A dose-ranging study of the physiological and self-reported effects of repeated, rapid infusion of remifentanil in people with opioid use disorder and physical dependence on fentanyl

Rationale Understanding mechanisms of drug use decisions will inform the development of treatments for opioid use disorder (OUD). Decision-making experiments using neurobehavioral approaches require many trials or events of interest for statistical analysis, but the pharmacokinetics of most opioids...

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Published inPsychopharmacology Vol. 241; no. 6; pp. 1227 - 1236
Main Authors Lile, Joshua A., Shellenberg, Thomas P., Babalonis, Shanna, Hatton, Kevin W., Hays, Lon R., Rayapati, Abner O., Stoops, William W., Wesley, Michael J.
Format Journal Article
LanguageEnglish
Published Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2024
Springer
Springer Nature B.V
Subjects
Adult
Analgesics, Opioid - administration & dosage
Analgesics, Opioid - pharmacokinetics
Biomedical and Life Sciences
Biomedicine
Blindness
Blood pressure
Blood Pressure - drug effects
Carbon dioxide
Decision making
Dosage
Dosage and administration
Dose-Response Relationship, Drug
Drug abuse
Drug addiction
Drug dependence
Drug dosages
Female
Fentanyl
Fentanyl - administration & dosage
Fentanyl - pharmacokinetics
Heart rate
Heart Rate - drug effects
Humans
Infusions, Intravenous
Male
Middle Aged
Narcotics
Neurosciences
Opioid-Related Disorders - drug therapy
Opioids
Original Investigation
Oxycodone
Oxycodone - administration & dosage
Oxycodone - pharmacokinetics
Pharmacokinetics
Pharmacology/Toxicology
Physiological aspects
Physiology
Piperidines - administration & dosage
Piperidines - pharmacokinetics
Piperidines - pharmacology
Psychiatry
Remifentanil
Remifentanil - administration & dosage
Remifentanil - pharmacology
Self Report
Single-Blind Method
Statistical analysis
Substance use disorder
Young Adult
United States
Street value questionnaire
Addiction
Capnography
Intravenous
Subjective effects
Pupillometry
Individualized dosing
Fentanyl
Tolerance
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Abstract Rationale Understanding mechanisms of drug use decisions will inform the development of treatments for opioid use disorder (OUD). Decision-making experiments using neurobehavioral approaches require many trials or events of interest for statistical analysis, but the pharmacokinetics of most opioids limit dosing in humans. Objectives This experiment characterized the effects of repeated infusions of the ultra-short acting opioid remifentanil in people with OUD and physical opioid dependence. Methods An inpatient study using a within-subjects, single-blind, escalating, within-session, pre-post design was conducted. Seven (3 female) subjects were maintained on oral oxycodone (40–60 mg, 4x/day = 160–240 total mg/day) for seven days prior to the dose-ranging session. Subjects received infusions of three ascending remifentanil doses (0.03, 0.1, 0.3 mcg/kg/infusion in 2 subjects; 0.1, 0.3, 1.0 mcg/kg/infusion in 5 subjects) every minute for 40 min per dose, with infusions administered over 5 s to model naturalistic delivery rates. End tidal carbon dioxide, respiration rate, oxygen saturation (SpO 2 ) and heart rate were measured continuously. Blood pressure (BP), pupil diameter and self-reported drug effects were measured every 5 min. Results Pupil diameter, SpO 2 and systolic BP decreased, and ratings on prototypic subjective effects questionnaire items increased, as a function of remifentanil dose. The number of infusions held because of sedation or physiological parameters exceeding predetermined cutoffs also increased with dose. Conclusions This experiment established doses and procedures for the safe delivery of rapid, repeated remifentanil infusions to individuals with OUD and physical fentanyl dependence, which can be applied to the mechanistic study of opioid use decisions.
