Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Biology of Mood & Anxiety Disorders
Published in: Biology of Mood & Anxiety Disorders 1/2013

Open Access 01-12-2013 | Review

Translational evidence for the involvement of the endocannabinoid system in stress-related psychiatric illnesses

Authors: Matthew N Hill, Sachin Patel

Published in: Biology of Mood & Anxiety Disorders | Issue 1/2013

Login to get access

Abstract

Accumulating evidence over the past decade has highlighted an important role of the endocannabinoid (eCB) system in the regulation of stress and emotional behavior across divergent species, from rodents to humans. The general findings from this work indicate that the eCB system plays an important role in gating and buffering the stress response, dampening anxiety and regulating mood. Work in rodents has allowed researchers to determine the neural mechanisms mediating this relationship while work in human populations has demonstrated the possible importance of this system in stress-related psychiatric diseases, such as post-traumatic stress disorder, generalized anxiety and major depression. These stress-protective effects of eCB signaling appear to be primarily mediated by their actions within corticolimbic structures, particularly the amygdala and the prefrontal cortex. The aim of this review is to provide an up-to-date discussion of the current level of knowledge in this field, as well as address the current gaps in knowledge and specific areas of research that require attention.
Appendix
Available only for authorised users
Literature
1.
Katona I, Freund TF: Multiple functions of endocannabinoid signaling in the brain. Annu Rev Neurosci. 2012, 35: 529-558. 10.1146/annurev-neuro-062111-150420.PubMedCentralPubMed
2.
Atwood BK, Straiker A, Mackie K: CB2: therapeutic target-in-waiting. Prog Neuropsychopharmacol Biol Psychiatry. 2012, 38 (1): 16-20. 10.1016/j.pnpbp.2011.12.001.PubMedCentralPubMed
3.
Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M: Endocannabinoid-mediated control of synaptic transmission. Physiological Rev. 2009, 89 (1): 309-380. 10.1152/physrev.00019.2008.
4.
Ahn K, McKinney MK, Cravatt BF: Enzymatic pathways that regulate endocannabinoid signaling in the nervous system. Chem Rev. 2008, 108 (5): 1687-1707. 10.1021/cr0782067.PubMedCentralPubMed
5.
Gorzalka BB, Hill MN, Hillard CJ: Regulation of endocannabinoid signaling by stress: implications for stress-related affective disorders. Neurosci Biobehav Rev. 2008, 32 (6): 1152-1160. 10.1016/j.neubiorev.2008.03.004.PubMed
6.
Blankman JL, Cravatt BF: Chemical probes of endocannabinoid metabolism. Pharmacol Rev. 2013, 65 (2): 849-871. 10.1124/pr.112.006387.PubMedCentralPubMed
7.
Haller J, Varga B, Ledent C, Barna I, Freund TF: Context-dependent effects of CB1 cannabinoid gene disruption on anxiety-like and social behaviour in mice. Eur J Neurosci. 2004, 19 (7): 1906-1912. 10.1111/j.1460-9568.2004.03293.x.PubMed
8.
Mikics E, Vas J, Aliczki M, Halasz J, Haller J: Interactions between the anxiogenic effects of CB1 gene disruption and 5-HT3 neurotransmission. Behav Pharmacol. 2009, 20 (3): 265-272. 10.1097/FBP.0b013e32832c70b1.PubMed
9.
Jacob W, Yassouridis A, Marsicano G, Monory K, Lutz B, Wotjak CT: Endocannabinoids render exploratory behaviour largely independent of the test aversiveness: role of glutamatergic transmission. Genes Brain Behav. 2009, 8 (7): 685-698. 10.1111/j.1601-183X.2009.00512.x.PubMed
10.
Maccarrone M, Valverde O, Barbaccia ML, Castane A, Maldonado R, Ledent C, Parmentier M, Finazzi-Agro A: Age-related changes of anandamide metabolism in CB1 cannabinoid receptor knockout mice: Correlation with behaviour. Eur J Neurosci. 2002, 15 (7): 1178-1186. 10.1046/j.1460-9568.2002.01957.x.PubMed
11.
Uriguen L, Perez-Rial S, Ledent C, Palomo T, Manzanares J: Impaired action of anxiolytic drugs in mice deficient in cannabinoid CB1 receptors. Neuropharmacology. 2004, 46 (7): 966-973. 10.1016/j.neuropharm.2004.01.003.PubMed
12.
Hill MN, Hillard CJ, McEwen BS: Alterations in corticolimbic dendritic morphology and emotional behavior in cannabinoid CB1 receptor-deficient mice parallel the effects of chronic stress. Cereb Cortex. 2011, 21 (9): 2056-2064. 10.1093/cercor/bhq280.PubMedCentralPubMed
13.
Martin M, Ledent C, Parmentier M, Maldonado R, Valverde O: Involvement of CB1 cannabinoid receptors in emotional behaviour. Psychopharmacology (Berl). 2002, 159 (4): 379-387. 10.1007/s00213-001-0946-5.
14.
Haller J, Bakos N, Szirmay M, Ledent C, Freund TF: The effects of genetic and pharmacological blockade of the CB1 cannabinoid receptor on anxiety. Eur J Neurosci. 2002, 16 (7): 1395-1398. 10.1046/j.1460-9568.2002.02192.x.PubMed
15.
