{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T13:11:11Z","timestamp":1785762671332,"version":"3.56.0"},"reference-count":119,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,10,11]],"date-time":"2018-10-11T00:00:00Z","timestamp":1539216000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002943","name":"Departament d\u2019Innovaci\u00c3\u00b3, Universitats i Empresa, Generalitat de Catalunya","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002943","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"DOI":"10.3389\/fphar.2018.01145","type":"journal-article","created":{"date-parts":[[2018,10,11]],"date-time":"2018-10-11T00:41:58Z","timestamp":1539218518000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":50,"title":["Drug Interactions With New Synthetic Opioids"],"prefix":"10.3389","volume":"9","author":[{"given":"Clara","family":"P\u00e9rez-Ma\u00f1\u00e1","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Papaseit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francina","family":"Fonseca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Farr\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Torrens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magi","family":"Farr\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,10,11]]},"reference":[{"key":"B1","author":"Ahmad","year":"2018","journal-title":"Provisional Drug Overdose Death Counts."},{"key":"B2","year":"2015","journal-title":"Opioid Overdose Treatment."},{"key":"B3","doi-asserted-by":"publisher","first-page":"119","DOI":"10.5055\/jom.2014.0201","article-title":"Preventing and managing aberrant drugrelated behavior in primary care: systematic review of outcomes evidence.","volume":"10","author":"Argoff","year":"2014","journal-title":"J. Opioid Manag."},{"key":"B4","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.neuropharm.2017.10.016","article-title":"Fentanyl, fentanyl analogs and novel synthetic opioids: a comprehensive review.","volume":"134","author":"Armenian","year":"2017","journal-title":"Neuropharmacology"},{"key":"B5","first-page":"1","article-title":"Interactions between pain medications and illicit street drugs.","volume":"7","author":"Atkinson","year":"2014","journal-title":"Pract. Pain Manag."},{"key":"B6","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.neuropharm.2017.08.016","article-title":"Pharmacological characterization of novel synthetic opioids (NSO) found in the recreational drug marketplace.","volume":"134","author":"Baumann","year":"2018","journal-title":"Neuropharmacology"},{"key":"B7","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/npp.2017.211","article-title":"Novel synthetic opioids and overdose deaths: tip of the iceberg?","volume":"43","author":"Baumann","year":"2018","journal-title":"Neuropsychopharmacology"},{"key":"B8","author":"Baxter","year":"2008","journal-title":"Stockley\u2019s Drug Interactions."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2103","DOI":"10.1056\/NEJMp1701553","article-title":"Abuse-deterrent opioid formulations - putting the potential benefits into perspective.","volume":"376","author":"Becker","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1111\/ajad.12711","article-title":"Antagonists in the medical management of opioid use disorders: historical and existing treatment strategies.","volume":"27","author":"Bisaga","year":"2018","journal-title":"Am. J. Addict."},{"key":"B11","doi-asserted-by":"publisher","first-page":"83","DOI":"10.2147\/SAR.S85667","article-title":"Opioid-use disorder among patients on long-term opioid therapy: impact of final DSM-5 diagnostic criteria on prevalence and correlates.","volume":"6","author":"Boscarino","year":"2015","journal-title":"Subst. Abuse Rehabil."},{"key":"B12","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1056\/NEJMra1202561","article-title":"Management of opioid analgesic overdose.","volume":"367","author":"Boyer","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1213\/00000539-199609000-00038","article-title":"Remifentanil: a novel, short-acting, mu-opioid.","volume":"83","author":"B\u00fcrkle","year":"1996","journal-title":"Anesth. Analg."