Intranasal Oxytocin Blocks Alcohol Withdrawal in Human Subjects

Background The neuropeptide, oxytocin (OT), has been reported to block tolerance formation to alcohol and decrease withdrawal symptoms in alcohol‐dependent rodents. Numerous recent studies in human subjects indicate that OT administered by the intranasal route penetrates into and exerts effects with...

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Veröffentlicht in:Alcoholism, clinical and experimental research Jg. 37; H. 3; S. 484 - 489
Hauptverfasser: Pedersen, Cort A., Smedley, Kelly L., Leserman, Jane, Jarskog, Lars Fredrik, Rau, Shane W., Kampov-Polevoi, Alexei, Casey, Robin L., Fender, Trace, Garbutt, James C.
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Sprache:Englisch
Veröffentlicht: England Blackwell Publishing Ltd 01.03.2013
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ISSN:0145-6008, 1530-0277, 1530-0277
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Abstract Background The neuropeptide, oxytocin (OT), has been reported to block tolerance formation to alcohol and decrease withdrawal symptoms in alcohol‐dependent rodents. Numerous recent studies in human subjects indicate that OT administered by the intranasal route penetrates into and exerts effects within the brain. Methods In a randomized, double‐blind clinical trial, intranasal OT (24 IU/dose, N = 7) or placebo (N = 4) was given twice daily for 3 days in alcohol‐dependent subjects admitted to a research unit for medical detoxification using Clinical Institute Withdrawal Assessment for Alcohol (CIWA) score‐driven PRN administration of lorazepam. Subjects rated themselves on the Alcohol Withdrawal Symptom Checklist (AWSC) each time CIWA scores were obtained. Subjects also completed the Penn Alcohol Craving Scale, an Alcohol Craving Visual Analog Scale (ACVAS) and the Profile of Mood States (POMS) on inpatient days 2 and 3. Results All subjects had drunk heavily each day for at least 2 weeks prior to study and had previously experienced withdrawal upon stopping/decreasing alcohol consumption. OT was superior to placebo in reducing alcohol withdrawal as evidenced by: less total lorazepam required to complete detoxification (3.4 mg [4.7, SD] vs. 16.5 [4.4], p = 0.0015), lower mean CIWA scores on admission day 1 (4.3 [2.3] vs. 11.8 [0.4], p < 0.0001) and day 2 (3.4 [2.2] vs. 11.1 [3.6], p < 0.002), lower AWSC scores on days 1 and 2 (p < 0.02; p = 0.07), and lower ACVAS ratings (p = 0.01) and lower POMS Tension/Anxiety subscale scores on day 2 (p < 0.01). Conclusions This is the first demonstration that OT treatment may block alcohol withdrawal in human subjects. Our results are consistent with previous findings in rodents that OT inhibits neuroadaptation to and withdrawal from alcohol. OT could have advantages over benzodiazepines in managing alcohol withdrawal because it may reverse rather than maintain sedative‐hypnotic tolerance. It will be important to test whether OT treatment is effective in reducing drinking in alcohol‐dependent outpatients.
