Google Scholar 

  68. Campolongo P, Trezza V, Cassano T, Gaetani S, Morgese MG, Ubaldi M, et al. Perinatal exposure to delta-9-tetrahydrocannabinol causes enduring cognitive deficits associated with alteration of cortical gene expression and neurotransmission in rats. Addict Biol. 2007;12(3–4):485–95.

    Article  CAS  PubMed  Google Scholar 

  69. O’Shea M, Mallet PE. Impaired learning in adulthood following neonatal delta9-THC exposure. Behav Pharmacol. 2005;16(5–6):455–61.

    Article  PubMed  Google Scholar 

  70. O’Shea M, McGregor IS, Mallet PE. Repeated cannabinoid exposure during perinatal, adolescent or early adult ages produces similar longlasting deficits in object recognition and reduced social interaction in rats. J Psychopharmacol. 2006;20(5):611–21.

    Article  PubMed  Google Scholar 

  71. Rubio P, Rodriguez de Fonseca F, Munoz RM, Ariznavarreta C, Martin-Calderon JL, Navarro M. Long-term behavioral effects of perinatal exposure to delta9-tetrahydrocannabinol in rats: possible role of pituitary-adrenal axis. Life Sci. 1995;56(23–24):2169–76.

    Article  CAS  PubMed  Google Scholar 

  72. Moreno M, Trigo JM, Escuredo L, Rodriguez de Fonseca F, Navarro M. Perinatal exposure to delta9-tetrahydrocannabinol increases presynaptic dopamine D2 receptor sensitivity: a behavioral study in rats. Pharmacol Biochem Behav. 2003;75(3):565–75.

    Article  CAS  PubMed  Google Scholar 

  73. Navarro M, de Miguel R, Rodriguez de Fonseca F, Ramos JA, Fernandez-Ruiz JJ. Perinatal cannabinoid exposure modifies the sociosexual approach behavior and the mesolimbic dopaminergic activity of adult male rats. Behav Brain Res. 1996;75(1–2):91–8.

    Article  CAS  PubMed  Google Scholar 

  74. Newsom RJ, Kelly SJ. Perinatal delta-9-tetrahydrocannabinol exposure disrupts social and open field behavior in adult male rats. Neurotoxicol Teratol. 2008;30(3):213–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Llorente R, Arranz L, Marco EM, Moreno E, Puerto M, Guaza C, et al. Early maternal deprivation and neonatal single administration with a cannabinoid agonist induce long-term sex-dependent psychoimmunoendocrine effects in adolescent rats. Psychoneuroendocrinology. 2007;32(6):636–50.

    Article  CAS  PubMed  Google Scholar 

  76. Schneider M, Drews E, Koch M. Behavioral effects in adult rats of chronic prepubertal treatment with the cannabinoid receptor agonist WIN 55,212–2. Behav Pharmacol. 2005;16(5–6):447–54.

    Article  CAS  PubMed  Google Scholar 

  77. Trezza V, Campolongo P, Cassano T, Macheda T, Dipasquale P, Carratu MR, et al. Effects of perinatal exposure to delta-9-tetrahydrocannabinol on the emotional reactivity of the offspring: a longitudinal behavioral study in Wistar rats. Psychopharmacology (Berl). 2008;198(4):529–37.

    Article  CAS  Google Scholar 

  78. Vela G, Martin S, Garcia-Gil L, Crespo JA, Ruiz-Gayo M, Fernandez-Ruiz JJ, et al. 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. 1998;807(1–2):101–9.

    Article  CAS  PubMed  Google Scholar 

  79. Gonzalez B, de Miguel R, Martin S, Perez-Rosado A, Romero J, Garcia-Lecumberri C, et al. Effects of perinatal exposure to delta9-tetrahydrocannabinol on operant morphine-reinforced behavior. Pharmacol Biochem Behav. 2003;75(3):577–84.

    Article  CAS  PubMed  Google Scholar 

  80. Economidou D, Mattioli L, Ubaldi M, Lourdusamy A, Soverchia L, Hardiman G, et al. Role of cannabinoidergic mechanisms in ethanol self-administration and ethanol seeking in rat adult offspring following perinatal exposure to Delta9-tetrahydrocannabinol. Toxicol Appl Pharmacol. 2007;223(1):73–85.

    Article  CAS  PubMed  Google Scholar 

  81. Fernandez-Ruiz JJ, Berrendero F, Hernandez ML, Romero J, Ramos JA. Role of endocannabinoids in brain development. Life Sci 1999;65(6–7):725–36.