},{"key":"B14","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1097\/AJP.0b013e3181f195ba","article-title":"Cross validation of the current Opioid Misuse Measure (COMM) to monitor chronic pain patients on opioid Therapy.","volume":"26","author":"Butler","year":"2010","journal-title":"Clin. J. Pain"},{"key":"B15","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/j.jpain.2007.11.014","article-title":"Validation of the revised screener and opioid assessment for patients with pain (SOAPP-R).","volume":"9","author":"Butler","year":"2008","journal-title":"J. Pain"},{"key":"B16","doi-asserted-by":"publisher","first-page":"35","DOI":"10.5055\/jom.2011.0047","article-title":"A systematic compilation of reports published on opioid-related problems.","volume":"7","author":"Butts","year":"2011","journal-title":"J. Opioid Manag."},{"key":"B17","doi-asserted-by":"publisher","first-page":"276","DOI":"10.7326\/M14-2559","article-title":"The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health pathways to prevention workshop.","volume":"162","author":"Chou","year":"2015","journal-title":"Ann. Intern. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"904","DOI":"10.15585\/mmwr.mm6634a3","article-title":"Overdose deaths related to fentanyl and its analogs - Ohio, January-February 2017.","volume":"66","author":"Daniulaityte","year":"2017","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"B19","doi-asserted-by":"publisher","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":"B20","first-page":"181","article-title":"Tramadol: a review of this atypical opioid.","volume":"14","author":"Dickman","year":"2007","journal-title":"Eur. J. Palliat. Care"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15585\/mmwr.rr6501e1","article-title":"Centers for disease control and prevention guideline for prescribing opioids for chronic pain - United States, 2016.","volume":"65","author":"Dowell","year":"2016","journal-title":"MMWR Recomm. Rep."},{"key":"B22","year":"2018","journal-title":"Controlled Susbtances Act."},{"key":"B23","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1097\/ADT.0000000000000078","article-title":"Treatment approaches for patients with opioid use disorder and chronic noncancer pain: a literature review.","volume":"15","author":"Eilender","year":"2016","journal-title":"Addict. Disord. Treat."},{"key":"B24","year":"2018","journal-title":"Summary of Product Characteristics Movetig (naloxegol), Nyxoid (naloxone Hydrochloride Dihydrate Nassal Spray), Relistor (Methylnaltrexone Bromide), Selincro (Nalmefene Oral)."},{"key":"B25","year":"2017","journal-title":"European Drug Report 2017: Trends and Developments."},{"key":"B26","year":"","journal-title":"European Drug Report."},{"key":"B27","year":"","journal-title":"Fentanils and Synthetic Cannabionoids: Driving Greater Complexity into the Drug Situation. An Update from EU Early Warning System."},{"key":"B28","year":"","journal-title":"Fentanyl Drug Profile."},{"key":"B29","year":"2015","journal-title":"European School Survey Project on Alcohol and Other Drugs."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1208\/s12248-016-9963-5","article-title":"Metabolism of carfentanil, an ultra-potent opioid, in human liver microsomes and human hepatocytes by high-resolution mass spectrometry.","volume":"18","author":"Feasel","year":"2016","journal-title":"AAPS J."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.2147\/JPR.S138698","article-title":"Opioid analgesics-related pharmacokinetic drug interactions: from the perspectives of evidence based on randomized controlled trials and clinical risk management.","volume":"10","author":"Feng","year":"2017","journal-title":"J. Pain Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/BF01225419","article-title":"Fatality due to fentanyl-cocaine intoxication resulting in a fall.","volume":"106","author":"Ferrara","year":"1994","journal-title":"Int. J. Legal Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.ypmed.2017.11.001","article-title":"The \u2019fentanyl epidemic\u2019 in Canada - Some cautionary observations focusing on opioid-related mortality.","volume":"107","author":"Fischer","year":"2018","journal-title":"Prev. Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1093\/jat\/bkw131","article-title":"Analysis of U-47700, a novel synthetic opioid, in human urine by LC-MS-MS and LC-QToF.","volume":"41","author":"Fleming","year":"2017","journal-title":"J. Anal. Toxicol."