AbstractList The neuropeptide, oxytocin (OT), has been reported to block tolerance formation to alcohol and decrease withdrawal symptoms in alcohol-dependent rodents. Numerous recent studies in human subjects indicate that OT administered by the intranasal route penetrates into and exerts effects within the brain.BACKGROUNDThe neuropeptide, oxytocin (OT), has been reported to block tolerance formation to alcohol and decrease withdrawal symptoms in alcohol-dependent rodents. Numerous recent studies in human subjects indicate that OT administered by the intranasal route penetrates into and exerts effects within the brain.In a randomized, double-blind clinical trial, intranasal OT (24 IU/dose, N = 7) or placebo (N = 4) was given twice daily for 3 days in alcohol-dependent subjects admitted to a research unit for medical detoxification using Clinical Institute Withdrawal Assessment for Alcohol (CIWA) score-driven PRN administration of lorazepam. Subjects rated themselves on the Alcohol Withdrawal Symptom Checklist (AWSC) each time CIWA scores were obtained. Subjects also completed the Penn Alcohol Craving Scale, an Alcohol Craving Visual Analog Scale (ACVAS) and the Profile of Mood States (POMS) on inpatient days 2 and 3.METHODSIn a randomized, double-blind clinical trial, intranasal OT (24 IU/dose, N = 7) or placebo (N = 4) was given twice daily for 3 days in alcohol-dependent subjects admitted to a research unit for medical detoxification using Clinical Institute Withdrawal Assessment for Alcohol (CIWA) score-driven PRN administration of lorazepam. Subjects rated themselves on the Alcohol Withdrawal Symptom Checklist (AWSC) each time CIWA scores were obtained. Subjects also completed the Penn Alcohol Craving Scale, an Alcohol Craving Visual Analog Scale (ACVAS) and the Profile of Mood States (POMS) on inpatient days 2 and 3.All subjects had drunk heavily each day for at least 2 weeks prior to study and had previously experienced withdrawal upon stopping/decreasing alcohol consumption. OT was superior to placebo in reducing alcohol withdrawal as evidenced by: less total lorazepam required to complete detoxification (3.4 mg [4.7, SD] vs. 16.5 [4.4], p = 0.0015), lower mean CIWA scores on admission day 1 (4.3 [2.3] vs. 11.8 [0.4], p < 0.0001) and day 2 (3.4 [2.2] vs. 11.1 [3.6], p < 0.002), lower AWSC scores on days 1 and 2 (p < 0.02; p = 0.07), and lower ACVAS ratings (p = 0.01) and lower POMS Tension/Anxiety subscale scores on day 2 (p < 0.01).RESULTSAll subjects had drunk heavily each day for at least 2 weeks prior to study and had previously experienced withdrawal upon stopping/decreasing alcohol consumption. OT was superior to placebo in reducing alcohol withdrawal as evidenced by: less total lorazepam required to complete detoxification (3.4 mg [4.7, SD] vs. 16.5 [4.4], p = 0.0015), lower mean CIWA scores on admission day 1 (4.3 [2.3] vs. 11.8 [0.4], p < 0.0001) and day 2 (3.4 [2.2] vs. 11.1 [3.6], p < 0.002), lower AWSC scores on days 1 and 2 (p < 0.02; p = 0.07), and lower ACVAS ratings (p = 0.01) and lower POMS Tension/Anxiety subscale scores on day 2 (p < 0.01).This is the first demonstration that OT treatment may block alcohol withdrawal in human subjects. Our results are consistent with previous findings in rodents that OT inhibits neuroadaptation to and withdrawal from alcohol. OT could have advantages over benzodiazepines in managing alcohol withdrawal because it may reverse rather than maintain sedative-hypnotic tolerance. It will be important to test whether OT treatment is effective in reducing drinking in alcohol-dependent outpatients.CONCLUSIONSThis is the first demonstration that OT treatment may block alcohol withdrawal in human subjects. Our results are consistent with previous findings in rodents that OT inhibits neuroadaptation to and withdrawal from alcohol. OT could have advantages over benzodiazepines in managing alcohol withdrawal because it may reverse rather than maintain sedative-hypnotic tolerance. It will be important to test whether OT treatment is effective in reducing drinking in alcohol-dependent outpatients.
