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Physiology of the Endocannabinoid System During Development

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Recent Advances in Cannabinoid Physiology and Pathology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1162))

Abstract

The endocannabinoid (eCB) system comprises endogenously produced cannabinoids (CBs), enzymes of their production and degradation, and CB-sensing receptors and transporters. The eCB system plays a critical role in virtually all stages of animal development. Studies on eCB system components and their physiological role have gained increasing attention with the rising legalization and medical use of marijuana products. The latter represent exogenous interventions that target the eCB system. This chapter summarizes knowledge in the field of CB contribution to gametogenesis, fertilization, embryo implantation, fetal development, birth, and adolescence-equivalent periods of ontogenesis. The material is complemented by the overview of data from our laboratory documenting the functional presence of the eCB system within cerebral arteries of baboons at different stages of development.

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Abbreviations

ABHD4:

α/β-hydrolase domain 4

AEA:

anandamide

CB:

cannabinoid

COX-2:

cyclooxygenase-2

CP55,940:

(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol

DAGL:

diacylglycerol lipase

eCB:

endocannabinoid (system)

ERK:

extracellular-signal-regulated kinase

FAAH:

fatty acid amide hydrolase

GABA:

gamma aminobutyric acid

LTP:

long-term potentiation

MAPK:

mitogen-activated protein kinase

MAGL:

monoacylglycerol lipase

NAE:

N-acylethanolamine

NAPE:

N-acylphosphatidylethanolamine

NAPE-PLD:

 N-acylphosphatidylethanolamine-specific phospholipase D

PCR:

polymerase chain reaction

THC:

Δ9-tetrahydrocannabinol

TRP:

transient receptor potential (protein, channel)

VGAT:

vesicular GABA transporter

2-AG:

2-arachidonoylglycerol.

References

  1. Mechoulam R, Parker LA (2013) The endocannabinoid system and the brain. Annu Rev Psychol 64:21–47

    Article  PubMed  Google Scholar 

  2. Hall W, Solowij N (1998) Adverse effects of cannabis. Lancet 352:1611–1616

    Article  CAS  PubMed  Google Scholar 

  3. Green B, Kavanagh D, Young R (2003) Being stoned: a review of self-reported cannabis effects. Drug Alcohol Rev 22:453–460

    Article  PubMed  Google Scholar 

  4. Cheung JT, Mann RE, Ialomiteanu A, Stoduto G, Chan V, Ala-Leppilampi K, Rehm J (2010) Anxiety and mood disorders and cannabis use. Am J Drug Alcohol Abuse 36:118–122

    Article  PubMed  Google Scholar 

  5. Hunault CC, Böcker KB, Stellato RK, Kenemans JL, de Vries I, Meulenbelt J (2014) Acute subjective effects after smoking joints containing up to 69 mg Δ9-tetrahydrocannabinol in recreational users: a randomized, crossover clinical trial. Psychopharmacology 231:4723–4733

    Article  CAS  PubMed  Google Scholar 

  6. Temple EC, Driver M, Brown RF (2014) Cannabis use and anxiety: is stress the missing piece of the puzzle? Front Psychiatry 5:168

    Article  PubMed  PubMed Central  Google Scholar 

  7. Schonhofen P, Bristot IJ, Crippa JA, Hallak JEC, Zuardi AW, Parsons RB, Klamt F (2018) Cannabinoid-based therapies and brain development: potential harmful effect of early modulation of the endocannabinoid system. CNS Drugs 32:697–712

    Article  CAS  PubMed  Google Scholar 

  8. Bortolato M, Mangieri RA, Fu J, Kim JH, Arguello O, Duranti A, Tontini A, Mor M, Tarzia G, Piomelli D (2007) Antidepressant-like activity of the fatty acid amide hydrolase inhibitor URB597 in a rat model of chronic mild stress. Biol Psychiatry 62:1103–1110

    Article  CAS  PubMed  Google Scholar 

  9. Mangieri RA, Piomelli D (2007) Enhancement of endocannabinoid signaling and the pharmacotherapy of depression. Pharmacol Res 56:360–366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hill TD, Cascio MG, Romano B, Duncan M, Pertwee RG, Williams CM, Whalley BJ, Hill AJ (2013) Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism. Br J Pharmacol 170:679–692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kaur R, Ambwani SR, Singh S (2016) Endocannabinoid system: a multi-facet therapeutic target. Curr Clin Pharmacol 11:110–117

    Article  CAS  PubMed  Google Scholar 

  12. Lu Y, Anderson HD (2017) Cannabinoid signaling in health and disease. Can J Physiol Pharmacol 95:311–327

    Article  CAS  PubMed  Google Scholar 

  13. Fride E (2008) Multiple roles for the endocannabinoid system during the earliest stages of life: pre- and postnatal development. J Neuroendocrinol 20:75–81

    Article  CAS  PubMed  Google Scholar 

  14. Correa F, Wolfson ML, Valchi P, Aisemberg J, Franchi AM (2016) Endocannabinoid system and pregnancy. Reproduction 152:R191–R200

    Article  CAS  PubMed  Google Scholar 

  15. Ko JY, Farr SL, Tong VT, Creanga AA, Callaghan WM (2015) Prevalence and patterns of marijuana use among pregnant and nonpregnant women of reproductive age. Am J Obstet Gynecol 213:e201–e210

    Article  Google Scholar 

  16. 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–F292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. El Marroun H, Hudziak JJ, Tiemeier H, Creemers H, Steegers EA, Jaddoe VW, Hofman A, Verhulst FC, van den Brink W, Huizink AC (2011) Intrauterine cannabis exposure leads to more aggressive behavior and attention problems in 18-month-old girls. Drug Alcohol Depend 118:470–474

    Article  PubMed  Google Scholar 

  18. Marco EM, Laviola G (2012) The endocannabinoid system in the regulation of emotions throughout lifespan: a discussion on therapeutic perspectives. J Psychopharmacol 26:150–163

    Article  CAS  PubMed  Google Scholar 

  19. Sun YX, Tsuboi K, Okamoto Y, Tonai T, Murakami M, Kudo I, Ueda N (2004) Biosynthesis of anandamide and N-palmitoylethanolamine by sequential actions of phospholipase A2 and lysophospholipase D. Biochem J 380:749–756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Romero TR, Resende LC, Guzzo LS, Duarte ID (2013) CB1 and CB2 cannabinoid receptor agonists induce peripheral antinociception by activation of the endogenous noradrenergic system. Anesth Analg 116:463–472

    Article  CAS  PubMed  Google Scholar 

  21. Borrelli F, Izzo AA (2009) Role of acylethanolamides in the gastrointestinal tract with special reference to food intake and energy balance. Best Pract Res Clin Endocrinol Metab 23:33–49

    Article  CAS  PubMed  Google Scholar 

  22. Hansen HS, Diep TA (2009) N-acylethanolamines, anandamide and food intake. Biochem Pharmacol 78:553–560

    Article  CAS  PubMed  Google Scholar 

  23. Caraceni P, Viola A, Piscitelli F, Giannone F, Berzigotti A, Cescon M, Domenicali M, Petrosino S, Giampalma E, Riili A, Grazi G, Golfieri R, Zoli M, Bernardi M, Di Marzo V (2010) Circulating and hepatic endocannabinoids and endocannabinoid-related molecules in patients with cirrhosis. Liver Int 30:816–825

    Article  CAS  PubMed  Google Scholar 

  24. Bambang KN, Lambert DG, Lam PM, Quenby S, Maccarrone M, Konje JC (2012) Immunity and early pregnancy events: are endocannabinoids the missing link? J Reprod Immunol 96:8–18

