{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:11:10Z","timestamp":1790017870285,"version":"4.0.1"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T00:00:00Z","timestamp":1586390400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T00:00:00Z","timestamp":1586390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neuropsychopharmacol."],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gilles de la Tourette syndrome (TS) is a complex neurodevelopmental disorder characterized by the presence of motor and vocal tics as well as psychiatric comorbidities such as attention-deficit\/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), depression, and anxiety. The underlying cause of the disease is still unknown, but several lines of evidence suggest a paramount role of the dopaminergic system. Based on the clinical observation that cannabis-based medicine including cannabis and delta-9-tetrahydrocannabinol (THC, dronabinol) may improve TS, alternatively, an involvement of the endocannabinoid system (ECS) has been suggested. In this study we measured cerebrospinal fluid (CSF) levels of the two most important endocannabinoids \u201cN\u201d-arachidonoylethanolamine (AEA, anandamide) and 2-arachidonoylglycerol (2-AG), the endocannabinoid-like molecule palmitoyl ethanolamide (PEA), and the lipid arachidonic acid (AA) in a sample of adult patients with TS (<jats:italic>n<\/jats:italic>\u2009=\u200920) compared with controls (<jats:italic>n<\/jats:italic>\u2009=\u200919) using liquid-liquid lipid extraction and simultaneous quantification by liquid chromatography multiple reaction monitoring (LC\/MRM). CSF levels of AEA (<jats:italic>p<\/jats:italic>\u2009=\u20090.0018), 2-AG (<jats:italic>p<\/jats:italic>\u2009=\u20090.0003), PEA (<jats:italic>p<\/jats:italic>\u2009=\u20090.02), and AA (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) were significantly increased in TS compared with controls. Levels of 2-AG correlated with the severity of comorbid ADHD (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). This is the first study, demonstrating alterations in the ECS suggesting an involvement of this system in the pathophysiology of TS. It can be speculated that elevated endocannabinoid levels either represent secondary changes in order to compensate for alterations in other neurotransmitter systems such as the dopaminergic system, are simply an epiphenomenon or, alternatively, represent the primary cause of TS.<\/jats:p>","DOI":"10.1038\/s41386-020-0671-6","type":"journal-article","created":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T12:03:34Z","timestamp":1586433814000},"page":"1323-1329","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Cerebrospinal fluid endocannabinoid levels in Gilles de la Tourette syndrome"],"prefix":"10.1038","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7181-7419","authenticated-orcid":false,"given":"Kirsten R.","family":"M\u00fcller-Vahl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Bindila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beat","family":"Lutz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Musshoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Skripuletz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Baumgaertel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt-Wolfram","family":"S\u00fchs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,9]]},"reference":[{"key":"671_CR1","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1111\/j.1600-0447.1998.tb10127.x","volume":"98","author":"KR M\u00fcller-Vahl","year":"1998","unstructured":"M\u00fcller-Vahl KR, Kolbe H, Schneider U, Emrich HM. Cannabinoids: possible role in patho-physiology and therapy of Gilles de la Tourette syndrome. Acta Psychiatr Scand. 