The neuropeptide, oxytocin (OT), has been reported to block tolerance formation to alcohol and decrease withdrawal symptoms in alcohol-dependent rodents. Numerous recent studies in human subjects indicate that OT administered by the intranasal route penetrates into and exerts effects within the brain. In a randomized, double-blind clinical trial, intranasal OT (24 IU/dose, N = 7) or placebo (N = 4) was given twice daily for 3 days in alcohol-dependent subjects admitted to a research unit for medical detoxification using Clinical Institute Withdrawal Assessment for Alcohol (CIWA) score-driven PRN administration of lorazepam. Subjects rated themselves on the Alcohol Withdrawal Symptom Checklist (AWSC) each time CIWA scores were obtained. Subjects also completed the Penn Alcohol Craving Scale, an Alcohol Craving Visual Analog Scale (ACVAS) and the Profile of Mood States (POMS) on inpatient days 2 and 3. All subjects had drunk heavily each day for at least 2 weeks prior to study and had previously experienced withdrawal upon stopping/decreasing alcohol consumption. OT was superior to placebo in reducing alcohol withdrawal as evidenced by: less total lorazepam required to complete detoxification (3.4 mg [4.7, SD] vs. 16.5 [4.4], p = 0.0015), lower mean CIWA scores on admission day 1 (4.3 [2.3] vs. 11.8 [0.4], p < 0.0001) and day 2 (3.4 [2.2] vs. 11.1 [3.6], p < 0.002), lower AWSC scores on days 1 and 2 (p < 0.02; p = 0.07), and lower ACVAS ratings (p = 0.01) and lower POMS Tension/Anxiety subscale scores on day 2 (p < 0.01). This is the first demonstration that OT treatment may block alcohol withdrawal in human subjects. Our results are consistent with previous findings in rodents that OT inhibits neuroadaptation to and withdrawal from alcohol. OT could have advantages over benzodiazepines in managing alcohol withdrawal because it may reverse rather than maintain sedative-hypnotic tolerance. It will be important to test whether OT treatment is effective in reducing drinking in alcohol-dependent outpatients.
Background The neuropeptide, oxytocin (OT), has been reported to block tolerance formation to alcohol and decrease withdrawal symptoms in alcohol‐dependent rodents. Numerous recent studies in human subjects indicate that OT administered by the intranasal route penetrates into and exerts effects within the brain. Methods In a randomized, double‐blind clinical trial, intranasal OT (24 IU/dose, N = 7) or placebo (N = 4) was given twice daily for 3 days in alcohol‐dependent subjects admitted to a research unit for medical detoxification using Clinical Institute Withdrawal Assessment for Alcohol (CIWA) score‐driven PRN administration of lorazepam. Subjects rated themselves on the Alcohol Withdrawal Symptom Checklist (AWSC) each time CIWA scores were obtained. Subjects also completed the Penn Alcohol Craving Scale, an Alcohol Craving Visual Analog Scale (ACVAS) and the Profile of Mood States (POMS) on inpatient days 2 and 3. Results All subjects had drunk heavily each day for at least 2 weeks prior to study and had previously experienced withdrawal upon stopping/decreasing alcohol consumption. OT was superior to placebo in reducing alcohol withdrawal as evidenced by: less total lorazepam required to complete detoxification (3.4 mg [4.7, SD] vs. 16.5 [4.4], p = 0.0015), lower mean CIWA scores on admission day 1 (4.3 [2.3] vs. 11.8 [0.4], p < 0.0001) and day 2 (3.4 [2.2] vs. 11.1 [3.6], p < 0.002), lower AWSC scores on days 1 and 2 (p < 0.02; p = 0.07), and lower ACVAS ratings (p = 0.01) and lower POMS Tension/Anxiety subscale scores on day 2 (p < 0.01). Conclusions This is the first demonstration that OT treatment may block alcohol withdrawal in human subjects. Our results are consistent with previous findings in rodents that OT inhibits neuroadaptation to and withdrawal from alcohol. OT could have advantages over benzodiazepines in managing alcohol withdrawal because it may reverse rather than maintain sedative‐hypnotic tolerance. It will be important to test whether OT treatment is effective in reducing drinking in alcohol‐dependent outpatients.
Author Jarskog, Lars Fredrik
Casey, Robin L.
Garbutt, James C.
Leserman, Jane
Rau, Shane W.
Fender, Trace
Smedley, Kelly L.
Kampov-Polevoi, Alexei
Pedersen, Cort A.