},{"key":"B35","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/S0022-3565(25)11084-7","article-title":"The cardiovascular and subjective effects of intravenous cocaine and morphine combinations in humans.","volume":"261","author":"Foltin","year":"1992","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B36","year":"2017","journal-title":"Draft Guidance for Industry. Clinical Drug Interaction Studies. Study Design, Data Analysis, and Clinical Implications."},{"key":"B37","year":"2018","journal-title":"Labels of Sublimaze (fentanyl), Duragesic (fentanyl), Fentora (fentanyl), Actiq (fentanyl), Alfenta (alfentanil), Rapifen (alfentanil), Sufenta (sufentanil), Ultiva (remifentanil), Avinza (morphine sulphate), Embeda (morphine sulfate and naltrexone hydrochloride), Duramorph (morphine sulfate injection), Narcan Nasal Spray (naloxone hydrochloride), Evzio (naloxone hydrochloride), Naloxone West Ward Pharms Int (naloxone hydrochloride), Entereg (alvimopan), Vivitrol (naltrexone for extended-release injectable suspension)."},{"key":"B38","year":"2017","journal-title":"Global Drug Survey."},{"key":"B39","year":"2018","journal-title":"Global Drug Survey."},{"key":"B40","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1097\/FPC.0000000000000057","article-title":"PharmGKB summary: tramadol pathway.","volume":"24","author":"Gong","year":"2014","journal-title":"Pharmacogenet. Genomics"},{"key":"B41","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1111\/bph.12305","article-title":"Levels of heroin and its metabolites in blood and brain extracellular fluid after i.v. heroin administration to freely moving rats.","volume":"170","author":"Gott\u00e5s","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"S4","DOI":"10.1016\/j.jpainsymman.2012.08.013","article-title":"Opioid therapies and cytochrome p450 interactions.","volume":"44","author":"Gudin","year":"2012","journal-title":"J. Pain Symptom Manage."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1016\/S0006-2952(96)00893-3","article-title":"Possible involvement of multiple cytochrome P450S in fentanyl and sufentanil metabolism as opposed to alfentanil.","volume":"53","author":"Guitton","year":"1997","journal-title":"Biochem. Pharmacol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1093\/bja\/54.12.1267","article-title":"Fentanyl pharmacokinetics in anaesthetized patients with cirrhosis.","volume":"54","author":"Haberer","year":"1982","journal-title":"Br. J. Anaesth."},{"key":"B45","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/S0022-3565(24)37952-2","article-title":"Synergistic elevations in nucleus accumbens extracellular dopamine concentrations during self-administration of cocaine\/heroin combinations (Speedball) in rats.","volume":"288","author":"Hemby","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1016\/j.bja.2018.03.009","article-title":"Incidence of iatrogenic opioid dependence or abuse in patients with pain who were exposed to opioid analgesic therapy: a systematic review and meta-analysis.","volume":"120","author":"Higgins","year":"2018","journal-title":"Br. J. Anaesth."},{"key":"B47","author":"Hoffman","year":"2015","journal-title":"Goldfrank\u2019s Toxicologic Emergencies, 10e."},{"key":"B48","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1111\/j.1556-4029.2007.00564.x","article-title":"Fatalities associated with fentanyl and co-administered cocaine or opiates.","volume":"52","author":"Hull","year":"2007","journal-title":"J. Forensic Sci."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0376-8716(86)90031-1","article-title":"Evaluation of mixtures of morphine and d-amphetamine for subjective and physiological effects.","volume":"17","author":"Jasinski","year":"1986","journal-title":"Drug Alcohol Depend."},{"key":"B50","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1080\/15563650.2016.1209767","article-title":"A case of U-47700 overdose with laboratory confirmation and metabolite identification.","volume":"55","author":"Jones","year":"2017","journal-title":"Clin. Toxicol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/0304-3959(87)90004-2","article-title":"Cocaine and morphine interaction in acute and chronic cancer pain.","volume":"31","author":"Kaiko","year":"1987","journal-title":"Pain"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1201\/b19536","author":"Karalliedde","year":"2016","journal-title":"Adverse Drug Interactions: A Handbook for Prescribers."