Abstract
The endocannabinoid system (ECS) is an old and evolutionarily well preserved neurobiologic system controlling some key elements of organ homeostasis. In contrast to its long biologic history, the scientific record of the ECS is very short. Whereas the occurrence of genes for the endocannabinoid receptors has been described in ancient animals reaching at least as far back as the predecessor of tetrapods (amphibians reptiles, birds, and mammals), modern science has only more recently demonstrated that the ECS is involved in the regulation of a wide range of essential central and peripheral processes which include metabolism and feeding behavior, inflammatory- and anti-inflammatory immunologic reactions, neurobehavioral changes during stress and anxiety and the regulation of central functions such as cognition and memory. One of the most important roles of the ECS lies in the regulation and orchestration of the central and immunologic stress response to aversive and threatening life conditions. There are already data that the ECS is affected in humans during highly aversive conditions of parabolic flights and space flights as well as in other extreme living conditions (e.g. Antarctica). The ECS may therefore have an important function for adaption processes in such aversive conditions.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Abdulnour J, Yasari S, Rabasa-Lhoret R, Faraj M, Petrosino S, Piscitelli F, Prud’ Homme D, Di Marzo V (2014) Circulating endocannabinoids in insulin sensitive vs. insulin resistant obese postmenopausal women. A MONET group study. Obesity (Silver Spring) 22(1):211–216
Alarcón-Yaquetto DE, Caballero L, Gonzales GF (2017) Association between plasma N-Acylethanolamides and high hemoglobin concentration in Southern Peruvian highlanders. High Alt Med Biol 18(4):322–329
Al Suleimani YM, Al Mahruqi AS (2017) The endogenous lipid N-arachidonoyl glycine is hypotensive and nitric oxide-cGMP-dependent vasorelaxant. Eur J Pharmacol 794:209–215
Bab I, Ofek O, Tam J, Rehnelt J, Zimmer A (2008) Endocannabinoids and the regulation of bone metabolism. J Neuroendocrinol 20(Suppl 1):69–74
Bab IA, Yirmiya R (2010) Depression and bone mass. Ann N Y Acad Sci 1192:170–175
Baldassarri S, Bertoni A, Bagarotti A, Sarasso C, Zanfa M, Catani MV, Avigliano L, Maccarrone M, Torti M, Sinigaglia F (2008) The endocannabinoid 2-arachidonoylglycerol activates human platelets through non-CB1/CB2 receptors. J Thromb Haemost 6:1772–1779
Basavarajappa BS, Hungund BL (2005) Role of the endocannabinoid system in the development of tolerance to alcohol. Alcohol Alcohol 40:15–24
Batkai S, Pacher P, Osei-Hyiaman D, Radaeva S, Liu J, Harvey-White J, Offertaler L, Mackie K, Rudd MA, Bukoski RD, Kunos G (2004) Endocannabinoids acting at cannabinoid-1 receptors regulate cardiovascular function in hypertension. Circulation 110:1996–2002
Begg M, Mo FM, Offertaler L, Batkai S, Pacher P, Razdan RK, Lovinger DM, Kunos G (2003) G protein-coupled endothelial receptor for atypical cannabinoid ligands modulates a Ca2+-dependent K+ current. J Biol Chem 278:46188–46194
Bo Tan HBB, Rimmerman N, Srinivasan H, Yu YW, Krey JF, Monn MF, Chen JS-C, Hu SS-J, Pickens SR, Walker JM (2006) Targeted lipidomics: discovery of new fatty acyl amides. AAPS J 8(3):E461–E465
Bowles NP, Karatsoreos IN, Li X, Vemuri VK, Wood JA, Li Z, Tamashiro KL, Schwartz GJ, Makriyannis AM, Kunos G, Hillard CJ, McEwen BS, Hill MN (2015) A peripheral endocannabinoid mechanism contributes to glucocorticoid-mediated metabolic syndrome. Proc Natl Acad Sci U S A 112(1):285–290