AuthorAffiliation 1 Department of Psychiatry, The University of North Carolina at Chapel Hill, Chapel Hill, NC
2 Department of Neurobiology Curriculum, The University of North Carolina at Chapel Hill, Chapel Hill, NC
4 North Carolina Psychiatric Research Center, Raleigh, NC
3 Bowles Center for Alcohol Studies The University of North Carolina at Chapel Hill, Chapel Hill, NC
AuthorAffiliation_xml – name: 3 Bowles Center for Alcohol Studies The University of North Carolina at Chapel Hill, Chapel Hill, NC
– name: 2 Department of Neurobiology Curriculum, The University of North Carolina at Chapel Hill, Chapel Hill, NC
– name: 1 Department of Psychiatry, The University of North Carolina at Chapel Hill, Chapel Hill, NC
– name: 4 North Carolina Psychiatric Research Center, Raleigh, NC
Author_xml – sequence: 1
  givenname: Cort A.
  surname: Pedersen
  fullname: Pedersen, Cort A.
  email: cort_pedersen@med.unc.edu
  organization: Department of Psychiatry, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
– sequence: 2
  givenname: Kelly L.
  surname: Smedley
  fullname: Smedley, Kelly L.
  organization: Department of Psychiatry, The University of North Carolina at Chapel Hill, North Carolina, Chapel Hill
– sequence: 3
  givenname: Jane
  surname: Leserman
  fullname: Leserman, Jane
  organization: Department of Psychiatry, The University of North Carolina at Chapel Hill, North Carolina, Chapel Hill
– sequence: 4
  givenname: Lars Fredrik
  surname: Jarskog
  fullname: Jarskog, Lars Fredrik
  organization: Department of Psychiatry, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
– sequence: 5
  givenname: Shane W.
  surname: Rau
  fullname: Rau, Shane W.
  organization: Department of Psychiatry, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
– sequence: 6
  givenname: Alexei
  surname: Kampov-Polevoi
  fullname: Kampov-Polevoi, Alexei
  organization: Department of Psychiatry, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
– sequence: 7
  givenname: Robin L.
  surname: Casey
  fullname: Casey, Robin L.
  organization: Department of Psychiatry, The University of North Carolina at Chapel Hill, North Carolina, Chapel Hill
– sequence: 8
  givenname: Trace
  surname: Fender
  fullname: Fender, Trace
  organization: Department of Psychiatry, The University of North Carolina at Chapel Hill, North Carolina, Chapel Hill
– sequence: 9
  givenname: James C.
  surname: Garbutt
  fullname: Garbutt, James C.
  organization: Department of Psychiatry, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
BackLink https://www.ncbi.nlm.nih.gov/pubmed/23025690$$D View this record in MEDLINE/PubMed
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References Flannery BA, Volpicelli JR, Pettinati HM (1999) Psychometric properties of the Penn Alcohol Craving Scale. Alcohol Clin Exp Res 23:1289-1295.
Szabó G, Kovács GL, Telegdy G (1988) Brain monoamines are involved in mediating the action of neurohypophyseal peptide hormones on ethanol tolerance. Acta Physiol Hung 71:459-466.
Domes G, Lischke A, Berger C, Grossmann A, Hauenstein K, Heinrichs M, Herpertz SC (2010) Effects of intranasal oxytocin on emotional face processing in women. Psychoneuroendocrinology 35:83-93.
MacDonald K, MacDonald TM (2010) The peptide that binds: a systematic review of oxytocin and its prosocial effects in humans. Harv Rev Psychiatry 18:1-21.
Szabó G, Kovács GL, Telegdy G (1989) Intraventricular administration of neurohypophyseal hormones interferes with the development of tolerance to ethanol. Acta Physiol Hung 73:97-103.
Ring RH, Malberg JE, Potestio L, Ping J, Boikess S, Luo B, Schechter LE, Rizzo S, Rahman Z, Rosensweig-Lipson S (2006) Anxiolytic-like activity of oxytocin in male mice: behavioral and autonomic evidence, therapeutic implications. Psychopharmacology 185:218-225.
Saitz R, O'Malley SS (1997) Pharmacotherapies for alcohol abuse. Withdrawal and treatment. Med Clin North Am 81:881-907.
Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM (1989) Assessment of alcohol withdrawal: the revised Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar). Br J Addict 84:1353-1357.
Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U (2003) Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biol Psychiatry 54:1389-1398.
Kushner MG, Abrams K, Borchardt C (2000) The relationship between anxiety disorders and alcohol use disorders: a review of major perspectives and findings. Clin Psychol Rev 20:149-171.
Szabó G, Kovács GL, Telegdy G (1987) Effects of neurohypophyseal peptide hormones on alcohol dependence and withdrawal. Alcohol Alcohol 22:71-74.
Pedersen CA, Gibson CM, Rau SW, Salimi K, Smedley KL, Casey RL, Leserman J, Jarskog LF, Penn DL (2011) Intranasal oxytocin reduces psychotic symptoms and improves Theory of Mind and social perception in schizophrenia. Schizophr Res 132:50-53.
Feifel D, MacDonald K, Nguyen A, Cobb P, Warlan H, Galangue B, Minassian A, Becker O, Cooper J, Perry W, Lefebvre M, Gonzales J, Hadley A (2010) Adjunctive intranasal oxytocin reduces symptoms in schizophrenia patients. Biol Psychiatry 68:678-680.
Windle RJ, Shanks N, Lightman SL, Ingram CD (1997) Central oxytocin administration reduces stress-induced corticosterone release and anxiety behavior in rats. Endocrinology 138:2829-2834.
den Boer JA, Westenberg HG (1992) Oxytocin in obsessive compulsive disorder. Peptides 13:1083-1085.
Lee H-J, Macbeth AH, Pagani JH, Young WS III (2009) Oxytocin: the great facilitator of life. Prog Neurobiol 88:127-151.
Mantella RC, Vollmer RR, Li X, Amico JA (2003) Female oxytocin-deficient mice display enhanced anxiety-related behavior. Endocrinology 144:2291-2296.
Pittman B, Gueorguieva F, Krupitsky E, Rudenko AA, Flannery BA, Krystal JH (2007) Multidimensionality of the Alcohol Withdrawal Symptom Checklist: a factor analysis of the Alcohol Withdrawal Symptom Checklist and CIWA-Ar. Alcohol Clin Exp Res 31:612-618.
Born J, Lange T, Kern W, McGregor GP, Bickel U, Fehm HL (2002) Sniffing neuropeptides: a transnasal approach to the human brain. Nat Neurosci 5:514-516.
Breese GR, Knapp DJ, Overstreet DH (2004) Stress sensitization of ethanol withdrawal-induced reduction in social interaction: inhibition by CRF-1 and benzodiazepine receptor antagonist and a 5-HT1A-receptor agonist. Neuropsychopharmacology 178:367-380.
Domes G, Heinrichs M, Michel A, Berger C, Herpertz SC (2007b) Oxytocin improves "mind-reading" in humans. Biol Psychiatry 61:731-733.
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Gimpl G, Fahrenholz F (2001) The oxytocin receptor system: structure, function, and regulation. Physiol Rev 81:629-683.
Bale TL, Davis AM, Auger AP, Dorsa DM, McCarthy MM (2001) CNS region-specific oxytocin receptor expression: importance in regulation of anxiety and sex behavior. J Neurosci 21:2546-2552.
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de Oliveira DC, Zuardi AW, Graeff FG, Queiroz RH, Crippa JA (2011) Anxiolytic-like effect of oxytocin in the simulated public speaking test. J Psychopharmacol 26:497-504.
Saitz R (2007) Baclofen for alcohol withdrawal: not comparable to the gold standard (benzodiazepines). Am J Med 120:e9.
Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC (1998) The Mini-International Neuropsychiatric Interview (MINI): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59:22-33.
Kovács GL, Sarnyai Z, Szabó G (1998) Oxytocin and addiction: a review. Psychoneuroendocrinology 23:945-962.
Overstreet DH, Knapp DJ, Breese GR (2007) Drug challenges reveal differences in mediation of stress facilitation of voluntary alcohol drinking and withdrawal-induced anxiety in alcohol-preferring P rats. Alcohol Clin Exp Res 31:1473-1481.
