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Intranasal Oxytocin Blocks Alcohol Withdrawal in Human Subjects
Open accessAbstract
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 A lcohol (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.
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“A small study showed that intranasal oxytocin blocked alcohol withdrawal in humans, based on such measures as the Alcohol Withdrawal Symptom Checklist of the Clinical Institute Withdrawal Assessment for Alcohol, and reduced the amount of benzodiazepines that were required for treatment (Pedersen et al., 2013).”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Pedersen et al., 2013
In the citing paper
“In two recent studies, OXT IN was found to suppress stress-induced craving in cannabis-dependent individuals (134) and to block alcohol withdrawal (135).”
From Dissecting the Role of Oxytocin in the Formation and Loss of Social Relationships (2016) · cites this paper as [135]
In the citing paper
“Safety and feasibility of daily dosing has been demonstrated in other human OT studies including those with alcohol-dependent patients (Pedersen et al., 2013), patients with schizophrenia (Pedersen et al., 2011) and individuals with trauma exposure (van Zuiden et al., 2016).”
From Augmenting Prolonged Exposure therapy for PTSD with intranasal oxytocin: a randomized, placebo-controlled pilot trial (2018) · cites this paper as Pedersen et al., 2013
In the citing paper
“Others have found that intranasal oxytocin produces significantly less craving and anxiety to a social stress task than placebo in marijuana-dependent subjects (Carson et al., 2013; McRae-Clark et al., 2013; Pedersen et al., 2013).”
From Effects of adverse childhood experiences on the association between intranasal oxytocin and social stress reactivity among individuals with cocaine dependence (2015) · cites this paper as Pedersen et al., 2013
In the citing paper
“For example, compared with placebo, intranasal oxytocin produced significantly lower symptoms of alcohol withdrawal and anxiety in alcohol-dependent subjects (Pedersen et al., 2013).”
From Effects of adverse childhood experiences on the association between intranasal oxytocin and social stress reactivity among individuals with cocaine dependence (2015) · cites this paper as Pedersen et al., 2013
In the citing paper
“The neuropeptide oxytocin appears to mitigate the effects of stress in individuals with SUDs.”
From Effects of adverse childhood experiences on the association between intranasal oxytocin and social stress reactivity among individuals with cocaine dependence (2015) · cites this paper as Pedersen et al., 2013
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Self-citation
Metadata
- Authors
- Pedersen, C. A., Smedley, K. L., Leserman, J., Jarskog, L. F., Rau, S. W., Kampov‐Polevoi, A., Casey, R. L., Fender, T., & Garbutt, J. C.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Pedersen, Cort A.
- Venue
- Alcoholism: Clinical and Experimental Research
- Publisher
- Wiley
- Published
- 2012-10
- Volume
- 37
- Issue
- 3
- Pages
- 484-489
- ISSN
- 0145-6008 (ISSN-L)
- 1530-0277
- PMC
- PMC3557665
- OpenAlex
- W2073015613
- Cited by
- 196
- References
- 51
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 8 · 2023: 8 · 2022: 16 · 2021: 16 · 2020: 16 · 2019: 12 · 2018: 23 · 2017: 28 · 2016: 23 · 2015: 9 · 2014: 12 · 2013: 9 · 2012: 2
- FWCI
- 6.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alcoholism Clinical and Experimental Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (5-P60-AA011605-08-13, P60AA011605)
- National Center for Research Resources (UL1RR025747)
- Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill
- Topics
- Health Sciences › Medicine › Clinical Neurology › Alcoholism and Thiamine Deficiency
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- oxytocin, intranasal administration, alcohol withdrawal, alcoholism, alcohol detoxification, alcohol craving, anxiety, mood states, benzodiazepine tolerance, neural adaptation
- MeSH terms
- Administration, Intranasal, Adult, Alcoholism, Double-Blind Method, Female, Humans, Male, Middle Aged, Oxytocin, Pilot Projects, Substance Withdrawal Syndrome
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