Braun A, Engel T, Aguilar-Pimentel JA, Zimmer A, Jakob T, Behrendt H, Mempel M (2011) Beneficial effects of cannabinoids (CB) in a murine model of allergen-induced airway inflammation: Role of CB(1)/CB(2) receptors. Immunobiology 216(4):466–476
Brozoski DT, Dean C, Hopp FA, Seagard JL (2005) Uptake blockade of endocannabinoids in the NTS modulates baroreflex-evoked sympathoinhibition. Brain Res 1059:197–202
Chen DJ, Gao M, Gao FF, Su QX, Wu J (2017) Brain cannabinoid receptor 2: expression, function and modulation. Acta Pharmacol Sin 38:312–316
Chen Y, McCarron RM, Ohara Y, Bembry J, Azzam N, Lenz FA, Shohami E, Mechoulam R, Spatz M (2000) Human brain capillary endothelium: 2-arachidonoglycerol (endocannabinoid) interacts with endothelin-1. Circ Res 87:323–327
Chiurchiù V, van der Stelt M, Centonze D, Maccarrone M (2018) The endocannabinoid system and its therapeutic exploitation in multiple sclerosis: clues for other neuroinflammatory diseases. Prog Neurobiol 160:82–100
Chouker A, Kaufmann I, Kreth S, Hauer D, Feuerecker M, Thieme D, Vogeser M, Thiel M, Schelling G (2010) Motion sickness, stress and the endocannabinoid system. PLoS One 5:e10752
del Carmen García MA-GE, Celuch SM (2003) Hypotensive effect of anandamide through the activation of CB1 and VR1 spinal receptors in urethane-anesthetized rats. Naunyn Schmiedeberg's Arch Pharmacol 368(4):270–276
De Luca R, Mazur K, Kernder A, Suvorava T, Kojda G, Haas HL, Sergeeva OA (2018) Mechanisms of N-oleoyldopamine activation of central histaminergic neurons. Neuropharmacology 143:327–338
Di Marzo V, Verrijken A, Hakkarainen A, Petrosino S, Mertens I, Lundbom N, Piscitelli F, Westerbacka J, Soro-Paavonen A, Matias I, Van Gaal L, Taskinen MR (2009) Role of insulin as a negative regulator of plasma endocannabinoid levels in obese and nonobese subjects. Eur J Endocrinol 161(5):715–722
Dotsey E, Ushach I, Pone E, Nakajima R, Jasinskas A, Argueta DA, Dillon A, DiPatrizio N, Davies H, Zlotnik A, Crompton PD, Felgner PL (2017) Transient cannabinoid Receptor 2 blockade during immunization heightens intensity and breadth of antigen-specific antibody responses in young and aged mice. Sci Rep 7:42584
Devane WA, Dysarz FA 3rd, Johnson MR, Melvin LS, Howlett AC (1988) Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 34:605–613
Dlugos A, Childs E, Stuhr KL, Hillard CJ, de Wit H (2012) Acute stress increases circulating anandamide and other N-acylethanolamines in healthy humans. Neuropsychopharmacology 37:2416–2427
Duncan M, Millns P, Smart D, Wright JE, Kendall DA, Ralevic V (2004) Noladin ether, a putative endocannabinoid, attenuates sensory neurotransmission in the rat isolated mesenteric arterial bed via a non-CB1/CB2 G(i/o) linked receptor. Br J Pharmacol 142:509–518
Durst R, Danenberg H, Gallily R, Mechoulam R, Meir K, Grad E, Beeri R, Pugatsch T, Tarsish E, Lotan C (2007) Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury. Am J Physiol Heart Circ Physiol 293:H3602–H3607
Effimia Gkoumassi BGJDMJD, Elzinga CRS, Hasenbosch RE, Meurs H, Nelemans SA, Schmidt M, Zaagsma J (2009) (Endo)cannabinoids mediate different Ca2+ entry mechanisms in human bronchial epithelial cells. Naunyn-Schmied Arch Pharmacol 380(1):67–77
Feuerecker M, Hauer D, Toth R, Demetz F, Holzl J, Thiel M, Kaufmann I, Schelling G, Chouker A (2012) Effects of exercise stress on the endocannabinoid system in humans under field conditions. Eur J Appl Physiol 112:2777–2781