AbstractList Understanding mechanisms of drug use decisions will inform the development of treatments for opioid use disorder (OUD). Decision-making experiments using neurobehavioral approaches require many trials or events of interest for statistical analysis, but the pharmacokinetics of most opioids limit dosing in humans.RATIONALEUnderstanding mechanisms of drug use decisions will inform the development of treatments for opioid use disorder (OUD). Decision-making experiments using neurobehavioral approaches require many trials or events of interest for statistical analysis, but the pharmacokinetics of most opioids limit dosing in humans.This experiment characterized the effects of repeated infusions of the ultra-short acting opioid remifentanil in people with OUD and physical opioid dependence.OBJECTIVESThis experiment characterized the effects of repeated infusions of the ultra-short acting opioid remifentanil in people with OUD and physical opioid dependence.An inpatient study using a within-subjects, single-blind, escalating, within-session, pre-post design was conducted. Seven (3 female) subjects were maintained on oral oxycodone (40-60 mg, 4x/day = 160-240 total mg/day) for seven days prior to the dose-ranging session. Subjects received infusions of three ascending remifentanil doses (0.03, 0.1, 0.3 mcg/kg/infusion in 2 subjects; 0.1, 0.3, 1.0 mcg/kg/infusion in 5 subjects) every minute for 40 min per dose, with infusions administered over 5 s to model naturalistic delivery rates. End tidal carbon dioxide, respiration rate, oxygen saturation (SpO2) and heart rate were measured continuously. Blood pressure (BP), pupil diameter and self-reported drug effects were measured every 5 min.METHODSAn inpatient study using a within-subjects, single-blind, escalating, within-session, pre-post design was conducted. Seven (3 female) subjects were maintained on oral oxycodone (40-60 mg, 4x/day = 160-240 total mg/day) for seven days prior to the dose-ranging session. Subjects received infusions of three ascending remifentanil doses (0.03, 0.1, 0.3 mcg/kg/infusion in 2 subjects; 0.1, 0.3, 1.0 mcg/kg/infusion in 5 subjects) every minute for 40 min per dose, with infusions administered over 5 s to model naturalistic delivery rates. End tidal carbon dioxide, respiration rate, oxygen saturation (SpO2) and heart rate were measured continuously. Blood pressure (BP), pupil diameter and self-reported drug effects were measured every 5 min.Pupil diameter, SpO2 and systolic BP decreased, and ratings on prototypic subjective effects questionnaire items increased, as a function of remifentanil dose. The number of infusions held because of sedation or physiological parameters exceeding predetermined cutoffs also increased with dose.RESULTSPupil diameter, SpO2 and systolic BP decreased, and ratings on prototypic subjective effects questionnaire items increased, as a function of remifentanil dose. The number of infusions held because of sedation or physiological parameters exceeding predetermined cutoffs also increased with dose.This experiment established doses and procedures for the safe delivery of rapid, repeated remifentanil infusions to individuals with OUD and physical fentanyl dependence, which can be applied to the mechanistic study of opioid use decisions.CONCLUSIONSThis experiment established doses and procedures for the safe delivery of rapid, repeated remifentanil infusions to individuals with OUD and physical fentanyl dependence, which can be applied to the mechanistic study of opioid use decisions.
Rationale Understanding mechanisms of drug use decisions will inform the development of treatments for opioid use disorder (OUD). Decision-making experiments using neurobehavioral approaches require many trials or events of interest for statistical analysis, but the pharmacokinetics of most opioids limit dosing in humans. Objectives This experiment characterized the effects of repeated infusions of the ultra-short acting opioid remifentanil in people with OUD and physical opioid dependence. Methods An inpatient study using a within-subjects, single-blind, escalating, within-session, pre-post design was conducted. Seven (3 female) subjects were maintained on oral oxycodone (40–60 mg, 4x/day = 160–240 total mg/day) for seven days prior to the dose-ranging session. Subjects received infusions of three ascending remifentanil doses (0.03, 0.1, 0.3 mcg/kg/infusion in 2 subjects; 0.1, 0.3, 1.0 mcg/kg/infusion in 5 subjects) every minute for 40 min per dose, with infusions administered over 5 s to model naturalistic delivery rates. End tidal carbon dioxide, respiration rate, oxygen saturation (SpO 2 ) and heart rate were measured continuously. Blood pressure (BP), pupil diameter and self-reported drug effects were measured every 5 min. Results Pupil diameter, SpO 2 and systolic BP decreased, and ratings on prototypic subjective effects questionnaire items increased, as a function of remifentanil dose. The number of infusions held because of sedation or physiological parameters exceeding predetermined cutoffs also increased with dose. Conclusions This experiment established doses and procedures for the safe delivery of rapid, repeated remifentanil infusions to individuals with OUD and physical fentanyl dependence, which can be applied to the mechanistic study of opioid use decisions.