    Article  CAS  PubMed  Google Scholar 

  25. Liu J, Wang L, Harvey-White J, Osei-Hyiaman D, Razdan R, Gong Q, Chan AC, Zhou Z, Huang BX, Kim HY, Kunos G (2006) A biosynthetic pathway for anandamide. Proc Natl Acad Sci U S A 103:13345–13350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Liu J, Wang L, Harvey-White J, Huang BX, Kim HY, Luquet S, Palmiter RD, Krystal G, Rai R, Mahadevan A, Razdan RK, Kunos G (2008) Multiple pathways involved in the biosynthesis of anandamide. Neuropharmacology 54(1):1–7

    Article  CAS  PubMed  Google Scholar 

  27. Simon GM, Cravatt BF (2008) Anandamide biosynthesis catalyzed by the phosphodiesterase GDE1 and detection of glycerophospho-N-acyl ethanolamine precursors in mouse brain. J Biol Chem 283:9341–9349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bisogno T, Howell F, Williams G, Minassi A, Cascio MG, Ligresti A, Matias I, Schiano-Moriello A, Paul P, Williams EJ, Gangadharan U, Hobbs C, Di Marzo V, Doherty P (2003) Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain. J Cell Biol 163:463–468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Taylor AH, Ang C, Bell SC, Konje JC (2007) The role of the endocannabinoid system in gametogenesis, implantation and early pregnancy. Hum Reprod Update 13:501–513

    Article  CAS  PubMed  Google Scholar 

  30. Maccarrone M, van der Stelt M, Rossi A, Veldink GA, Vliegenthart JF, Agrò AF (1998) Anandamide hydrolysis by human cells in culture and brain. J Biol Chem 273:32332–32339

    Article  CAS  PubMed  Google Scholar 

  31. Burstein SH, Rossetti RG, Yagen B, Zurier RB (2000) Oxidative metabolism of anandamide. Prostaglandins Other Lipid Mediat 61:29–41

    Article  CAS  PubMed  Google Scholar 

  32. Kozak KR, Crews BC, Morrow JD, Wang LH, Ma YH, Weinander R, Jakobsson PJ, Marnett LJ (2002) Metabolism of the endocannabinoids, 2-arachidonylglycerol and anandamide, into prostaglandin, thromboxane, and prostacyclin glycerol esters and ethanolamides. J Biol Chem 277:44877–44885

    Article  CAS  PubMed  Google Scholar 

  33. Ross RA, Craib SJ, Stevenson LA, Pertwee RG, Henderson A, Toole J, Ellington HC (2002) Pharmacological characterization of the anandamide cyclooxygenase metabolite: prostaglandin E2 ethanolamide. J Pharmacol Exp Ther 301:900–907

    Article  CAS  PubMed  Google Scholar 

  34. Blankman JL, Simon GM, Cravatt BF (2007) A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol. Chem Biol 14:1347–1356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Muccioli GG, Xu C, Odah E, Cudaback E, Cisneros JA, Lambert DM, López Rodríguez ML, Bajjalieh S, Stella N (2007) Identification of a novel endocannabinoid-hydrolyzing enzyme expressed by microglial cells. J Neurosci 27:2883–2889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564

    Article  CAS  PubMed  Google Scholar 

  37. Slipetz DM, O’Neill GP, Favreau L, Dufresne C, Gallant M, Gareau Y, Guay D, Labelle M, Metters KM (1995) Activation of the human peripheral cannabinoid receptor results in inhibition of adenylyl cyclase. Mol Pharmacol 48:352–361

    CAS  PubMed  Google Scholar 

  38. Shire D, Calandra B, Rinaldi-Carmona M, Oustric D, Pessègue B, Bonnin-Cabanne O, Le Fur G, Caput D, Ferrara P (1996) Molecular cloning, expression and function of the murine CB2 peripheral cannabinoid receptor. Biochim Biophys Acta 1307:132–136

    Article  PubMed  Google Scholar 

  39. Mukhopadhyay S, McIntosh HH, Houston DB, Howlett AC (2000) The CB(1) cannabinoid receptor juxtamembrane C-terminal peptide confers activation to specific G proteins in brain. Mol Pharmacol 57:162–170

    CAS  PubMed  Google Scholar 

  40. Kenakin T, Onaran O (2002) The ligand paradox between affinity and efficacy: can you be there and not make a difference? Trends Pharmacol Sci 23:275–280

    Article  CAS  PubMed  Google Scholar 

  41. Psychoyos D, Vinod KY, Cao J, Xie S, Hyson RL, Wlodarczyk B, He W, Cooper TB, Hungund BL, Finnell RH (2012) Cannabinoid receptor 1 signaling in embryo neurodevelopment. Birth Defects Res B Dev Reprod Toxicol 95:137–150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Lee TT, Hill MN, Lee FS (2016) Developmental regulation of fear learning and anxiety behavior by endocannabinoids. Genes Brain Behav 15:108–124

    Article  CAS  PubMed  Google Scholar 

  43. Fernández-Ruiz JJ, Berrendero F, Hernández ML, Romero J, Ramos JA (1999) Role of endocannabinoids in brain development. Life Sci 65:725–736

    Article  PubMed  Google Scholar 

  44. Oliveira da Cruz JF, Robin LM, Drago F, Marsicano G, Metna-Laurent M (2016) Astroglial type-1 cannabinoid receptor (CB1): a new player in the tripartite synapse. Neuroscience 323:35–42

    Article  CAS  PubMed  Google Scholar 

  45. Galiègue S, Mary S, Marchand J, Dussossoy D, Carrière D, Carayon P, Bouaboula M, Shire D, Le Fur G, Casellas P (1995) Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem 232:54–61

    Article  PubMed  Google Scholar 

  46. Barutta F, Mastrocola R, Bellini S, Bruno G, Gruden G (2018) Cannabinoid receptors in diabetic kidney disease. Curr Diab Rep 18:9

    Article  CAS  PubMed  Google Scholar 

  47. Buznikov GA, Nikitina LA, Bezuglov VV, Francisco ME, Boysen G, Obispo-Peak IN, Peterson RE, Weiss ER, Schuel H, Temple BR, Morrow AL, Lauder JM (2010) A putative ‘pre-nervous’ endocannabinoid system in early echinoderm development. Dev Neurosci 32:1–18

    Article  CAS  PubMed  Google Scholar 

  48. Elphick MR, Egertová M (2001) The neurobiology and evolution of cannabinoid signalling. Philos Trans R Soc Lond Ser B Biol Sci 356:381–408

    Article  CAS  Google Scholar 

  49. Rodriguez-Sanchez IP, Guindon J, Ruiz M, Tejero ME, Hubbard G, Martinez-de-Villarreal LE, Barrera-Saldaña HA, Dick EJ Jr, Comuzzie AG, Schlabritz-Loutsevitch NE (2016) The endocannabinoid system in the baboon (Papio spp.) as a complex framework for developmental pharmacology. Neurotoxicol Teratol 58:23–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Seleverstov O, Tobiasz A, Jackson JS, Sullivan R, Ma D, Sullivan JP, Davison S, Akkhawattanangkul Y, Tate DL, Costello T, Barnett S, Li W, Mari G, Dopico AM, Bukiya AN (2017) Maternal alcohol exposure during mid-pregnancy dilates fetal cerebral arteries via endocannabinoid receptors. Alcohol 61:51–61

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Cabral GA, Raborn ES, Griffin L, Dennis J, Marciano-Cabral F (2008) CB2 receptors in the brain: role in central immune function. Br J Pharmacol 153:240–251