1998;98:502\u20136.","journal-title":"Acta Psychiatr Scand"},{"key":"671_CR2","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1176\/appi.neuropsych.16110310","volume":"29","author":"E Abi-Jaoude","year":"2017","unstructured":"Abi-Jaoude E, Chen L, Cheung P, Bhikram T, Sandor P. Preliminary evidence on cannabis effectiveness and tolerability for adults with Tourette syndrome. J Neuropsychiatry Clin Neurosci. 2017;29:391\u2013400.","journal-title":"J Neuropsychiatry Clin Neurosci"},{"key":"671_CR3","doi-asserted-by":"crossref","unstructured":"Jakubovski E, M\u00fcller-Vahl K. Speechlessness in Gilles de la Tourette sndrome: cannabis-based medicines improve severe vocal blocking tics in two patients. Int J Mol Sci. 2017;18: pii: E1739.","DOI":"10.3390\/ijms18081739"},{"key":"671_CR4","doi-asserted-by":"crossref","unstructured":"Kanaan AS, Jakubovski E, M\u00fcller-Vahl K. Significant tic reduction in an otherwise treatment-resistant patient with Gilles de la Tourette syndrome following treatment with nabiximols. Brain Sci. 2017;7: pii: E47.","DOI":"10.3390\/brainsci7050047"},{"key":"671_CR5","doi-asserted-by":"publisher","unstructured":"Trainor D, Evans L, Bird R. Severe motor and vocal tics controlled with Sativex\u00ae. Australas Psychiatry. 2016. https:\/\/doi.org\/10.1177\/1039856216663737.","DOI":"10.1177\/1039856216663737"},{"key":"671_CR6","first-page":"43","volume":"2","author":"N Szejko","year":"2018","unstructured":"Szejko N, Jakubovski E, Fremer C, Kunert K, M\u00fcller-Vahl K. Delta-9-tetrahydrocannabinol for the treatment of a child with Tourette syndrome\u2014case report. Eur J Med Case Rep. 2018;2:43\u20136.","journal-title":"Eur J Med Case Rep"},{"key":"671_CR7","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1097\/JCP.0b013e3181d236ec","volume":"30","author":"A Hasan","year":"2010","unstructured":"Hasan A, Rothenberger A, M\u00fcnchau A, Wobrock T, Falkai P, Roessner V. Oral delta 9-tetrahydrocannabinol improved refractory Gilles de la Tourette syndrome in an adolescent by increasing intracortical inhibition: a case report. J Clin Psychopharmacol. 2010;30:190\u20132.","journal-title":"J Clin Psychopharmacol"},{"key":"671_CR8","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1055\/s-2002-25028","volume":"35","author":"KR M\u00fcller-Vahl","year":"2002","unstructured":"M\u00fcller-Vahl KR, Schneider U, Koblenz A, J\u00f6bges M, Kolbe H, Daldrup T, et al. Treatment of Tourette\u2019s syndrome with Delta 9-tetrahydrocannabinol (THC): a randomized crossover trial. Pharmacopsychiatry. 2002;35:57\u201361.","journal-title":"Pharmacopsychiatry."},{"key":"671_CR9","doi-asserted-by":"crossref","first-page":"459","DOI":"10.4088\/JCP.v64n0417","volume":"64","author":"KR M\u00fcller-Vahl","year":"2003","unstructured":"M\u00fcller-Vahl KR, Schneider U, Prevedel H, Theloe K, Kolbe H, Daldrup T, et al. Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial. J Clin Psychiatry. 2003;64:459\u201365.","journal-title":"J Clin Psychiatry"},{"key":"671_CR10","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1111\/j.1476-5381.2008.00088.x","volume":"156","author":"J Fern\u00e1ndez-Ruiz","year":"2009","unstructured":"Fern\u00e1ndez-Ruiz J. The endocannabinoid system as a target for the treatment of motor dysfunction. Br J Pharm. 2009;156:1029\u201340.","journal-title":"Br J Pharm"},{"key":"671_CR11","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/978-1-4939-3539-0_2","volume":"1412","author":"L Bindila","year":"2016","unstructured":"Bindila L, Lutz B. Extraction and simultaneous quantification of endocannabinoids and endocannabinoid-like lipids in biological tissues. Methods Mol Biol. 2016;1412:9\u201318.","journal-title":"Methods Mol Biol"},{"key":"671_CR12","doi-asserted-by":"crossref","first-page":"732","DOI":"10.3389\/fneur.2019.00732","volume":"10","author":"C Baumgaertel","year":"2019","unstructured":"Baumgaertel C, Skripuletz T, Kronenberg J, Stangel M, Schwenkenbecher P, Sinke C, et al. Immunity in Gilles de la Tourette-Syndrome: results from a cerebrospinal fluid study. Front Neurol. 