{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:49:49Z","timestamp":1792788589162,"version":"4.5.0"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T00:00:00Z","timestamp":1637020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Azienda Ospedaliera Universitaria Careggi"},{"DOI":"10.13039\/501100015694","name":"Fondazione Cassa di Risparmio di Firenze","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100015694","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cocaine use disorder (CUD) is a global health issue with no effective treatment. Repetitive Transcranial Magnetic Stimulation (rTMS) is a recently proposed therapy for CUD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a single-center, randomised, sham-controlled, blinded, parallel-group research with patients randomly allocated to rTMS (15 Hz) or Sham group (1:1) using a computerised block randomisation process. We enrolled 62 of 81 CUD patients in two years. Patients were followed for eight weeks after receiving 15 15 Hz rTMS\/sham sessions over the left dorsolateral prefrontal cortex (DLPFC) during the first three weeks of the study. We targeted the DLFPC following the 5 cm method. Cocaine lapses in twice a week urine tests were the primary outcome. The secondary outcomes were craving severity, cocaine use pattern, and psychometric assessments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>We randomly allocated patients to either an active rTMS group (32 subjects) or a sham treatment group (30 subjects). Thirteen (42%) and twelve (43.3%) of the subjects in rTMS and sham groups, respectively, completed the full trial regimen, displaying a high dropout rate. Ten\/30 (33%) of rTMS-treated patients tested negative for cocaine in urine, in contrast to 4\/27 of placebo controls (p = 0.18, odd ratio 2.88, CI 0.9\u201310). The Kaplan-Meier survival curve did not state a significant change between the treated and sham groups in the time of cocaine urine negativisation (p = 0.20). However, the severity of cocaine-related cues mediated craving (VAS peak) was substantially decreased in the rTMS treated group (p&lt;0.03) after treatment at T1, corresponding to the end of rTMS treatment. Furthermore, in the rTMS and sham groups, self-reported days of cocaine use decreased significantly (p&lt;0.03). Finally, psychometric impulsivity parameters improved in rTMS-treated patients, while depression scales improved in both groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In CUD, rTMS could be a useful tool for lowering cocaine craving and consumption.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      The study number on clinicalTrials.gov is\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03607591\" xlink:type=\"simple\">NCT03607591<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0259860","type":"journal-article","created":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T13:31:58Z","timestamp":1637069518000},"page":"e0259860","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":28,"title":["A randomised, double-blind, sham-controlled study of left prefrontal cortex 15 Hz repetitive transcranial magnetic stimulation in cocaine consumption and craving"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7181-6806","authenticated-orcid":true,"given":"Francesco","family":"Lolli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Salimova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maenia","family":"Scarpino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Lanzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesarina","family":"Cossu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Bastianelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brunella","family":"Occupati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Gori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amedeo","family":"Del Vecchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Ercolini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Pascolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Cimino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicol\u00f2","family":"Meneghin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Fierini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"D\u2019Anna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Innocenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ballerini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Pallanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonello","family":"Grippo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Mannaioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,11,16]]},"reference":[{"issue":"4","key":"pone.0259860.ref001","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1080\/10550490802139283","article-title":"Daily