Ford WR, Honan SA, White R, Hiley CR (2002) Evidence of a novel site mediating anandamide-induced negative inotropic and coronary vasodilatator responses in rat isolated hearts. Br J Pharmacol 135:1191–1198
Freemon FR (1972) Effects of marihuana on sleeping states. JAMA 220:1364–1365
Gatta-Cherifi B, Matias I, Vallée M, Tabarin A, Marsicano G, Piazza PV, Cota D (2012) Simultaneous postprandial deregulation of the orexigenic endocannabinoid anandamide and the anorexigenic peptide YY in obesity. Int J Obes (Lond) 36(6):880–885
Gauthier KM, Baewer DV, Hittner S, Hillard CJ, Nithipatikom K, Reddy DS, Falck JR, Campbell WB (2005) Endothelium-derived 2-arachidonylglycerol: an intermediate in vasodilatory eicosanoid release in bovine coronary arteries. Am J Physiol Heart Circ Physiol 288:H1344–H1351
Godlewski G, Offertaler L, Osei-Hyiaman D, Mo FM, Harvey-White J, Liu J, Davis MI, Zhang L, Razdan RK, Milman G, Pacher P, Mukhopadhyay P, Lovinger DM, Kunos G (2009) The endogenous brain constituent N-arachidonoyl L-serine is an activator of large conductance Ca2+-activated K+ channels. J Pharmacol Exp Ther 328:351–361
Grabiec U, Dehghani F (2017) N-Arachidonoyl dopamine: a novel endocannabinoid and endovanilloid with widespread physiological and pharmacological activities. Cannabis Cannabinoid Res 2(1):183–196. https://doi.org/10.1089/can
Hanlon EC, Tasali E, Leproult R, Stuhr KL, Doncheck E, de Wit H, Hillard CJ, Van Cauter E (2016) Sleep restriction enhances the daily rhythm of circulating levels of endocannabinoid 2-arachidonoylglycerol. Sleep 39(3):653–664
Hauer D, Schelling G, Gola H, Campolongo P, Morath J, Roozendaal B, Hamuni G, Karabatsiakis A, Atsak P, Vogeser M, Kolassa IT (2013) Plasma concentrations of endocannabinoids and related primary fatty acid amides in patients with post-traumatic stress disorder. PLoS One 8:e62741
Hauer D, Weis F, Papassotiropoulos A, Schmoeckel M, Lieke J, Kaufmann I, Kirchhoff F, Vogeser M, Roozendaal B, Briegel J, de Quervain D, Schelling G (2010) Relationship of a common polymorphism of the glucocorticoid receptor gene to traumatic memories and posttraumatic stress disorder in patients after intensive care therapy. Crit Care Med 30:7
Hayase T (2007) Chronologically overlapping occurrences of nicotine-induced anxiety- and depression-related behavioral symptoms: effects of anxiolytic and cannabinoid drugs. BMC Neurosci 8:76
Hayase T (2008) Nicotine (NC)-induced “depressive” behavioral symptoms and effects of antidepressants including cannabinoids (CBs). J Toxicol Sci 33:555–564
Herrera-Solis A, Vasquez KG, Prospero-Garcia O (2010) Acute and subchronic administration of anandamide or oleamide increases REM sleep in rats. Pharmacol Biochem Behav 95:106–112
Hill MN, McEwen BS (2009a) Involvement of the endocannabinoid system in the neurobehavioural effects of stress and glucocorticoids. Prog Neuro-Psychopharmacol Biol Psychiatry. https://doi.org/10.1016/j.pnpbp.2009.11.001
Hill MN, McEwen BS (2009b) Endocannabinoids: the silent partner of glucocorticoids in the synapse. Proc Natl Acad Sci U S A 106:4579–4580
Hill MN, Miller GE, Carrier EJ, Gorzalka BB, Hillard CJ (2009) Circulating endocannabinoids and N-acyl ethanolamines are differentially regulated in major depression and following exposure to social stress. Psychoneuroendocrinology 34:1257–1262
Hill MN, Bierer LM, Makotkine I, Golier JA, Galea S, McEwen BS, Hillard CJ, Yehuda R (2013) Reductions in circulating endocannabinoid levels in individuals with post-traumatic stress disorder following exposure to the World Trade Center attacks. Psychoneuroendocrinology 38:2952–2961