2019;10:732.","journal-title":"Front Neurol"},{"key":"671_CR13","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1097\/00004583-198907000-00015","volume":"28","author":"JF Leckman","year":"1989","unstructured":"Leckman JF, Riddle MA, Hardin MT, Ort SI, Swartz KL, Stevenson J, et al. The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity. J Am Acad Child Adolesc Psychiatry. 1989;28:566\u201373.","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"key":"671_CR14","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1097\/00004703-200512000-00001","volume":"26","author":"DW Woods","year":"2005","unstructured":"Woods DW, Piacentini J, Himle MB, Chang S. Premonitory Urge for Tics Scale (PUTS): initial psychometric results and examination of the premonitory urge phenomenon in youths with Tic disorders. J Dev Behav Pediatr. 2005;26:397\u2013403.","journal-title":"J Dev Behav Pediatr"},{"key":"671_CR15","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1212\/01.wnl.0000327890.02893.61","volume":"71","author":"AE Cavanna","year":"2008","unstructured":"Cavanna AE, Schrag A, Morley D, Orth M, Robertson MM, Joyce E, et al. The Gilles de la Tourette syndrome-quality of life scale (GTS-QOL): development and validation. Neurology. 2008;71:1410\u20136.","journal-title":"Neurology."},{"key":"671_CR16","unstructured":"Beck AT, Steer RA, Brown GK. Manual for the beck depression inventory-II. San Antonio, TX: Psychological Corporation; 1993."},{"key":"671_CR17","unstructured":"Conners CK, Erhardt D, Sparrow E. Conners\u2019 Adult ADHD Rating Scales (CAARS) technical manual. New York: Multihealth Systems, Inc., 1999."},{"key":"671_CR18","unstructured":"American Psychiatric Association. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text Revision. Washington: American Psychiatric Association; 2000."},{"key":"671_CR19","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1007\/s00115-001-1215-x","volume":"73","author":"P Retz-Junginger","year":"2002","unstructured":"Retz-Junginger P, Retz W, Blocher D, Weijers H-G, Trott G-E, Wender PH, et al. Wender Utah Rating Scale (WURS-k) Die deutsche Kurzform zur retrospektiven Erfassung des hyperkinetischen Syndroms bei Erwachsenen. Nervenarzt 2002;73:830\u20138.","journal-title":"Nervenarzt"},{"key":"671_CR20","unstructured":"Beck AT, Steer RA. Beck anxiety inventory manual. San Antonio, TX: Psychological Corporation. 1993."},{"key":"671_CR21","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1001\/archpsyc.1989.01810110048007","volume":"46","author":"WK Goodman","year":"1989","unstructured":"Goodman WK, Price LH, Rasmussen R. The Yale-Brown obsessive compulsive scale: I. development, use, and reliability. Arch Gen Psychiatry. 1989;46:1006\u201311.","journal-title":"Arch Gen Psychiatry"},{"key":"671_CR22","unstructured":"Franke G. Brief symptom inventory von L. R. Derogatis (Kurzform der SCL-90-R). G\u00f6ttingen: Beltz. 2000."},{"key":"671_CR23","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1007\/s00406-017-0789-7","volume":"267","author":"L Kranaster","year":"2017","unstructured":"Kranaster L, Hoyer C, Aksay SS, Bumb JM, Leweke FM, Janke C, et al. Electroconvulsive therapy enhances endocannabinoids in the cerebrospinal fluid of patients with major depression: a preliminary prospective study. Eur Arch Psychiatry Clin Neurosci. 2017;267:781\u20136.","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"671_CR24","doi-asserted-by":"publisher","unstructured":"Lerner R, Lutz B, Bindila L. Tricks and tracks in the identification and quantification of endocannabinoids. In: eLS, John Wiley & Sons, Ltd: Chichester. 