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Sobell LC, Sobell MB, Leo GL, Cancilla A (1988) Reliability of a timeline followback method: assessing normal drinkers' reports of recent drinking and a comparative evaluation across several populations. Br J Addict 83:393-402.
Domes G, Heinrichs M, Gläscher J, Büchel C, Braus DF, Herpertz SC (2007a) Oxytocin attenuates amygdala responses to emotional faces regardless of valence. Biol Psychiatry 62:1187-1190.
Myrick H, Malcolm R, Randall PK, Boyle E, Anton RF, Becker HC, Randall CL (2009) A double-blind trial of gabapentin versus lorazepam in the treatment of alcohol withdrawal. Alcohol Clin Exp Res 33:1582-1588.
McNair DM, Lorr M, Droppleman LF (1971) EDITS Manual for the Profile of Mood States. Educational and Industrial Testing Service, San Diego, CA.
Vadlamudi S, Pedersen CA, Amico JA, Breese GR, Knapp D (2004) Neuroadaptation to alcohol and morphine is altered in oxytocin knockout mice. Society for Neuroscience Annual Meeting, Washington, DC. Abstract #577.12.
Baumgartner T, Heinrichs M, Vonlanthen A, Fischbacher U, Fehr E (2008) Oxytocin shapes the neural circuitry of trust and trust adaptation in humans. Neuron 58:639-650.
McCarthy MM, McDonald CH, Brooks PJ, Goldman D (1996) An anxiolytic action of oxytocin is enhanced by estrogen in the mouse. Physiol Behav 60:1209-1215.
Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E (2005) Oxytocin increases trust in humans. Nature 435:673-676.
Guastella AJ, Mitchell PB, Dadds MR (2008) Oxytocin increases gaze to the eye region of human faces. Biol Psychiatry 63:3-5.
Szabó G, Kovács GL, Székeki S, Telegdy G (1985) The effects of neurohypophyseal hormones on tolerance to the hypothermic effect of ethanol. Alcohol 2:567-574.
Jodogne C, Tirelli E, Klingbiel P, Legros JJ (1991) Oxytocin attenuates tolerance not only to the hypothermic but also to the myorelaxant and akinesic effects of ethanol in mice. Pharmacol Biochem Behav 40:261-265.
Amico JA, Mantella RC, Vollmer RR, Li X (2004) Anxiety and stress responses in female oxytocin deficient mice. J Neuroendocrinol 16:319-324.
Epperson CN, McDougle CJ, Price LH (1996) Intranasal oxytocin in obsessive-compulsive disorder. Biol Psychiatry 40:547-549.
Pucilowski O, Kotowski W, Trzaskowa E (1985) The effect of oxytocin and fragment (MIF-1) on the development of tolerance to hypothermic and hypnotic action of ethanol in the rat. Peptides 6:7-10.
Kirsch P, Esslinger C, Chen Q, Mier D, Lis S, Siddhanti S, Gruppe H, Mattay VS, Gallhofer B, Meyer-Lindenberg A (2005) Oxytocin modulates neural circuitry for social cognition and fear in humans. J Neurosci 25:11489-11493.
Knapp DJ, Overstreet DH, Hubka JC, Breese GR, Pedersen CA (2010) Inhibitory effects of oxytocin on anxiety-like behavior and alcohol consumption in P-rats subjected to repeated cycles of voluntary ethanol consumption and stress. Alcohol Clin Exp Res 34:145A.
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1997; 278
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1989; 73
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2009; 33
1998; 59
1987; 22
2010; 68
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2002; 162
1980; 13
1991; 40
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1996; 40
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23614612 - Alcohol Clin Exp Res. 2013 May;37(5):720-1
References_xml – reference: Domes G, Heinrichs M, Michel A, Berger C, Herpertz SC (2007b) Oxytocin improves "mind-reading" in humans. Biol Psychiatry 61:731-733.
– reference: Szabó G, Kovács GL, Telegdy G (1987) Effects of neurohypophyseal peptide hormones on alcohol dependence and withdrawal. Alcohol Alcohol 22:71-74.
