{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:21:12Z","timestamp":1783660872966,"version":"3.55.0"},"reference-count":40,"publisher":"Georg Thieme Verlag KG","issue":"03","license":[{"start":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T00:00:00Z","timestamp":1638230400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Abide Therapeutics, USA. Funding for\n                        editorial support was provided by H. Lundbeck A\/S, Denmark."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacopsychiatry"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Introduction Tourette syndrome (TS) is a complex neurodevelopmental\n                    disorder characterized by chronic motor and vocal tics. While consistently\n                    effective treatment is lacking, evidence indicates that the modulation of\n                    endocannabinoid system is potentially beneficial. Lu AG06466 (previously\n                    ABX-1431) is a highly selective inhibitor of monoacylglycerol lipase, the\n                    primary enzyme responsible for the degradation of the endocannabinoid ligand\n                    2-arachidonoylglycerol. This exploratory study aimed to determine the effect of\n                    Lu AG06466 versus placebo on tics and other symptoms in patients with TS.<\/jats:p>\n                  <jats:p>Methods In this phase 1b cross-over study, 20 adult patients with TS on\n                    standard-of-care medications were randomized to a single fasted dose of Lu\n                    AG06466 (40\u2009mg) or placebo in period 1, followed by the other treatment\n                    in period 2. The effects on tics, premonitory urges, and psychiatric\n                    comorbidities were evaluated using a variety of scaled approaches at different\n                    time points before and after treatment.<\/jats:p>\n                  <jats:p>Results All scales showed an overall trend of tic reduction, with two out\n                    of three tic scales (including the Total Tic Score of the Yale Global Tic\n                    Severity Score) showing a significant effect of a single dose of Lu AG06466\n                    versus placebo at various timepoints. Treatment with Lu AG06466 resulted in a\n                    significant reduction in premonitory urges versus placebo. Single doses of Lu\n                    AG06466 were generally well-tolerated, and the most common adverse events were\n                    headache, somnolence, and fatigue.<\/jats:p>\n                  <jats:p>Conclusion In this exploratory trial, a single dose of Lu AG06466 showed\n                    statistically significant positive effects on key measures of TS symptoms.<\/jats:p>","DOI":"10.1055\/a-1675-3494","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T18:53:46Z","timestamp":1638298426000},"page":"148-156","source":"Crossref","is-referenced-by-count":27,"title":["Endocannabinoid Modulation Using Monoacylglycerol Lipase Inhibition\n                    in Tourette Syndrome: A Phase 1 Randomized, Placebo-Controlled\n                    Study"],"prefix":"10.1055","volume":"55","clinical-trial-number":[{"clinical-trial-number":"nct03058562","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7181-7419","authenticated-orcid":false,"given":"Kirsten R.","family":"M\u00fcller-Vahl","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover\n                    Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Fremer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover\n                    Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan","family":"Beals","sequence":"additional","affiliation":[{"name":"Abide Therapeutics, San Diego, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Ivkovic","sequence":"additional","affiliation":[{"name":"H. Lundbeck A\/S, Valby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Loft","sequence":"additional","affiliation":[{"name":"H. Lundbeck A\/S, Valby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Schindler","sequence":"additional","affiliation":[{"name":"Clinical Research Center Core Facility, Hannover Medical School,\n                    Hannover, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2021,11,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.jpsychores.2009.09.002","article-title":"Clinical course of Tourette syndrome","volume":"67","author":"M H Bloch","year":"2009","journal-title":"J Psychosom Res"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1016\/bs.irn.2017.05.006","article-title":"Tourette syndrome and chronic tic disorders: The clinical spectrum beyond\n                    tics","volume":"134","author":"D Martino","year":"2017","journal-title":"Int Rev Neurobiol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1001\/jamapsychiatry.2014.2650","article-title":"Lifetime prevalence, age of risk, and genetic relationships of comorbid\n                    psychiatric disorders in Tourette syndrome","volume":"72","author":"M E Hirschtritt","year":"2015","journal-title":"JAMA Psychiatry"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s40263-017-0486-0","article-title":"Current approaches and new developments in the pharmacological management of\n                    Tourette syndrome","volume":"32","author":"J Quezada","year":"2018","journal-title":"CNS drugs"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1212\/wnl.0000000000007467","article-title":"Comprehensive systematic review summary: Treatment of tics in people with\n                    Tourette syndrome and