},{"key":"B53","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/clpt.2011.59","article-title":"Sensitivity of intravenous and oral alfentanil and pupillary miosis as minimal and noninvasive probes for hepatic and first-pass CYP3A induction.","volume":"90","author":"Kharasch","year":"2011","journal-title":"Clin. Pharmacol. Ther."},{"key":"B54","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1146\/annurev.pharmtox.010909.105826","article-title":"Pharmacogenetics of drug dependence: role of gene variations in susceptibility and treatment.","volume":"50","author":"Khokhar","year":"2009","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1124\/dmd.104.002709","article-title":"Metabolism of alfentanil by cytochrome p4503a (cyp3a) enzymes.","volume":"33","author":"Klees","year":"2005","journal-title":"Drug Metab. Dispos."},{"key":"B56","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1093\/jat\/bkw087","article-title":"Illicit fentanyl-related fatalities in florida: toxicological findings.","volume":"40","author":"Lee","year":"2016","journal-title":"J. Anal. Toxicol."},{"key":"B57","first-page":"E1003","article-title":"Current impact and application of abuse-deterrent opioid formulations in clinical practice.","volume":"20","author":"Lee","year":"2017","journal-title":"Pain Phys."},{"key":"B58","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1038\/278740a0","article-title":"Naloxone dose dependently produces analgesia and hyperalgesia in postoperative pain.","volume":"278","author":"Levine","year":"1979","journal-title":"Nature"},{"key":"B59","doi-asserted-by":"publisher","first-page":"334","DOI":"10.3109\/00952990.2011.643997","article-title":"Drug interactions between common illicit drugs and prescription therapies.","volume":"38","author":"Lindsey","year":"2012","journal-title":"Am. J. Drug Alcohol Abuse"},{"key":"B60","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/S0885-3924(03)00142-8","article-title":"Cannabis reduces opioid dose in the treatment of chronic non-cancer pain.","volume":"25","author":"Lynch","year":"2003","journal-title":"J. Pain Symptom Manage."},{"key":"B61","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1093\/jat\/bkw124","article-title":"A fatality related to the synthetic opioid U-47700: postmortem concentration distribution.","volume":"41","author":"McIntyre","year":"2017","journal-title":"J. Anal. Toxicol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.pain.2010.11.006","article-title":"Identifying prescription opioid use disorder in primary care diagnostic characteristics on the Current Opioid Misuse Measure (COMM).","volume":"152","author":"Melzer","year":"2011","journal-title":"Pain"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1007\/s00216-011-5528-8","article-title":"Qualitative studies on the metabolism and the toxicological detection of the fentanyl-derived designer drugs 3-methylfentanyl and isofentanyl in rats using liquid chromatography-linear ion trap-mass spectrometry (LC-MS(n)).","volume":"402","author":"Meyer","year":"2012","journal-title":"Anal. Bioanal. Chem."},{"key":"B64","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1016\/j.drugpo.2015.04.003","article-title":"Fentanyls: are we missing the signs? Highly potent and on the rise in Europe.","volume":"26","author":"Mounteney","year":"2015","journal-title":"Int. J. Drug Pol."},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59259-654-6","author":"Mozayani","year":"2004","journal-title":"Handbook of Drug Interactions."},{"key":"B66","doi-asserted-by":"publisher","first-page":"897","DOI":"10.15585\/mmwr.mm6634a2","article-title":"Trends in deaths involving heroin and synthetic opioids excluding methadone, and law enforcement drug product reports, by census region - United States, 2006-2015.","volume":"66","author":"O\u2019Donnell","year":"","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"B67","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.15585\/mmwr.mm6643e1","article-title":"Deaths Involving Fentanyl, Fentanyl Analogs, and U-47700 \u2014 10 States.","volume":"66","author":"O\u2019Donnell","year":"","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"B68","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.je.2016.08.010","article-title":"Epidemiology of overdose episodes from the period prior to hospitalization for drug poisoning until discharge in Japan: an exploratory descriptive study using a nationwide claims database.","volume":"27","author":"Okumura","year":"2017","journal-title":"J. Epidemiol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1097\/JCP.0b013e318184ff6e","article-title":"The consequences of 3,4-methylenedioxymethamphetamine induced CYP2D6 inhibition in humans.","volume":"28","author":"O\u2019Math\u00fana","year":"2008","journal-title":"J. Clin. Psychopharmacol."