{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T17:13:51Z","timestamp":1775582031806,"version":"3.50.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:p>3,4-Methylenedioxymethamphetamine (MDMA), is investigated as a treatment for post-traumatic stress disorder and other anxiety-related conditions in multiple placebo-controlled and open label studies. MDMA-assisted therapy is projected for approval by the United States Food and Drug Administration (FDA) and other regulatory agencies worldwide within the next few years. MDMA is a monoamine releaser and uptake inhibitor affecting serotonin, potentially increasing the risk of serotonin syndrome (SS). No instances of SS have occurred in clinical trials. The relatively small number of patients in controlled trials warranted a survey of FDA Adverse Event Reporting System data for the occurrence of SS in a larger database. We found 20 SS cases in people exposed to MDMA, all of which had also taken one or more substances with serotonergic properties in addition to MDMA, including amphetamines, stimulants, and opioids. There were no cases of SS associated with MDMA where MDMA was the sole reported compound taken.<\/jats:p>","DOI":"10.3389\/fpsyt.2021.824288","type":"journal-article","created":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T06:57:26Z","timestamp":1643007446000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Reported Cases of Serotonin Syndrome in MDMA Users in FAERS Database"],"prefix":"10.3389","volume":"12","author":[{"given":"Tigran","family":"Makunts","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Jerome","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruben","family":"Abagyan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberdina","family":"de Boer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1038\/s41591-021-01336-3","article-title":"MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study","volume":"27","author":"Mitchell","year":"2021","journal-title":"Nat Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"20442","DOI":"10.1038\/s41598-020-75706-1","article-title":"MDMA-assisted psychotherapy for treatment of anxiety and other psychological distress related to life-threatening illnesses: a randomized pilot study","volume":"10","author":"Wolfson","year":"2020","journal-title":"Sci Rep"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2735","DOI":"10.1007\/s00213-019-05249-5","article-title":"MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials","volume":"236","author":"Mithoefer","year":"2019","journal-title":"Psychopharmacology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2485","DOI":"10.1007\/s00213-020-05548-2","article-title":"Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials","volume":"237","author":"Jerome","year":"2020","journal-title":"Psychopharmacology"},{"key":"B5","first-page":"917","article-title":"The pharmacology and toxicology of \u201cecstasy\u201d (MDMA) and related drugs","volume":"165","author":"Kalant","year":"2001","journal-title":"CMAJ"},{"key":"B6","doi-asserted-by":"publisher","first-page":"83","DOI":"10.2147\/SAR.S37258","article-title":"3,4-methylenedioxymethamphetamine (MDMA): current perspectives","volume":"4","author":"Meyer","year":"2013","journal-title":"Subst Abuse Rehabil"},{"key":"B7","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1111\/j.1476-5381.2012.02145.x","article-title":"Pharmacological characterization of designer cathinones in vitro","volume":"168","author":"Simmler","year":"2013","journal-title":"Br J Pharmacol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/s00213-005-0174-5","article-title":"MDMA (Ecstasy) and human dopamine, norepinephrine, and serotonin transporters: implications for MDMA-induced neurotoxicity and treatment","volume":"189","author":"Verrico","year":"2007","journal-title":"Psychopharmacology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1177\/0269881116663120","article-title":"The effects of MDMA on socio-emotional processing: does MDMA differ from other stimulants?","volume":"30","author":"Bershad","year":"2016","journal-title":"J Psychopharmacol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1002\/cpt.565","article-title":"Potential psychiatric uses for MDMA","volume":"101","author":"Yazar-Klosinski","year":"2017","journal-title":"Clin Pharmacol Ther"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1093\/scan\/nst161","article-title":"MDMA enhances emotional empathy and prosocial behavior","volume":"9","author":"Hysek","year":"2014","journal-title":"Soc