    Article  CAS  PubMed  Google Scholar 

  82. Vela G, Fuentes JA, Bonnin A, Fernandez-Ruiz J, Ruiz-Gayo M. Perinatal exposure to delta9-tetrahydrocannabinol (delta9-THC) leads to changes in opioid-related behavioral patterns in rats. Brain Res. 1995;680(1–2):142–7.

    Article  CAS  PubMed  Google Scholar 

  83. Corchero J, Garcia-Gil L, Manzanares J, Fernandez-Ruiz JJ, Fuentes JA, Ramos JA. Perinatal delta9-tetrahydrocannabinol exposure reduces proenkephalin gene expression in the caudate-putamen of adult female rats. Life Sci. 1998;63(10):843–50.

    Article  CAS  PubMed  Google Scholar 

  84. Suarez I, Bodega G, Fernandez-Ruiz J, Ramos JA, Rubio M, Fernandez B. Down-regulation of the AMPA glutamate receptor subunits GluR1 and GluR2/3 in the rat cerebellum following pre- and perinatal delta9-tetrahydrocannabinol exposure. Cerebellum. 2004;3(2):66–74.

    Article  CAS  PubMed  Google Scholar 

  85. Ferraro L, Tomasini MC, Beggiato S, Gaetani S, Cassano T, Cuomo V, et al. Short- and long-term consequences of prenatal exposure to the cannabinoid agonist WIN55,212–2 on rat glutamate transmission and cognitive functions. J Neural Transm. 2009;116(8):1017–27.

    Article  CAS  PubMed  Google Scholar 

  86. Suarez I, Bodega G, Fernandez-Ruiz JJ, Ramos JA, Rubio M, Fernandez B. 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. 2002;24(4):300–12.

    Article  CAS  PubMed  Google Scholar 

  87. Stella N. Cannabinoid signaling in glial cells. Glia. 2004;48(4):267–77.

    Article  PubMed  Google Scholar 

  88. Blakemore SJ. Teenage kicks: cannabis and the adolescent brain. Lancet. 2013;381(9870):888–9.

    Article  PubMed  Google Scholar 

  89. SAMHSA. Results from the 2008 National Survey on Drug Use and Health National Findings: U.S. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration, Office of Applied Studies, North Carolina. 2008.

    Google Scholar 

  90. Pope HG, Jr., Gruber AJ, Hudson JI, Cohane G, Huestis MA, Yurgelun-Todd D. Early-onset cannabis use and cognitive deficits: what is the nature of the association? Drug Alcohol Depend. 2003;69(3):303–10.

    Article  PubMed  Google Scholar 

  91. Zammit S, Allebeck P, Andreasson S, Lundberg I, Lewis G. Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study. BMJ. 2002;325(7374):1199.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Di Forti M, Morgan C, Dazzan P, Pariante C, Mondelli V, Marques TR, et al. High-potency cannabis and the risk of psychosis. Br J Psychiatry. 2009;195(6):488–91.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Schneider M, Schomig E, Leweke FM. Acute and chronic cannabinoid treatment differentially affects recognition memory and social behavior in pubertal and adult rats. Addict Biol. 2008;13(3–4):345–57.

    Article  CAS  PubMed  Google Scholar 

  94. Schneider M, Koch M. Chronic pubertal, but not adult chronic cannabinoid treatment impairs sensorimotor gating, recognition memory, and the performance in a progressive ratio task in adult rats. Neuropsychopharmacology. 2003;28(10):1760–9.

    Article  CAS  PubMed  Google Scholar 

  95. O’Shea M, Singh ME, McGregor IS, Mallet PE. Chronic cannabinoid exposure produces lasting memory impairment and increased anxiety in adolescent but not adult rats. J Psychopharmacol. 2004;18(4):502–8.

    Article  PubMed  Google Scholar 

  96. Quinn HR, Matsumoto I, Callaghan PD, Long LE, Arnold JC, Gunasekaran N, et al. 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. 2008;33(5):1113–26.

    Article  PubMed  Google Scholar 

  97. Harte LC, Dow-Edwards D. Sexually dimorphic alterations in locomotion and reversal learning after adolescent tetrahydrocannabinol exposure in the rat. Neurotoxicol Teratol. 2010;32(5):515–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Viveros MP, Mendrek A, Paus T, Lopez-Rodriguez AB, Marco EM, Yehuda R, et al. A comparative, developmental, and clinical perspective of neurobehavioral sexual dimorphisms. Front Neurosci. 2012;6:84.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Chadwick B, Miller ML, Hurd YL. Cannabis Use during Adolescent Development: Susceptibility to Psychiatric Illness. Front Psychiatry. 2013;4:129.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Biscaia M, Marin S, Fernandez B, Marco EM, Rubio M, Guaza C, et al. Chronic treatment with CP 55,940 during the peri-adolescent period differentially affects the behavioural responses of male and female rats in adulthood. Psychopharmacology (Berl). 2003;170(3):301–8.