Understanding mechanisms of drug use decisions will inform the development of treatments for opioid use disorder (OUD). Decision-making experiments using neurobehavioral approaches require many trials or events of interest for statistical analysis, but the pharmacokinetics of most opioids limit dosing in humans. This experiment characterized the effects of repeated infusions of the ultra-short acting opioid remifentanil in people with OUD and physical opioid dependence. An inpatient study using a within-subjects, single-blind, escalating, within-session, pre-post design was conducted. Seven (3 female) subjects were maintained on oral oxycodone (40-60 mg, 4x/day = 160-240 total mg/day) for seven days prior to the dose-ranging session. Subjects received infusions of three ascending remifentanil doses (0.03, 0.1, 0.3 mcg/kg/infusion in 2 subjects; 0.1, 0.3, 1.0 mcg/kg/infusion in 5 subjects) every minute for 40 min per dose, with infusions administered over 5 s to model naturalistic delivery rates. End tidal carbon dioxide, respiration rate, oxygen saturation (SpO.sub.2) and heart rate were measured continuously. Blood pressure (BP), pupil diameter and self-reported drug effects were measured every 5 min. Pupil diameter, SpO.sub.2 and systolic BP decreased, and ratings on prototypic subjective effects questionnaire items increased, as a function of remifentanil dose. The number of infusions held because of sedation or physiological parameters exceeding predetermined cutoffs also increased with dose. This experiment established doses and procedures for the safe delivery of rapid, repeated remifentanil infusions to individuals with OUD and physical fentanyl dependence, which can be applied to the mechanistic study of opioid use decisions.
Understanding mechanisms of drug use decisions will inform the development of treatments for opioid use disorder (OUD). Decision-making experiments using neurobehavioral approaches require many trials or events of interest for statistical analysis, but the pharmacokinetics of most opioids limit dosing in humans. This experiment characterized the effects of repeated infusions of the ultra-short acting opioid remifentanil in people with OUD and physical opioid dependence. An inpatient study using a within-subjects, single-blind, escalating, within-session, pre-post design was conducted. Seven (3 female) subjects were maintained on oral oxycodone (40-60 mg, 4x/day = 160-240 total mg/day) for seven days prior to the dose-ranging session. Subjects received infusions of three ascending remifentanil doses (0.03, 0.1, 0.3 mcg/kg/infusion in 2 subjects; 0.1, 0.3, 1.0 mcg/kg/infusion in 5 subjects) every minute for 40 min per dose, with infusions administered over 5 s to model naturalistic delivery rates. End tidal carbon dioxide, respiration rate, oxygen saturation (SpO ) and heart rate were measured continuously. Blood pressure (BP), pupil diameter and self-reported drug effects were measured every 5 min. Pupil diameter, SpO and systolic BP decreased, and ratings on prototypic subjective effects questionnaire items increased, as a function of remifentanil dose. The number of infusions held because of sedation or physiological parameters exceeding predetermined cutoffs also increased with dose. This experiment established doses and procedures for the safe delivery of rapid, repeated remifentanil infusions to individuals with OUD and physical fentanyl dependence, which can be applied to the mechanistic study of opioid use decisions.
RationaleUnderstanding mechanisms of drug use decisions will inform the development of treatments for opioid use disorder (OUD). Decision-making experiments using neurobehavioral approaches require many trials or events of interest for statistical analysis, but the pharmacokinetics of most opioids limit dosing in humans.ObjectivesThis experiment characterized the effects of repeated infusions of the ultra-short acting opioid remifentanil in people with OUD and physical opioid dependence.MethodsAn inpatient study using a within-subjects, single-blind, escalating, within-session, pre-post design was conducted. Seven (3 female) subjects were maintained on oral oxycodone (40–60 mg, 4x/day = 160–240 total mg/day) for seven days prior to the dose-ranging session. Subjects received infusions of three ascending remifentanil doses (0.03, 0.1, 0.3 mcg/kg/infusion in 2 subjects; 0.1, 0.3, 1.0 mcg/kg/infusion in 5 subjects) every minute for 40 min per dose, with infusions administered over 5 s to model naturalistic delivery rates. End tidal carbon dioxide, respiration rate, oxygen saturation (SpO2) and heart rate were measured continuously. Blood pressure (BP), pupil diameter and self-reported drug effects were measured every 5 min.ResultsPupil diameter, SpO2 and systolic BP decreased, and ratings on prototypic subjective effects questionnaire items increased, as a function of remifentanil dose. The number of infusions held because of sedation or physiological parameters exceeding predetermined cutoffs also increased with dose.ConclusionsThis experiment established doses and procedures for the safe delivery of rapid, repeated remifentanil infusions to individuals with OUD and physical fentanyl dependence, which can be applied to the mechanistic study of opioid use decisions.