sessions of transcranial magnetic stimulation to the left prefrontal cortex gradually reduce cocaine craving","volume":"17","author":"E Politi","year":"2008","journal-title":"Am J Addict"},{"issue":"12","key":"pone.0259860.ref002","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/nrn.2017.130","article-title":"The dopamine motive system: implications for drug and food addiction","volume":"18","author":"ND Volkow","year":"2017","journal-title":"Nature Reviews Neuroscience"},{"issue":"11","key":"pone.0259860.ref003","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/nrn.2017.113","article-title":"Rehabilitating the addicted brain with transcranial magnetic stimulation","volume":"18","author":"M Diana","year":"2017","journal-title":"Nature Reviews Neuroscience"},{"key":"pone.0259860.ref004","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3389\/fnins.2020.00137","article-title":"rTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use Disorders","volume":"14","author":"J Moretti","year":"2020","journal-title":"Front Neurosci."},{"key":"pone.0259860.ref005","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3389\/fpsyt.2011.00064","article-title":"The dopamine hypothesis of drug addiction and its potential therapeutic value","volume":"2","author":"M Diana","year":"2011","journal-title":"Front Psychiatry"},{"issue":"3","key":"pone.0259860.ref006","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.brs.2021.04.018","article-title":"Targeting repetitive transcranial magnetic stimulation in depression: do we really know what we are stimulating and how best to do it?","volume":"14","author":"PB Fitzgerald","journal-title":"Brain Stimulation. 2021"},{"issue":"7445","key":"pone.0259860.ref007","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nature12024","article-title":"Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking","volume":"496","author":"BT Chen","year":"2013","journal-title":"Nature"},{"issue":"5","key":"pone.0259860.ref008","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1212\/WNL.48.5.1398","article-title":"Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation","volume":"48","author":"R Chen","year":"1997","journal-title":"Neurology"},{"key":"pone.0259860.ref009","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1093\/brain\/117.4.847","article-title":"RESPONSES TO RAPID-RATE TRANSCRANIAL MAGNETIC STIMULATION OF THE HUMAN MOTOR CORTEX","volume":"117","author":"A Pascualleone","year":"1994","journal-title":"Brain"},{"issue":"12","key":"pone.0259860.ref010","doi-asserted-by":"crossref","first-page":"e1002715","DOI":"10.1371\/journal.pmed.1002715","article-title":"Comparative efficacy and acceptability of psychosocial interventions for individuals with cocaine and amphetamine addiction: A systematic review and network meta-analysis","volume":"15","author":"F De Crescenzo","year":"2018","journal-title":"Plos Medicine"},{"issue":"1","key":"pone.0259860.ref011","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.drugalcdep.2006.06.002","article-title":"One session of high frequency repetitive transcranial magnetic stimulation (rTMS) to the right prefrontal cortex transiently reduces cocaine craving","volume":"86","author":"JA Camprodon","year":"2007","journal-title":"Drug Alcohol Depend"},{"key":"pone.0259860.ref012","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.neulet.2016.06.049","article-title":"Add-on high frequency deep transcranial magnetic stimulation (dTMS) to bilateral prefrontal cortex reduces cocaine craving in patients with cocaine use disorder","volume":"629","author":"C Rapinesi","year":"2016","journal-title":"Neurosci Lett"},{"key":"pone.0259860.ref013","doi-asserted-by":"crossref","first-page":"621","DOI":"10.3389\/fpsyt.2019.00621","article-title":"rTMS Reduces Psychopathological Burden and Cocaine Consumption in Treatment-Seeking Subjects With Cocaine Use Disorder: An Open Label, Feasibility Study","volume":"10","author":"M Pettorruso","year":"2019","journal-title":"Frontiers in Psychiatry"},{"issue":"1","key":"pone.0259860.ref014","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.euroneuro.2015.11.011","article-title":"Transcranial magnetic stimulation of dorsolateral prefrontal cortex reduces cocaine use: A pilot study","volume":"26","author":"A Terraneo","year":"2016","journal-title":"Eur