    Article  CAS  Google Scholar 

  101. Rubino T, Vigano D, Realini N, Guidali C, Braida D, Capurro V, et al. Chronic delta9-tetrahydrocannabinol during adolescence provokes sex-dependent changes in the emotional profile in adult rats: behavioral and biochemical correlates. Neuropsychopharmacology. 2008;33(11):2760–71.

    Article  CAS  PubMed  Google Scholar 

  102. Patton GC, Coffey C, Carlin JB, Degenhardt L, Lynskey M, Hall W. Cannabis use and mental health in young people: cohort study. BMJ. 2002;325(7374):1195–8.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Lynskey MT, Heath AC, Bucholz KK, Slutske WS, Madden PA, Nelson EC, et al. Escalation of drug use in early-onset cannabis users vs co-twin controls. JAMA. 2003 22–29;289(4):427–33.

    Article  PubMed  Google Scholar 

  104. Agrawal A, Neale MC, Prescott CA, Kendler KS. Cannabis and other illicit drugs: comorbid use and abuse/dependence in males and females. Behav Genet. 2004;34(3):217–28.

    Article  PubMed  Google Scholar 

  105. Fergusson DM, Boden JM, Horwood LJ. Cannabis use and other illicit drug use: testing the cannabis gateway hypothesis. Addiction. 2006;101(4):556–69.

    Article  PubMed  Google Scholar 

  106. Ellgren M, Spano SM, Hurd YL. Adolescent cannabis exposure alters opiate intake and opioid limbic neuronal populations in adult rats. Neuropsychopharmacology. 2007;32(3):607–15.

    Article  CAS  PubMed  Google Scholar 

  107. Biscaia M, Fernandez B, Higuera-Matas A, Miguens M, Viveros MP, Garcia-Lecumberri C, et al. Sex-dependent effects of periadolescent exposure to the cannabinoid agonist CP-55,940 on morphine self-administration behaviour and the endogenous opioid system. Neuropharmacology. 2008;54(5):863–73.

    Article  CAS  PubMed  Google Scholar 

  108. Spano MS, Ellgren M, Wang X, Hurd YL. Prenatal cannabis exposure increases heroin seeking with allostatic changes in limbic enkephalin systems in adulthood. Biol Psychiatry. 2007;61(4):554–63.

    Article  CAS  PubMed  Google Scholar 

  109. Higuera-Matas A, Soto-Montenegro ML, del Olmo N, Miguens M, Torres I, Vaquero JJ, et al. 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. 2008;33(4):806–13.

    Article  CAS  PubMed  Google Scholar 

  110. Tomasiewicz HC, Jacobs MM, Wilkinson MB, Wilson SP, Nestler EJ, Hurd YL. Proenkephalin mediates the enduring effects of adolescent cannabis exposure associated with adult opiate vulnerability. Biol Psychiatry. 2012;72(10):803–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Pistis M, Perra S, Pillolla G, Melis M, Muntoni AL, Gessa GL. Adolescent exposure to cannabinoids induces long-lasting changes in the response to drugs of abuse of rat midbrain dopamine neurons. Biol Psychiatry 2004.;56(2):86–94.

    Article  CAS  PubMed  Google Scholar 

  112. Hajos M, Hoffmann WE, Kocsis B. Activation of cannabinoid-1 receptors disrupts sensory gating and neuronal oscillation: relevance to schizophrenia. Biol Psychiatry. 2008;63(11):1075–83.

    Article  CAS  PubMed  Google Scholar 

  113. Raver SM, Haughwout SP, Keller A. Adolescent cannabinoid exposure permanently suppresses cortical oscillations in adult mice. Neuropsychopharmacology. 2013;38(12):2338–47.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Gleason KA, Birnbaum SG, Shukla A, Ghose S. Susceptibility of the adolescent brain to cannabinoids: long-term hippocampal effects and relevance to schizophrenia. Transl Psychiatry. 2012;2:e199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Page ME, Oropeza VC, Sparks SE, Qian Y, Menko AS, Van Bockstaele EJ. Repeated cannabinoid administration increases indices of noradrenergic activity in rats. Pharmacol Biochem Behav. 2007;86(1):162–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Bambico FR, Nguyen NT, Katz N, Gobbi G. Chronic exposure to cannabinoids during adolescence but not during adulthood impairs emotional behaviour and monoaminergic neurotransmission. Neurobiol Dis. 2010;37(3):641–55.