– reference: Mayo-Smith MF (1997) Pharmacological management of alcohol withdrawal: a meta-analysis and evidence-based practice guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal. JAMA 278:144-151.
– reference: Windle RJ, Shanks N, Lightman SL, Ingram CD (1997) Central oxytocin administration reduces stress-induced corticosterone release and anxiety behavior in rats. Endocrinology 138:2829-2834.
– reference: Amico JA, Mantella RC, Vollmer RR, Li X (2004) Anxiety and stress responses in female oxytocin deficient mice. J Neuroendocrinol 16:319-324.
– reference: McCarthy MM, McDonald CH, Brooks PJ, Goldman D (1996) An anxiolytic action of oxytocin is enhanced by estrogen in the mouse. Physiol Behav 60:1209-1215.
– reference: Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC (1998) The Mini-International Neuropsychiatric Interview (MINI): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59:22-33.
– reference: Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM (1989) Assessment of alcohol withdrawal: the revised Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar). Br J Addict 84:1353-1357.
– reference: Andari E, Duhamel J-R, Zalla T, Herbrecht E, Leboyer M, Sirigu A (2010) Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc Natl Acad Sci U S A 107:4389-4394.
– reference: Lee H-J, Macbeth AH, Pagani JH, Young WS III (2009) Oxytocin: the great facilitator of life. Prog Neurobiol 88:127-151.
– reference: Mantella RC, Vollmer RR, Li X, Amico JA (2003) Female oxytocin-deficient mice display enhanced anxiety-related behavior. Endocrinology 144:2291-2296.
– reference: Domes G, Lischke A, Berger C, Grossmann A, Hauenstein K, Heinrichs M, Herpertz SC (2010) Effects of intranasal oxytocin on emotional face processing in women. Psychoneuroendocrinology 35:83-93.
– reference: Gimpl G, Fahrenholz F (2001) The oxytocin receptor system: structure, function, and regulation. Physiol Rev 81:629-683.
– reference: Overstreet DH, Knapp DJ, Breese GR (2007) Drug challenges reveal differences in mediation of stress facilitation of voluntary alcohol drinking and withdrawal-induced anxiety in alcohol-preferring P rats. Alcohol Clin Exp Res 31:1473-1481.
– reference: Sobell LC, Sobell MB, Leo GL, Cancilla A (1988) Reliability of a timeline followback method: assessing normal drinkers' reports of recent drinking and a comparative evaluation across several populations. Br J Addict 83:393-402.
– reference: Kirsch P, Esslinger C, Chen Q, Mier D, Lis S, Siddhanti S, Gruppe H, Mattay VS, Gallhofer B, Meyer-Lindenberg A (2005) Oxytocin modulates neural circuitry for social cognition and fear in humans. J Neurosci 25:11489-11493.
– reference: Myrick H, Malcolm R, Randall PK, Boyle E, Anton RF, Becker HC, Randall CL (2009) A double-blind trial of gabapentin versus lorazepam in the treatment of alcohol withdrawal. Alcohol Clin Exp Res 33:1582-1588.
– reference: Born J, Lange T, Kern W, McGregor GP, Bickel U, Fehm HL (2002) Sniffing neuropeptides: a transnasal approach to the human brain. Nat Neurosci 5:514-516.
– reference: MacDonald K, MacDonald TM (2010) The peptide that binds: a systematic review of oxytocin and its prosocial effects in humans. Harv Rev Psychiatry 18:1-21.
– reference: Szabó G, Kovács GL, Székeki S, Telegdy G (1985) The effects of neurohypophyseal hormones on tolerance to the hypothermic effect of ethanol. Alcohol 2:567-574.
– reference: McNair DM, Lorr M, Droppleman LF (1971) EDITS Manual for the Profile of Mood States. Educational and Industrial Testing Service, San Diego, CA.
– reference: Rigter H, Dortmans C, Crabbe JC Jr (1980) Effects of peptides related to neurohypophyseal hormones on ethanol tolerance. Pharmacol Biochem Behav 13:285-290.