Marsicano G, Wotjak CT, Azad SC, Bisogno T, Rammes G, Cascio MG, Hermann H, Tang J, Hofmann C, Zieglgansberger W, Di Marzo V, et al: The endogenous cannabinoid system controls extinction of aversive memories. Nature. 2002, 418 (6897): 530-534. 10.1038/nature00839.PubMed
16.
Rey AA, Purrio M, Viveros MP, Lutz B: Biphasic effects of cannabinoids in anxiety responses: CB1 and GABAB receptors in the balance of GABAergic and glutamatergic neurotransmission. Neuropsychopharmacology. 2012, 37 (12): 2624-2634. 10.1038/npp.2012.123.PubMedCentralPubMed
17.
Dubreucq S, Matias I, Cardinal P, Haring M, Lutz B, Marsicano G, Chaouloff F: Genetic dissection of the role of cannabinoid type-1 receptors in the emotional consequences of repeated social stress in mice. Neuropsychopharmacology. 2012, 37 (8): 1885-1900. 10.1038/npp.2012.36.PubMedCentralPubMed
18.
Navarro M, Hernandez E, Munoz RM, Del Arco I, Villanua MA, Carrera MR, Rodriguez DeFonseca F: Acute administration of the CB1 cannabinoid receptor antagonist SR 141716A induces anxiety-like responses in the rat. Neuroreport. 1997, 8 (2): 491-496. 10.1097/00001756-199701200-00023.PubMed
19.
Patel S, Hillard CJ: Pharmacological evaluation of cannabinoid receptor ligands in a mouse model of anxiety: further evidence for an anxiolytic role for endogenous cannabinoid signaling. J Pharmacol Exp Ther. 2006, 318 (1): 304-311. 10.1124/jpet.106.101287.PubMed
20.
Arevalo C, De Miguel R, Hernandez-Tristan R: Cannabinoid effects on anxiety-related behaviours and hypothalamic neurotransmitters. Pharmacol Biochem Behav. 2001, 70 (1): 123-131. 10.1016/S0091-3057(01)00578-0.PubMed
21.
Haller J, Varga B, Ledent C, Freund TF: CB1 cannabinoid receptors mediate anxiolytic effects: convergent genetic and pharmacological evidence with CB1-specific agents. Behav Pharmacol. 2004, 15 (4): 299-304. 10.1097/01.fbp.0000135704.56422.40.PubMed
22.
Rodgers RJ, Evans PM, Murphy A: Anxiogenic profile of AM-251, a selective cannabinoid CB1 receptor antagonist, in plus-maze-naive and plus-maze-experienced mice. Behav Pharmacol. 2005, 16 (5–6): 405-413.PubMed
23.
Gamble-George JC, Conger JR, Hartley ND, Gupta P, Sumislawski JJ, Patel S: Dissociable effects of CB1 receptor blockade on anxiety-like and consummatory behaviors in the novelty-induced hypophagia test in mice. Psychopharmacology (Berl). 2013, 228: 401-409. 10.1007/s00213-013-3042-8.
24.
Litvin Y, Phan A, Hill MN, Pfaff DW, McEwen BS: CB1 receptor signaling regulates social anxiety and memory. Genes Brain Behav. 2013, 12 (5): 479-489. 10.1111/gbb.12045.PubMed
25.
O’Brien LD, Wills KL, Segsworth B, Dashney B, Rock EM, Limebeer CL, Parker LA: Effect of chronic exposure to rimonabant and phytocannabinoids on anxiety-like behavior and saccharin palatability. Pharmacol Biochem Behav. 2013, 103 (3): 597-602. 10.1016/j.pbb.2012.10.008.PubMed
26.
Varga B, Kassai F, Gyertyan I: Interactions of CB1 and mGLU5 receptor antagonists in food intake, anxiety and memory models in rats. Pharmacol Biochem Behav. 2012, 103 (2): 425-430. 10.1016/j.pbb.2012.09.016.PubMed
27.
Rodgers RJ, Haller J, Halasz J, Mikics E: 'One-trial sensitization’ to the anxiolytic-like effects of cannabinoid receptor antagonist SR141716A in the mouse elevated plus-maze. Eur J Neurosci. 2003, 17 (6): 1279-1286. 10.1046/j.1460-9568.2003.02548.x.PubMed
28.
Degroot A, Nomikos GG: Genetic deletion and pharmacological blockade of CB1 receptors modulates anxiety in the shock-probe burying test. Eur J Neurosci. 2004, 20 (4): 1059-1064. 10.1111/j.1460-9568.2004.03556.x.PubMed
29.
Rubio M, Fernandez-Ruiz J, De Miguel R, Maestro B, Michael Walker J, Ramos JA: CB1 receptor blockade reduces the anxiogenic-like response and ameliorates the neurochemical imbalances associated with alcohol withdrawal in rats. Neuropharmacology. 2008, 54 (6): 976-988. 10.1016/j.neuropharm.2008.02.005.PubMed
30.
Kathuria S, Gaetani S, Fegley D, Valino F, Duranti A, Tontini A, Mor M, Tarzia G, La Rana G, Calignano A, Giustino A, et al: Modulation of anxiety through blockade of anandamide hydrolysis. Nat Med. 2003, 9 (1): 76-81.PubMed
31.
Moreira FA, Kaiser N, Monory K, Lutz B: Reduced anxiety-like behaviour induced by genetic and pharmacological inhibition of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) is mediated by Cb1 receptors. Neuropharmacology. 2008, 54 (1): 141-150. 10.1016/j.neuropharm.2007.07.005.PubMed
32.
Naderi N, Haghparast A, Saber-Tehrani A, Rezaii N, Alizadeh AM, Khani A, Motamedi F: Interaction between cannabinoid compounds and diazepam on anxiety-like behaviour of mice. Pharmacol Biochem Behav. 2008, 89 (1): 64-75. 10.1016/j.pbb.2007.11.001.PubMed
33.
Hill MN, Karacabeyli ES, Gorzalka BB: Estrogen recruits the endocannabinoid system to modulate emotionality. Psychoneuroendocrinology. 2007, 32 (4): 350-357. 10.1016/j.psyneuen.2007.02.003.PubMed