Cogn Affect Neurosci"},{"key":"B12","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1177\/0269881117691569","article-title":"Safety pharmacology of acute MDMA administration in healthy subjects","volume":"31","author":"Vizeli","year":"2017","journal-title":"J Psychopharmacol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2288","DOI":"10.3390\/ijms20092288","article-title":"The Serotonin Syndrome: from molecular mechanisms to clinical practice","volume":"20","author":"Francescangeli","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1056\/NEJMra041867","article-title":"The serotonin syndrome","volume":"352","author":"Boyer","year":"2005","journal-title":"N Engl J Med"},{"key":"B15","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1515\/ijamh-2013-0052","article-title":"Ecstasy use and serotonin syndrome: a neglected danger to adolescents and young adults prescribed selective serotonin reuptake inhibitors","volume":"25","author":"Dobry","year":"2013","journal-title":"Int J Adolesc Med Health"},{"key":"B16","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1080\/00048670701449237","article-title":"Qualitative review of serotonin syndrome, ecstasy (MDMA) and the use of other serotonergic substances: hierarchy of risk","volume":"41","author":"Silins","year":"2007","journal-title":"Aust N Z J Psychiatry"},{"key":"B17","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1093\/anatox\/35.4.219","article-title":"Deaths involving MDMA and the concomitant use of pharmaceutical drugs","volume":"35","author":"Pilgrim","year":"2011","journal-title":"J Anal Toxicol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.forsciint.2011.04.008","article-title":"Serotonin toxicity involving MDMA (ecstasy) and moclobemide","volume":"215","author":"Pilgrim","year":"2012","journal-title":"Forensic Sci Int"},{"key":"B19","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1345\/aph.1D344","article-title":"Serotonin syndrome resulting from coadministration of tramadol, venlafaxine, and mirtazapine","volume":"38","author":"Houlihan","year":"2004","journal-title":"Ann Pharmacother"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1176\/appi.ajp.161.6.1129","article-title":"Serotonin syndrome with tramadol and citalopram","volume":"161","author":"Mahlberg","year":"2004","journal-title":"Am J Psychiatry"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e2421","DOI":"10.7759\/cureus.2421","article-title":"serotonin syndrome presenting with concomitant tramadol and diphenhydramine use: a case report of an unlikely side-effect","volume":"10","author":"Khan","year":"2018","journal-title":"Cureus"},{"key":"B22","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1345\/aph.1E523","article-title":"Serotonin toxicity associated with concomitant use of linezolid","volume":"39","author":"Bergeron","year":"2005","journal-title":"Ann Pharmacother"},{"key":"B23","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/S0033-3182(09)70868-0","article-title":"Serotonin syndrome in a chronic-pain patient receiving concurrent methadone, ciprofloxacin, and venlafaxine","volume":"50","author":"Lee","year":"2009","journal-title":"Psychosomatics"},{"key":"B24","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1046\/j.1440-1819.2002.01050.x","article-title":"Can olanzapine be implicated in causing serotonin syndrome?","volume":"56","author":"Haslett","year":"2002","journal-title":"Psychiatry Clin Neurosci"},{"key":"B25","doi-asserted-by":"publisher","first-page":"4175","DOI":"10.3390\/jcm10184175","article-title":"Treatment guidelines for PTSD: a systematic review","volume":"10","author":"Martin","year":"2021","journal-title":"J Clin Med"},{"key":"B26","doi-asserted-by":"publisher","first-page":"373","DOI":"10.9740\/mhc.2019.11.373","article-title":"Treatment of posttraumatic stress disorder: focus on pharmacotherapy","volume":"9","author":"Ehret","year":"2019","journal-title":"Ment Health Clin"},{"key":"B27","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/j.chc.2016.05.006","article-title":"Substance abuse and trauma","volume":"25","author":"Simmons","year":"2016","journal-title":"Child Adolesc Psychiatr Clin N Am"},{"key":"B28","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1007\/s11606-006-0101-4","article-title":"Prevalence of depression-PTSD comorbidity: implications for clinical practice guidelines and primary care-based interventions","volume":"22","author":"Campbell","year":"2007","journal-title":"J Gen Intern