Neuropsychopharmacol"},{"issue":"1","key":"pone.0259860.ref015","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neucli.2018.10.002","article-title":"Efficacy of high-frequency (15Hz) repetitive transcranial magnetic stimulation (rTMS) of the left premotor cortex\/dorsolateral prefrontal cortex in decreasing cocaine intake (the MagneTox study): A study protocol for a randomized placebo-controlled pilot trial","volume":"49","author":"M Scarpino","year":"2019","journal-title":"Neurophysiol Clin"},{"issue":"1","key":"pone.0259860.ref016","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1002\/hbm.20360","article-title":"Transcranial magnetic stimulation and the challenge of coil placement: a comparison of conventional and stereotaxic neuronavigational strategies","volume":"29","author":"R Sparing","year":"2008","journal-title":"Hum Brain Mapp"},{"issue":"9022","key":"pone.0259860.ref017","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0140-6736(96)01219-6","article-title":"Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression","volume":"348","author":"A Pascual-Leone","year":"1996","journal-title":"Lancet"},{"key":"pone.0259860.ref018","first-page":"59","volume-title":"Transcranial magnetic stimulation in clinical psychiatry","author":"U Ziemann","year":"2000"},{"issue":"3","key":"pone.0259860.ref019","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.drugalcdep.2007.10.002","article-title":"Craving predicts time to cocaine relapse: further validation of the Now and Brief versions of the cocaine craving questionnaire","volume":"93","author":"P Paliwal","year":"2008","journal-title":"Drug Alcohol Depend"},{"issue":"2","key":"pone.0259860.ref020","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.clinph.2019.11.002","article-title":"Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014\u20132018)","volume":"131","author":"J-P Lefaucheur","year":"2020","journal-title":"Clinical Neurophysiology."},{"key":"pone.0259860.ref021","doi-asserted-by":"crossref","first-page":"133","DOI":"10.3389\/fpsyt.2016.00133","article-title":"Bilateral Transcranial Magnetic Stimulation of the Prefrontal Cortex Reduces Cocaine Intake: A Pilot Study","volume":"7","author":"C Bolloni","year":"2016","journal-title":"Front Psychiatry"},{"key":"pone.0259860.ref022","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3389\/fpsyt.2018.00080","article-title":"Transcranial Magnetic Stimulation of Medial Prefrontal and Cingulate Cortices Reduces Cocaine Self-Administration: A Pilot Study","volume":"9","author":"D Martinez","year":"2018","journal-title":"Front Psychiatry"},{"key":"pone.0259860.ref023","first-page":"745","article-title":"Clinical and functional connectivity outcomes of 5-Hz repeated transcranial magnetic stimulation as an add-on treatment in cocaine use disorder: a double-blind randomized controlled trial","volume":"6","author":"EA Garza-Villarreal","year":"2021","journal-title":"Biol Psychiatry Cogn Neurosci Neuroimaging"},{"issue":"Pt A","key":"pone.0259860.ref024","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.brainres.2015.02.053","article-title":"What goes up, can come down: Novel brain stimulation paradigms may attenuate craving and craving-related neural circuitry in substance dependent individuals","volume":"1628","author":"CA Hanlon","year":"2015","journal-title":"Brain Res"},{"key":"pone.0259860.ref025","doi-asserted-by":"crossref","first-page":"158","DOI":"10.3389\/fpsyt.2020.00158","article-title":"Long-Term Outcome of Repetitive Transcranial Magnetic Stimulation in a Large Cohort of Patients With Cocaine-Use Disorder: An Observational Study","volume":"11","author":"G Madeo","year":"2020","journal-title":"Front Psychiatry"},{"issue":"12","key":"pone.0259860.ref026","first-page":"CD002950","article-title":"Antidepressants for cocaine dependence and problematic cocaine use","author":"PP Pani","year":"2011","journal-title":"Cochrane Database Syst Rev"},{"issue":"2\u20133","key":"pone.0259860.ref027","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.drugalcdep.2007.05.025","article-title":"Negative emotion-driven impulsivity predicts substance dependence problems","volume":"91","author":"A Verdejo-Garc\u00eda","year":"2007","journal-title":"Drug Alcohol Depend"},{"key":"pone.0259860.ref028","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.addbeh.2014.09.017","article-title":"Causal pathways between impulsiveness, cocaine use consequences, and depression","volume":"41","author":"JJ Lister","year":"2015","journal-title":"Addict