chronic tic disorders","volume":"92","author":"T Pringsheim","year":"2019","journal-title":"Neurology"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1097\/wco.0000000000000356","article-title":"Tics and Tourette\u2019s: update on pathophysiology and tic control","volume":"29","author":"C Ganos","year":"2016","journal-title":"Curr Opin Neurol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1111\/j.1600-0447.1998.tb10127.x","article-title":"Cannabinoids: Possible role in patho-physiology and therapy of Gilles de la\n                    Tourette syndrome","volume":"98","author":"K R M\u00fcller-Vahl","year":"1998","journal-title":"Acta Psychiatr Scand"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1176\/appi.neuropsych.16110310","article-title":"Preliminary evidence on cannabis effectiveness and tolerability for adults with\n                    Tourette syndrome","volume":"29","author":"E Abi-Jaoude","year":"2017","journal-title":"J Neuropsychiatry Clin Neurosci"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.parkreldis.2018.10.004","article-title":"Single center experience with medical cannabis in Gilles de la Tourette\n                    syndrome","volume":"61","author":"A Thaler","year":"2019","journal-title":"Parkinsonism Relat Disord"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1055\/s-2002-25028","article-title":"Treatment of Tourette\u2019s syndrome with Delta 9-tetrahydrocannabinol\n                    (THC): a randomized crossover trial","volume":"35","author":"K R M\u00fcller-Vahl","year":"2002","journal-title":"Pharmacopsychiatry"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"459","DOI":"10.4088\/jcp.v64n0417","article-title":"Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in\n                    Tourette syndrome: a 6-week randomized trial","volume":"64","author":"K R M\u00fcller-Vahl","year":"2003","journal-title":"J Clin Psychiatry"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/s0090-6980(02)00060-6","article-title":"The cannabinoid receptors","volume":"68-69","author":"A C Howlett","year":"2002","journal-title":"Prostaglandins Other Lipid Mediat"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.tins.2011.03.003","article-title":"Supply and demand for endocannabinoids","volume":"34","author":"B E Alger","year":"2011","journal-title":"Trends Neurosci"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1124\/pr.112.006387","article-title":"Chemical probes of endocannabinoid metabolism","volume":"65","author":"J L Blankman","year":"2013","journal-title":"Pharmacol Rev"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1097\/00004583-198907000-00015","article-title":"The Yale Global Tic Severity Scale: Initial testing of a clinician-rated scale\n                    of tic severity","volume":"28","author":"J F Leckman","year":"1989","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1002\/1531-8257(199905)14:3<502::aid-mds1020>3.0.co;2-g","article-title":"Advantages of a modified scoring method for the Rush Video-Based Tic Rating\n                    Scale","volume":"14","author":"C G Goetz","year":"1999","journal-title":"Mov Disord"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1016\/j.beth.2015.06.002","article-title":"Psychometric properties of a self-report instrument for the assessment of tic\n                    severity in adults with tic disorders","volume":"46","author":"A Abramovitch","year":"2015","journal-title":"Behav Ther"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.jpsychires.2016.09.007","article-title":"The premonitory urge revisited: An individualized premonitory urge for tics\n                    scale","volume":"83","author":"J F McGuire","year":"2016","journal-title":"J Psychiatr Res"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1001\/archpsyc.1989.01810110048007","article-title":"The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and\n                    reliability","volume":"46","author":"W K Goodman","year":"1989","journal-title":"Arch Gen Psychiatry"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1037\/pas0000530","article-title":"Utility of the Conners\u2019 Adult ADHD Rating Scale validity scales in\n                    identifying simulated attention-deficit hyperactivity disorder and random\n                    responding","volume":"29","author":"B D Walls","year":"2017","journal-title":"Psychol Assess"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1037\/\/0022-006x.56.6.893","article-title":"An inventory for measuring clinical anxiety: Psychometric properties","volume":"56","author":"A T Beck","year":"1988","journal-title":"J Consult Clin Psychol"},{"key":"ref22","first-page":"1196","article-title":"BDI-II, Beck Depression Inventory: Manual San Antonio, Tex","author":"A Beck","journal-title":"Psychological Corp"},{"key":"ref23","first-page":"218","volume-title":"Clinical global impressions. In: ECDEU Assessment Manual for\n                    Psychopharmacology","author":"W Guy","year":"1976"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1124\/jpet.118.252296","article-title":"Monoacylglycerol lipase inhibition in human and rodent systems supports clinical\n                    evaluation of endocannabinoid modulators","volume":"367","author":"J R Clapper","year":"2018","journal-title":"J Pharmacol Exp Ther"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1007\/s00787-016-0823-8","article-title":"The effects of Gilles de la Tourette syndrome and other chronic tic disorders on\n                    quality of life across the lifespan: a systematic