Med"},{"key":"B29","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1037\/tra0000383","article-title":"Comorbid mood and anxiety disorders and severity of posttraumatic stress disorder symptoms in treatment-seeking veterans","volume":"11","author":"Knowles","year":"2019","journal-title":"Psychol Trauma"},{"key":"B30","doi-asserted-by":"publisher","first-page":"173","DOI":"10.3928\/00485713-20160125-01","article-title":"Sleep disturbances in posttraumatic stress disorder: updated review and implications for treatment","volume":"46","author":"Koffel","year":"2016","journal-title":"Psychiatr Ann"},{"key":"B31","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s11916-019-0828-3","article-title":"The interaction between chronic pain and PTSD","volume":"23","author":"Kind","year":"2019","journal-title":"Curr Pain Headache Rep"},{"key":"B32","doi-asserted-by":"publisher","first-page":"224","DOI":"10.3163\/1536-5050.95.2.224","article-title":"MedWatch: the FDA safety information and adverse event reporting program","volume":"95","author":"Craigle","year":"2007","journal-title":"J Med Libr Assoc"},{"key":"B33","doi-asserted-by":"publisher","first-page":"2765","DOI":"10.1001\/jama.269.21.2765","article-title":"Introducing MEDWatch. A new approach to reporting medication and device adverse effects and product problems","volume":"269","author":"Kessler","year":"1993","journal-title":"JAMA"},{"key":"B34","doi-asserted-by":"publisher","first-page":"17324","DOI":"10.1038\/s41598-021-96467-5","article-title":"Myocarditis occurrence with cancer immunotherapy across indications in clinical trial and post-marketing data","volume":"11","author":"Makunts","year":"2021","journal-title":"Sci Rep"},{"key":"B35","doi-asserted-by":"publisher","first-page":"5997","DOI":"10.1038\/s41598-021-85389-x","article-title":"Concomitant drugs associated with increased mortality for MDMA users reported in a drug safety surveillance database","volume":"11","author":"Cohen","year":"2021","journal-title":"Sci Rep"},{"key":"B36","doi-asserted-by":"publisher","first-page":"235","DOI":"10.3389\/fgene.2012.00235","article-title":"MDMA, methamphetamine, and CYP2D6 pharmacogenetics: what is clinically relevant?","volume":"3","author":"de la Torre","year":"2012","journal-title":"Front Genet"},{"key":"B37","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.bcp.2018.08.010","article-title":"Kinetic mechanism of time-dependent inhibition of CYP2D6 by 3,4-methylenedioxymethamphetamine (MDMA): functional heterogeneity of the enzyme and the reversibility of its inactivation","volume":"156","author":"Rodgers","year":"2018","journal-title":"Biochem Pharmacol"},{"key":"B38","volume-title":"World Drug Report 2021","year":"2021"},{"key":"B39","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1124\/jpet.107.129056","article-title":"Pharmacological interaction between 3,4-methylenedioxymethamphetamine (ecstasy) and paroxetine: pharmacological effects and pharmacokinetics","volume":"323","author":"Farr\u00e9","year":"2007","journal-title":"J Pharmacol Exp Ther"},{"key":"B40","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/S0893-133X(99)00148-7","article-title":"Acute psychological effects of 3,4-methylenedioxymethamphetamine (MDMA, \u201cEcstasy\u201d) are attenuated by the serotonin uptake inhibitor citalopram","volume":"22","author":"Liechti","year":"2000","journal-title":"Neuropsychopharmacology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1177\/026988110001400313","article-title":"The serotonin uptake inhibitor citalopram reduces acute cardiovascular and vegetative effects of 3,4-methylenedioxymethamphetamine (\u2018Ecstasy\u2019) in healthy volunteers","volume":"14","author":"Liechti","year":"2000","journal-title":"J Psychopharmacol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1007\/s00213-006-0576-z","article-title":"The effects of fluoxetine on the subjective and physiological effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans","volume":"189","author":"Tancer","year":"2007","journal-title":"Psychopharmacology"}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2021.824288\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T06:57:29Z","timestamp":1643007449000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2021.824288\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,24]]},"references-count":42,"alternative-id":["10.3389\/fpsyt.2021.824288"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2021.824288","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,24]]},"article-number":"824288"}}