},{"key":"B70","first-page":"S276","article-title":"Opioid pharmacokinetic drug-drug interactions.","volume":"17","author":"Overholser","year":"2011","journal-title":"Am. J. Manag. Care"},{"key":"B71","first-page":"54","article-title":"[Abuse-related adverse drug reactions and abuse deterrent formulations].","volume":"141","author":"Papaseit","year":"2013","journal-title":"Med. Clin."},{"key":"B72","doi-asserted-by":"publisher","first-page":"1760","DOI":"10.1021\/ac4036197","article-title":"Quantitative measurement of acetyl fentanyl and acetyl norfentanyl in human urine by LC-MS\/MS.","volume":"86","author":"Patton","year":"2014","journal-title":"Anal. Chem."},{"key":"B73","year":"2017","journal-title":"Australia\u2019s Annual Overdose Report 2017."},{"key":"B74","first-page":"1","article-title":"Common opioid-drug interactions:what clinicians need to know.","volume":"12","author":"Pergolizzi","year":"2017","journal-title":"Pract. Pain Manage."},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00785","article-title":"European drug users at risk from illicit fentanyls mix.","volume":"31","author":"Pichini","year":"2017","journal-title":"Front. Pharmacol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1097\/FTD.0000000000000465","article-title":"Acute intoxications and fatalities from illicit fentanyl and analogues: an update.","volume":"40","author":"Pichini","year":"2018","journal-title":"Ther. Drug Monit."},{"key":"B77","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1016\/j.amepre.2018.01.034","article-title":"Trends in medical use of Opioids in the U.S., 2006-2016.","volume":"54","author":"Piper","year":"2018","journal-title":"Am. J. Prev. Med."},{"key":"B78","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1093\/jat\/23.7.570","article-title":"The role of alcohol abuse in the etiology of heroin-related deaths. Evidence for pharmacokinetic interactions between heroin and alcohol.","volume":"23","author":"Polettini","year":"1999","journal-title":"J. Anal. Toxicol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.forsciint.2005.04.017","article-title":"The role of cocaine in heroin-related deaths. Hypothesis on the interaction between heroin and cocaine.","volume":"4","author":"Polettini","year":"2005","journal-title":"Forensic Sci. Int."},{"key":"B80","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1097\/ADM.0000000000000324","article-title":"Misuse of novel synthetic opioids: a deadly new trend.","volume":"11","author":"Prekupec","year":"2017","journal-title":"J. Addict Med."},{"key":"B81","author":"Preston","year":"2015","journal-title":"Stockley\u2019s Drug Interactions: Pocket Companion 2015."},{"key":"B82","year":"2017","journal-title":"National Report: Apparent Opioid-Related Deaths in Canada (December 2017)."},{"key":"B83","doi-asserted-by":"publisher","first-page":"2621","DOI":"10.1097\/00001756-200008210-00003","article-title":"Intravenous self-administration of methamphetamine-heroin (speedball) combinations under a progressive-ratio schedule of reinforcement in rats.","volume":"11","author":"Ranaldi","year":"2000","journal-title":"Neuroreport"},{"key":"B84","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1111\/bph.14105","article-title":"Opioid-induced inhibition of the human 5-HT and noradrenaline transporters in vitro: link to clinical reports of serotonin syndrome.","volume":"175","author":"Rickli","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"B85","doi-asserted-by":"publisher","first-page":"109","DOI":"10.2174\/157488406775268219","article-title":"Pharmacokinetics and pharmacokinetic variability of heroin and its metabolites: review of the literature.","volume":"1","author":"Rook","year":"2006","journal-title":"Curr. Clin. Pharmacol."},{"key":"B86","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.drugalcdep.2017.07.018","article-title":"Trends in heroin and pharmaceutical opioid overdose deaths in Australia.","volume":"179","author":"Roxburgh","year":"2017","journal-title":"Drug Alcohol Depend."