Rationale Understanding mechanisms of drug use decisions will inform the development of treatments for opioid use disorder (OUD). Decision-making experiments using neurobehavioral approaches require many trials or events of interest for statistical analysis, but the pharmacokinetics of most opioids limit dosing in humans. Objectives This experiment characterized the effects of repeated infusions of the ultra-short acting opioid remifentanil in people with OUD and physical opioid dependence. Methods An inpatient study using a within-subjects, single-blind, escalating, within-session, pre-post design was conducted. Seven (3 female) subjects were maintained on oral oxycodone (40-60 mg, 4x/day = 160-240 total mg/day) for seven days prior to the dose-ranging session. Subjects received infusions of three ascending remifentanil doses (0.03, 0.1, 0.3 mcg/kg/infusion in 2 subjects; 0.1, 0.3, 1.0 mcg/kg/infusion in 5 subjects) every minute for 40 min per dose, with infusions administered over 5 s to model naturalistic delivery rates. End tidal carbon dioxide, respiration rate, oxygen saturation (SpO.sub.2) and heart rate were measured continuously. Blood pressure (BP), pupil diameter and self-reported drug effects were measured every 5 min. Results Pupil diameter, SpO.sub.2 and systolic BP decreased, and ratings on prototypic subjective effects questionnaire items increased, as a function of remifentanil dose. The number of infusions held because of sedation or physiological parameters exceeding predetermined cutoffs also increased with dose. Conclusions This experiment established doses and procedures for the safe delivery of rapid, repeated remifentanil infusions to individuals with OUD and physical fentanyl dependence, which can be applied to the mechanistic study of opioid use decisions.
Audience Academic
Author Shellenberg, Thomas P.
Hays, Lon R.
Wesley, Michael J.
Hatton, Kevin W.
Stoops, William W.
Lile, Joshua A.
Babalonis, Shanna
Rayapati, Abner O.
AuthorAffiliation 4 Department of Anesthesiology, University of Kentucky College of Medicine, Chandler Medical Center, 800 Rose St, Lexington, KY 40536
2 Department of Psychology, University of Kentucky College of Arts and Sciences, Kastle Hall, Lexington, KY 40506
5 Department of Surgery, University of Kentucky College of Medicine, Chandler Medical Center, 800 Rose St, Lexington, KY 40536
6 Department of Internal Medicine, University of Kentucky College of Medicine, University Health Service, 830 South Limestone, Lexington, KY 40536
1 Department of Behavioral Science, University of Kentucky College of Medicine, Medical Behavioral Science Building, 1100 Veterans Dr., Lexington, KY 40536
3 Department of Psychiatry, University of Kentucky College of Medicine, 245 Fountain Court, Lexington, KY 40509
AuthorAffiliation_xml – name: 5 Department of Surgery, University of Kentucky College of Medicine, Chandler Medical Center, 800 Rose St, Lexington, KY 40536
– name: 2 Department of Psychology, University of Kentucky College of Arts and Sciences, Kastle Hall, Lexington, KY 40506
– name: 4 Department of Anesthesiology, University of Kentucky College of Medicine, Chandler Medical Center, 800 Rose St, Lexington, KY 40536
– name: 3 Department of Psychiatry, University of Kentucky College of Medicine, 245 Fountain Court, Lexington, KY 40509
– name: 6 Department of Internal Medicine, University of Kentucky College of Medicine, University Health Service, 830 South Limestone, Lexington, KY 40536
– name: 1 Department of Behavioral Science, University of Kentucky College of Medicine, Medical Behavioral Science Building, 1100 Veterans Dr., Lexington, KY 40536
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Tue Jul 01 04:17:02 EDT 2025
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Issue 6
Keywords Street value questionnaire
Addiction
Capnography
Intravenous
Subjective effects
Pupillometry
Individualized dosing
Fentanyl
Tolerance
Language English
License 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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The authors appreciate the contributions of the members of the Psychopharmacology of Addiction Laboratory, the Investigational Drug Service staff, the nursing staff in the Center for Clinical and Translational Science Clinical Research Core and the administrative staff in the Department of Behavioral Science at the University of Kentucky.