    Article  CAS  PubMed  Google Scholar 

  52. Li Y, Kim J (2017) Distinct roles of neuronal and microglial CB2 cannabinoid receptors in the mouse hippocampus. Neuroscience 363:11–25

    Article  CAS  PubMed  Google Scholar 

  53. 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 310:329–332

    Article  PubMed  CAS  Google Scholar 

  54. Onaivi ES, Ishiguro H, Gong JP, Patel S, Perchuk A, Meozzi PA, Myers L, Mora Z, Tagliaferro P, Gardner E, Brusco A, Akinshola BE, Liu QR, Hope B, Iwasaki S, Arinami T, Teasenfitz L, Uhl GR (2006) Discovery of the presence and functional expression of cannabinoid CB2 receptors in brain. Ann N Y Acad Sci 1074:514–536

    Article  CAS  PubMed  Google Scholar 

  55. Galve-Roperh I, Palazuelos J, Aguado T, Guzmán M (2009) The endocannabinoid system and the regulation of neural development: potential implications in psychiatric disorders. Eur Arch Psychiatry Clin Neurosci 259:371–382

    Article  PubMed  Google Scholar 

  56. Rom S, Persidsky Y (2013) Cannabinoid receptor 2: potential role in immunomodulation and neuroinflammation. J NeuroImmune Pharmacol 8:608–620

    Article  PubMed  PubMed Central  Google Scholar 

  57. Felder CC, Joyce KE, Briley EM, Mansouri J, Mackie K, Blond O, Lai Y, Ma AL, Mitchell RL (1995) Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors. Mol Pharmacol 48:443–450

    CAS  PubMed  Google Scholar 

  58. Gebremedhin D, Lange AR, Campbell WB, Hillard CJ, Harder DR (1999) Cannabinoid CB1 receptor of cat cerebral arterial muscle functions to inhibit L-type Ca2+ channel current. Am J Phys 276:H2085–H2093

    CAS  Google Scholar 

  59. Hillard CJ (2000) Biochemistry and pharmacology of the endocannabinoids arachidonylethanolamide and 2-arachidonylglycerol. Prostaglandins Other Lipid Mediat 61:3–18

    Article  CAS  PubMed  Google Scholar 

  60. Demuth DG, Molleman A (2006) Cannabinoid signalling. Life Sci 78:549–563

    Article  CAS  PubMed  Google Scholar 

  61. Turu G, Hunyady L (2010) Signal transduction of the CB1 cannabinoid receptor. J Mol Endocrinol 44:75–85

    Article  CAS  PubMed  Google Scholar 

  62. Franklin JM, Carrasco GA (2013) Cannabinoid receptor agonists upregulate and enhance serotonin 2A (5-HT(2A)) receptor activity via ERK1/2 signaling. Synapse 67:145–159

    Article  CAS  PubMed  Google Scholar 

  63. Sánchez-Pastor E, Andrade F, Sánchez-Pastor JM, Elizalde A, Huerta M, Virgen-Ortiz A, Trujillo X, Rodríguez-Hernández A (2014) Cannabinoid receptor type 1 activation by arachidonylcyclopropylamide in rat aortic rings causes vasorelaxation involving calcium-activated potassium channel subunit alpha-1 and calcium channel, voltage-dependent, L type, alpha 1C subunit. Eur J Pharmacol 729:100–106

    Article  PubMed  CAS  Google Scholar 

  64. Szabó GG, Lenkey N, Holderith N, Andrási T, Nusser Z, Hájos N (2014) Presynaptic calcium channel inhibition underlies CB1 cannabinoid receptor-mediated suppression of GABA release. J Neurosci 34:7958–7963

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Bondarenko AI, Panasiuk O, Okhai I, Montecucco F, Brandt KJ, Mach F (2018) Ca2+-dependent potassium channels and cannabinoid signaling in the endothelium of apolipoprotein E knockout mice before plaque formation. J Mol Cell Cardiol 115:54–63

    Article  CAS  PubMed  Google Scholar 

  66. Hillard CJ (2000) Endocannabinoids and vascular function. J Pharmacol Exp Ther 294:27–32

    CAS  PubMed  Google Scholar 

  67. Caterina MJ (2014) TRP channel cannabinoid receptors in skin sensation, homeostasis, and inflammation. ACS Chem Neurosci 5:1107–1116

    Article  CAS  PubMed  Google Scholar 

  68. Godlewski G, Offertáler L, Wagner JA, Kunos G (2009) Receptors for acylethanolamides-GPR55 and GPR119. Prostaglandins Other Lipid Mediat 89:105–111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Bambang KN, Karasu T, Gebeh A, Taylor AH, Marczylo TH, Lam P, Willets JM, Konje JC (2010) From fertilization to implantation in mammalian pregnancy-modulation of early human reproduction by the endocannabinoid system. Pharmaceuticals (Basel) 3:2910–2929

    Article  CAS  Google Scholar 

  70. Maccarrone M, Valensise H, Bari M, Lazzarin N, Romanini C, Finazzi-Agrò A (2001) Progesterone up-regulates anandamide hydrolase in human lymphocytes: role of cytokines and implications for fertility. J Immunol 166:7183–7189

    Article  CAS  PubMed  Google Scholar 

  71. Wenger T, Tóth BE, Martin BR (1995) Effects of anandamide (endogen cannabinoid) on anterior pituitary hormone secretion in adult ovariectomized rats. Life Sci 56:2057–2063

    Article  CAS  PubMed  Google Scholar 

  72. Hill MN, Carrier EJ, Ho WS, Shi L, Patel S, Gorzalka BB, Hillard CJ (2008) Prolonged glucocorticoid treatment decreases cannabinoid CB1 receptor density in the hippocampus. Hippocampus 18:221–226

    Article  CAS  PubMed  Google Scholar 

  73. Maccarrone M, Finazzi-Agrò A (2004) Anandamide hydrolase: a guardian angel of human reproduction? Trends Pharmacol Sci 25:353–357

    Article  CAS  PubMed  Google Scholar 

  74. Schuel H, Goldstein E, Mechoulam R, Zimmerman AM, Zimmerman S (1994) Anandamide (arachidonylethanolamide), a brain cannabinoid receptor agonist, reduces sperm fertilizing capacity in sea urchins by inhibiting the acrosome reaction. Proc Natl Acad Sci U S A 91:7678–7682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Maccarrone M, Cecconi S, Rossi G, Battista N, Pauselli R, Finazzi-Agrò A (2003) Anandamide activity and degradation are regulated by early postnatal aging and follicle-stimulating hormone in mouse Sertoli cells. Endocrinology 144:20–28

    Article  CAS  PubMed  Google Scholar 

  76. Peralta L, Agirregoitia E, Mendoza R, Expósito A, Casis L, Matorras R, Agirregoitia N (2011) Expression and localization of cannabinoid receptors in human immature oocytes and unfertilized metaphase-II oocytes. Reprod BioMed Online 23:372–379

    Article  CAS  PubMed  Google Scholar 

  77. Grimaldi P, Orlando P, Di Siena S, Lolicato F, Petrosino S, Bisogno T, Geremia R, De Petrocellis L, Di Marzo V (2009) The endocannabinoid system and pivotal role of the CB2 receptor in mouse spermatogenesis. Proc Natl Acad Sci U S A 106:11131–11136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Cobellis G, Ricci G, Cacciola G, Orlando P, Petrosino S, Cascio MG, Bisogno T, De Petrocellis L, Chioccarelli T, Altucci L, Fasano S, Meccariello R, Pierantoni R, Ledent C, Di Marzo V (2010) A gradient of 2-arachidonoylglycerol regulates mouse epididymal sperm cell start-up. Biol Reprod 82:451–458