34.
Naidu PS, Varvel SA, Ahn K, Cravatt BF, Martin BR, Lichtman AH: Evaluation of fatty acid amide hydrolase inhibition in murine models of emotionality. Psychopharmacology (Berl). 2007, 192 (1): 61-70. 10.1007/s00213-006-0689-4.
35.
Busquets-Garcia A, Puighermanal E, Pastor A, de la Torre R, Maldonado R, Ozaita A: Differential role of anandamide and 2-arachidonoylglycerol in memory and anxiety-like responses. Biol Psychiatry. 2011, 70 (5): 479-486. 10.1016/j.biopsych.2011.04.022.PubMed
36.
Scherma M, Medalie J, Fratta W, Vadivel SK, Makriyannis A, Piomelli D, Mikics E, Haller J, Yasar S, Tanda G, Goldberg SR: The endogenous cannabinoid anandamide has effects on motivation and anxiety that are revealed by fatty acid amide hydrolase (FAAH) inhibition. Neuropharmacology. 2008, 54 (1): 129-140. 10.1016/j.neuropharm.2007.08.011.PubMedCentralPubMed
37.
Haller J, Barna I, Barsvari B, Gyimesi Pelczer K, Yasar S, Panlilio LV, Goldberg S: Interactions between environmental aversiveness and the anxiolytic effects of enhanced cannabinoid signaling by FAAH inhibition in rats. Psychopharmacology (Berl). 2009, 204 (4): 607-616. 10.1007/s00213-009-1494-7.
38.
Rossi S, De Chiara V, Musella A, Sacchetti L, Cantarella C, Castelli M, Cavasinni F, Motta C, Studer V, Bernardi G, Cravatt BF, et al: Preservation of striatal cannabinoid CB1 receptor function correlates with the antianxiety effects of fatty acid amide hydrolase inhibition. Mol Pharmacol. 2010, 78 (2): 260-268. 10.1124/mol.110.064196.PubMed
39.
Hill MN, Kumar SA, Filipski SB, Iverson M, Stuhr KL, Keith JM, Cravatt BF, Hillard CJ, Chattarji S, McEwen BS: Disruption of fatty acid amide hydrolase activity prevents the effects of chronic stress on anxiety and amygdalar microstructure. Mol Psychiatry. 2013, 18: 1125-1135. 10.1038/mp.2012.90.PubMedCentralPubMed
40.
Kinsey SG, O’Neal ST, Long JZ, Cravatt BF, Lichtman AH: Inhibition of endocannabinoid catabolic enzymes elicits anxiolytic-like effects in the marble burying assay. Pharmacol Biochem Behav. 2010, 98 (1): 21-27.PubMedCentralPubMed
41.
Sumislawski JJ, Ramikie TS, Patel S: Reversible gating of endocannabinoid plasticity in the amygdala by chronic stress: a potential role for monoacylglycerol lipase inhibition in the prevention of stress-induced behavioral adaptation. Neuropsychopharmacology. 2011, 36 (13): 2750-2761. 10.1038/npp.2011.166.PubMedCentralPubMed
42.
Aliczki M, Balogh Z, Tulogdi A, Haller J: The temporal dynamics of the effects of monoacylglycerol lipase blockade on locomotion, anxiety, and body temperature. Behav Pharmacol. 2012, 23 (4): 348-357. 10.1097/FBP.0b013e3283564dfa.PubMed
43.
Aliczki M, Zelena D, Mikics E, Varga ZK, Pinter O, Bakos NV, Varga J, Haller J: Monoacylglycerol lipase inhibition-induced changes in plasma corticosterone levels, anxiety and locomotor activity in male CD1 mice. Horm Behav. 2013, 63 (5): 752-758. 10.1016/j.yhbeh.2013.03.017.PubMed
44.
Sciolino NR, Zhou W, Hohmann AG: Enhancement of endocannabinoid signaling with JZL184, an inhibitor of the 2-arachidonoylglycerol hydrolyzing enzyme monoacylglycerol lipase, produces anxiolytic effects under conditions of high environmental aversiveness in rats. Pharmacol Res. 2011, 64: 226-234. 10.1016/j.phrs.2011.04.010.PubMedCentralPubMed
45.
Rubino T, Realini N, Castiglioni C, Guidali C, Vigano D, Marras E, Petrosino S, Perletti G, Maccarrone M, Di Marzo V, Parolaro D: Role in anxiety behavior of the endocannabinoid system in the prefrontal cortex. Cereb Cortex. 2008, 18 (6): 1292-1301. 10.1093/cercor/bhm161.PubMed
46.
Dono LM, Currie PJ: The cannabinoid receptor CB1 inverse agonist AM251 potentiates the anxiogenic activity of urocortin I in the basolateral amygdala. Neuropharmacology. 2012, 62 (1): 192-199. 10.1016/j.neuropharm.2011.06.019.PubMed
47.
John CS, Currie PJ: N-arachidonoyl-serotonin in the basolateral amygdala increases anxiolytic behavior in the elevated plus maze. Behav Brain Res. 2012, 233 (2): 382-388. 10.1016/j.bbr.2012.05.025.PubMed
48.
Hill MN, McLaughlin RJ, Pan B, Fitzgerald ML, Roberts CJ, Lee TT, Karatsoreos IN, Mackie K, Viau V, Pickel VM, McEwen BS, et al: Recruitment of prefrontal cortical endocannabinoid signaling by glucocorticoids contributes to termination of the stress response. J Neurosci. 2011, 31 (29): 10506-10515. 10.1523/JNEUROSCI.0496-11.2011.PubMedCentralPubMed
49.
Kiritoshi T, Sun H, Ren W, Stauffer SR, Lindsley CW, Conn PJ, Neugebauer V: Modulation of pyramidal cell output in the medial prefrontal cortex by mGluR5 interacting with CB1. Neuropharmacology. 2013, 66: 170-178.PubMedCentralPubMed
50.