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References FoltinRWHaneyMIntranasal cocaine in humans: acute tolerance, cardiovascular and subjective effectsPharmacol Biochem Behav200478931011:CAS:528:DC%2BD2cXkt1SrsLg%3D10.1016/j.pbb.2004.02.01815159138
NivYDanielRGeanaAGershmanSJLeongYCRadulescuAWilsonRCReinforcement learning in multidimensional environments relies on attention mechanismsJ Neurosci201535814581571:CAS:528:DC%2BC2MXpvFKktbc%3D10.1523/JNEUROSCI.2978-14.2015260193314444538
American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edition. American Psychiatric Association: Washington, DC
ChowJJBeckmannJSRemifentanil-food choice follows predictions of relative subjective valueDrug Alcohol Depend20212181083691:CAS:528:DC%2BB3cXitlWhu7rP10.1016/j.drugalcdep.2020.10836933109461
HayJLWhiteJMBochnerFSomogyiAAAntinociceptive effects of high dose remifentanil in male methadone-maintained patientsEur J Pain2008129269331:CAS:528:DC%2BD1cXps1GhtLg%3D10.1016/j.ejpain.2007.12.01218262451
PanlilioLVSecciMESchindlerCWBradberryCWChoice between delayed food and immediate opioids in rats: treatment effects and individual differencesPsychopharmacology2017234336133731:CAS:528:DC%2BC2sXhsVarur7L10.1007/s00213-017-4726-2288685765664176
LofwallMRBabalonisSNuzzoPAElayiSCWalshSLOpioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humansDrug Alcohol Depend20161641431501:CAS:528:DC%2BC28XnvFartrY%3D10.1016/j.drugalcdep.2016.05.002272346584910823
MartinezSJonesJDBrandtLCampbellANCAbbottRAComerSDThe increasing prevalence of fentanyl: a urinalysis-based study among individuals with opioid use disorder in New York CityAm J Addict202130657110.1111/ajad.1309232776640
KoMCTernerJHurshSWoodsJHWingerGRelative reinforcing effects of three opioids with different durations of actionJ Pharmacol Exp Ther20023016987041:CAS:528:DC%2BD38XjtlKis7o%3D10.1124/jpet.301.2.69811961075
SmithAPBeckmannJSQuantifying value-based determinants of drug and non-drug decision dynamicsPsychopharmacology20212382037205710.1007/s00213-021-05830-x
AntoineDHuhnASStrainECTurnerGJardotJHammondASDunnKEMethod for successfully inducting individuals who use illicit fentanyl onto buprenorphine/naloxoneAm J Addict202130838710.1111/ajad.1306932572978
VearrierDGrundmannOClinical pharmacology, toxicity and abuse potential of opioidsJ Clin Pharmacol202161Suppl 2S70S881:CAS:528:DC%2BB3MXhsl2rs7zM34396552
WessonDRLingWThe clinical opiate withdrawal scaleJ Psychoact Drugs20033525325910.1080/02791072.2003.10400007
PoldrackRMumfordJNicholsTStatistical modeling: single subject analysisHandbook of functional MRI Data Analysis2011CambridgeCambridge University Press709910.1017/CBO9780511895029.006
MossRBCarloDJHigher doses of naloxone are needed in the synthetic opioid eraSubst Abuse Treat Prev Policy201914610.1186/s13011-019-0195-4307770886379922
StoopsWWPikeEHaysLRGlaserPERushCRNaltrexone and bupropion, alone or combined, do not alter the reinforcing effects of intranasal methamphetaminePharmacol Biochem Behav201512945501:CAS:528:DC%2BC2cXitVeisrbP10.1016/j.pbb.2014.11.01825459104
StrangJVolkowNDDegenhardtLHickmanMJohnsonKKoobGFMarshallBDLTyndallMWalshSOpioid use disorderNat Rev Dis Primers20206310.1038/s41572-019-0137-531919349
VolkowNDBlancoCFentanyl and other opioid use disorders: treatment and research needsAm J Psychiatry202318041041710.1176/appi.ajp.2023027337259512
BeylonGJKaplanHLSomerGBustoUESellersEMComparative abuse liability of intravenously administered remifentanil and fentanylJ Clin Pharmacol200020597606
Joint Economic Committee (2022) Accessed at https://www.jec.senate.gov/public/_cache/files/67bced7f-4232-40ea-9263-f033d280c567/jec-cost-of-opioids-issue-brief.pdf
DuthieDJStevensJJDoyleARBaddooHHGuptaSKMuirKTKirkhamAJRemifentanil and pulmonary extraction during and after cardiac anesthesiaAnesth Analg1997847407441:CAS:528:DyaK2sXis1Gktr0%3D10.1213/00000539-199704000-000079085949