– reference: Baumgartner T, Heinrichs M, Vonlanthen A, Fischbacher U, Fehr E (2008) Oxytocin shapes the neural circuitry of trust and trust adaptation in humans. Neuron 58:639-650.
– reference: Vadlamudi S, Pedersen CA, Amico JA, Breese GR, Knapp D (2004) Neuroadaptation to alcohol and morphine is altered in oxytocin knockout mice. Society for Neuroscience Annual Meeting, Washington, DC. Abstract #577.12.
– reference: Domes G, Heinrichs M, Gläscher J, Büchel C, Braus DF, Herpertz SC (2007a) Oxytocin attenuates amygdala responses to emotional faces regardless of valence. Biol Psychiatry 62:1187-1190.
– reference: Saitz R, O'Malley SS (1997) Pharmacotherapies for alcohol abuse. Withdrawal and treatment. Med Clin North Am 81:881-907.
– reference: Szabó G, Kovács GL, Telegdy G (1988) Brain monoamines are involved in mediating the action of neurohypophyseal peptide hormones on ethanol tolerance. Acta Physiol Hung 71:459-466.
– reference: den Boer JA, Westenberg HG (1992) Oxytocin in obsessive compulsive disorder. Peptides 13:1083-1085.
– reference: Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E (2005) Oxytocin increases trust in humans. Nature 435:673-676.
– reference: Pedersen CA, Gibson CM, Rau SW, Salimi K, Smedley KL, Casey RL, Leserman J, Jarskog LF, Penn DL (2011) Intranasal oxytocin reduces psychotic symptoms and improves Theory of Mind and social perception in schizophrenia. Schizophr Res 132:50-53.
– reference: Pucilowski O, Kotowski W, Trzaskowa E (1985) The effect of oxytocin and fragment (MIF-1) on the development of tolerance to hypothermic and hypnotic action of ethanol in the rat. Peptides 6:7-10.
– reference: Szabó G, Kovács GL, Telegdy G (1989) Intraventricular administration of neurohypophyseal hormones interferes with the development of tolerance to ethanol. Acta Physiol Hung 73:97-103.
– reference: Saitz R (2007) Baclofen for alcohol withdrawal: not comparable to the gold standard (benzodiazepines). Am J Med 120:e9.
– reference: Flannery BA, Volpicelli JR, Pettinati HM (1999) Psychometric properties of the Penn Alcohol Craving Scale. Alcohol Clin Exp Res 23:1289-1295.
– reference: Jodogne C, Tirelli E, Klingbiel P, Legros JJ (1991) Oxytocin attenuates tolerance not only to the hypothermic but also to the myorelaxant and akinesic effects of ethanol in mice. Pharmacol Biochem Behav 40:261-265.
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Snippet Background The neuropeptide, oxytocin (OT), has been reported to block tolerance formation to alcohol and decrease withdrawal symptoms in alcohol‐dependent...
The neuropeptide, oxytocin (OT), has been reported to block tolerance formation to alcohol and decrease withdrawal symptoms in alcohol-dependent rodents....
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StartPage 484
SubjectTerms Administration, Intranasal
Adult
Alcohol Withdrawal
Alcoholism - drug therapy
Alcoholism - epidemiology
Alcoholism - psychology
Dependence
Detoxification
Double-Blind Method
Female
Human Subjects
Humans
Male
Middle Aged
Oxytocin
Oxytocin - administration & dosage
Pilot Projects
Substance Withdrawal Syndrome - epidemiology
Substance Withdrawal Syndrome - prevention & control
Substance Withdrawal Syndrome - psychology
Tolerance
Title Intranasal Oxytocin Blocks Alcohol Withdrawal in Human Subjects
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https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fj.1530-0277.2012.01958.x
https://www.ncbi.nlm.nih.gov/pubmed/23025690
https://www.proquest.com/docview/1314336717
https://pubmed.ncbi.nlm.nih.gov/PMC3557665
Volume 37
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