Shin RM, Tully K, Li Y, Cho JH, Higuchi M, Suhara T, Bolshakov VY: Hierarchical order of coexisting pre- and postsynaptic forms of long-term potentiation at synapses in amygdala. Proc Natl Acad Sci U S A. 2010, 107 (44): 19073-19078. 10.1073/pnas.1009803107.PubMedCentralPubMed
51.
Azad SC, Eder M, Marsicano G, Lutz B, Zieglgansberger W, Rammes G: Activation of the cannabinoid receptor type 1 decreases glutamatergic and GABAergic synaptic transmission in the lateral amygdala of the mouse. Learn Mem. 2003, 10 (2): 116-128. 10.1101/lm.53303.PubMedCentralPubMed
52.
Perra S, Pillolla G, Luchicchi A, Pistis M: Alcohol inhibits spontaneous activity of basolateral amygdala projection neurons in the rat: involvement of the endocannabinoid system. Alcohol Clin Exp Res. 2008, 32 (3): 443-449. 10.1111/j.1530-0277.2007.00588.x.PubMed
53.
Huang YC, Wang SJ, Chiou LC, Gean PW: Mediation of amphetamine-induced long-term depression of synaptic transmission by CB1 cannabinoid receptors in the rat amygdala. J Neurosci. 2003, 23 (32): 10311-10320.PubMed
54.
Riebe CJ, Pamplona FA, Kamprath K, Wotjak CT: Fear relief-toward a new conceptual frame work and what endocannabinoids gotta do with it. Neuroscience. 2012, 204: 159-185.PubMed
55.
Gunduz-Cinar O, Hill MN, McEwan BS, Holmes A: Amygdala FAAH and anandamide: mediating protection and recovery from stress. Trends Pharmacol Sci. 2013, In press
56.
Hill MN, Hillard CJ, Bambico FR, Patel S, Gorzalka BB, Gobbi G: The therapeutic potential of the endocannabinoid system for the development of a novel class of antidepressants. Trends Pharmacol Sci. 2009, 30 (9): 484-493. 10.1016/j.tips.2009.06.006.PubMed
57.
Gorzalka BB, Hill MN: Putative role of endocannabinoid signaling in the etiology of depression and actions of antidepressants. Prog Neuropsychopharmacol Biol Psychiatry. 2011, 35 (7): 1575-1585. 10.1016/j.pnpbp.2010.11.021.PubMed
58.
Bambico FR, Gobbi G: The cannabinoid CB1 receptor and the endocannabinoid anandamide: possible antidepressant targets. Expert Opin Ther Targets. 2008, 12 (11): 1347-1366. 10.1517/14728222.12.11.1347.PubMed
59.
Steiner MA, Wanisch K, Monory K, Marsicano G, Borroni E, Bachli H, Holsboer F, Lutz B, Wotjak CT: Impaired cannabinoid receptor type 1 signaling interferes with stress-coping behavior in mice. Pharmacogenomics J. 2008, 8 (3): 196-208. 10.1038/sj.tpj.6500466.PubMed
60.
Aso E, Ozaita A, Valdizan EM, Ledent C, Pazos A, Maldonado R, Valverde O: BDNF impairment in the hippocampus is related to enhanced despair behavior in CB1 knockout mice. J Neurochem. 2007, 105: 565-572.PubMed
61.
Jardinaud F, Crete D, Canestrelli C, Ledent C, Roques BP, Noble F: CB1 receptor knockout mice show similar behavioral modifications to wild-type mice when enkephalin catabolism is inhibited. Brain Res. 2005, 1063 (1): 77-83. 10.1016/j.brainres.2005.09.015.PubMed
62.
Steiner MA, Marsicano G, Nestler EJ, Holsboer F, Lutz B, Wotjak CT: Antidepressant-like behavioral effects of impaired cannabinoid receptor type 1 signaling coincide with exaggerated corticosterone secretion in mice. Psychoneuroendocrinology. 2008, 33 (1): 54-67. 10.1016/j.psyneuen.2007.09.008.PubMedCentralPubMed
63.
Hill MN, Gorzalka BB: Is there a role for the endocannabinoid system in the etiology and treatment of melancholic depression?. Behav Pharmacol. 2005, 16 (5–6): 333-352.PubMed
64.
Valverde O, Torrens M: CB1 receptor-deficient mice as a model for depression. Neuroscience. 2012, 204: 193-206.PubMed
65.
Steiner MA, Marsicano G, Wotjak CT, Lutz B: Conditional cannabinoid receptor type 1 mutants reveal neuron subpopulation-specific effects on behavioral and neuroendocrine stress responses. Psychoneuroendocrinology. 2008, 33 (8): 1165-1170. 10.1016/j.psyneuen.2008.06.004.PubMed
66.
Haring M, Grieb M, Monory K, Lutz B, Moreira FA: Cannabinoid CB1 receptor in the modulation of stress coping behavior in mice: the role of serotonin and different forebrain neuronal subpopulations. Neuropharmacology. 2013, 65: 83-89.PubMed
67.
Shearman LP, Rosko KM, Fleischer R, Wang J, Xu S, Tong XS, Rocha BA: Antidepressant-like and anorectic effects of the cannabinoid CB1 receptor inverse agonist AM251 in mice. Behav Pharmacol. 2003, 14 (8): 573-582. 10.1097/00008877-200312000-00001.PubMed
68.
Griebel G, Stemmelin J, Scatton B: Effects of the cannabinoid CB1 receptor antagonist rimonabant in models of emotional reactivity in rodents. Biol Psychiatry. 2005, 57 (3): 261-267. 10.1016/j.biopsych.2004.10.032.PubMed
69.
Tzavara ET, Davis RJ, Perry KW, Li X, Salhoff C, Bymaster FP, Witkin JM, Nomikos GG: The CB1 receptor antagonist SR141716A selectively increases monoaminergic neurotransmission in the medial prefrontal cortex: implications for therapeutic actions. Br J Pharmacol. 2003, 138 (4): 544-553. 10.1038/sj.bjp.0705100.PubMedCentralPubMed
70.