    Article  CAS  PubMed  Google Scholar 

  79. Rossato M, Ion Popa F, Ferigo M, Clari G, Foresta C (2005) Human sperm express cannabinoid receptor Cb1, the activation of which inhibits motility, acrosome reaction, and mitochondrial function. J Clin Endocrinol Metab 90:984–991

    Article  CAS  PubMed  Google Scholar 

  80. Lazzarin N, Valensise H, Bari M, Ubaldi F, Battista N, Finazzi-Agrò A, Maccarrone M (2004) Fluctuations of fatty acid amide hydrolase and anandamide levels during the human ovulatory cycle. Gynecol Endocrinol 18:212–218

    Article  CAS  PubMed  Google Scholar 

  81. El-Talatini MR, Taylor AH, Konje JC (2010) The relationship between plasma levels of the endocannabinoid, anandamide, sex steroids, and gonadotrophins during the menstrual cycle. Fertil Steril 93:1989–1996

    Article  CAS  PubMed  Google Scholar 

  82. Habayeb OM, Taylor AH, Bell SC, Taylor DJ, Konje JC (2008) Expression of the endocannabinoid system in human first trimester placenta and its role in trophoblast proliferation. Endocrinology 149:5052–5060

    Article  CAS  PubMed  Google Scholar 

  83. Ayalon D, Nir I, Cordova T, Bauminger S, Puder M, Naor Z, Kashi R, Zor U, Harell A, Lindner HR (1977) Acute effect of delta1-tetrahydrocannabinol on the hypothalamo-pituitary-ovarian axis in the rat. Neuroendocrinology 23:31–42

    Article  CAS  PubMed  Google Scholar 

  84. Du Plessis SS, Agarwal A, Syriac A (2015) Marijuana, phytocannabinoids, the endocannabinoid system, and male fertility. J Assist Reprod Genet 32:1575–1588

    Article  PubMed  PubMed Central  Google Scholar 

  85. Brents LK (2016) Marijuana, the endocannabinoid system and the female reproductive system. Yale J Biol Med 89:175–191

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Wang H, Dey SK, Maccarrone M (2006) Jekyll and hyde: two faces of cannabinoid signaling in male and female fertility. Endocr Rev 27:427–448

    Article  CAS  PubMed  Google Scholar 

  87. Wang H, Xie H, Dey SK (2006) Endocannabinoid signaling directs periimplantation events. AAPS J 8:E425–E432

    Article  PubMed  PubMed Central  Google Scholar 

  88. Wenger T, Ledent C, Csernus V, Gerendai I (2001) The central cannabinoid receptor inactivation suppresses endocrine reproductive functions. Biochem Biophys Res Commun 284:363–368

    Article  CAS  PubMed  Google Scholar 

  89. Nahas GG, Frick HC, Lattimer JK, Latour C, Harvey D (2002) Pharmacokinetics of THC in brain and testis, male gametotoxicity and premature apoptosis of spermatozoa. Hum Psychopharmacol 17:103–113

    Article  CAS  PubMed  Google Scholar 

  90. Schuel H, Burkman LJ (2005) A tale of two cells: endocannabinoid-signaling regulates functions of neurons and sperm. Biol Reprod 73:1078–1086

    CAS  PubMed  Google Scholar 

  91. Oltrabella F, Melgoza A, Nguyen B, Guo S (2017) Role of the endocannabinoid system in vertebrates: Emphasis on the zebrafish model. Develop Growth Differ 59:194–210

    Article  CAS  Google Scholar 

  92. Ahmed KT, Amin MR, Shah P, Ali DW (2018) Motor neuron development in zebrafish is altered by brief (5-hr) exposures to THC (∆9-tetrahydrocannabinol) or CBD (cannabidiol) during gastrulation. Sci Rep 8:10518

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Begbie J, Doherty P, Graham A (2004) Cannabinoid receptor, CB1, expression follows neuronal differentiation in the early chick embryo. J Anat 205:213–218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. 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 38:89–97

    Article  CAS  PubMed  Google Scholar 

  95. Newgreen DF, Howard MJ, Nishi R (2009) Encyclopedia of neuroscience. Autonomic nervous system development, pp 837–848

    Chapter  Google Scholar 

  96. Taylor AH, Amoako AA, Bambang K, Karasu T, Gebeh A, Lam PM, Marzcylo TH, Konje JC (2010) Endocannabinoids and pregnancy. Clin Chim Acta 411:921–930

    Article  CAS  PubMed  Google Scholar 

  97. Wang H, Guo Y, Wang D, Kingsley PJ, Marnett LJ, Das SK, DuBois RN, Dey SK (2004) Aberrant cannabinoid signaling impairs oviductal transport of embryos. Nat Med 10:1074–1080

    Article  CAS  PubMed  Google Scholar 

  98. Horne AW, Phillips JA 3rd, Kane N, Lourenco PC, McDonald SE, Williams AR, Simon C, Dey SK, Critchley HO (2008) CB1 expression is attenuated in Fallopian tube and decidua of women with ectopic pregnancy. PLoS One 3:e3969

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Wang H, Matsumoto H, Guo Y, Paria BC, Roberts RL, Dey SK (2003) Differential G protein-coupled cannabinoid receptor signaling by anandamide directs blastocyst activation for implantation. Proc Natl Acad Sci U S A 100:14914–14919

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Wang H, Xie H, Guo Y, Zhang H, Takahashi T, Kingsley PJ, Marnett LJ, Das SK, Cravatt BF, Dey SK (2006) Fatty acid amide hydrolase deficiency limits early pregnancy events. J Clin Invest 116:2122–2131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Paria BC, Song H, Wang X, Schmid PC, Krebsbach RJ, Schmid HH, Bonner TI, Zimmer A, Dey SK (2001) Dysregulated cannabinoid signaling disrupts uterine receptivity for embryo implantation. J Biol Chem 276:20523–20528

    Article  CAS  PubMed  Google Scholar 

  102. Schmid PC, Paria BC, Krebsbach RJ, Schmid HH, Dey SK (1997) Changes in anandamide levels in mouse uterus are associated with uterine receptivity for embryo implantation. Proc Natl Acad Sci U S A 94:4188–4192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Guo Y, Wang H, Okamoto Y, Ueda N, Kingsley PJ, Marnett LJ, Schmid HH, Das SK, Dey SK (2005) N-acylphosphatidylethanolamine-hydrolyzing phospholipase D is an important determinant of uterine anandamide levels during implantation. J Biol Chem 280:23429–23432

    Article  CAS  PubMed  Google Scholar 

  104. Habayeb OM, Taylor AH, Finney M, Evans MD, Konje JC (2008) Plasma anandamide concentration and pregnancy outcome in women with threatened miscarriage. JAMA 299:1135–1136

    Article  CAS  PubMed  Google Scholar 

  105. Habayeb OM, Taylor AH, Evans MD, Cooke MS, Taylor DJ, Bell SC, Konje JC (2004) Plasma levels of the endocannabinoid anandamide in women – a potential role in pregnancy maintenance and labor? J Clin Endocrinol Metab 89:5482–5487