2013. https:\/\/doi.org\/10.1002\/9780470015902.a0023407.","DOI":"10.1002\/9780470015902.a0023407"},{"key":"671_CR25","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1194\/jlr.M080093","volume":"59","author":"R Lerner","year":"2018","unstructured":"Lerner R, Post JM, Ellis SR, Vos DRN, Heeren RMA, Lutz B, et al. Simultaneous lipidomic and transcriptomic profiling in mouse brain punches of acute epileptic seizure model compared to controls. J Lipid Res. 2018;59:283\u201397.","journal-title":"J Lipid Res"},{"key":"671_CR26","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1038\/nrn1247","volume":"4","author":"D Piomelli","year":"2003","unstructured":"Piomelli D. The molecular logic of endocannabinoid signalling. Nat Rev Neurosci. 2003;4:873\u201384.","journal-title":"Nat Rev Neurosci"},{"key":"671_CR27","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1111\/bph.13215","volume":"173","author":"C Garc\u00eda","year":"2016","unstructured":"Garc\u00eda C, Palomo-Garo C, G\u00f3mez-G\u00e1lvez Y, Fern\u00e1ndez-Ruiz J. Cannabinoid-dopamine interactions in the physiology and physiopathology of the basal ganglia. Br J Pharm. 2016;173:2069\u201379.","journal-title":"Br J Pharm"},{"key":"671_CR28","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/nn2042","volume":"11","author":"M Maccarrone","year":"2008","unstructured":"Maccarrone M, Rossi S, Bari M, De Chiara V, Fezza F, Musella A, et al. Anandamide inhibits metabolism and physiological actions of 2-arachidonoylglycerol in the striatum. Nat Neurosci. 2008;11:152\u20139.","journal-title":"Nat Neurosci."},{"key":"671_CR29","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1038\/sj.npp.1300458","volume":"29","author":"D Centonze","year":"2004","unstructured":"Centonze D, Battista N, Rossi S, Mercuri NB, Finazzi-Agr\u00f2 A, Bernardi G, et al. A critical interaction between dopamine D2 receptors and endocannabinoids mediates the effects of cocaine on striatal gabaergic Transmission. Neuropsychopharmacology. 2004;29:1488\u201397.","journal-title":"Neuropsychopharmacology."},{"key":"671_CR30","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/sj.bjp.0703050","volume":"129","author":"D Smart","year":"2000","unstructured":"Smart D, Gunthorpe MJ, Jerman JC, Nasir S, Gray J, Muir AI, et al. The endogenous lipid anandamide is a full agonist at the human vanilloid receptor (hVR1). Br J Pharm. 2000;129:227\u201330.","journal-title":"Br J Pharm"},{"key":"671_CR31","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.brainres.2004.02.016","volume":"1007","author":"E de Lago","year":"2004","unstructured":"de Lago E, de Miguel R, Lastres-Becker I, Ramos JA, Fern\u00e1ndez-Ruiz J. Involvement of vanilloid-like receptors in the effects of anandamide on motor behavior and nigrostriatal dopaminergic activity: in vivo and in vitro evidence. Brain Res. 2004;1007:152\u20139.","journal-title":"Brain Res."},{"key":"671_CR32","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0014-2999(01)01012-3","volume":"420","author":"V Di Marzo","year":"2001","unstructured":"Di Marzo V, Lastres-Becker I, Bisogno T, De Petrocellis L, Milone A, Davis JB, et al. Hypolocomotor effects in rats of capsaicin and two long chain capsaicin homologues. Eur J Pharm. 2001;420:123\u201331.","journal-title":"Eur J Pharm"},{"key":"671_CR33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neulet.2014.12.003","volume":"587","author":"MC Garc\u00eda","year":"2015","unstructured":"Garc\u00eda MC, Cinquina V, Palomo-Garo C, R\u00e1bano A, Fern\u00e1ndez-Ruiz J. Identification of CB2 receptors in human nigral neurons that degenerate in Parkinson\u2019s disease. Neurosci Lett. 2015;587:1\u20134.","journal-title":"Neurosci Lett."},{"key":"671_CR34","unstructured":"Emerging science. https:\/\/www.aan.com\/conferences-community\/annual-meeting\/abstracts-and-awards\/emerging-science\/. Accessed 12 Aug 2018."