Adamczyk P, Golda A, McCreary AC, Filip M, Przegalinski E: Activation of endocannabinoid transmission induces antidepressant-like effects in rats. J Physiol Pharmacol. 2008, 59 (2): 217-228.PubMed
71.
Gobbi G, Bambico FR, Mangieri R, Bortolato M, Campolongo P, Solinas M, Cassano T, Morgese MG, Debonnel G, Duranti A, Tontini A, et al: Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis. Proc Natl Acad Sci U S A. 2005, 102 (51): 18620-18625. 10.1073/pnas.0509591102.PubMedCentralPubMed
72.
Hill MN, Gorzalka BB: Pharmacological enhancement of cannabinoid CB1 receptor activity elicits an antidepressant-like response in the rat forced swim test. Eur Neuropsychopharmacol. 2005, 15 (6): 593-599. 10.1016/j.euroneuro.2005.03.003.PubMed
73.
Gobshtis N, Ben-Shabat S, Fride E: Antidepressant-induced undesirable weight gain: prevention with rimonabant without interference with behavioral effectiveness. Eur J Pharmacol. 2007, 554 (2–3): 155-163.PubMed
74.
Beyer CE, Dwyer JM, Piesla MJ, Platt BJ, Shen R, Rahman Z, Chan K, Manners MT, Samad TA, Kennedy JD, Bingham B, et al: Depression-like phenotype following chronic CB1 receptor antagonism. Neurobiol Dis. 2010, 39 (2): 148-155. 10.1016/j.nbd.2010.03.020.PubMed
75.
Bambico FR, Cassano T, Dominguez-Lopez S, Katz N, Walker CD, Piomelli D, Gobbi G: Genetic deletion of fatty acid amide hydrolase alters emotional behavior and serotonergic transmission in the dorsal raphe, prefrontal cortex, and hippocampus. Neuropsychopharmacology. 2010, 35 (10): 2083-2100. 10.1038/npp.2010.80.PubMedCentralPubMed
76.
McLaughlin RJ, Hill MN, Bambico FR, Stuhr KL, Gobbi G, Hillard CJ, Gorzalka BB: Prefrontal cortical anandamide signaling coordinates coping responses to stress through a serotonergic pathway. Eur Neuropsychopharmacol. 2012, 22 (9): 664-671. 10.1016/j.euroneuro.2012.01.004.PubMedCentralPubMed
77.
Bambico FR, Katz N, Debonnel G, Gobbi G: Cannabinoids elicit antidepressant-like behavior and activate serotonergic neurons through the medial prefrontal cortex. J Neurosci. 2007, 27 (43): 11700-11711. 10.1523/JNEUROSCI.1636-07.2007.PubMed
78.
Fride E, Suris R, Weidenfeld J, Mechoulam R: Differential response to acute and repeated stress in cannabinoid CB1 receptor knockout newborn and adult mice. Behav Pharmacol. 2005, 16 (5–6): 431-440.PubMed
79.
Dubreucq S, Kambire S, Conforzi M, Metna-Laurent M, Cannich A, Soria-Gomez E, Richard E, Marsicano G, Chaouloff F: Cannabinoid type 1 receptors located on single-minded 1-expressing neurons control emotional behaviors. Neuroscience. 2012, 204: 230-244.PubMed
80.
Racz I, Bilkei-Gorzo A, Toth ZE, Michel K, Palkovits M, Zimmer A: A critical role for the cannabinoid CB1 receptors in alcohol dependence and stress-stimulated ethanol drinking. J Neurosci. 2003, 23 (6): 2453-2458.PubMed
81.
Patel S, Roelke CT, Rademacher DJ, Hillard CJ: Inhibition of restraint stress-induced neural and behavioural activation by endogenous cannabinoid signalling. Eur J Neurosci. 2005, 21 (4): 1057-1069. 10.1111/j.1460-9568.2005.03916.x.PubMed
82.
Rademacher DJ, Hillard CJ: Interactions between endocannabinoids and stress-induced decreased sensitivity to natural reward. Prog Neuropsychopharmacol Biol Psychiatry. 2007, 31 (3): 633-641. 10.1016/j.pnpbp.2006.12.013.PubMedCentralPubMed
83.
Hill MN, Carrier EJ, McLaughlin RJ, Morrish AC, Meier SE, Hillard CJ, Gorzalka BB: Regional alterations in the endocannabinoid system in an animal model of depression: effects of concurrent antidepressant treatment. J Neurochem. 2008, 106 (6): 2322-2336. 10.1111/j.1471-4159.2008.05567.x.PubMedCentralPubMed
84.
Rademacher DJ, Meier SE, Shi L, Ho WS, Jarrahian A, Hillard CJ: Effects of acute and repeated restraint stress on endocannabinoid content in the amygdala, ventral striatum, and medial prefrontal cortex in mice. Neuropharmacology. 2008, 54 (1): 108-116. 10.1016/j.neuropharm.2007.06.012.PubMed
85.
Hill MN, McLaughlin RJ, Morrish AC, Viau V, Floresco SB, Hillard CJ, Gorzalka BB: Suppression of amygdalar endocannabinoid signaling by stress contributes to activation of the hypothalamic-pituitary-adrenal axis. Neuropsychopharmacology. 2009, 34 (13): 2733-2745. 10.1038/npp.2009.114.PubMedCentralPubMed
86.
Hill MN, McLaughlin RJ, Bingham B, Shrestha L, Lee TT, Gray JM, Hillard CJ, Gorzalka BB, Viau V: Endogenous cannabinoid signaling is essential for stress adaptation. Proc Natl Acad Sci U S A. 2010, 107 (20): 9406-9411. 10.1073/pnas.0914661107.PubMedCentralPubMed
87.
Patel S, Roelke CT, Rademacher DJ, Cullinan WE, Hillard CJ: Endocannabinoid signaling negatively modulates stress-induced activation of the hypothalamic-pituitary-adrenal axis. Endocrinology. 2004, 145 (12): 5431-5438. 10.1210/en.2004-0638.PubMed
88.