    Article  CAS  PubMed  Google Scholar 

  106. Taylor AH, Finney M, Lam PM, Konje JC (2011) Modulation of the endocannabinoid system in viable and non-viable first trimester pregnancies by pregnancy-related hormones. Reprod Biol Endocrinol 9:152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Trabucco E, Acone G, Marenna A, Pierantoni R, Cacciola G, Chioccarelli T, Mackie K, Fasano S, Colacurci N, Meccariello R, Cobellis G, Cobellis L (2009) Endocannabinoid system in first trimester placenta: low FAAH and high CB1 expression characterize spontaneous miscarriage. Placenta 30:516–522

    Article  CAS  PubMed  Google Scholar 

  108. Tsuboi K, Okamoto Y, Ikematsu N, Inoue M, Shimizu Y, Uyama T, Wang J, Deutsch DG, Burns MP, Ulloa NM, Tokumura A, Ueda N (1811) Enzymatic formation of N-acylethanolamines from N-acylethanolamine plasmalogen through N-acylphosphatidylethanolamine-hydrolyzing phospholipase D-dependent and -independent pathways. Biochim Biophys Acta 2011:565–577

    Google Scholar 

  109. Straszewski-Chavez SL, Abrahams VM, Mor G (2005) The role of apoptosis in the regulation of trophoblast survival and differentiation during pregnancy. Endocr Rev 26:877–897

    Article  CAS  PubMed  Google Scholar 

  110. Turco MY, Matsukawa K, Czernik M, Gasperi V, Battista N, Della Salda L, Scapolo PA, Loi P, Maccarrone M, Ptak G (2008) High levels of anandamide, an endogenous cannabinoid, block the growth of sheep preimplantation embryos by inducing apoptosis and reversible arrest of cell proliferation. Hum Reprod 23:2331–2338

    Article  CAS  PubMed  Google Scholar 

  111. Fonseca BM, Correia-da-Silva G, Teixeira NA (2013) The endocannabinoid anandamide induces apoptosis of rat decidual cells through a mechanism involving ceramide synthesis and p38 MAPK activation. Apoptosis 18:1526–1535

    Article  CAS  PubMed  Google Scholar 

  112. Almada M, Piscitelli F, Fonseca BM, Di Marzo V, Correia-da-Silva G, Teixeira N (1851) Anandamide and decidual remodelling: COX-2 oxidative metabolism as a key regulator. Biochim Biophys Acta 2015:1473–1481

    Google Scholar 

  113. Weber A, Ni J, Ling KH, Acheampong A, Tang-Liu DD, Burk R, Cravatt BF, Woodward D (2004) Formation of prostamides from anandamide in FAAH knockout mice analyzed by HPLC with tandem mass spectrometry. J Lipid Res 45:757–763

    Article  CAS  PubMed  Google Scholar 

  114. 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 82:1131–1149

    Article  CAS  PubMed  Google Scholar 

  115. Jiang S, Fu Y, Williams J, Wood J, Pandarinathan L, Avraham S, Makriyannis A, Avraham S, Avraham HK (2007) Expression and function of cannabinoid receptors CB1 and CB2 and their cognate cannabinoid ligands in murine embryonic stem cells. PLoS One 2:e641

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  116. Fonseca BM, Correia-da-Silva G, Taylor AH, Konje JC, Bell SC, Teixeira NA (2009) Spatio-temporal expression patterns of anandamide-binding receptors in rat implantation sites: evidence for a role of the endocannabinoid system during the period of placental development. Reprod Biol Endocrinol 7:121

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  117. Cabral GA, Ferreira GA, Jamerson MJ (2015) Endocannabinoids and the immune system in health and disease. Handb Exp Pharmacol 231:185–211

    Article  CAS  PubMed  Google Scholar 

  118. Moffett-King A (2002) Natural killer cells and pregnancy. Nat Rev Immunol 2:656–663

    Article  CAS  PubMed  Google Scholar 

  119. Xu YY, Wang SC, Li DJ, Du MR (2017) Co-signaling molecules in maternal-fetal immunity. Trends Mol Med 23:46–58

    Article  CAS  PubMed  Google Scholar 

  120. Berrendero F, Sepe N, Ramos JA, Di Marzo V, Fernández-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 33:181–191

    Article  CAS  PubMed  Google Scholar 

  121. Semple BD, Blomgren K, Gimlin K, Ferriero DM, Noble-Haeusslein LJ (2013) Brain development in rodents and humans: identifying benchmarks of maturation and vulnerability to injury across species. Prog Neurobiol 106–107:1–16

    Article  PubMed  Google Scholar 

  122. Sun X, Xie H, Yang J, Wang H, Bradshaw HB, Dey SK (2010) Endocannabinoid signaling directs differentiation of trophoblast cell lineages and placentation. Proc Natl Acad Sci U S A 107:16887–16892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Basavarajappa BS, Nixon RA, Arancio O (2009) Endocannabinoid system: emerging role from neurodevelopment to neurodegeneration. Mini-Rev Med Chem 9:448–462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  125. Vitalis T, Lainé 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 28:1705–1718

    Article  PubMed  Google Scholar 

  126. Saez TM, Aronne MP, Caltana L, Brusco AH (2014) Prenatal exposure to the CB1 and CB2 cannabinoid receptor agonist WIN 55,212-2 alters migration of early-born glutamatergic neurons and GABAergic interneurons in the rat cerebral cortex. J Neurochem 129:637–648

    Article  CAS  PubMed  Google Scholar 

  127. Berghuis P, Rajnicek AM, Morozov YM, Ross RA, Mulder J, Urbán 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 316:1212–1216

    Article  CAS  PubMed  Google Scholar 

  128. Aguado T, Monory K, Palazuelos J, Stella N, Cravatt B, Lutz B, Marsicano G, Kokaia Z, Guzmán M, Galve-Roperh I (2005) The endocannabinoid system drives neural progenitor proliferation. FASEB J 19:1704–1706

    Article  CAS  PubMed  Google Scholar 

  129. Palazuelos J, Aguado T, Egia A, Mechoulam R, Guzmán M, Galve-Roperh I (2006) Non-psychoactive CB2 cannabinoid agonists stimulate neural progenitor proliferation. FASEB J 20:2405–2407

    Article  CAS  PubMed  Google Scholar 

  130. Aguado T, Palazuelos J, Monory K, Stella N, Cravatt B, Lutz B, Marsicano G, Kokaia Z, Guzmán M, Galve-Roperh I (2006) The endocannabinoid system promotes astroglial differentiation by acting on neural progenitor cells. J Neurosci 26:1551–1561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Rueda D, Navarro B, Martinez-Serrano A, Guzman M, Galve-Roperh I (2002) The endocannabinoid anandamide inhibits neuronal progenitor cell differentiation through attenuation of the Rap1/B-Raf/ERK pathway. J Biol Chem 277:46645–46650

    Article  CAS  PubMed  Google Scholar 

  132. Bromberg KD, Ma’ayan A, Neves SR, Iyengar R (2008) Design logic of a cannabinoid receptor signaling network that triggers neurite outgrowth. Science 320:903–909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Jutras-Aswad D, DiNieri JA, Harkany T, Hurd YL (2009) Neurobiological consequences of maternal cannabis on human fetal development and its neuropsychiatric outcome. Eur Arch Psychiatry Clin Neurosci 259:395–412

    Article  PubMed  Google Scholar 

  134. 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 56:909–915

    Article  CAS  PubMed  Google Scholar 

  135. 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 7:291–308

    Article  CAS  PubMed  Google Scholar 

  136. Suárez I, Bodega G, Fernández-Ruiz J, Ramos JA, Rubio M, Fernández 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 3:66–74