Behav"},{"issue":"4","key":"pone.0259860.ref029","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1097\/00132576-200211000-00005","article-title":"A Comparison of Single-Item Visual Analog Scales With a Multiitem Likert-Type Scale for Assessment of Cocaine Craving in Persons With Bipolar Disorder","volume":"1","author":"JW Lee","year":"2002","journal-title":"Addictive Disorders & Their Treatment"},{"issue":"3","key":"pone.0259860.ref030","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.1016\/j.biopsych.2016.02.006","article-title":"10-Hz Repetitive Transcranial Magnetic Stimulation of the Left Dorsolateral Prefrontal Cortex Reduces Heroin Cue Craving in Long-Term Addicts","volume":"80","author":"Y Shen","year":"2016","journal-title":"Biol Psychiatry"},{"issue":"1","key":"pone.0259860.ref031","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1037\/pha0000289","article-title":"A case report illustrating the effects of repetitive transcranial magnetic stimulation on cue-induced craving in an individual with opioid and cocaine use disorder","volume":"28","author":"JJ Mahoney","year":"2020","journal-title":"Exp Clin Psychopharmacol."},{"key":"pone.0259860.ref032","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.drugalcdep.2017.03.039","article-title":"Left frontal pole theta burst stimulation decreases orbitofrontal and insula activity in cocaine users and alcohol users","volume":"178","author":"CA Hanlon","year":"2017","journal-title":"Drug Alcohol Depend"},{"issue":"3","key":"pone.0259860.ref033","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.jbmt.2019.05.016","article-title":"Effects of myofascial trigger point dry cupping on pain and function in patients with plantar heel pain: A randomized controlled trial","volume":"23","author":"N AlKhadhrawi","year":"2019","journal-title":"J Bodyw Mov Ther"},{"issue":"1","key":"pone.0259860.ref034","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/j.1360-0443.2012.04010.x","article-title":"Effects of independent and substance-induced major depressive disorder on remission and relapse of alcohol, cocaine and heroin dependence","volume":"108","author":"S Samet","year":"2013","journal-title":"Addiction"},{"issue":"5","key":"pone.0259860.ref035","first-page":"1","article-title":"Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"16","author":"HQ Ontario","year":"2016","journal-title":"Ont Health Technol Assess Ser"},{"issue":"1","key":"pone.0259860.ref036","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/ana.25387","article-title":"Challenges of differential placebo effects in contemporary medicine: The example of brain stimulation","volume":"85","author":"MJ Burke","year":"2019","journal-title":"Ann Neurol"},{"key":"pone.0259860.ref037","doi-asserted-by":"crossref","first-page":"103027","DOI":"10.1016\/j.ebiom.2020.103027","article-title":"The exploration of optimized protocol for repetitive transcranial magnetic stimulation in the treatment of methamphetamine use disorder: A randomized sham-controlled study","volume":"60","author":"TZ Chen","year":"2020","journal-title":"Ebiomedicine."},{"issue":"11","key":"pone.0259860.ref038","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1111\/cns.13230","article-title":"Anhedonia across borders: Transdiagnostic relevance of reward dysfunction for noninvasive brain stimulation endophenotypes","volume":"25","author":"MC Spano","year":"2019","journal-title":"Cns Neuroscience & Therapeutics"},{"key":"pone.0259860.ref039","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.bandc.2018.11.003","article-title":"Effects of intermittent theta burst stimulation applied to the left dorsolateral prefrontal cortex on empathy and impulsivity in healthy adult males","volume":"128","author":"CC Yang","year":"2018","journal-title":"Brain and Cognition"},{"key":"pone.0259860.ref040","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3389\/fnhum.2013.00043","article-title":"Emotional and non-emotional pathways to impulsive behavior and addiction","volume":"7","author":"A Torres","year":"2013","journal-title":"Front Hum Neurosci"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0259860","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T13:32:49Z","timestamp":1637069569000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0259860"}},"subtitle":[],"editor":[{"given":"Bernard","family":"Le Foll","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,11,16]]},"references-count":40,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0259860","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,16]]}}}