Patel S, Kingsley PJ, Mackie K, Marnett LJ, Winder DG: Repeated homotypic stress elevates 2-arachidonoylglycerol levels and enhances short-term endocannabinoid signaling at inhibitory synapses in basolateral amygdala. Neuropsychopharmacology. 2009, 34 (13): 2699-2709. 10.1038/npp.2009.101.PubMedCentralPubMed
89.
Hill MN, Patel S, Carrier EJ, Rademacher DJ, Ormerod BK, Hillard CJ, Gorzalka BB: Downregulation of endocannabinoid signaling in the hippocampus following chronic unpredictable stress. Neuropsychopharmacology. 2005, 30 (3): 508-515. 10.1038/sj.npp.1300601.PubMed
90.
Hill MN, Ho WS, Meier SE, Gorzalka BB, Hillard CJ: Chronic corticosterone treatment increases the endocannabinoid 2-arachidonylglycerol in the rat amygdala. Eur J Pharmacol. 2005, 528 (1–3): 99-102.PubMed
91.
Bortolato M, Mangieri RA, Fu J, Kim JH, Arguello O, Duranti A, Tontini A, Mor M, Tarzia G, Piomelli D: Antidepressant-like activity of the fatty acid amide hydrolase inhibitor URB597 in a rat model of chronic mild stress. Biol Psychiatry. 2007, 62 (10): 1103-1110. 10.1016/j.biopsych.2006.12.001.PubMed
92.
Jiang W, Zhang Y, Xiao L, Van Cleemput J, Ji SP, Bai G, Zhang X: Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects. J Clin Invest. 2005, 115 (11): 3104-3116. 10.1172/JCI25509.PubMedCentralPubMed
93.
Hill MN, Kambo JS, Sun JC, Gorzalka BB, Galea LA: Endocannabinoids modulate stress-induced suppression of hippocampal cell proliferation and activation of defensive behaviours. Eur J Neurosci. 2006, 24 (7): 1845-1849. 10.1111/j.1460-9568.2006.05061.x.PubMed
94.
Halikas JA, Goodwin DW, Guze SB: Marihuana effects. a survey of regular users. JAMA. 1971, 217 (5): 692-694. 10.1001/jama.1971.03190050148017.PubMed
95.
Fabre LF, McLendon D: The efficacy and safety of nabilone (a synthetic cannabinoid) in the treatment of anxiety. J Clin Pharmacol. 1981, 21 (8–9 Suppl): 377S-382S.PubMed
96.
Fraser GA: The use of a synthetic cannabinoid in the management of treatment-resistant nightmares in posttraumatic stress disorder (PTSD). CNS Neurosci Ther. 2009, 15 (1): 84-88. 10.1111/j.1755-5949.2008.00071.x.PubMed
97.
Phan KL, Angstadt M, Golden J, Onyewuenyi I, Popovska A, De Wit H: Cannabinoid modulation of amygdala reactivity to social signals of threat in humans. J Neurosci. 2008, 28 (10): 2313-2319. 10.1523/JNEUROSCI.5603-07.2008.PubMedCentralPubMed
98.
Cornelius JR, Aizenstein HJ, Hariri AR: Amygdala reactivity is inversely related to level of cannabis use in individuals with comorbid cannabis dependence and major depression. Addict Behav. 2010, 35 (6): 644-646. 10.1016/j.addbeh.2010.02.004.PubMedCentralPubMed
99.
Gruber SA, Rogowska J, Yurgelun-Todd DA: Altered affective response in marijuana smokers: An FMRI study. Drug Alcohol Depend. 2009, 105 (1–2): 139-153.PubMedCentralPubMed
100.
O’Leary DS, Block RI, Koeppel JA, Flaum M, Schultz SK, Andreasen NC, Ponto LB, Watkins GL, Hurtig RR, Hichwa RD: Effects of smoking marijuana on brain perfusion and cognition. Neuropsychopharmacology. 2002, 26 (6): 802-816. 10.1016/S0893-133X(01)00425-0.PubMed
101.
Hill MN, Gorzalka BB: Impairments in endocannabinoid signaling and depressive illness. JAMA. 2009, 301 (11): 1165-1166. 10.1001/jama.2009.369.PubMed
102.
Mitchell PB, Morris MJ: Depression and anxiety with rimonabant. Lancet. 2007, 370 (9600): 1671-1672. 10.1016/S0140-6736(07)61705-X.PubMed
103.
Christensen R, Kristensen PK, Bartels EM, Bliddal H, Astrup A: Efficacy and safety of the weight-loss drug rimonabant: A meta-analysis of randomised trials. Lancet. 2007, 370 (9600): 1706-1713. 10.1016/S0140-6736(07)61721-8.PubMed
104.
Topol EJ, Bousser MG, Fox KA, Creager MA, Despres JP, Easton JD, Hamm CW, Montalescot G, Steg PG, Pearson TA, Cohen E, et al: Rimonabant for prevention of cardiovascular events (crescendo): A randomised, multicentre, placebo-controlled trial. Lancet. 2010, 376 (9740): 517-523. 10.1016/S0140-6736(10)60935-X.PubMed
105.
De Mattos VB, Prais HA, Daker MV: Melancholic features related to rimonabant. Gen Hosp Psychiatry. 2009, 31 (6): 583-585. 10.1016/j.genhosppsych.2008.12.009.
106.
Goodwin RS, Baumann MH, Gorelick DA, Schwilke E, Schwope DM, Darwin WD, Kelly DL, Schroeder JR, Ortemann-Renon C, Bonnet D, Huestis MA: CB1 - cannabinoid receptor antagonist effects on cortisol in cannabis-dependent men. Am J Drug Alcohol Abuse. 2012, 38 (1): 114-119. 10.3109/00952990.2011.600398.PubMedCentralPubMed
107.
Horder J, Harmer CJ, Cowen PJ, McCabe C: Reduced neural response to reward following 7 days treatment with the cannabinoid CB1 antagonist rimonabant in healthy volunteers. Int J Neuropsychopharmacol. 2010, 13 (8): 1103-1113. 10.1017/S1461145710000453.PubMed
108.
Horder J, Cowen PJ, Di Simplicio M, Browning M, Harmer CJ: Acute administration of the cannabinoid CB1 antagonist rimonabant impairs positive affective memory in healthy volunteers. Psychopharmacology (Berl). 2009, 205 (1): 85-91. 10.1007/s00213-009-1517-4.
