Suvorexant and Alcohol

Influence of Orexin Antagonism on Motivation for Alcohol

This research will translate findings from preclinical research and provide the initial clinical evidence that orexin antagonism reduces motivation for alcohol, as well as other alcohol-associated maladaptive behaviors in people with Alcohol Use Disorder. This study will also provide basic science information about the orexinergic mechanisms underlying the pharmacodynamic effects of alcohol in humans. As such, the outcomes will contribute to our understanding of the clinical neurobiology of Alcohol Use Disorder. Overall, the proposed work seeks to expand the scope of current clinical neuroscience research on alcohol addiction by focusing on orexin, which has strong preclinical evidence supporting its critical role in addiction but remains unstudied in humans.

Study Overview

• Status: Recruiting
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Suvorexant; Drug: Suvorexant; Drug: Alcohol

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: William W Stoops, PhD; Phone Number: 8592575388; Email: william.stoops@uky.edu

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40507
      • Recruiting
      • Psychopharmacology of Addiction Laboratory
      • Contact: William Walton Stoops; Phone Number: 8592575388; Email: william.stoops@uky.edu
      • Principal Investigator: William W Stoops, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion/Exclusion Criteria:

1. Able to speak and read English.
2. Not seeking treatment at the time of the study.
3. Between the ages of 21 and 55 years.
4. Engaging in at least one binge drinking episode, per the NIAAA definition, in the last 30 days.
5. Fulfillment of moderate or severe DSM-5 diagnostic criteria for AUD based on computerized SCID results reviewed by a psychiatrist or psychologist.
6. ECG, read by cardiologist, within normal limits.
7. Body mass index of 19 - 35.
8. Birthing individuals using an effective form of birth control and not pregnant or breast feeding.
9. Judged by the medical staff to be psychiatrically and physically healthy (i.e., no current severe SUD or psychiatric diagnoses other than AUD or Tobacco Use Disorder; no current physical diagnoses that would interfere with study participation according to study physician judgment).
10. Not currently physiologically dependent on any substances.
11. Able to abstain from alcohol during admission (i.e., not physically dependent on alcohol and scores less than 8 on Clinical Institute Withdrawal Assessment for Alcohol [CIWA-Ar] at screening).
12. Not currently taking any prescribed medications for a chronic condition (other than birth control).
13. No indication of sleep apnea on the STOP-Bang questionnaire (score of 5 or greater).
14. No contraindications/allergies to suvorexant.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Subjects will be treated daily with an oral placebo.	Drug: Placebo; The effects of placebo will be determined.; Drug: Alcohol; The pharmacodynamic effects of alcohol (0.2 and 0.4 g/kg) will be determined.
Experimental: Suvorexant Dose 1; Subjects will be treated daily with oral suvorexant (10 mg).	Drug: Suvorexant; The effects of suvorexant dose 1 will be determined.; Drug: Suvorexant; The effects of suvorexant dose 2 will be determined.; Drug: Alcohol; The pharmacodynamic effects of alcohol (0.2 and 0.4 g/kg) will be determined.
Experimental: Suvorexant Dose 2; Subjects will be treated daily with oral suvorexant (20 mg).	Drug: Suvorexant; The effects of suvorexant dose 1 will be determined.; Drug: Suvorexant; The effects of suvorexant dose 2 will be determined.; Drug: Alcohol; The pharmacodynamic effects of alcohol (0.2 and 0.4 g/kg) will be determined.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reinforcing Effects of Alcohol	Number of Times Subjects Choose Alcohol (Maximum of 5 Choices) Over Money	6 times over approximately 3 week inpatient admission.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Craving	Subjects will report their craving during 6 sessions while they are admitted to our inpatient unit. Measured using a 10 point craving questionnaire with higher scores meaning greater craving.	6 times over approximately 3 week inpatient admission.
Mood	Subjects will complete the Profile of Mood States during 6 sessions while they are admitted to our inpatient unit. Scores range from 0 to 4 with higher scores indicating stronger mood.	6 times over approximately 3 week inpatient admission.
Alcohol Response	Subjects will complete the Biphasic Alcohol Effects Scale during 6 sessions while they are admitted to our inpatient unit. Scores range from 0 to 10 with higher scores indicating greater responses.	6 times over approximately 3 week inpatient admission.
Heart rate	Beats per minute. Measured daily during inpatient admission.	Daily over approximately 3 week inpatient admission.
Blood pressure	mm Hg. Measured daily during inpatient admission.	Daily over approximately 3 week inpatient admission.
Breath Alcohol Level	Percent. Measured daily during inpatient admission.	Daily over approximately 3 week inpatient admission.
Temperature	Degrees Fahrenheit. Measured daily during inpatient admission.	Daily over approximately 3 week inpatient admission.
Side Effects	Subjects will complete a side effects questionnaire daily while they reside on the inpatient unit. Side Effects questions will query subjects about common effects of centrally active medications.	Daily over approximately 3 week inpatient admission.
Delay Discounting	Subjects will complete the delay discounting task during 6 sessions while they are admitted to our inpatient unit. Responses will be used to calculate discounting slope (i.e., K).	6 times over approximately 3 week inpatient admission.
n-back Task	Subjects will complete the n-back task during 6 sessions while they are admitted to our inpatient unit. Percentage of correct responses will be the outcome.	6 times over approximately 3 week inpatient admission.
Stop-Signal Task Inhibitory Failures	Subjects will complete the stop-signal task during 6 sessions while they are admitted to our inpatient unit. Proportion of inhibitory failures will be the outcome variable.	6 times over approximately 3 week inpatient admission.
Sleep	Subjects will complete the St. Mary's Sleep Questionnaire daily while they are admitted to our inpatient unit. Total sleep time will be the outcome variable and will be recorded in minutes. Higher scores indicate more sleep. Total sleep time is measured by self-report; minimum score=0, maximum score=1440 per day.	Daily over approximately 3 week inpatient admission.

Collaborators and Investigators

• Sponsor: William Stoops
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: William W Stoops, PhD, University Of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2024
• Primary Completion (Estimated): March 15, 2027
• Study Completion (Estimated): March 15, 2027

Study Registration Dates

• First Submitted: March 15, 2024
• First Submitted That Met QC Criteria: March 15, 2024
• First Posted (Actual): March 22, 2024

Study Record Updates

• Last Update Posted (Actual): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 20, 2025
• Last Verified: December 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; Organic Chemicals; Alcohols; Ethanol; suvorexant
• Other Study ID Numbers: 88524; R01AA030775 (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
• product manufactured in and exported from the U.S.: No