Hillard CJ. (2018) Circulating endocannabinoids: from whence do they come and where are they going? Neuropsychopharmacology:155–172
Ho WS, Barrett DA, Randall MD (2008) ‘Entourage’ effects of N-palmitoylethanolamide and N-oleoylethanolamide on vasorelaxation to anandamide occur through TRPV1 receptors. Br J Pharmacol 155:837–846
Howlett AC (2005) Cannabinoid receptor signaling. Handb Exp Pharmacol 168:53–79
Im DS (2009) New intercellular lipid mediators and their GPCRs: an update. Prostaglandins Other Lipid Mediat 89:53–56
Jhaveri MD, Richardson D, Kendall DA, Barrett DA, Chapman V (2006) Analgesic effects of fatty acid amide hydrolase inhibition in a rat model of neuropathic pain. J Neurosci 26:13318–13327
Joseph J, Niggemann B, Zaenker KS, Entschladen F (2004) Anandamide is an endogenous inhibitor for the migration of tumor cells and T lymphocytes. Cancer Immunol Immunother 53:723–728
Jones EK, Kirkham TC (2012) Noladin ether, a putative endocannabinoid, enhances motivation to eat after acute systemic administration in rats. Br J Pharmacol 166(6):1815–1821
Jumpertz R, Wiesner T, Bluher M, Engeli S, Batkai S, Wirtz H, Bosse-Henck A, Stumvoll M (2010) Circulating endocannabinoids and N-acyl-ethanolamides in patients with sleep apnea-specific role of oleoylethanolamide. Exp Clin Endocrinol Diabetes 118:591–595
Jyotaki M, Shigemura N, Ninomiya Y (2010) Modulation of sweet taste sensitivity by orexigenic and anorexigenic factors. Endocr J 57:467–475
Karsak M, Cohen-Solal M, Freudenberg J, Ostertag A, Morieux C, Kornak U, Essig J, Erxlebe E, Bab I, Kubisch C, de Vernejoul MC, Zimmer A (2005) Cannabinoid receptor type 2 gene is associated with human osteoporosis. Hum Mol Genet 14:3389–3396
Kaufmann I, Hauer D, Huge V, Vogeser M, Campolongo P, Chouker A, Thiel M, Schelling G (2009) Enhanced anandamide plasma levels in patients with complex regional pain syndrome following traumatic injury: a preliminary report. Eur Surg Res 43:325–329
Klein TW, Newton C, Larsen K, Lu L, Perkins I, Nong L, Friedman H (2003) The cannabinoid system and immune modulation. J Leukoc Biol 74:486–496
Knight JM, Szabo A, Zhao S, Lyness JM, Sahler OJ, Liesveld JL, Sander T, Rizzo JD, Hillard CJ, Moynihan JA (2015) Circulating endocannabinoids during hematopoietic stem cell transplantation: a pilot study. Neurobiol Stress 2:44–50
Koethe D, Schreiber D, Giuffrida A, Mauss C, Faulhaber J, Heydenreich B, Hellmich M, Graf R, Klosterkotter J, Piomelli D, Leweke FM (2009) Sleep deprivation increases oleoylethanolamide in human cerebrospinal fluid. J Neural Transm 116:301–305
Konieczny J, Przegalinski E, Pokorski M (2009) N-Oleoyl-dopamine decreases muscle rigidity induced by reserpine in rats. Int J Immunopathol Pharmacol 22:21–28
Kozlowska H, Baranowska M, Schlicker E, Kozlowski M, Laudanski J, Malinowska B (2008) Virodhamine relaxes the human pulmonary artery through the endothelial cannabinoid receptor and indirectly through a COX product. Br J Pharmacol 155:1034–1042
Krumbholz A, Anielski P, Reisch N, Schelling G, Thieme D (2013) Diagnostic value of concentration profiles of glucocorticosteroids and endocannabinoids in hair. Ther Drug Monit 35:600–607
Krylatov AV, Maslov LN, Ermakov S, Lasukova OV, Barzakh EI, Crawford D, Pertwee RG (2007) Significance of cardiac cannabinoid receptors in regulation of cardiac rhythm, myocardial contractility, and electrophysiologic processes in heart. Izv Akad Nauk Ser Biol 1:35–44