LileJAJohnsonARBanksMLHattonKWHaysLRNicholsonKLPoklisJLRayapatiAORushCRStoopsWWNegusSSPharmacological validation of a translational model of cocaine use disorder: effects of d-amphetamine maintenance on choice between intravenous cocaine and a non-drug alternative in humans and rhesus monkeysExp Clin Psychopharmacol2020281691801:CAS:528:DC%2BB3cXitF2mtr7M10.1037/pha000030231259593
CiccaroneDThe rise of illicit fentanyls, stimulants and the fourth wave of the opioid overdose crisisCurr Opin Psychiatry20213434435010.1097/YCO.0000000000000717339659728154745
LileJAStoopsWWRushCRNegusSSGlaserPEAHattonKWHaysLRDevelopment of a translational model to screen medications for cocaine use disorder II: choice between cocaine and money in humansDrug Alcohol Depend201616511111910.1016/j.drugalcdep.2016.05.022272693684939714
HuhnASHobelmannJGOylerGAStrainECProtracted renal clearance of fentanyl in persons with opioid use disorderDrug Alcohol Depend20202141081471:CAS:528:DC%2BB3cXhtlGmsLvP10.1016/j.drugalcdep.2020.108147326501927594258
SuttonRSBartoAGReinforcement learning: an introduction1998Cambridge, MAMIT Press
Oxecta® Product Information (2013) King Pharmaceuticals Inc., Bristol, Tennessee 37620, USA
Center for Disease Control and Prevention (2022) Provisional Drug Overdose Death Counts. Accessed at https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm
CooperZDTruongNTShiYGWoodsJHMorphine deprivation increases self-administration of the fast and short-acting mu-opioid agonist remifentanil in the ratJ Pharmacol Exp Ther20083269209291:CAS:528:DC%2BD1cXhtVGqurfE10.1124/jpet.108.13919618515643
GureckisTMLoveBCLearning in noise: dynamic decision-making in a variable environmentJ Math Psychol20095318019310.1016/j.jmp.2009.02.004201613282678746
LileJAStoopsWWGlaserPEAHaysLRRushCRPhysiological and subjective effects of acute intranasal methamphetamine during extended-release alprazolam maintenanceDrug Alcohol Depend20111191871931:CAS:528:DC%2BC3MXhsFOgu77E10.1016/j.drugalcdep.2011.06.006217372144384330
StoopsWWStricklandJCHattonKWHaysLRRayapatiAOLileJARushCRSuvorexant maintenance enhances the reinforcing but not subjective and physiological effects of intravenous cocaine in humansPharmacol Biochem Behav20222201734661:CAS:528:DC%2BB38XisVKntLjF10.1016/j.pbb.2022.173466361528769588557
Ultiva® Product InformationAbbot Laboratories, North Chicago2001USAIL 60064
TorralvaRJanowskyANoradrenergic mechanisms in fentanyl-mediated rapid death explain failure of naloxone in the opioid crisisJ Pharmacol Exp Ther20193714534751:CAS:528:DC%2BC1MXitlCmsbfJ10.1124/jpet.119.258566314928246863461
BodnerRJEndogenous opiates and behavior: 2007Peptides2008292292237510.1016/j.peptides.2008.09.007
BanksMLNegusSSInsights from preclinical choice models on treating drug addictionTrends Pharmacol Sci2017381811941:CAS:528:DC%2BC28XhvFSiu73O10.1016/j.tips.2016.11.00227916279
MartinTJWalkerLESizemoreGMSmithJEDworkinSIWithin-session determination of dose-response curves for heroin self-administration in rats: comparison with between-session determination and effects of naltrexoneDrug Alcohol Depend199641931001:CAS:528:DyaK28XkslSgt78%3D10.1016/0376-8716(96)01245-88809497
ZernigGGiacomuzziSRiemerYWakoniggGSturmKSariaAIntravenous drug injection habits: drug users’ self-reports versus researchers’ perceptionPharmacology20036849561:CAS:528:DC%2BD3sXitl2hsrY%3D10.1159/00006873112660479
MiezinFMMaccottaLOllingerJMPetersenSEBucknerRLCharacterizing the hemodynamic response: effects of presentation rate, sampling procedure, and the possibility of ordering brain activity based on relative timingNeuroImage2000117357591:STN:280:DC%2BD3cvgt1ChsQ%3D%3D10.1006/nimg.2000.056810860799
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References_xml – reference: MartinezSJonesJDBrandtLCampbellANCAbbottRAComerSDThe increasing prevalence of fentanyl: a urinalysis-based study among individuals with opioid use disorder in New York CityAm J Addict202130657110.1111/ajad.1309232776640
– reference: StoopsWWStricklandJCHattonKWHaysLRRayapatiAOLileJARushCRSuvorexant maintenance enhances the reinforcing but not subjective and physiological effects of intravenous cocaine in humansPharmacol Biochem Behav20222201734661:CAS:528:DC%2BB38XisVKntLjF10.1016/j.pbb.2022.173466361528769588557