    Article  PubMed  CAS  Google Scholar 

  137. Suárez I, Bodega G, Rubio M, Fernández-Ruiz JJ, Ramos JA, Fernández B (2004) Prenatal cannabinoid exposure down- regulates glutamate transporter expressions (GLAST and EAAC1) in the rat cerebellum. Dev Neurosci 26:45–53

    Article  PubMed  CAS  Google Scholar 

  138. Basavarajappa BS (2015) Fetal alcohol spectrum disorder: potential role of endocannabinoids signaling. Brain Sci 5:456–493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Bukiya AN, Dopico AM (2018) Fetal cerebral circulation as target of maternal alcohol consumption. Alcohol Clin Exp Res 42:1006–1018

    Article  PubMed  PubMed Central  Google Scholar 

  140. Tobiasz AM, Duncan JR, Bursac Z, Sullivan RD, Tate DL, Dopico AM, Bukiya AN, Mari G (2018) The effect of prenatal alcohol exposure on fetal growth and cardiovascular parameters in a baboon model of pregnancy. Reprod Sci 25:1116–1123

    Article  CAS  PubMed  Google Scholar 

  141. Zurolo E, Iyer AM, Spliet WG, Van Rijen PC, Troost D, Gorter JA, Aronica E (2010) CB1 and CB2 cannabinoid receptor expression during development and in epileptogenic developmental pathologies. Neuroscience 170:28–41

    Article  CAS  PubMed  Google Scholar 

  142. Wang X, Dow-Edwards D, Keller E, Hurd YL (2003) Preferential limbic expression of the cannabinoid receptor mRNA in the human fetal brain. Neuroscience 118:681–694

    Article  CAS  PubMed  Google Scholar 

  143. Hurd YL, Wang X, Anderson V, Beck O, Minkoff H, Dow-Edwards D (2005) Marijuana impairs growth in mid-gestation fetuses. Neurotoxicol Teratol 27:221–229

    Article  CAS  PubMed  Google Scholar 

  144. Day NL, Goldschmidt L, Thomas CA (2006) Prenatal marijuana exposure contributes to the prediction of marijuana use at age 14. Addiction 101:1313–1322

    Article  PubMed  Google Scholar 

  145. Brocato B, Zoerner AA, Janjetovic Z, Skobowiat C, Gupta S, Moore BM 2nd, Slominski A, Zhang J, Schenone M, Phinehas R, Ferry RJ Jr, Dick E Jr, Hubbard GB, Mari G, Schlabritz-Loutsevitch N (2013) Endocannabinoid crosstalk between placenta and maternal fat in a baboon model (Papio spp.) of obesity. Placenta 34:983–989

    Article  CAS  PubMed  Google Scholar 

  146. Fride E, Ginzburg Y, Breuer A, Bisogno T, Di Marzo V, Mechoulam R (2001) Critical role of the endogenous cannabinoid system in mouse pup suckling and growth. Eur J Pharmacol 419:207–214

    Article  CAS  PubMed  Google Scholar 

  147. Fride E, Gobshtis N, Dahan H, Weller A, Giuffrida A, Ben-Shabat S (2009) The endocannabinoid system during development: emphasis on perinatal events and delayed effects. Vitam Horm 81:139–158

    Article  CAS  PubMed  Google Scholar 

  148. Fernández-Ruiz J, Berrendero F, Hernández ML, Ramos JA (2000) The endogenous cannabinoid system and brain development. Trends Neurosci 23:14–20

    Article  PubMed  Google Scholar 

  149. 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 17:1747–1754

    Article  PubMed  Google Scholar 

  150. Gomes FV, Edelson JR, Volk DW, Grace AA (2018) Altered brain cannabinoid 1 receptor mRNA expression across postnatal development in the MAM model of schizophrenia. Schizophr Res 201:254–260

    Article  PubMed  PubMed Central  Google Scholar 

  151. Yoneda T, Kameyama K, Esumi K, Daimyo Y, Watanabe M, Hata Y (2013) Developmental and visual input-dependent regulation of the CB1 cannabinoid receptor in the mouse visual cortex. PLoS One 8:e53082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Fride E, Mechoulam R (1996) Developmental aspects of anandamide: ontogeny of response and prenatal exposure. Psychoneuroendocrinology 21:157–172

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  154. Trezza V, Campolongo P, Cassano T, Macheda T, Dipasquale P, Carratù MR, Gaetani S, Cuomo V (2008) Effects of perinatal exposure to delta-9-tetrahydrocannabinol on the emotional reactivity of the offspring: a longitudinal behavioral study in Wistar rats. Psychopharmacology 198:529–537

    Article  CAS  PubMed  Google Scholar 

  155. McGregor IS, Dastur FN, McLellan RA, Brown RE (1996) Cannabinoid modulation of rat pup ultrasonic vocalizations. Eur J Pharmacol 313:43–49

    Article  CAS  PubMed  Google Scholar 

  156. Navarro M, Rubio P, de Fonseca FR (1995) Behavioural consequences of maternal exposure to natural cannabinoids in rats. Psychopharmacology 122:1–14

    Article  CAS  PubMed  Google Scholar 

  157. 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 23:1–11

    Article  CAS  PubMed  Google Scholar 

  158. Schneider M (2009) Cannabis use in pregnancy and early life and its consequences: animal models. Eur Arch Psychiatry Clin Neurosci 259:383–393

    Article  PubMed  Google Scholar 

  159. Campolongo P, Trezza V, Ratano P, Palmery M, Cuomo V (2011) Developmental consequences of perinatal cannabis exposure: behavioral and neuroendocrine effects in adult rodents. Psychopharmacology 214:5–15

    Article  CAS  PubMed  Google Scholar 

  160. del Arco I, Muñoz R, Rodríguez De Fonseca F, Escudero L, Martín-Calderón JL, Navarro M, Villanúa MA (2000) Maternal exposure to the synthetic cannabinoid HU-210: effects on the endocrine and immune systems of the adult male offspring. Neuroimmunomodulation 7:16–26

    Article  PubMed  Google Scholar 

  161. Economidou D, Mattioli L, Ubaldi M, Lourdusamy A, Soverchia L, Hardiman G, Campolongo P, Cuomo V, Ciccocioppo R (2007) Role of cannabinoidergic mechanisms in ethanol self-administration and ethanol seeking in rat adult offspring following perinatal exposure to Delta9-tetrahydrocannabinol. Toxicol Appl Pharmacol 223:73–85

    Article  CAS  PubMed  Google Scholar 

  162. 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 61:554–563

    Article  CAS  PubMed  Google Scholar 

  163. 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 12:485–495

    Article  CAS  PubMed  Google Scholar 

  164. 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 43:173–178

    Article  CAS  PubMed  Google Scholar 

  165. Mereu G, Fà 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 U S A 100:4915–4920

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. 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 124:367–375

    Article  CAS  PubMed  Google Scholar 

  167. Castaldo P, Magi S, Gaetani S, Cassano T, Ferraro L, Antonelli T, Amoroso S, Cuomo V (2007) Prenatal exposure to the cannabinoid receptor agonist WIN 55,212-2 increases glutamate uptake through overexpression of GLT1 and EAAC1 glutamate transporter subtypes in rat frontal cerebral cortex. Neuropharmacology 53:369–378

    Article  CAS  PubMed  Google Scholar 

  168. Ferraro L, Tomasini MC, Beggiato S, Gaetani S, Cassano T, Cuomo V, Amoroso S, Tanganelli S, Antonelli T (2009) 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 (Vienna) 116:1017–1027