},{"key":"B87","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1177\/2042098617744161","article-title":"Naloxone dosage for opioid reversal: current evidence and clinical implications.","volume":"9","author":"Rzasa Lynn","year":"2018","journal-title":"Ther. Adv. Drug Saf."},{"key":"B88","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1002\/cpt.1033","article-title":"Misconceptions and realities of the prescription opioid epidemic.","volume":"103","author":"Schnoll","year":"2018","journal-title":"Clin. Pharmacol. Ther."},{"key":"B89","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1080\/15563650701877374","article-title":"Fentanyl epidemic in Chicago. Illinois and surrounding Cook County.","volume":"46","author":"Schumann","year":"2008","journal-title":"Clin. Toxicol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"349","DOI":"10.15585\/mmwr.mm6712a1","article-title":"Overdose deaths involving opioids, cocaine, and psychostimulants - United States, 2015-2016.","volume":"67","author":"Seth","year":"2018","journal-title":"Morb. Mortal. Wkly. Rep."},{"key":"B91","doi-asserted-by":"publisher","first-page":"265","DOI":"10.15585\/mmwr.mm6610a1","article-title":"Characteristics of initial prescription episodes and likelihood of long-term opioid use - United States, 2006-2015.","volume":"17","author":"Shah","year":"2017","journal-title":"Morb. Mortal. Wkly. Rep."},{"key":"B92","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1016\/S0025-6196(11)60750-7","article-title":"Opioid metabolism.","volume":"84","author":"Smith","year":"2009","journal-title":"Mayo Clin. Proc."},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00654","article-title":"Pharmatoxicology of non-fentanyl derived new synthetic opioids.","volume":"9","author":"Solimini","year":"2018","journal-title":"Front. Pharmacol."},{"key":"B94","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1038\/npp.2017.181","article-title":"Fentanyl-Induced brain hypoxia triggers brain hyperglycemia and biphasic changes in brain temperature.","volume":"43","author":"Solis","year":"2018","journal-title":"Neuropsychopharmacology"},{"key":"B95","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.drugpo.2016.03.007","article-title":"The users of novel psychoactive substances: online survey about their characteristics, attitudes and motivations.","volume":"32","author":"Soussan","year":"2016","journal-title":"Int. J. Drug Policy"},{"key":"B96","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1002\/dta.2111","article-title":"Studies on the metabolism of the fentanyl-derived designer drug butyrfentanyl in human in vitro liver preparations and authentic human samples using liquid chromatography-high resolution mass spectrometry (LC-HRMS).","volume":"9","author":"Steuer","year":"2017","journal-title":"Drug Test Anal."},{"key":"B97","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.drugalcdep.2016.11.033","article-title":"A review: fentanyl and non-pharmaceutical fentanyls.","volume":"1","author":"Suzuki","year":"2017","journal-title":"Drug Alcohol Depend."},{"key":"B98","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.legalmed.2016.05.006","article-title":"An autopsy case of acetyl fentanyl intoxication caused by insufflation of \u2019designer drugs\u2019.","volume":"21","author":"Takase","year":"2016","journal-title":"Leg Med."},{"key":"B99","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1097\/01.paf.0000127398.67081.11","article-title":"Fatal intravenous fentanyl abuse: four cases involving extraction of fentanyl from transdermal patches.","volume":"25","author":"Tharp","year":"2004","journal-title":"Am. J. Forensic Med. Pathol."},{"key":"B100","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.forsciint.2014.06.032","article-title":"Pharmacokinetic interactions between ethanol and heroin: a study on post-mortem cases.","volume":"242","author":"Thaulow","year":"2014","journal-title":"Forensic Sci. Int."},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i6848","article-title":"Novel psychoactive substances: types, mechanisms of action, and effects.","volume":"25","author":"Tracy","year":"2017","journal-title":"BMJ"},{"key":"B102","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.pbb.2011.04.014","article-title":"Powerful behavioral interactions between methamphetamine and morphine.","volume":"99","author":"Trujillo","year":"2011","journal-title":"Pharmacol. Biochem. Behav."