    Article  CAS  PubMed  Google Scholar 

  117. Tagliaferro P, Javier Ramos A, Onaivi ES, Evrard SG, Lujilde J, Brusco A. Neuronal cytoskeleton and synaptic densities are altered after a chronic treatment with the cannabinoid receptor agonist WIN 55,212–2. Brain Res. 2006;1085(1):163–76.

    Article  CAS  PubMed  Google Scholar 

  118. Rubino T, Realini N, Braida D, Guidi S, Capurro V, Vigano D, et al. Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are associated with cognitive impairment in adulthood. Hippocampus. 2009;19(8):763–72.

    Article  CAS  PubMed  Google Scholar 

  119. Lopez-Gallardo M, Lopez-Rodriguez AB, Llorente-Berzal A, Rotllant D, Mackie K, Armario A, et al. Maternal deprivation and adolescent cannabinoid exposure impact hippocampal astrocytes, CB1 receptors and brain-derived neurotrophic factor in a sexually dimorphic fashion. Neuroscience. 2012;204:90–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Realini N, Vigano D, Guidali C, Zamberletti E, Rubino T, Parolaro D. Chronic URB597 treatment at adulthood reverted most depressive-like symptoms induced by adolescent exposure to THC in female rats. Neuropharmacology. 2011;60(2–3):235–43.

    Article  CAS  PubMed  Google Scholar 

  121. Rubino T, Realini N, Braida D, Alberio T, Capurro V, Vigano D, et al. The depressive phenotype induced in adult female rats by adolescent exposure to THC is associated with cognitive impairment and altered neuroplasticity in the prefrontal cortex. Neurotox Res. 2009;15(4):291–302.

    Article  CAS  PubMed  Google Scholar 

  122. Yucel M, Solowij N, Respondek C, Whittle S, Fornito A, Pantelis C, et al. Regional brain abnormalities associated with long-term heavy cannabis use. Arch Gen Psychiatry. 2008;65(6):694–701.

    Article  PubMed  Google Scholar 

  123. Mata I, Perez-Iglesias R, Roiz-Santianez R, Tordesillas-Gutierrez D, Pazos A, Gutierrez A, et al. Gyrification brain abnormalities associated with adolescence and early-adulthood cannabis use. Brain Res. 2010;1317:297–304.

    Article  CAS  PubMed  Google Scholar 

  124. Arnone D, Barrick TR, Chengappa S, Mackay CE, Clark CA, Abou-Saleh MT. Corpus callosum damage in heavy marijuana use: preliminary evidence from diffusion tensor tractography and tract-based spatial statistics. Neuroimage. 2008;41(3):1067–74.

    Article  CAS  PubMed  Google Scholar 

  125. Zalesky A, Solowij N, Yucel M, Lubman DI, Takagi M, Harding IH, et al. Effect of long-term cannabis use on axonal fibre connectivity. Brain. 2012;135(Pt 7):2245–55.

    Article  PubMed  Google Scholar 

  126. Gruber SA, Silveri MM, Dahlgren MK, Yurgelun-Todd D. Why so impulsive? White matter alterations are associated with impulsivity in chronic marijuana smokers. Exp Clin Psychopharmacol. 2011;19(3):231–42.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Lorenzetti V, Solowij N, Fornito A, Lubman DI, Yucel M. The Association between Regular Cannabis Exposure and Alterations of Human Brain Morphology: An Updated Review of the Literature. Curr Pharm Des. 2014;20(13):2138–67.

    Article  CAS  PubMed  Google Scholar 

  128. Mehmedic Z, Chandra S, Slade D, Denham H, Foster S, Patel AS, et al. Potency trends of Delta9-THC and other cannabinoids in confiscated cannabis preparations from 1993 to 2008. J Forensic Sci. 2010;55(5):1209–17.

    Article  CAS  PubMed  Google Scholar 

  129. Seely KA, Lapoint J, Moran JH, Fattore L. Spice drugs are more than harmless herbal blends: a review of the pharmacology and toxicology of synthetic cannabinoids. Prog Neuropsychopharmacol Biol Psychiatry. 2012;39(2):234–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. EMCDDA. Thematic paper- Understanding the ‘Spice’ phenomenon. Luxembourg: Office for Official Publications of the European Communities 2009 Contract No.: ISBN 978–92-9168–411–3, doi:10.2810/27063.