– reference: AntoineDHuhnASStrainECTurnerGJardotJHammondASDunnKEMethod for successfully inducting individuals who use illicit fentanyl onto buprenorphine/naloxoneAm J Addict202130838710.1111/ajad.1306932572978
– reference: MossRBCarloDJHigher doses of naloxone are needed in the synthetic opioid eraSubst Abuse Treat Prev Policy201914610.1186/s13011-019-0195-4307770886379922
– reference: Ultiva® Product InformationAbbot Laboratories, North Chicago2001USAIL 60064
– reference: Center for Disease Control and Prevention (2022) Provisional Drug Overdose Death Counts. Accessed at https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm
– reference: LileJAStoopsWWRushCRNegusSSGlaserPEAHattonKWHaysLRDevelopment of a translational model to screen medications for cocaine use disorder II: choice between cocaine and money in humansDrug Alcohol Depend201616511111910.1016/j.drugalcdep.2016.05.022272693684939714
– reference: MartinTJWalkerLESizemoreGMSmithJEDworkinSIWithin-session determination of dose-response curves for heroin self-administration in rats: comparison with between-session determination and effects of naltrexoneDrug Alcohol Depend199641931001:CAS:528:DyaK28XkslSgt78%3D10.1016/0376-8716(96)01245-88809497
– reference: NivYDanielRGeanaAGershmanSJLeongYCRadulescuAWilsonRCReinforcement learning in multidimensional environments relies on attention mechanismsJ Neurosci201535814581571:CAS:528:DC%2BC2MXpvFKktbc%3D10.1523/JNEUROSCI.2978-14.2015260193314444538
– reference: PanlilioLVSecciMESchindlerCWBradberryCWChoice between delayed food and immediate opioids in rats: treatment effects and individual differencesPsychopharmacology2017234336133731:CAS:528:DC%2BC2sXhsVarur7L10.1007/s00213-017-4726-2288685765664176
– reference: CooperZDTruongNTShiYGWoodsJHMorphine deprivation increases self-administration of the fast and short-acting mu-opioid agonist remifentanil in the ratJ Pharmacol Exp Ther20083269209291:CAS:528:DC%2BD1cXhtVGqurfE10.1124/jpet.108.13919618515643
– reference: ZernigGGiacomuzziSRiemerYWakoniggGSturmKSariaAIntravenous drug injection habits: drug users’ self-reports versus researchers’ perceptionPharmacology20036849561:CAS:528:DC%2BD3sXitl2hsrY%3D10.1159/00006873112660479
– reference: VearrierDGrundmannOClinical pharmacology, toxicity and abuse potential of opioidsJ Clin Pharmacol202161Suppl 2S70S881:CAS:528:DC%2BB3MXhsl2rs7zM34396552
– reference: HayJLWhiteJMBochnerFSomogyiAAAntinociceptive effects of high dose remifentanil in male methadone-maintained patientsEur J Pain2008129269331:CAS:528:DC%2BD1cXps1GhtLg%3D10.1016/j.ejpain.2007.12.01218262451
– reference: DuthieDJStevensJJDoyleARBaddooHHGuptaSKMuirKTKirkhamAJRemifentanil and pulmonary extraction during and after cardiac anesthesiaAnesth Analg1997847407441:CAS:528:DyaK2sXis1Gktr0%3D10.1213/00000539-199704000-000079085949
– reference: KoMCTernerJHurshSWoodsJHWingerGRelative reinforcing effects of three opioids with different durations of actionJ Pharmacol Exp Ther20023016987041:CAS:528:DC%2BD38XjtlKis7o%3D10.1124/jpet.301.2.69811961075
– reference: HuhnASHobelmannJGOylerGAStrainECProtracted renal clearance of fentanyl in persons with opioid use disorderDrug Alcohol Depend20202141081471:CAS:528:DC%2BB3cXhtlGmsLvP10.1016/j.drugalcdep.2020.108147326501927594258
– reference: StoopsWWPikeEHaysLRGlaserPERushCRNaltrexone and bupropion, alone or combined, do not alter the reinforcing effects of intranasal methamphetaminePharmacol Biochem Behav201512945501:CAS:528:DC%2BC2cXitVeisrbP10.1016/j.pbb.2014.11.01825459104
– reference: FoltinRWHaneyMIntranasal cocaine in humans: acute tolerance, cardiovascular and subjective effectsPharmacol Biochem Behav200478931011:CAS:528:DC%2BD2cXkt1SrsLg%3D10.1016/j.pbb.2004.02.01815159138
– reference: StrangJVolkowNDDegenhardtLHickmanMJohnsonKKoobGFMarshallBDLTyndallMWalshSOpioid use disorderNat Rev Dis Primers20206310.1038/s41572-019-0137-531919349