    Article  CAS  Google Scholar 

  169. 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 15:2013–2020

    Article  PubMed  Google Scholar 

  170. Dalterio S, Thomford PJ, Michael SD, DeAngelo L, Mayfield D (1986) Perinatal cannabinoid exposure: effects on hepatic cytochrome P-450 and plasma protein levels in male mice. Teratology 33:195–201

    Article  CAS  PubMed  Google Scholar 

  171. Dalterio S, Blum K, DeLallo L, Sweeney C, Briggs A, Bartke A (1980) Perinatal exposure to delta 9-THC in mice: altered enkephalin and norepinephrine sensitivity in vas deferens. Subst Alcohol Actions Misuse 1:467–471

    CAS  PubMed  Google Scholar 

  172. Mokler DJ, Robinson SE, Johnson JH, Hong JS, Rosecrans JA (1987) Neonatal administration of delta-9-tetrahydrocannabinol (THC) alters the neurochemical response to stress in the adult Fischer-344 rat. Neurotoxicol Teratol 9:321–327

    Article  CAS  PubMed  Google Scholar 

  173. Newsom RJ, Kelly SJ (2008) Perinatal delta-9-tetrahydrocannabinol exposure disrupts social and open field behavior in adult male rats. Neurotoxicol Teratol 30:213–219

    Article  CAS  PubMed  Google Scholar 

  174. Vela G, Martín S, García-Gil L, Crespo JA, Ruiz-Gayo M, Fernández-Ruiz JJ, García-Lecumberri C, Pélaprat 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 807:101–109

    Article  CAS  PubMed  Google Scholar 

  175. Llorente R, Llorente-Berzal A, Petrosino S, Marco EM, Guaza C, Prada C, López-Gallardo M, Di Marzo V, Viveros MP (2008) Gender-dependent cellular and biochemical effects of maternal deprivation on the hippocampus of neonatal rats: a possible role for the endocannabinoid system. Dev Neurobiol 68:1334–1347

    Article  CAS  PubMed  Google Scholar 

  176. Suárez J, Rivera P, Llorente R, Romero-Zerbo SY, Bermúdez-Silva FJ, de Fonseca FR, Viveros MP (2010) Early maternal deprivation induces changes on the expression of 2-AG biosynthesis and degradation enzymes in neonatal rat hippocampus. Brain Res 1349:162–173

    Article  PubMed  CAS  Google Scholar 

  177. Suárez J, Llorente R, Romero-Zerbo SY, Mateos B, Bermúdez-Silva FJ, de Fonseca FR, Viveros MP (2009) Early maternal deprivation induces gender-dependent changes on the expression of hippocampal CB(1) and CB(2) cannabinoid receptors of neonatal rats. Hippocampus 19:623–632

    Article  PubMed  CAS  Google Scholar 

  178. Fride E, Suris R, Weidenfeld J, Mechoulam R (2005) Differential response to acute and repeated stress in cannabinoid CB1 receptor knockout newborn and adult mice. Behav Pharmacol 16:431–440

    Article  CAS  PubMed  Google Scholar 

  179. Marco EM, Echeverry-Alzate V, López-Moreno JA, Giné E, Peñasco S, Viveros MP (2014) Consequences of early life stress on the expression of endocannabinoid-related genes in the rat brain. Behav Pharmacol 25:547–556

    CAS  PubMed  Google Scholar 

  180. Viveros MP, Llorente R, Suarez J, Llorente-Berzal A, López-Gallardo M, de Fonseca FR (2012) The endocannabinoid system in critical neurodevelopmental periods: sex differences and neuropsychiatric implications. J Psychopharmacol 26:164–176

    Article  CAS  PubMed  Google Scholar 

  181. Craft RM, Marusich JA, Wiley JL (2013) Sex differences in cannabinoid pharmacology: a reflection of differences in the endocannabinoid system? Life Sci 92:476–481

    Article  CAS  PubMed  Google Scholar 

  182. Dow-Edwards D, Frank A, Wade D, Weedon J, Izenwasser S (2016) Sexually-dimorphic alterations in cannabinoid receptor density depend upon prenatal/early postnatal history. Neurotoxicol Teratol 58:31–39

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Wagner EJ (2016) Sex differences in cannabinoid-regulated biology: a focus on energy homeostasis. Front Neuroendocrinol 40:101–109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Cooper ZD, Craft RM (2018) Sex-dependent effects of cannabis and cannabinoids: a translational perspective. Neuropsychopharmacology 43:34–51

    Article  CAS  PubMed  Google Scholar 

  185. Lee TT, Gorzalka BB (2012) Timing is everything: evidence for a role of corticolimbic endocannabinoids in modulating hypothalamic-pituitary-adrenal axis activity across developmental periods. Neuroscience 204:17–30

    Article  CAS  PubMed  Google Scholar 

  186. Schreiner F, Ackermann M, Michalik M, Hucklenbruch-Rother E, Bilkei-Gorzo A, Racz I, Bindila L, Lutz B, Dötsch J, Zimmer A, Woelfle J (2017) Developmental programming of somatic growth, behavior and endocannabinoid metabolism by variation of early postnatal nutrition in a cross-fostering mouse model. PLoS One 12:e0182754

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  187. Almeida MM, Dias-Rocha CP, Souza AS, Muros MF, Mendonca LS, Pazos-Moura CC, Trevenzoli IH (2017) Perinatal maternal high-fat diet induces early obesity and sex-specific alterations of the endocannabinoid system in white and brown adipose tissue of weanling rat offspring. Br J Nutr 118:788–803

    Article  CAS  PubMed  Google Scholar 

  188. Dias-Rocha CP, Almeida MM, Santana EM, Costa JCB, Franco JG, Pazos-Moura CC, Trevenzoli IH (2018) Maternal high-fat diet induces sex-specific endocannabinoid system changes in newborn rats and programs adiposity, energy expenditure and food preference in adulthood. J Nutr Biochem 51:56–68

    Article  CAS  PubMed  Google Scholar 

  189. Subbanna S, Shivakumar M, Psychoyos D, Xie S, Basavarajappa BS (2013) Anandamide-CB1 receptor signaling contributes to postnatal ethanol-induced neonatal neurodegeneration, adult synaptic, and memory deficits. J Neurosci 33:6350–6366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Subbanna S, Psychoyos D, Xie S, Basavarajappa BS (2015) Postnatal ethanol exposure alters levels of 2-arachidonylglycerol-metabolizing enzymes and pharmacological inhibition of monoacylglycerol lipase does not cause neurodegeneration in neonatal mice. J Neurochem 134:276–287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Gandhi K, Li C, German N, Skobowiat C, Carrillo M, Kallem RR, Larumbe E, Martinez S, Chuecos M, Ventolini G, Nathanielsz P, Schlabritz-Loutsevitch N (2018) Effect of maternal high-fat diet on key components of the placental and hepatic endocannabinoid system. Am J Physiol Endocrinol Metab 314:E322–E323

    Article  CAS  PubMed  Google Scholar 

  192. Long LE, Lind J, Webster M, Weickert CS (2012) Developmental trajectory of the endocannabinoid system in human dorsolateral prefrontal cortex. BMC Neurosci 13:87

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Fried PA (1982) Marihuana use by pregnant women and effects on offspring: an update. Neurobehav Toxicol Teratol 4:451–454

    CAS  PubMed  Google Scholar 

  194. Fried PA, O’Connell CM (1987) A comparison of the effects of prenatal exposure to tobacco, alcohol, cannabis and caffeine on birth size and subsequent growth. Neurotoxicol Teratol 9:79–85

    Article  CAS  PubMed  Google Scholar 

  195. Leech SL, Richardson GA, Goldschmidt L, Day NL (1999) Prenatal substance exposure: effects on attention and impulsivity of 6-year-olds. Neurotoxicol Teratol 21:109–118

