Does Oxytocin Alter Tolerance to or Motivation for Alcohol

Does Oxytocin Alter Tolerance to Alcohol or Motivation for Alcohol in Heavy Drinking Human Subjects: Testing a Novel Anti-Addiction Mechanism

This pilot study is intended to demonstrate feasibility and acquire preliminary data. If successful, this data could support a future project studying the effect of oxytocin on tolerance and alcohol seeking in humans.

Study Overview

• Status: Terminated
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: Intranasal oxytocin; Drug: Intranasal placebo

Detailed Description

This pilot study is designed to demonstrate feasibility and provide preliminary data supporting use of intranasal oxytocin in treatment of alcohol use disorders. Specifically, experiments are planned to test the ability of oxytocin to reverse tolerance and alcohol seeking in humans by employing state-of-the-art computer-assisted intravenous alcohol administration. Two separate experiments will be run. In the first, tolerance will be assessed using sensitive tests of subjective response and cognitive function during an intravenous infusion that maintains a steady breath and therefore brain exposure to alcohol. In the second, an intravenous alcohol self-administration paradigm that requires increasing effort for each additional infusion will be used to assess change in motivation for alcohol. Demonstrating that oxytocin (compared to placebo) worsens test performances in alcohol-dependent individuals and/or reduces the compulsive drive to self-administer alcohol would be strong evidence for its potential to treat alcohol use disorders.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Heavy alcohol drinkers.
• Able to understand/complete questionnaires and procedures in English.
• Have venous access sufficient to allow blood sampling.

Exclusion Criteria:

• Latex allergy.
• Nasal condition that compromises delivery and/or absorption of intra-nasal oxytocin
• Pregnant or breast-feeding women.
• Desire to be treated for any substance use disorder or court ordered to not drink alcohol
• Medical disorders or other conditions such as alcohol withdrawal seizures or delirium tremens that may influence study outcome or participant safety.
• Positive urine drug screen for amphetamines/ methamphetamines, barbiturates, benzodiazepines, cocaine, opiates, or phencyclidine if determined by the PI to adversely affect participant safety or data integrity.
• Medications (past 30 days) that could influence participant safety or data integrity (e.g. antidepressants, antipsychotics, benzodiazepines, etc.) as determined by the PI.
• DSM 5 Disorders (other than alcohol) or current/history of neurological disease of cerebral origin, or head injury with > 20 min loss of consciousness, if determined by the PI to affect participant safety or data integrity.
• Positive breath alcohol reading at beginning of the experimental session.
• Actively suicidal (for example, any current suicidal intent, including a plan) or are at serious suicidal risk, by clinical judgment of the PI.
• Any condition for which the PI and investigative team determine it is unsafe or not prudent to enroll a participant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clamp; Repeated subjective and cognitive tests during a 4 hour session that includes a baseline period, an oxytocin or placebo delivery, absorption and testing period, and a 2 hour alcohol clamp. Oxytocin or placebo were delivered intranasally in two sessions, scheduled 3-4 weeks apart, double blind.	Drug: Intranasal oxytocin; Initial dose 40 IU in 1 ml; 2 booster doses of 24 IU in 0.6 mls each, spaced about 1 hour apart; Drug: Intranasal placebo; Initial volume 1 ml; 2 booster volumes of 0.6 mls each, spaced about 1 hour apart
Experimental: Progressive work for alcohol; Progressive work alcohol exposure, 2 sessions (intranasal oxytocin or placebo), double blind. Note this Arm was not completed (see Overall Status for explanation of study termination)	Drug: Intranasal oxytocin; Initial dose 40 IU in 1 ml; 2 booster doses of 24 IU in 0.6 mls each, spaced about 1 hour apart; Drug: Intranasal placebo; Initial volume 1 ml; 2 booster volumes of 0.6 mls each, spaced about 1 hour apart