Ledent C, Valverde O, Cossu G, Petitet F, Aubert JF, Beslot F, Bohme GA, Imperato A, Pedrazzini T, Roques BP, Vassart G, Fratta W, Parmentier M (1999) Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. Science 283:401–404
Maccarrone M, Pauselli R, Di Rienzo M, Finazzi-Agro A (2002) Binding, degradation and apoptotic activity of stearoylethanolamide in rat C6 glioma cells. Biochem J 366:137–144
Maccarrone M, Lorenzon T, Bari M, Melino G, Finazzi-Agro A (2000) Anandamide induces apoptosis in human cells via vanilloid receptors. Evidence for a protective role of cannabinoid receptors. J Biol Chem 275:31938–31945
Mach F, Steffens S (2008) The role of the endocannabinoid system in atherosclerosis. J Neuroendocrinol 20(Suppl 1):53–57
Maeda N, Osanai T, Kushibiki M, Fujiwara T, Tamura Y, Oowada S, Higuma T, Sasaki S, Yokoyama J, Yoshimachi F, Matsunaga T, Hanada H, Okumura K (2009) Increased serum anandamide level at ruptured plaque site in patients with acute myocardial infarction. Fundam Clin Pharmacol 23:351–357
Mallet PEB, Beninger RJ (1996) The endogenous cannabinoid receptor agonist anandamide impairs memory in rats. Behav Pharmacol 7:261–275
Mechoulam R, Gaoni Y (1965) A total synthesis of Dl-delta-1-tetrahydrocannabinol, the active constituent of hashish. J Am Chem Soc 87:3273–3275
Mechoulam R, Fride E, Hanus L, Sheskin T, Bisogno T, Di Marzo V, Bayewitch M, Vogel Z (1997) Anandamide may mediate sleep induction. Nature 389:25–26
Monteleone AM, Di Marzo V, Monteleone P, Dalle Grave R, Aveta T, Ghoch ME, Piscitelli F, Volpe U, Calugi S, Maj M (2016) Responses of peripheral endocannabinoids and endocannabinoid-related compounds to hedonic eating in obesity. Eur J Nutr 55(4):1799–1805
Movahed P, Evilevitch V, Andersson TL, Jonsson BA, Wollmer P, Zygmunt PM, Hogestatt ED (2005) Vascular effects of anandamide and N-acylvanillylamines in the human forearm and skin microcirculation. Br J Pharmacol 146:171–179
Mulawa EA, Kirkwood JS, Wolfe LM, Wojda SJ, Prenni JE, Florant GL, Donahue SW (2018) Seasonal changes in endocannabinoid concentrations between active and hibernating marmots (marmota flaviventris). J Biol Rhythms 33(4):388–401
Murillo-Rodriguez E, Sanchez-Alavez M, Navarro L, Martinez-Gonzalez D, Drucker-Colin R, Prospero-Garcia O (1998) Anandamide modulates sleep and memory in rats. Brain Res 812:270–274
Neumeister A, Normandin MD, Pietrzak RH, Piomelli D, Zheng MQ, Gujarro-Anton A, Potenza MN, Bailey CR, Lin SF, Najafzadeh S, Ropchan J, Henry S, Corsi-Travali S, Carson RE, Huang Y (2013) Elevated brain cannabinoid CB receptor availability in post-traumatic stress disorder: a positron emission tomography study. Mol Psychiatry 18(9):1034–1040
Niederhoffer N, Szabo B (1999) Effect of the cannabinoid receptor agonist WIN55212-2 on sympathetic cardiovascular regulation. Br J Pharmacol 126:457–466
O’Sullivan SE, Kendall DA (2009) Cannabinoid activation of peroxisome proliferator-activated receptors: potential for modulation of inflammatory disease. Immunobiology 215(8):611–616
Ofek O, Karsak M, Leclerc N, Fogel M, Frenkel B, Wright K, Tam J, Attar-Namdar M, Kram V, Shohami E, Mechoulam R, Zimmer A, Bab I (2006) Peripheral cannabinoid receptor, CB2, regulates bone mass. Proc Natl Acad Sci U S A 103:696–701
Offertaler L, Mo FM, Batkai S, Liu J, Begg M, Razdan RK, Martin BR, Bukoski RD, Kunos G (2003) Selective ligands and cellular effectors of a G protein-coupled endothelial cannabinoid receptor. Mol Pharmacol 63:699–705
