The Effects of Sedatives on Tobacco Use Disorder Version 2

NCT05505630 | Completed Early Phase 1 FDA Drug

• 2 other identifiers: IRB00081012R21DA053393
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Double-blind, placebo-controlled, randomized mechanistic clinical trial to test an intravenous dose of either ketamine, midazolam, dexmedetomidine, or a placebo (saline) on cigarette smoking behavior, craving, and neural effects.

Conditions

Tobacco Smoking

Keywords

nicotine addiction; smoking; placebo; sedatives

Outcome Measures

Primary Outcomes (4)

• Difference in craving between drug and placebo

  difference in self-reported craving for cigarettes after infusions

  24-hours post infusion

• Difference in tobacco withdrawal symptoms

  difference in self-reported withdrawal symptoms after infusions

  24-hours post infusion

• Difference in cigarette demand

  difference in self-reported cigarette demand after infusions

  24-hours post infusion

• Number of cigarettes smoked ad lib

  24-hours post infusion

Study Arms (12)

Saline first injection; ketamine second injection

EXPERIMENTAL

Subjects in this arm will receive a single intravenous infusion of placebo at the first injection visit and a single intravenous infusion ketamine at the second injection visit.

Drug: Ketamine; Drug: Saline

Saline first injection; midazolam second injection

EXPERIMENTAL

Subjects in this arm will receive a single intravenous infusion of placebo at the first injection visit and a single intravenous infusion midazolam at the second injection visit

Drug: Midazolam; Drug: Saline

Saline first injection; dexmedetomidine second injection

EXPERIMENTAL

Subjects in this arm will receive a single intravenous infusion of placebo at the first injection visit and a single intravenous infusion dexmedetomidine at the second injection visit.

Drug: Dexmedetomidine; Drug: Saline

Ketamine first injection; Saline second injection

EXPERIMENTAL

Subjects in this arm will receive a single intravenous infusion of ketamine at the first injection visit and a single intravenous infusion placebo at the second injection visit.

Drug: Ketamine; Drug: Saline

Ketamine first injection; midazolam second injection

EXPERIMENTAL

Subjects in this arm will receive a single intravenous infusion of ketamine at the first injection visit and a single intravenous infusion midazolam at the second injection visit.

Drug: Ketamine; Drug: Midazolam

Ketamine first injection; dexmedetomidine second injection

EXPERIMENTAL

Subjects in this arm will receive a single intravenous infusion of ketamine at the first injection visit and a single intravenous infusion dexmedetomidine at the second injection visit.

Drug: Ketamine; Drug: Dexmedetomidine

Midazolam first injection; Saline second injection

EXPERIMENTAL

Subjects in this arm will receive a single intravenous infusion of midazolam at the first injection visit and a single intravenous infusion placebo at the second injection visit.

Drug: Midazolam; Drug: Saline

Midazolam first injection; ketamine second injection

EXPERIMENTAL

Subjects in this arm will receive a single intravenous infusion of midazolam at the first injection visit and a single intravenous infusion ketamine at the second injection visit.

Drug: Ketamine; Drug: Midazolam

Midazolam first injection; dexmedetomidine second injection

EXPERIMENTAL

Subjects in this arm will receive a single intravenous infusion of midazolam at the first injection visit and a single intravenous infusion dexmedetomidine at the second injection visit.

Drug: Midazolam; Drug: Dexmedetomidine

Dexmedetomidine first injection; Saline second injection

EXPERIMENTAL

Subjects in this arm will receive a single intravenous infusion of dexmedetomidine at the first injection visit and a single intravenous infusion placebo at the second injection visit.

Drug: Dexmedetomidine; Drug: Saline

Dexmedetomidine first injection; ketamine second injection

EXPERIMENTAL

Subjects in this arm will receive a single intravenous infusion of dexmedetomidine at the first injection visit and a single intravenous infusion ketamine at the second injection visit.

Drug: Ketamine; Drug: Dexmedetomidine

Dexmedetomidine first injection; midazolam second injection

EXPERIMENTAL

Subjects in this arm will receive a single intravenous infusion of dexmedetomidine at the first injection visit and a single intravenous infusion midazolam at the second injection visit.

Drug: Midazolam; Drug: Dexmedetomidine

Interventions

Ketamine DRUG

A single dose of IV ketamine will be administered.

Also known as: a dissociative anesthetic used medically for induction and maintenance of anesthesia

Dexmedetomidine first injection; ketamine second injection; Ketamine first injection; Saline second injection; Ketamine first injection; dexmedetomidine second injection; Ketamine first injection; midazolam second injection; Midazolam first injection; ketamine second injection; Saline first injection; ketamine second injection

Midazolam DRUG

A single dose of IV midazolam will be administered

Also known as: benzodiazepine medication

Dexmedetomidine first injection; midazolam second injection; Ketamine first injection; midazolam second injection; Midazolam first injection; Saline second injection; Midazolam first injection; dexmedetomidine second injection; Midazolam first injection; ketamine second injection; Saline first injection; midazolam second injection

Dexmedetomidine DRUG

A single dose of IV dexmedetomidine will be administered

Also known as: benzodiazepine medication

Dexmedetomidine first injection; Saline second injection; Dexmedetomidine first injection; ketamine second injection; Dexmedetomidine first injection; midazolam second injection; Ketamine first injection; dexmedetomidine second injection; Midazolam first injection; dexmedetomidine second injection; Saline first injection; dexmedetomidine second injection

Saline DRUG

A single dose of IV saline will be administered

Dexmedetomidine first injection; Saline second injection; Ketamine first injection; Saline second injection; Midazolam first injection; Saline second injection; Saline first injection; dexmedetomidine second injection; Saline first injection; ketamine second injection; Saline first injection; midazolam second injection

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Smokes cigarettes daily for at least 2 years
• Afternoon expired breath carbon monoxide at least 5 ppm or morning urinary cotinine at least 100 ng/ml
• Negative urine drug screen for psychoactive drugs and negative breath alcohol

You may not qualify if:

• Have an unstable medical condition or stable medical condition that would interact with study drug or participation, including chronic pulmonary disease, coronary artery disease, current brain tumor, current increased intracranial pressure or impaired consciousness
• History of serious head trauma or neurological disorder (e.g., seizure disorder)
• Have any of the following: hypertension (i.e., systolic \>140 mm Hg and/or diastolic \>90 mm Hg on three separate measures; systolic \>170 or diastolic \> 110 on any occasion), pre-existing severe gastrointestinal narrowing (pathologic or iatrogenic).
• Use of drugs that would interact with study drug or increase risk of adverse events
• Among women, pregnancy or lactation

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Tobacco Smoking; Tobacco Use Disorder; Smoking

Interventions

Ketamine; Neoadjuvant Therapy; Midazolam; Dexmedetomidine; Sodium Chloride

Condition Hierarchy (Ancestors)

Behavior; Tobacco Use; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Combined Modality Therapy; Therapeutics; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Merideth A Addicott, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2022
• First Posted: August 18, 2022
• Study Start: January 31, 2023
• Primary Completion: December 10, 2025
• Study Completion: December 10, 2025
• Last Updated: April 1, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)