Effect of Allopregnanolone on Stress-induced Craving

The goal of this study is to determine whether intravenous infusion of allopregnanolone (ALLO) attenuates stress-induced craving and stress-induced anxiety in a clinical laboratory setting. The secondary objective of this project is to characterize the behavioral effects of ALLO in heavy drinkers.

Study Overview

• Status: Completed
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: Placebos; Drug: Allopregnanolone

Detailed Description

This is a double-blind, placebo-controlled study that will randomize heavy "at risk" drinkers to 2 groups: targeted dose of 100 nM of ALLO or placebo. Participants will receive a continuous infusion of ALLO (or placebo) for approximately 175 min. Sixty minutes after the start of the infusion, when ALLO levels are relatively stable, the stress induction paradigm will be introduced. Participants will be presented with a stress cue and a neutral cue in random order. Stress and neutral cues will consist of personalized 5-minute scripts created prior to testing. Measures of stress-induced craving and stress-induced anxiety will be presented before the cue (pre), immediately following the cue (post) and 10 minutes after (recovery). An alcohol infusion (40mg%) begins at approximately 120 minutes into ALLO Infusion. Once the alcohol infusion has reached the targeted dose of 40mg% the infusion is clamped for approximately 20 minutes. The study outcomes will include measures of stress-induced craving and stress-induced anxiety as well as measures of subjective mood effects, cognitive performance, and motor coordination.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • VA Connecticut Healtcase System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Non-treatment seeking individuals with current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) alcohol use disorder (AUD)
• No current substance use disorder (except tobacco, alcohol, and marijuana)
• No current medical problems and normal electrocardiogram (ECG)
• For women, not pregnant as determined by pregnancy screening, not breast feeding.

Exclusion Criteria:

• Current major psychiatric illnesses including mood, psychotic, or anxiety disorders
• History of major medical illnesses; including liver diseases, heart disease, chronic pain or other medical conditions that the physician investigator deems contraindicated for the subject to be in the study
• Liver function tests (ALT or AST) greater than 3 times normal
• weight >120kg
• renal impairment
• patients on the following medications: a) medications for alcoholism (e.g. naltrexone, disulfiram, topiramate, acamprosate); b) psychotropic medications that promote sedation (please note patients on psychotropic medications for current psychiatric conditions will also be excluded); and c) patients currently taking antibiotics or antifungals

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: allopregnanolone; Allopregnanolone infusion dose of 100nM over 175 min	Drug: Allopregnanolone; neurosteroid
Placebo Comparator: placebo; Placebo infusion	Drug: Placebos; placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alcohol Urge Questionnaire (AUQ) Pre-script	The Alcohol Urge Questionnaire (AUQ) is an 8-question, self-administered measure of drinking urges. Questions are in the form of a 7-point scale with participants endorsing the extent to which they agree or disagree with statements relating to desire to drink (4 items), expectation of a desired outcome from drinking (2 items), and inability to avoid drinking if alcohol was available (2 items). Total scores range from 8 (strongly disagree) to 56 (strongly agree).	Pre-Script 40 minutes before trauma/neutral script is presented
The State-Trait Anxiety Inventory (STAI-6) I Feel Upset - Pre-Script	The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 3. "I feel upset" (scored individually): the scoring for "I feel upset is: a = 1, b = 2, c = 3, and d = 4 (1 not at all upset to 4 very much upset)	Pre-Script 40 minutes before trauma/neutral script is presented
Alcohol Urge Questionnaire (AUQ) Post-Script	The Alcohol Urge Questionnaire (AUQ) is an 8-question, self-administered measure of drinking urges. Questions are in the form of a 7-point scale with participants endorsing the extent to which they agree or disagree with statements relating to desire to drink (4 items), expectation of a desired outcome from drinking (2 items), and inability to avoid drinking if alcohol was available (2 items). Total scores range from 8 (strongly disagree) to 56 (strongly agree).	Post-Script 5 minutes after trauma/neutral script is presented
Alcohol Urge Questionnaire (AUQ) Recovery	The Alcohol Urge Questionnaire (AUQ) is an 8-question, self-administered measure of drinking urges. Questions are in the form of a 7-point scale with participants endorsing the extent to which they agree or disagree with statements relating to desire to drink (4 items), expectation of a desired outcome from drinking (2 items), and inability to avoid drinking if alcohol was available (2 items). Total scores range from 8 (strongly disagree) to 56 (strongly agree).	Recovery 10 minutes after trauma/neutral script is presented
The State-Trait Anxiety Inventory (STAI-6) I Feel Upset - Post-Script	The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 3. "I feel upset" (scored individually): the scoring for "I feel upset is: a = 1, b = 2, c = 3, and d = 4 (1 not at all upset to 4 very much upset)	Post-Script 5 minutes after trauma/neutral script is presented
The State-Trait Anxiety Inventory (STAI-6) I Feel Upset - Recovery	The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 3. "I feel upset" (scored individually): the scoring for "I feel upset is: a = 1, b = 2, c = 3, and d = 4 (1 not at all upset to 4 very much upset)	Recovery 10 minutes after trauma/neutral script is presented
The State-Trait Anxiety Inventory (STAI-6) I Feel Content - Pre-Script	The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 5. "I feel content" (scored individually): the scoring for "I feel content is: a = 4, b = 3, c = 2, and d = 1 (4 not at all content to 1 very much content)	Pre-Script 40 minutes before trauma/neutral script is presented
The State-Trait Anxiety Inventory (STAI-6) I Feel Content - Post-Script	The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 5. "I feel content" (scored individually): the scoring for "I feel content is: a = 4, b = 3, c = 2, and d = 1 (4 not at all content to 1 very much content)	Post-Script 5 minutes after trauma/neutral script is presented
The State-Trait Anxiety Inventory (STAI-6) I Feel Content - Recovery	The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 5. "I feel content" (scored individually): the scoring for "I feel content is: a = 4, b = 3, c = 2, and d = 1 (4 not at all content to 1 very much content)	Recovery10 minutes after trauma/neutral script is presented
The State-Trait Anxiety Inventory (STAI-6) I am Worried - Pre-Script	The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 6. "I am worried" (scored individually): the scoring for "I feel content is: a = 1, b = 2, c = 3, and d = 4 (1 not at all worried to 4 very much worried)	Pre-Script 40 minutes before trauma/neutral script is presented
The State-Trait Anxiety Inventory (STAI-6) I am Worried - Post-Script	The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 6. "I am worried" (scored individually): the scoring for "I feel content is: a = 1, b = 2, c = 3, and d = 4 (1 not at all worried to 4 very much worried)	Post-Script 5 minutes after trauma/neutral script is presented
The State-Trait Anxiety Inventory (STAI-6) I am Worried - Recovery	The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 6. "I am worried" (scored individually): the scoring for "I feel content is: a = 1, b = 2, c = 3, and d = 4 (1 not at all worried to 4 very much worried)	Recovery 10 minutes after trauma/neutral script is presented