109.
Horder J, Browning M, Di Simplicio M, Cowen PJ, Harmer CJ: Effects of 7 days of treatment with the cannabinoid type 1 receptor antagonist, rimonabant, on emotional processing. J Psychopharmacol. 2012, 26 (1): 125-132. 10.1177/0269881111400649.PubMed
110.
Hill MN, Miller GE, Carrier EJ, Gorzalka BB, Hillard CJ: Circulating endocannabinoids and N-acyl ethanolamines are differentially regulated in major depression and following exposure to social stress. Psychoneuroendocrinology. 2009, 34 (8): 1257-1262. 10.1016/j.psyneuen.2009.03.013.PubMedCentralPubMed
111.
Chouker A, Kaufmann I, Kreth S, Hauer D, Feuerecker M, Thieme D, Vogeser M, Thiel M, Schelling G: Motion sickness, stress and the endocannabinoid system. PLoS One. 2010, 5 (5): e10752-10.1371/journal.pone.0010752.PubMedCentralPubMed
112.
Dlugos A, Childs E, Stuhr KL, Hillard CJ, De Wit H: Acute stress increases circulating anandamide and other N-acylethanolamines in healthy humans. Neuropsychopharmacology. 2012, 37 (11): 2416-2427. 10.1038/npp.2012.100.PubMedCentralPubMed
113.
Hill MN, Miller GE, Ho WS, Gorzalka BB, Hillard CJ: Serum endocannabinoid content is altered in females with depressive disorders: a preliminary report. Pharmacopsychiatry. 2008, 41 (2): 48-53. 10.1055/s-2007-993211.PubMedCentralPubMed
114.
Hauer D, Weis F, Campolongo P, Schopp M, Beiras-Fernandez A, Strewe C, Giehl M, Toth R, Kilger E, Schelling G: Glucocorticoid-endocannabinoid interaction in cardiac surgical patients: relationship to early cognitive dysfunction and late depression. Rev Neurosci. 2012, 23 (5–6): 681-690.PubMed
115.
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: Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study. Mol Psychiatry. 2013, 18: 1034-1040. 10.1038/mp.2013.61.PubMedCentralPubMed
116.
Hill MN, Bierer LM, Makotkine I, Golier JA, Galea S, McEwen BS, Hillard CJ, Yehuda R: Reductions in circulating endocannabinoid levels in individuals with post-traumatic stress disorder following exposure to the world trade center attacks. Psychoneuroendocrinology. 2013, doi:pii: S0306-4530(13)00292-8
117.
Hauer D, Schelling G, Gola H, Campolongo P, Morath J, Roozendaal B, Hamuni G, Karabatsiakis A, Atsak P, Vogeser M, Kolassa IT: Plasma concentrations of endocannabinoids and related primary fatty acid amides in patients with post-traumatic stress disorder. PLoS One. 2013, 8 (5): e62741-10.1371/journal.pone.0062741.PubMedCentralPubMed
118.
Agrawal A, Nelson EC, Littlefield AK, Bucholz KK, Degenhardt L, Henders AK, Madden PA, Martin NG, Montgomery GW, Pergadia ML, Sher KJ, et al: Cannabinoid receptor genotype moderation of the effects of childhood physical abuse on anhedonia and depression. Arch Gen Psychiatry. 2012, 69 (7): 732-740. 10.1001/archgenpsychiatry.2011.2273.PubMedCentralPubMed
119.
Pearson JF, Fergusson DM, Horwood LJ, Miller AL, Sullivan PF, Youfang LE, Kennedy MA: Increased risk of major depression by childhood abuse is not modified by CNR1 genotype. Am J Med Genet B Neuropsychiatr Genet. 2013, 162B (2): 224-226.PubMed
120.
Domschke K, Dannlowski U, Ohrmann P, Lawford B, Bauer J, Kugel H, Heindel W, Young R, Morris P, Arolt V, Deckert J, Suslowa T, Baunea BT: Cannabinoid receptor 1 (CNR1) gene: impact on antidepressant treatment response and emotion processing in major depression. Eur Neuropsychopharmacol. 2008, 18 (10): 751-759. 10.1016/j.euroneuro.2008.05.003.PubMed
121.
Mitjans M, Gasto C, Catalan R, Fananas L, Arias B: Genetic variability in the endocannabinoid system and 12-week clinical response to citalopram treatment: the role of the CNR1, CNR2 and FAAH genes. J Psychopharmacol. 2012, 26 (10): 1391-1398. 10.1177/0269881112454229.PubMed
122.
Juhasz G, Chase D, Pegg E, Downey D, Toth ZG, Stones K, Platt H, Mekli K, Payton A, Elliott R, Anderson IM, Deakin JFW: CNR1 gene is associated with high neuroticism and low agreeableness and interacts with recent negative life events to predict current depressive symptoms. Neuropsychopharmacology. 2009, 34 (8): 2019-2027. 10.1038/npp.2009.19.PubMed
123.
Chakrabarti B, Kent L, Suckling J, Bullmore E, Baron-Cohen S: Variations in the human cannabinoid receptor (CNR1) gene modulate striatal responses to happy faces. Eur J Neurosci. 2006, 23 (7): 1944-1948. 10.1111/j.1460-9568.2006.04697.x.PubMed
124.
Hutchison KE, Haughey H, Niculescu M, Schacht J, Kaiser A, Stitzel J, Horton WJ, Filbey F: The incentive salience of alcohol: translating the effects of genetic variant in CNR1. Arch Gen Psychiatry. 2008, 65 (7): 841-850. 10.1001/archpsyc.65.7.841.PubMedCentralPubMed
125.