    Google Scholar 

  131. Thomas A, Baillie GL, Phillips AM, Razdan RK, Ross RA, Pertwee RG. Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Br J Pharmacol. 2007;150(5):613–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Bhattacharyya S, Morrison PD, Fusar-Poli P, Martin-Santos R, Borgwardt S, Winton-Brown T, et al. Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology. 2010;35(3):764–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Caspi A, Moffitt TE, Cannon M, McClay J, Murray R, Harrington H, et al. 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. 2005;57(10):1117–27.

    Article  CAS  PubMed  Google Scholar 

  134. Henquet C, Rosa A, Krabbendam L, Papiol S, Fananas L, Drukker M, et al. An experimental study of catechol-o-methyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology. 2006;31(12):2748–57.

    Article  CAS  PubMed  Google Scholar 

  135. Zammit S, Spurlock G, Williams H, Norton N, Williams N, O’Donovan MC, et al. Genotype effects of CHRNA7, CNR1 and COMT in schizophrenia: interactions with tobacco and cannabis use. Br J Psychiatry. 2007;191:402–7.

    Article  PubMed  Google Scholar 

  136. van Winkel R van Beveren NJ Simons C. AKT1 moderation of cannabis-induced cognitive alterations in psychotic disorder. Neuropsychopharmacology. 2011;36(12):2529–37.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  137. Agrawal A, Lynskey MT. Correlates of later-onset cannabis use in the National Epidemiological Survey on Alcohol and Related Conditions (NESARC). Drug Alcohol Depend. 2009;105(1–2):71–5.

    Article  PubMed  PubMed Central  Google Scholar 

  138. Wegener N, Koch M. Neurobiology and systems physiology of the endocannabinoid system. Pharmacopsychiatry. 2009;42 Suppl 1:S79–86.

    Article  CAS  PubMed  Google Scholar 

  139. Llorente-Berzal A, Fuentes S, Gagliano H, Lopez-Gallardo M, Armario A, Viveros MP, et al. Sex-dependent effects of maternal deprivation and adolescent cannabinoid treatment on adult rat behaviour. Addict Biol. 2011;16(4):624–37.

    Article  CAS  PubMed  Google Scholar 

  140. Llorente-Berzal A, Puighermanal E, Burokas A, Ozaita A, Maldonado R, Marco EM, et al. Sex-dependent psychoneuroendocrine effects of THC and MDMA in an animal model of adolescent drug consumption. PLoS ONE 2013;8(11):e78386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Higuera-Matas A, Botreau F, Miguens M, Del Olmo N, Borcel E, Perez-Alvarez L, et al. Chronic periadolescent cannabinoid treatment enhances adult hippocampal PSA-NCAM expression in male Wistar rats but only has marginal effects on anxiety, learning and memory. Pharmacol Biochem Behav. 2009;93(4):482–90.

    Article  CAS  PubMed  Google Scholar 

  142. Abush H, Akirav I. Short- and long-term cognitive effects of chronic cannabinoids administration in late-adolescence rats. PLoS ONE. 2012;7(2):e31731.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. O’Tuathaigh CM, Clarke G, Walsh J, Desbonnet L, Petit E, O’Leary C, et al. Genetic vs. pharmacological inactivation of COMT influences cannabinoid-induced expression of schizophrenia-related phenotypes. Int J Neuropsychopharmacol. 2012;15(9):1331–42.

    Article  PubMed  CAS  Google Scholar 

  144. Cha YM, Jones KH, Kuhn CM, Wilson WA, Swartzwelder HS. Sex differences in the effects of delta9-tetrahydrocannabinol on spatial learning in adolescent and adult rats. Behav Pharmacol. 2007;18(5–6):563–9.

    Article  CAS  PubMed  Google Scholar 

  145. Renard J, Krebs MO, Jay TM, Le Pen G. Long-term cognitive impairments induced by chronic cannabinoid exposure during adolescence in rats: a strain comparison. Psychopharmacology (Berl). 2013;225(4):781–90.

    Article  CAS  Google Scholar 

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  1. Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense de Madrid (UCM), Madrid, Spain

    María-Paz Viveros & Eva María Marco

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  1. María-Paz Viveros
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  2. Eva María Marco
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Correspondence to María-Paz Viveros .

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  1. Dept. of Physiology and Pharmacology, Sapienza University, Rome, Italy

    Patrizia Campolongo

  2. Institute of Neuroscience CNR, University of Cagliari, Cagliari, Italy

    Liana Fattore

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Viveros, MP., Marco, E. (2015). Age-Dependent Effects of Cannabinoids on Neurophysiological, Emotional, and Motivational States. In: Campolongo, P., Fattore, L. (eds) Cannabinoid Modulation of Emotion, Memory, and Motivation. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2294-9_11

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