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biphasic Alcohol Effects Scale (BAES) Sedation Items - Pre-Script	Biphasic Alcohol Effects Scale (BAES) Sedation items - sum of subjective responses - 0(not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES sedation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater sedative effects of alcohol.	Pre-Script 40 minutes before trauma/neutral script is presented
Biphasic Alcohol Effects Scale (BAES) Sedation Items	Biphasic Alcohol Effects Scale (BAES) Sedation items - sum of subjective responses - 0(not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES sedation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater sedative effects of alcohol. Data presented here is mean at 90 minutes.	Pre-infusion (at 0 minutes), during infusion (approximately 20 minutes) and post-infusion (approximately 90 minutes)
Biphasic Alcohol Effects Scale (BAES) Sedation Items - Target Alcohol Dose (40mg%)	Biphasic Alcohol Effects Scale (BAES) Sedation items - sum of subjective responses - 0(not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES sedation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater sedative effects of alcohol.	Target Alcohol dose (40mg%) 90 minutes after trauma/neutral script is presented
Biphasic Alcohol Effects Scale (BAES) Sedation Items - End of Test Day	Biphasic Alcohol Effects Scale (BAES) Sedation items - sum of subjective responses - 0(not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES sedation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater sedative effects of alcohol.	End of test day 150 minutes after trauma/neutral script is presented
Biphasic Alcohol Effects Scale (BAES) Stimulation Items - Pre-Script	Biphasic Alcohol Effects Scale (BAES) Simulation items - sum of subjective responses - 0 (not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES stimulation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater stimulating effects of alcohol.	Pre-Script 40 minutes before trauma/neutral script is presented
Biphasic Alcohol Effects Scale (BAES) Stimulation Items	Biphasic Alcohol Effects Scale (BAES) Simulation items - sum of subjective responses - 0 (not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES stimulation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater stimulating effects of alcohol. Data presented here is mean at 90 minutes.	Pre-infusion (at 0 minutes), during infusion (approximately 20 minutes) and post-infusion (approximately 90 minutes)
Biphasic Alcohol Effects Scale (BAES) Stimulation Items - Target Alcohol Dose (40mg%)	Biphasic Alcohol Effects Scale (BAES) Simulation items - sum of subjective responses - 0 (not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES stimulation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater stimulating effects of alcohol.	Target Alcohol Dose (40mg%) 90 minutes after trauma/neutral script is presented
Biphasic Alcohol Effects Scale (BAES) Stimulation Items - End of Test Day	Biphasic Alcohol Effects Scale (BAES) Simulation items - sum of subjective responses - 0 (not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES stimulation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater stimulating effects of alcohol.	End of Test Day 150 minutes after trauma/neutral script is presented

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Elizabeth Ralevski, PhD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Actual): September 1, 2023
• Study Completion (Actual): September 1, 2023

Study Registration Dates

• First Submitted: April 11, 2019
• First Submitted That Met QC Criteria: July 10, 2019
• First Posted (Actual): July 11, 2019

Study Record Updates

• Last Update Posted (Actual): August 22, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Alcoholism; Physiological Effects of Drugs; Anesthetics; Central Nervous System Depressants; Pregnanolone
• Other Study ID Numbers: 2000021601; 1R21AA024917-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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