    Article  CAS  PubMed  Google Scholar 

  196. 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 20:293–306

    Article  CAS  PubMed  Google Scholar 

  197. Goldschmidt L, Richardson GA, Cornelius MD, Day NL (2004) Prenatal marijuana and alcohol exposure and academic achievement at age 10. Neurotoxicol Teratol 26:521–532

    Article  CAS  PubMed  Google Scholar 

  198. 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 28:286–295

    Article  CAS  PubMed  Google Scholar 

  199. Smith A, Fried P, Hogan M, Cameron I (2004) The effects of prenatal and current marijuana exposure on response inhibition: a functional magnetic resonance imaging study. Brain Cogn 54:147–149

    CAS  PubMed  Google Scholar 

  200. Fried PA, James DS, Watkinson B (2001) Growth and pubertal milestones during adolescence in offspring prenatally exposed to cigarettes and marihuana. Neurotoxicol Teratol 23:431–436

    Article  CAS  PubMed  Google Scholar 

  201. Spear LP (2000) The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev 24:417–463

    Article  CAS  PubMed  Google Scholar 

  202. Meruelo AD, Castro N, Cota CI, Tapert SF (2017) Cannabis and alcohol use, and the developing brain. Behav Brain Res 325:44–50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Hall W, Degenhardt L (2009) Adverse health effects of non-medical cannabis use. Lancet 374:1383–1391

    Article  CAS  PubMed  Google Scholar 

  204. Galve-Roperh I, Chiurchiù V, Díaz-Alonso J, Bari M, Guzmán M, Maccarrone M (2013) Cannabinoid receptor signaling in progenitor/stem cell proliferation and differentiation. Prog Lipid Res 52:633–650

    Article  CAS  PubMed  Google Scholar 

  205. Kozela E, Juknat A, Vogel Z (2017) Modulation of astrocyte activity by cannabidiol, a nonpsychoactive cannabinoid. Int J Mol Sci 18:E1669

    Article  PubMed  CAS  Google Scholar 

  206. Rodríguez de Fonseca F, Ramos JA, Bonnin A, Fernández-Ruiz JJ (1993) Presence of cannabinoid binding sites in the brain from early postnatal ages. Neuroreport 4:135–138

    Article  PubMed  Google Scholar 

  207. Heng L, Beverley JA, Steiner H, Tseng KY (2011) Differential developmental trajectories for CB1 cannabinoid receptor expression in limbic/associative and sensorimotor cortical areas. Synapse 65:278–286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. 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 18:826–834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. 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 33:1113–1126

    Article  PubMed  Google Scholar 

  210. Schneider M, Koch M (2003) 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 28:1760–1769

    Article  CAS  PubMed  Google Scholar 

  211. 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 18:502–508

    Article  PubMed  Google Scholar 

  212. O’Shea M, McGregor IS, Mallet PE (2006) Repeated cannabinoid exposure during perinatal, adolescent or early adult ages produces similar long-lasting deficits in object recognition and reduced social interaction in rats. J Psychopharmacol 20:611–621

    Article  PubMed  Google Scholar 

  213. Marco EM, Rubino T, Adriani W, Viveros MP, Parolaro D, Laviola G (2009) Long-term consequences of URB597 administration during adolescence on cannabinoid CB1 receptor binding in brain areas. Brain Res 1257:25–31

    Article  CAS  PubMed  Google Scholar 

  214. Realini N, Vigano’ D, Guidali C, Zamberletti E, Rubino T, Parolaro D (2011) Chronic URB597 treatment at adulthood reverted most depressive-like symptoms induced by adolescent exposure to THC in female rats. Neuropharmacology 60:235–243

    Article  CAS  PubMed  Google Scholar 

  215. Lovelace JW, Corches A, Vieira PA, Hiroto AS, Mackie K, Korzus E (2015) An animal model of female adolescent cannabinoid exposure elicits a long-lasting deficit in presynaptic long-term plasticity. Neuropharmacology 99:242–255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  216. Ellgren M, Spano SM, Hurd YL (2007) Adolescent cannabis exposure alters opiate intake and opioid limbic neuronal populations in adult rats. Neuropsychopharmacology 32:607–615

    Article  CAS  PubMed  Google Scholar 

  217. Rubino T, Viganò D, Realini N, Guidali C, Braida D, Capurro V, Castiglioni C, Cherubino F, Romualdi P, Candeletti S, Sala M, Parolaro D (2008) Chronic delta 9-tetrahydrocannabinol during adolescence provokes sex-dependent changes in the emotional profile in adult rats: behavioral and biochemical correlates. Neuropsychopharmacology 33:2760–2771

    Article  CAS  PubMed  Google Scholar 

  218. Rubino T, Realini N, Braida D, Alberio T, Capurro V, Viganò D, Guidali C, Sala M, Fasano M, Parolaro D (2009) 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 15:291–302

    Article  CAS  PubMed  Google Scholar 

  219. Rubino T, Realini N, Braida D, Guidi S, Capurro V, Viganò D, Guidali C, Pinter M, Sala M, Bartesaghi R, Parolaro D (2009) Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are associated with cognitive impairment in adulthood. Hippocampus 19:763–772

    Article  CAS  PubMed  Google Scholar 

  220. Choi K, Le T, McGuire J, Xing G, Zhang L, Li H, Parker CC, Johnson LR, Ursano RJ (2012) Expression pattern of the cannabinoid receptor genes in the frontal cortex of mood disorder patients and mice selectively bred for high and low fear. J Psychiatr Res 46:882–889

    Article  PubMed  Google Scholar 

  221. 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 142:295–301

    Article  CAS  PubMed  Google Scholar 

  222. Bambico FR, Nguyen NT, Katz N, Gobbi G (2010) Chronic exposure to cannabinoids during adolescence but not during adulthood impairs emotional behavior and monoaminergic neurotransmission. Neurobiol Dis 37:641–655

    Article  CAS  PubMed  Google Scholar 

  223. Pijlman FT, Rigter SM, Hoek J, Goldschmidt HM, Niesink RJ (2005) Strong increase in total delta-THC in cannabis preparations sold in Dutch coffee shops. Addict Biol 10:171–180

    Article  CAS  PubMed  Google Scholar 

  224. Mehmedic Z, Chandra S, Slade D, Denham H, Foster S, Patel AS, Ross SA, Khan IA, ElSohly MA (2010) Potency trends of Δ9-THC and other cannabinoids in confiscated cannabis preparations from 1993 to 2008. J Forensic Sci 55:1209–1217

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The author is thankful to Dr. Dejian Ma and Dr. Wei Li (Dept. Pharmaceutical Sciences, University of Tennessee Health Science Center) for mass spectroscopy quantifications of cannabinoid levels in baboon blood and tissue samples. The author also extends gratitude to Dr. Syed Ali (US Food and Drug Administration) for critical reading of the manuscript and Dr. Richard Redfearn (Office of Scientific Writing, Office of Research, University of Tennessee Health Science Center) for editorial assistance. This work was supported by the National Institutes of Health grant number R21 AA022433 [ANB].

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  1. Department of Pharmacology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA

    Anna N. Bukiya

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    Anna N. Bukiya

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Bukiya, A.N. (2019). Physiology of the Endocannabinoid System During Development. In: Bukiya, A. (eds) Recent Advances in Cannabinoid Physiology and Pathology. Advances in Experimental Medicine and Biology, vol 1162. Springer, Cham. https://doi.org/10.1007/978-3-030-21737-2_2

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