},{"key":"B103","year":"2011","journal-title":"The Non-Medical use of Prescription Drugs."},{"key":"B104","year":"2017","journal-title":"Fentanyl and its Analogues 50 Years on. Global Smart Update 2017."},{"key":"B105","year":"","journal-title":"Early Warning Advisory on New Psychoactive Substances."},{"key":"B106","year":"","journal-title":"The International Drug Control Conventions \u2013Schedule of the Single Convention on Narcotic Drugs of 1961 as amended by the 1972 Protocol."},{"key":"B107","year":"","journal-title":"World Drug Report 2018."},{"key":"B108","doi-asserted-by":"publisher","first-page":"3","DOI":"10.2174\/187447370801150611184218","article-title":"The misuse of prescription opioids: a threat for Europe?","volume":"8","author":"van Amsterdam","year":"2015","journal-title":"Curr. Drug Abuse Rev."},{"key":"B109","doi-asserted-by":"publisher","first-page":"97","DOI":"10.2174\/1874467210666170704110146","article-title":"Opioids in the frame of new psychoactive substances network: a complex pharmacological and toxicological issue.","volume":"11","author":"Ventura","year":"2018","journal-title":"Curr. Mol. Pharmacol."},{"key":"B110","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/S0140-6736(17)32893-3","article-title":"Medications for opioid use disorder: bridging the gap in care.","volume":"391","author":"Volkow","year":"2018","journal-title":"Lancet"},{"key":"B111","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1056\/NEJMsr1706626","article-title":"the role of science in addressing the opioid crisis.","volume":"377","author":"Volkow","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan2595","article-title":"Medication development in opioid addiction: meaningful clinical end points.","volume":"10","author":"Volkow","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1186\/s13011-017-0120-7","article-title":"Chronic pain and opioid misuse: a review of reviews.","volume":"15","author":"Voon","year":"2017","journal-title":"Subst. Abuse Treat. Prev. Policy"},{"key":"B114","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1208\/s12248-017-0070-z","article-title":"In Vitro and In Vivo Metabolite Identification Studies for the New Synthetic Opioids Acetylfentanyl, Acrylfentanyl, Furanylfentanyl, and 4-Fluoro-Isobutyrylfentanyl.","volume":"19","author":"Watanabe","year":"2017","journal-title":"AAPS J."},{"key":"B115","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1111\/j.1526-4637.2005.00072.x","article-title":"Predicting aberrant behaviors in opioid-treated patients: validation of the Opioid Risk Tool.","volume":"6","author":"Webster","year":"2005","journal-title":"Pain Med."},{"key":"B116","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1002\/dta.1856","article-title":"Metabolic characterization of AH-7921, a synthetic opioid designer drug: in vitro metabolic stability assessment and metabolite identification, evaluation of in silico prediction, and in vivo confirmation.","volume":"8","author":"Wohlfarth","year":"2016","journal-title":"Drug Test Anal."},{"key":"B117","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1016\/j.jpainsymman.2006.05.010","article-title":"The addiction behaviors checklist: validation of a new clinician- based measure of inappropriate opioid use in chronic pain.","volume":"32","author":"Wu","year":"2006","journal-title":"J. Pain Symptom Manage."},{"key":"B118","doi-asserted-by":"publisher","first-page":"e6","DOI":"10.1016\/j.forsciint.2016.08.025","article-title":"A fatal poisoning case by intravenous injection of \u201cbath salts\u201d containing acetyl fentanyl and 4-methoxy PV8.","volume":"267","author":"Yonemitsu","year":"2016","journal-title":"Forensic Sci. Int."},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2017.00110","article-title":"An expanding world of novel psychoactive substances: opioids.","volume":"30","author":"Zawilska","year":"2017","journal-title":"Front. Psychiatry"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2018.01145\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T19:27:37Z","timestamp":1775244457000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2018.01145\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,11]]},"references-count":119,"alternative-id":["10.3389\/fphar.2018.01145"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2018.01145","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,11]]},"article-number":"1145"}}