Hirvonen J, Zanotti-Fregonara P, Umhau JC, George DT, Rallis-Frutos D, Lyoo CH, Li CT, Hines CS, Sun H, Terry GE, Morse C, Zoghbi SS, Pike VW, Innis RB, Heilig M: Reduced cannabinoid CB1 receptor binding in alcohol dependence measured with positron emission tomography. Mol Psychiatry. 2012, 18: 916-921.PubMedCentralPubMed
126.
Schacht JP, Hutchison KE, Filbey FM: Associations between cannabinoid receptor-1 (CNR1) variation and hippocampus and amygdala volumes in heavy cannabis users. Neuropsychopharmacology. 2012, 37 (11): 2368-2376. 10.1038/npp.2012.92.PubMedCentralPubMed
127.
Campbell S, Marriott M, Nahmias C, MacQueen GM: Lower hippocampal volume in patients suffering from depression: a meta-analysis. Am J Psychiatry. 2004, 161 (4): 598-607. 10.1176/appi.ajp.161.4.598.PubMed
128.
Gilbertson MW, Shenton ME, Ciszewski A, Kasai K, Lasko NB, Orr SP, Pitman RK: Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nat Neurosci. 2002, 5 (11): 1242-1247. 10.1038/nn958.PubMedCentralPubMed
129.
Galve-Roperh I, Aguado T, Palazuelos J, Guzman M: The endocannabinoid system and neurogenesis in health and disease. Neuroscientist. 2007, 13 (2): 109-114. 10.1177/1073858406296407.PubMed
130.
Marsicano G, Goodenough S, Monory K, Hermann H, Eder M, Cannich A, Azad SC, Cascio MG, Gutierrez SO, van der Stelt M, Lopez-Rodriguez ML, Casanova E, Schütz G, Zieglgänsberger W, Di Marzo V, Behl C, Lutz B, et al: CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science. 2003, 302 (5642): 84-88. 10.1126/science.1088208.PubMed
131.
Lazary J, Lazary A, Gonda X, Benko A, Molnar E, Hunyady L, Juhasz G, Bagdy G: Promoter variants of the cannabinoid receptor 1 gene (CNR1) in interaction with 5-HTTLPR affect the anxious phenotype. Am J Med Genet B Neuropsychiatr Genet. 2009, 150B (8): 1118-1127. 10.1002/ajmg.b.31024.PubMed
132.
Sipe JC, Chiang K, Gerber AL, Beutler E, Cravatt BF: A missense mutation in human fatty acid amide hydrolase associated with problem drug use. Proc Natl Acad Sci U S A. 2002, 99 (12): 8394-8399. 10.1073/pnas.082235799.PubMedCentralPubMed
133.
Chiang KP, Gerber AL, Sipe JC, Cravatt BF: Reduced cellular expression and activity of the P129T mutant of human fatty acid amide hydrolase: Evidence for a link between defects in the endocannabinoid system and problem drug use. Hum Mol Genet. 2004, 13 (18): 2113-2119. 10.1093/hmg/ddh216.PubMed
134.
Sipe JC, Scott TM, Murray S, Harismendy O, Simon GM, Cravatt BF, Waalen J: Biomarkers of endocannabinoid system activation in severe obesity. PLoS One. 2010, 5 (1): e8792-10.1371/journal.pone.0008792.PubMedCentralPubMed
135.
Hariri AR, Gorka A, Hyde LW, Kimak M, Halder I, Ducci F, Ferrell RE, Goldman D, Manuck SB: Divergent effects of genetic variation in endocannabinoid signaling on human threat- and reward-related brain function. Biol Psychiatry. 2009, 66 (1): 9-16. 10.1016/j.biopsych.2008.10.047.PubMedCentralPubMed
136.
Gunduz-Cinar O, Macpherson KP, Cinar R, Gamble-George J, Sugden K, Williams B, Godlewski G, Ramikie TS, Gorka AX, Alapafuja SO, Nikas SP, et al: Convergent translational evidence of a role for anandamide in amygdala-mediated fear extinction, threat processing and stress-reactivity. Mol Psychiatry. 2013, 18 (7): 813-823. 10.1038/mp.2012.72.PubMedCentralPubMed
137.
Conzelmann A, Reif A, Jacob C, Weyers P, Lesch KP, Lutz B, Pauli P: A polymorphism in the gene of the endocannabinoid-degrading enzyme FAAH (FAAH C385A) is associated with emotional-motivational reactivity. Psychopharmacology (Berl). 2012, 224 (4): 573-579. 10.1007/s00213-012-2785-y.
138.
Patel S, Hillard CJ: Adaptations in endocannabinoid signaling in response to repeated homotypic stress: a novel mechanism for stress habituation. Eur J Neurosci. 2008, 27 (11): 2821-2829. 10.1111/j.1460-9568.2008.06266.x.PubMedCentralPubMed
Metadata
Title
Translational evidence for the involvement of the endocannabinoid system in stress-related psychiatric illnesses
Authors
Matthew N Hill
Sachin Patel
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Biology of Mood & Anxiety Disorders / Issue 1/2013
Electronic ISSN: 2045-5380
DOI
https://doi.org/10.1186/2045-5380-3-19

Other articles of this Issue 1/2013

Biology of Mood & Anxiety Disorders 1/2013 Go to the issue

Review

Neuroimaging predictors of treatment response in anxiety disorders

Meeting report

Meeting report: “Depression and Anxiety Spectrum disorders: from basic science to the clinic and back”

Review

Early experiences and the development of emotional learning systems in rats

Erratum

Erratum to: Somatic therapies for treatment-resistant depression: ECT, TMS, VNS, DBS

Research

Genetic moderation of the association between regulatory focus and reward responsiveness: a proof-of-concept study

Review

Therapygenetics: Using genetic markers to predict response to psychological treatment for mood and anxiety disorders