Olatinsu AO, Sihag J, Jones PJH (2017) Relationship between circulating fatty acids and fatty acid ethanolamide levels after a single 2-h dietary fat feeding in male Sprague-dawley rats: elevated levels of oleoylethanolamide, palmitoylethanolamide, linoleoylethanolamide, arachidonoylethanolamide and docosahexanoylethanolamide after a single 2 h dietary fat feeding in male Sprague Dawley rats. Lipids 52(11):901–906
Pacher P, Mechoulam R (2011) Is lipid signaling through cannabinoid 2 receptors part of a protective system? Prog Lipid Res 50(2):193–211
Pacher P, Batkai S, Kunos G (2006) The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 58:389–462
Pandey R, Mousawy K, Nagarkatti M, Nagarkatti P (2009) Endocannabinoids and immune regulation. Pharmacol Res 60:85–92
Panikashvili D, Shein NA, Mechoulam R, Trembovler V, Kohen R, Alexandrovich A, Shohami E (2006) The endocannabinoid 2-AG protects the blood-brain barrier after closed head injury and inhibits mRNA expression of proinflammatory cytokines. Neurobiol Dis 22(2):257–264
Parmar N, Ho WS (2010) N-Arachidonoyl glycine, an endogenous lipid that acts as a vasorelaxant via nitric oxide and large conductance calcium-activated potassium channels. Br J Pharmacol 160:594–603
Pertwee RG (2001) Cannabinoid receptors and pain. Prog Neurobiol 63:569–611
Pertwee RG, Ross RA (2002) Cannabinoid receptors and their ligands. Prostaglandins Leukot Essent Fatty Acids 66:101–121
Pfitzer T, Niederhoffer N, Szabo B (2005) Search for an endogenous cannabinoid-mediated effect in the sympathetic nervous system. Naunyn Schmiedeberg’s Arch Pharmacol 371:9–17
Piro JR, Suidan GL, Quan J, Pi Y, O’Neill SM, Ilardi M, Pozdnyakov N, Lanz TA, Xi H, Bell RD, Samad TA (2018) Inhibition of 2-AG hydrolysis differentially regulates blood brain barrier permeability after injury. J Neuroinflammation 15(1):142
Pisanti S, Borselli C, Oliviero O, Laezza C, Gazzerro P, Bifulco M (2007) Antiangiogenic activity of the endocannabinoid anandamide: correlation to its tumor-suppressor efficacy. J Cell Physiol 211:495–503
Przegalinski E, Filip M, Zajac D, Pokorski M (2006) N-Oleoyl-dopamine increases locomotor activity in the rat. Int J Immunopathol Pharmacol 19:897–904
Randall MD, Kendall DA, O’Sullivan S (2004) The complexities of the cardiovascular actions of cannabinoids. Br J Pharmacol 142:20–26
Sah P (2002) Never fear, cannabinoids are here. Nature 418:488–489
Sancho R, Macho A, de La Vega L, Calzado MA, Fiebich BL, Appendino G, Munoz E (2004) Immunosuppressive activity of endovanilloids: N-arachidonoyl-dopamine inhibits activation of the NF-kappa B, NFAT, and activator protein 1 signaling pathways. J Immunol 172:2341–2351
Schmidt A, Brune K, Hinz B (2006) Determination of the endocannabinoid anandamide in human plasma by high-performance liquid chromatography. Biomed Chromatogr 20:336–342
Schroeder C, Batkai S, Engeli S, Tank J, Diedrich A, Luft FC, Jordan J (2009) Circulating endocannabinoid concentrations during orthostatic stress. Clin Auton Res 19:343–346
Schloss MJ, Horckmans M, Guillamat-Prats R, Hering D, Lauer E, Lenglet S, Weber C, Thomas A, Steffens S (2019) 2-Arachidonoylglycerol mobilizes myeloid cells and worsens heart function after acute myocardial infarction. Cardiovasc Res 115(3):602–613
Selye H (1936) Syndrome produced by diverse nocuous agents. Nature 138:32
Sergeeva OA, De Luca R, Mazur K, Chepkova AN, Haas HL, Bauer A (2017) N-oleoyldopamine modulates activity of midbrain dopaminergic neurons through multiple mechanisms. Neuropharmacology 119:111–122
Sido JM, Nagarkatti PS, Nagarkatti M (2016) Production of endocannabinoids by activated T cells and B cells modulates inflammation associated with delayed-type hypersensitivity. Eur J Immunol 46:1472–1479