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective Effect of Alcohol - Craving	Participants rated their subjective feeling of craving on a scale of 0-100. Tolerance to alcohol is assessed by subtracting subjective ratings at the beginning of the 2 hour alcohol infusion from ratings at the end; a negative value indicates tolerance. Possible scores ranged from -100 to 100; negative scores indicate the development of tolerance. Values reported here compare tolerance developed during the oxytocin session to tolerance developed during the placebo session.	2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo, scheduled 3-4 weeks apart, order counter-balanced.
Subjective Effects of Alcohol - Intoxication	Participants rated their subjective feeling of intoxication on a scale of 0-100. Tolerance to alcohol is assessed by subtracting subjective ratings at the beginning of the 2 hour alcohol infusion from ratings at the end. Using this calculation, theoretical scores in this dataset could range from -100-100; negative scores indicate the development of tolerance. Values reported here compare tolerance developed during the oxytocin session to tolerance developed during the placebo session.	2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo, scheduled 3-4 weeks apart, order counter-balanced.
Stop Signal Response Task	The Stop Signal task asks participants to respond as quickly as they can to one stimulus (the "Go" signal) but withhold this response when a second, much rarer stimulus appears (the "Stop" signal). Performance reported here uses the variable ssRT Med, which is an estimate of the time (in ms) needed to stop and withdraw the response; alcohol is known to increase ssRT Med. To assess tolerance, the value of ssRT Med measured at the beginning of the 2 hour alcohol clamp was subtracted from the value measured at the end. The theoretical range of possible scores on this measure range from about -100 to 200; negative scores indicate the development of tolerance. Values reported here compare tolerance developed during the oxytocin session to tolerance developed during the placebo session.	2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo, scheduled 3-4 weeks apart, order counter-balanced.
Stroop Test	The Stroop Interference task asks participants to respond to one aspect of a stimulus (in this case, the color of the text in which a word is printed) under conditions in which the word meaning either enhances or interferes with the task (for example, the word Green in a Green font speeds performance, while the word Green in a Yellow font slows performance). Tolerance to alcohol was assessed by subtracting response latency (ms) on correct trials at the beginning of the 2 hour alcohol infusion from latency on correct trials at the end. Theoretical scores ranged from about -200 to 250; negative scores indicate the development of tolerance. Values reported here compare tolerance developed during the oxytocin session to tolerance developed during the placebo session.	2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo, scheduled 3-4 weeks apart, order counter-balanced.
Alcohol Purchase Task (Variable OMax)	The Alcohol Purchase task (APT) tests the value participants place on alcohol at specific times and conditions of the experimental session. To complete the APT, participants fill out a table reporting how many drinks (allowed range 0-50) they would purchase during an evening out, for a cost ranging from $0 to $30/drink. From this, a value for # of drinks * cost of drink is calculated; OMax is the highest amount in dollars that a participant would spend (possible range = $0 to $1,500). Tolerance to the effect of alcohol is calculated as OMax (end of infusion) - OMax (beginning of infusion), possible values range from -$1,500 to $1,500. Negative scores indicate the development of tolerance. Values reported here compare tolerance developed during the oxytocin session to tolerance developed during the placebo session.	2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo

Collaborators and Investigators

• Sponsor: Indiana University
• Investigators: Principal Investigator: Martin H Plawecki, MD, PhD, Psychiatry, Indiana University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2022
• Primary Completion (Actual): December 21, 2023
• Study Completion (Actual): December 21, 2023

Study Registration Dates

• First Submitted: February 26, 2022
• First Submitted That Met QC Criteria: March 28, 2022
• First Posted (Actual): April 5, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 11, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Alcohol use disorder; Oxytocin, intranasal; Alcohol tolerance; Alcohol intake; Alcohol treatment; Alcohol, intravenous
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Alcoholism; Alcohol Drinking; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: 10002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The final raw dataset will be available to other researchers when we have collected all subjects, completed our own planned analyses, and, if warranted, sought and obtained funding based on the outcome of this pilot study.
• IPD Sharing Time Frame: The dataset will be available indefinitely
• IPD Sharing Access Criteria: On request to the PI
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No