review","volume":"25","author":"J Evans","year":"2016","journal-title":"Eur Child Adolesc Psychiatry"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1002\/mds.26891","article-title":"Systematic review of severity scales and screening instruments for tics:\n                    Critique and recommendations","volume":"32","author":"D Martino","year":"2017","journal-title":"Mov Disord"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"e27850","DOI":"10.1371\/journal.pone.0027850","article-title":"Motor-cortical interaction in Gilles de la Tourette syndrome","volume":"7","author":"S Franzkowiak","year":"2012","journal-title":"PLoS One"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"416","DOI":"10.3389\/fnins.2016.00416","article-title":"Aripiprazole improves associated comorbid conditions in addition to tics in\n                    adult patients with Gilles de la Tourette syndrome","volume":"10","author":"S Gerasch","year":"2016","journal-title":"Front Neurosci"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3390\/brainsci7050047","article-title":"Significant tic reduction in an otherwise treatment-resistant patient with\n                    Gilles de la Tourette syndrome following treatment with nabiximols","author":"A S Kanaan","year":"2017","journal-title":"Brain Sci"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e44215","DOI":"10.1371\/journal.pone.0044215","article-title":"Increased thalamic gamma band activity correlates with symptom relief following\n                    deep brain stimulation in humans with Tourette\u2019s syndrome","volume":"7","author":"N Maling","year":"2012","journal-title":"PLoS One"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"e1711","DOI":"10.1212\/WNL.0000000000005474","article-title":"A multicenter examination and strategic revisions of the Yale Global Tic\n                    Severity Scale","volume":"90","author":"J F McGuire","year":"2018","journal-title":"Neurology"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"626459","DOI":"10.3389\/fpsyt.2021.626459","article-title":"Yale Global Tic Severity Scale (YGTSS): Psychometric quality of the gold\n                    standard for tic assessment based on the large-scale EMTICS Study","volume":"12","author":"M Haas","year":"2021","journal-title":"Front Psychiatry"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1089\/can.2018.0050","article-title":"Treatment of Gilles de la Tourette syndrome with cannabis-based medicine:\n                    Results from a retrospective analysis and online survey","volume":"4","author":"L M Milosev","year":"2019","journal-title":"Cannabis Cannabinoid Res"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1176\/appi.neuropsych.16070141","article-title":"Neurobiology of the premonitory urge in Tourette\u2019s syndrome:\n                    Pathophysiology and treatment implications","volume":"29","author":"A E Cavanna","year":"2017","journal-title":"J Neuropsych Clin Neurosci"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1038\/s41386-020-0671-6","article-title":"Cerebrospinal fluid endocannabinoid levels in Gilles de la Tourette\n                    syndrome","volume":"45","author":"K R Muller-Vahl","year":"2020","journal-title":"Neuropsychopharmacology"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.3389\/conf.fphar.2017.62.00011","article-title":"Preclinical characterization and first-in-human administration of a selective\n                    monoacylglycerol lipase inhibitor, ABX-1431","author":"I P Fraser","year":"2017","journal-title":"Conference Abstract: EUFEMED"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1517\/14740338.2011.575778","article-title":"Abuse potential and psychoactive effects of delta-9-tetrahydrocannabinol and\n                    cannabidiol oromucosal spray (Sativex), a new cannabinoid medicine","volume":"10","author":"P Robson","year":"2011","journal-title":"Expert Opin Drug Saf"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"11252","DOI":"10.1523\/jneurosci.1067-15.2015","article-title":"Sex differences in molecular signaling at inhibitory synapses in the\n                    hippocampus","volume":"35","author":"N Tabatadze","year":"2015","journal-title":"J Neurosci"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/j.lfs.2012.06.009","article-title":"Sex differences in cannabinoid pharmacology: A reflection of differences in the\n                    endocannabinoid system?","volume":"92","author":"R M Craft","year":"2013","journal-title":"Life Sci"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"249","DOI":"10.3389\/fnbeh.2018.00249","article-title":"The modulating role of sex and anabolic-androgenic steroid hormones in\n                    cannabinoid sensitivity","volume":"12","author":"D Struik","year":"2018","journal-title":"Front Behav Neurosci"}],"container-title":["Pharmacopsychiatry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1675-3494.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T11:23:38Z","timestamp":1764069818000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1675-3494"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,30]]},"references-count":40,"journal-issue":{"issue":"03","published-online":{"date-parts":[[2022,5,16]]},"published-print":{"date-parts":[[2022,5]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1675-3494","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0176-3679","1439-0795"],"issn-type":[{"value":"0176-3679","type":"print"},{"value":"1439-0795","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,30]]}}}