– reference: LileJAStoopsWWGlaserPEAHaysLRRushCRPhysiological and subjective effects of acute intranasal methamphetamine during extended-release alprazolam maintenanceDrug Alcohol Depend20111191871931:CAS:528:DC%2BC3MXhsFOgu77E10.1016/j.drugalcdep.2011.06.006217372144384330
– reference: MiezinFMMaccottaLOllingerJMPetersenSEBucknerRLCharacterizing the hemodynamic response: effects of presentation rate, sampling procedure, and the possibility of ordering brain activity based on relative timingNeuroImage2000117357591:STN:280:DC%2BD3cvgt1ChsQ%3D%3D10.1006/nimg.2000.056810860799
– reference: PoldrackRMumfordJNicholsTStatistical modeling: single subject analysisHandbook of functional MRI Data Analysis2011CambridgeCambridge University Press709910.1017/CBO9780511895029.006
– reference: BodnerRJEndogenous opiates and behavior: 2007Peptides2008292292237510.1016/j.peptides.2008.09.007
– reference: BanksMLNegusSSInsights from preclinical choice models on treating drug addictionTrends Pharmacol Sci2017381811941:CAS:528:DC%2BC28XhvFSiu73O10.1016/j.tips.2016.11.00227916279
– reference: BeylonGJKaplanHLSomerGBustoUESellersEMComparative abuse liability of intravenously administered remifentanil and fentanylJ Clin Pharmacol200020597606
– reference: VolkowNDBlancoCFentanyl and other opioid use disorders: treatment and research needsAm J Psychiatry202318041041710.1176/appi.ajp.2023027337259512
– reference: SmithAPBeckmannJSQuantifying value-based determinants of drug and non-drug decision dynamicsPsychopharmacology20212382037205710.1007/s00213-021-05830-x
– reference: American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edition. American Psychiatric Association: Washington, DC
– reference: WessonDRLingWThe clinical opiate withdrawal scaleJ Psychoact Drugs20033525325910.1080/02791072.2003.10400007
– reference: GureckisTMLoveBCLearning in noise: dynamic decision-making in a variable environmentJ Math Psychol20095318019310.1016/j.jmp.2009.02.004201613282678746
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Snippet Rationale Understanding mechanisms of drug use decisions will inform the development of treatments for opioid use disorder (OUD). Decision-making experiments...
Understanding mechanisms of drug use decisions will inform the development of treatments for opioid use disorder (OUD). Decision-making experiments using...
Rationale Understanding mechanisms of drug use decisions will inform the development of treatments for opioid use disorder (OUD). Decision-making experiments...
RationaleUnderstanding mechanisms of drug use decisions will inform the development of treatments for opioid use disorder (OUD). Decision-making experiments...
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SourceType Open Access Repository
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StartPage 1227
SubjectTerms Adult
Analgesics, Opioid - administration & dosage
Analgesics, Opioid - pharmacokinetics
Biomedical and Life Sciences
Biomedicine
Blindness
Blood pressure
Blood Pressure - drug effects
Carbon dioxide
Decision making
Dosage
Dosage and administration
Dose-Response Relationship, Drug
Drug abuse
Drug addiction
Drug dependence
Drug dosages
Female
Fentanyl
Fentanyl - administration & dosage
Fentanyl - pharmacokinetics
Heart rate
Heart Rate - drug effects
Humans
Infusions, Intravenous
Male
Middle Aged
Narcotics
Neurosciences
Opioid-Related Disorders - drug therapy
Opioids
Original Investigation
Oxycodone
Oxycodone - administration & dosage
Oxycodone - pharmacokinetics
Pharmacokinetics
Pharmacology/Toxicology
Physiological aspects
Physiology
Piperidines - administration & dosage
Piperidines - pharmacokinetics
Piperidines - pharmacology
Psychiatry
Remifentanil
Remifentanil - administration & dosage
Remifentanil - pharmacology
Self Report
Single-Blind Method
Statistical analysis
Substance use disorder
Young Adult
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Title A dose-ranging study of the physiological and self-reported effects of repeated, rapid infusion of remifentanil in people with opioid use disorder and physical dependence on fentanyl
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