},{"key":"671_CR35","doi-asserted-by":"crossref","unstructured":"Singer HS. The neurochemistry of Tourette syndrome. In: Martino D, Leckman JF, editors. Tourette syndrome, New York: Oxford University Press; 2013. p. 276\u2013300.","DOI":"10.1093\/med\/9780199796267.003.0013"},{"key":"671_CR36","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/ajmg.b.20159","volume":"127B","author":"D Gadzicki","year":"2004","unstructured":"Gadzicki D, M\u00fcller-Vahl KR, Heller D, Ossege S, N\u00f6then MM, Hebebrand J, et al. Tourette syndrome is not caused by mutations in the central cannabinoid receptor (CNR1) gene. Am J Med Genet B Neuropsychiatr Genet. 2004;127B:97\u2013103.","journal-title":"Am J Med Genet B Neuropsychiatr Genet."},{"key":"671_CR37","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.biopsych.2004.01.005","volume":"55","author":"G Berding","year":"2004","unstructured":"Berding G, M\u00fcller-Vahl K, Schneider U, Gielow P, Fitschen J, Stuhrmann M, et al. [123I]AM281 single-photon emission computed tomography imaging of central cannabinoid CB1 receptors before and after Delta9-tetrahydrocannabinol therapy and whole-body scanning for assessment of radiation dose in Tourette patients. Biol Psychiatry. 2004;55:904\u201315.","journal-title":"Biol Psychiatry."},{"key":"671_CR38","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1152\/physrev.00019.2008","volume":"89","author":"M Kano","year":"2009","unstructured":"Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M. Endocannabinoid-mediated control of synaptic transmission. Physiol Rev. 2009;89:309\u201380.","journal-title":"Physiol Rev."},{"key":"671_CR39","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1089\/can.2016.0009","volume":"1","author":"EB Russo","year":"2016","unstructured":"Russo EB. Clinical endocannabinoid deficiency reconsidered: current research supports the theory in migraine, fibromyalgia, irritable bowel, and other treatment-resistant syndromes. Cannabis Cannabinoid Res. 2016;1:154\u201365.","journal-title":"Cannabis Cannabinoid Res"},{"key":"671_CR40","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1002\/mds.23014","volume":"25","author":"V Pisani","year":"2010","unstructured":"Pisani V, Moschella V, Bari M, Fezza F, Galati S, Bernardi G, et al. Dynamic changes of anandamide in the cerebrospinal fluid of Parkinson\u2019s disease patients. Mov Disord. 2010;25:920\u20134.","journal-title":"Mov Disord."},{"key":"671_CR41","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1111\/j.1528-1167.2009.02334.x","volume":"51","author":"A Romigi","year":"2010","unstructured":"Romigi A, Bari M, Placidi F, Marciani MG, Malaponti M, Torelli F, et al. Cerebrospinal fluid levels of the endocannabinoid anandamide are reduced in patients with untreated newly diagnosed temporal lobe epilepsy. Epilepsia. 2010;51:768\u201372.","journal-title":"Epilepsia."},{"key":"671_CR42","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1136\/jnnp.2007.139071","volume":"79","author":"M Di Filippo","year":"2008","unstructured":"Di Filippo M, Pini LA, Pelliccioli GP, Calabresi P, Sarchielli P. Abnormalities in the cerebrospinal fluid levels of endocannabinoids in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2008;79:1224\u20139.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"671_CR43","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1038\/sj.npp.1301246","volume":"32","author":"P Sarchielli","year":"2007","unstructured":"Sarchielli P, Pini LA, Coppola F, Rossi C, Baldi A, Mancini ML, et al. Endocannabinoids in chronic migraine: CSF findings suggest a system failure. Neuropsychopharmacology. 2007;32:1384\u201390.","journal-title":"Neuropsychopharmacology."},{"key":"671_CR44","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1038\/mp.2013.61","volume":"18","author":"A Neumeister","year":"2013","unstructured":"Neumeister A, Normandin MD, Pietrzak RH, Piomelli D, Zheng M-Q, Gujarro-Anton A, et al. Elevated brain cannabinoid CB1 receptor availability in posttraumatic stress disorder: a positron emission tomography study. Mol Psychiatry. 2013;18:1034\u201340.","journal-title":"Mol Psychiatry."