Singh P, Sharma P, Nakade UP, Sharma A, Gari M, Choudhury S, Shukla A, Garg SK (2018) Endocannabinoid-mediated modulation of Gq protein-coupled receptor mediates vascular hyporeactivity to nor-adrenaline during polymicrobial sepsis. Pharmacol Rep 70(6):1150–1157
Sophocleous A, Marino S, Kabir D, Ralston SH, Idris AI (2017) Combined deficiency of the Cnr1 and Cnr2 receptors protects against age-related bone loss by osteoclast inhibition. Aging Cell 16(5):1051–1061
Steiner MA, Wotjak CT (2008) Role of the endocannabinoid system in regulation of the hypothalamic-pituitary-adrenocortical axis. Prog Brain Res 170:397–432
Stephen V, Mahler KSS, Berridge KC (2007) Endocannabinoid hedonic hotspot for sensory pleasure: anandamide in nucleus accumbens shell enhances ‘liking’ of a sweet reward. Neuropsychopharmacology 32(11):2267–2278
Steudte S, Kirschbaum C, Gao W, Alexander N, Schonfeld S, Hoyer J, Stalder T (2013) Hair cortisol as a biomarker of traumatization in healthy individuals and posttraumatic stress disorder patients. Biol Psychiatry 74:639–646
Sticht MA, Limebeer CL, Rafla BR, Abdullah RA, Poklis JL, Ho W, Niphakis MJ, Cravatt BF, Sharkey KA, Lichtman AH, Parker LA (2016) Endocannabinoid regulation of nausea is mediated by 2-arachidonoylglycerol (2-AG) in the rat visceral insular cortex. Neuropharmacology 102:92–102
Storozhuk MV, Zholos AV (2018) TRP channels as novel targets for endogenous ligands: focus on endocannabinoids and nociceptive signalling. Curr Neuropharmacol 16:137–150
Strewe C, Feuerecker M, Nichiporuk I, Kaufmann I, Hauer D, Morukov B, Schelling G, Chouker A (2012) Effects of parabolic flight and spaceflight on the endocannabinoid system in humans. Rev Neurosci 23:673–680
Strewe C, Thieme D, Dangoisse C, Fiedel B, van den Berg F, Bauer H, Salam AP, Gössmann-Lang P, Campolongo P, Moser D, Quintens R, Moreels M, Baatout S, Kohlberg E, Schelling G, Choukèr A, Feuerecker M (2018) Modulations of neuroendocrine stress responses during confinement in antarctica and the role of hypobaric hypoxia. Front Physiol 9:1647
Strollo F (1999) Hormonal changes in humans during spaceflight. Adv Space Biol Med 7:99–129
Su JY, Vo AC (2007) 2-Arachidonylglyceryl ether and abnormal cannabidiol-induced vascular smooth muscle relaxation in rabbit pulmonary arteries via receptor-pertussis toxin sensitive G proteins-ERK1/2 signaling. Eur J Pharmacol 559:189–195
Sun Y, Alexander SP, Garle MJ, Gibson CL, Hewitt K, Murphy SP, Kendall DA, Bennett AJ (2007) Cannabinoid activation of PPAR alpha; a novel neuroprotective mechanism. Br J Pharmacol 152:734–743
Sunano S, Watanabe H, Tanaka S, Sekiguchi F, Shimamura K (1999) Endothelium-derived relaxing, contracting and hyperpolarizing factors of mesenteric arteries of hypertensive and normotensive rats. Br J Pharmacol 126:709–716
Tanasescu R, Constantinescu CS (2010) Cannabinoids and the immune system: an overview. Immunobiology 215:588–597
Tasker J (2004) Endogenous cannabinoids take the edge off neuroendocrine responses to stress. Endocrinology 145:5429–5430
Terrazzino S, Berto F, Dalle Carbonare M, Fabris M, Guiotto A, Bernardini D, Leon A (2004) Stearoylethanolamide exerts anorexic effects in mice via down-regulation of liver stearoyl-coenzyme A desaturase-1 mRNA expression. FASEB J 18:1580–1582
Thieme U, Schelling G, Hauer D, Greif R, Dame T, Laubender RP, Bernhard W, Thieme D, Campolongo P, Theiler L (2014) Quantification of anandamide and 2-arachidonoylglycerol plasma levels to examine potential influences of tetrahydrocannabinol application on the endocannabinoid system in humans. Drug Test Anal 6:17–23