},{"key":"671_CR45","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.pnpbp.2016.01.004","volume":"67","author":"B Yi","year":"2016","unstructured":"Yi B, Nichiporuk I, Nicolas M, Schneider S, Feuerecker M, Vassilieva G, et al. Reductions in circulating endocannabinoid 2-arachidonoylglycerol levels in healthy human subjects exposed to chronic stressors. Prog Neuropsychopharmacol Biol Psychiatry. 2016;67:92\u20137.","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"671_CR46","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.neubiorev.2012.10.010","volume":"37","author":"PJ Hoekstra","year":"2013","unstructured":"Hoekstra PJ, Dietrich A, Edwards MJ, Elamin I, Martino D. Environmental factors in Tourette syndrome. Neurosci Biobehav Rev. 2013;37:1040\u20139.","journal-title":"Neurosci Biobehav Rev"},{"key":"671_CR47","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1146\/annurev-pharmtox-010716-104615","volume":"57","author":"ND Volkow","year":"2017","unstructured":"Volkow ND, Hampson AJ, Baler RD. Don\u2019t worry, be happy: endocannabinoids and cannabis at the intersection of stress and reward. Annu Rev Pharm Toxicol. 2017;57:285\u2013308.","journal-title":"Annu Rev Pharm Toxicol"},{"key":"671_CR48","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.euroneuro.2017.05.005","volume":"27","author":"RE Cooper","year":"2017","unstructured":"Cooper RE, Williams E, Seegobin S, Tye C, Kuntsi J, Asherson P. Cannabinoids in attention-deficit\/hyperactivity disorder: a randomised-controlled trial. Eur Neuropsychopharmacol. 2017;27:795\u2013808.","journal-title":"Eur Neuropsychopharmacol."},{"key":"671_CR49","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1212\/WNL.0b013e3181a2e8f6","volume":"72","author":"D Centonze","year":"2009","unstructured":"Centonze D, Bari M, Di Michele B, Rossi S, Gasperi V, Pasini A, et al. Altered anandamide degradation in attention-deficit\/hyperactivity disorder. Neurology. 2009;72:1526\u20137.","journal-title":"Neurology."},{"key":"671_CR50","first-page":"635","volume":"22","author":"LE Walker","year":"2017","unstructured":"Walker LE, Griffiths MJ, McGill F, Lewthwaite P, Sills GJ, Jorgensen A, et al. A comparison of HMGB1 concentrations between cerebrospinal fluid and blood in patients with neurological disease. Biomarkers. 2017;22:635\u201342.","journal-title":"Biomarkers."},{"key":"671_CR51","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3389\/fnbeh.2011.00064","volume":"5","author":"T Rubino","year":"2011","unstructured":"Rubino T, Parolaro D. Sexually dimorphic effects of cannabinoid compounds on emotion and cognition. Front Behav Neurosci. 2011;5:64.","journal-title":"Front Behav Neurosci"},{"key":"671_CR52","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1159\/000492600","volume":"87","author":"D Baumeister","year":"2018","unstructured":"Baumeister D, Eich W, Lerner R, Lutz B, Bindila L, Tesarz J. Plasma parameters of the endocannabinoid system are unaltered in fibromyalgia. Psychother Psychosom. 2018;87:377\u20139.","journal-title":"Psychother Psychosom."}],"container-title":["Neuropsychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41386-020-0671-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41386-020-0671-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41386-020-0671-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T21:08:47Z","timestamp":1684616927000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41386-020-0671-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,9]]},"references-count":52,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["671"],"URL":"https:\/\/doi.org\/10.1038\/s41386-020-0671-6","relation":{},"ISSN":["0893-133X","1740-634X"],"issn-type":[{"value":"0893-133X","type":"print"},{"value":"1740-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,9]]},"assertion":[{"value":"9 November 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 April 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}