Tsuboi K, Uyama T, Okamoto Y, Ueda N (2018) Endocannabinoids and related N-acylethanolamines: biological activities and metabolism. Inflamm Regen. 38:28
Vaughn LK, Denning G, Stuhr KL, de Wit H, Hill MN, Hillard CJ (2010) Endocannabinoid signalling: has it got rhythm? Br J Pharmacol 160:530–543
Venderova K, Brown TM, Brotchie JM (2005) Differential effects of endocannabinoids on [(3)H]-GABA uptake in the rat globus pallidus. Exp Neurol 194:284–287
Vogeser M, Schelling G (2007) Pitfalls in measuring the endocannabinoid 2-arachidonoyl glycerol in biological samples. Clin Chem Lab Med 45:1023–1025
Vogeser M, Hauer D, Christina Azad S, Huber E, Storr M, Schelling G (2006) Release of anandamide from blood cells. Clin Chem Lab Med 44:488–491
Vuong LA, Mitchell VA, Vaughan CW (2008) Actions of N-arachidonyl-glycine in a rat neuropathic pain model. Neuropharmacology 54:189–193
Wagner JA, Abesser M, Karcher J, Laser M, Kunos G (2005) Coronary vasodilator effects of endogenous cannabinoids in vasopressin-preconstricted unpaced rat isolated hearts. J Cardiovasc Pharmacol 46:348–355
Wagner JA, Varga K, Ellis EF, Rzigalinski BA, Martin BR, Kunos G (1997) Activation of peripheral CB1 cannabinoid receptors in haemorrhagic shock. Nature 390:518–521
Wagner JA, Hu K, Bauersachs J, Karcher J, Wiesler M, Goparaju SK, Kunos G, Ertl G (2001) Endogenous cannabinoids mediate hypotension after experimental myocardial infarction. J Am Coll Cardiol 38:2048–2054
Weis F, Beiras-Fernandez A, Sodian R, Kaczmarek I, Reichart B, Beiras A, Schelling G, Kreth S (2010) Substantially altered expression pattern of cannabinoid receptor 2 and activated endocannabinoid system in patients with severe heart failure. J Mol Cell Cardiol 48:1187–1193
Wheal AJ, Alexander SP, Randall MD (2010) Vasorelaxation to N-oleoylethanolamine in rat isolated arteries: mechanisms of action and modulation via cyclooxygenase activity. Br J Pharmacol 160:701–711
White R, Hiley CR (1998) The actions of some cannabinoid receptor ligands in the rat isolated mesenteric artery. Br J Pharmacol 125:533–541
Wilker S, Pfeiffer A, Elbert T, Ovuga E, Karabatsiakis A, Krumbholz A, Thieme D, Schelling G, Kolassa IT (2016) Endocannabinoid concentrations in hair are associated with PTSD symptom severity. Psychoneuroendocrinology 67:198–206
Yi B, Nichiporuk I, Nicolas M, Schneider S, Feuerecker M, Vassilieva G, Thieme D, Schelling G, Choukèr A (2016) Reductions in circulating endocannabinoid 2-arachidonoylglycerol levels in healthy human subjects exposed to chronic stressors. Prog Neuropsychopharmacol Biol Psychiatry 67:92–97
Zona LC, Fry BR, LaLonde JA, Cromwell HC (2017) Effects of anandamide administration on components of reward processing during free choice. Pharmacol Biochem Behav 158:14–21
Zhang X, Maor Y, Wang JF, Kunos G, Groopman JE (2010) Endocannabinoid-like N-arachidonoyl serine is a novel pro-angiogenic mediator. Br J Pharmacol 160:1583–1594
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Hauer, D., Toth, R., Schelling, G. (2020). Endocannabinoids, “New-Old” Mediators of Stress Homeostasis. In: Choukèr, A. (eds) Stress Challenges and Immunity in Space. Springer, Cham. https://doi.org/10.1007/978-3-030-16996-1_10
Download citation
DOI: https://doi.org/10.1007/978-3-030-16996-1_10
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-16995-4
Online ISBN: 978-3-030-16996-1
eBook Packages: MedicineMedicine (R0)