The Effects of Sedatives on Tobacco Use Disorder Version 2 (SED-TUD2)

March 26, 2026 updated by: Wake Forest University Health Sciences
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This double-blind, placebo-controlled, randomized mechanistic clinical trial will test non-treatment seeking smokers with an intravenous infusion of ketamine (0.71 mg/kg), midazolam (0.025 mg/kg), dexmedetomidine (0.025 mg/kg), or placebo, at least 2 weeks apart. Participants will complete 7-day ecological momentary assessment (EMA) of daily craving, withdrawal, and smoking behavior before and after each infusion. They will be asked to abstain from tobacco/nicotine for twenty-four hours post-infusion to induce withdrawal symptoms and return to the lab the following day to complete measures of craving, withdrawal, an MRI scan, and smoking latency. After this study visit, participants will be allowed to smoke as usual for the rest of the EMA diary period. Physical and subjective effects and adverse effects will be closely monitored throughout.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ketamine first injection; midazolam second injection
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
A single dose of IV ketamine will be administered.
Other Names:
  • a dissociative anesthetic used medically for induction and maintenance of anesthesia
Drug: Midazolam
A single dose of IV midazolam will be administered
Other Names:
  • benzodiazepine medication
Experimental: Ketamine first injection; dexmedetomidine second injection
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
A single dose of IV ketamine will be administered.
Other Names:
  • a dissociative anesthetic used medically for induction and maintenance of anesthesia
Drug: Dexmedetomidine
A single dose of IV dexmedetomidine will be administered
Other Names:
  • benzodiazepine medication
Experimental: Midazolam first injection; ketamine second injection
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
A single dose of IV ketamine will be administered.
Other Names:
  • a dissociative anesthetic used medically for induction and maintenance of anesthesia
Drug: Midazolam
A single dose of IV midazolam will be administered
Other Names:
  • benzodiazepine medication
Experimental: Midazolam first injection; dexmedetomidine second injection
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
A single dose of IV midazolam will be administered
Other Names:
  • benzodiazepine medication
Drug: Dexmedetomidine
A single dose of IV dexmedetomidine will be administered
Other Names:
  • benzodiazepine medication
Experimental: Dexmedetomidine first injection; ketamine second injection
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
A single dose of IV ketamine will be administered.
Other Names:
  • a dissociative anesthetic used medically for induction and maintenance of anesthesia
Drug: Dexmedetomidine
A single dose of IV dexmedetomidine will be administered
Other Names:
  • benzodiazepine medication
Experimental: Dexmedetomidine first injection; midazolam second injection
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
A single dose of IV midazolam will be administered
Other Names:
  • benzodiazepine medication
Drug: Dexmedetomidine
A single dose of IV dexmedetomidine will be administered
Other Names:
  • benzodiazepine medication
Experimental: Saline first injection; ketamine second injection
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
A single dose of IV ketamine will be administered.
Other Names:
  • a dissociative anesthetic used medically for induction and maintenance of anesthesia
Drug: Saline
A single dose of IV saline will be administered
Experimental: Saline first injection; midazolam second injection
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
A single dose of IV midazolam will be administered
Other Names:
  • benzodiazepine medication
Drug: Saline
A single dose of IV saline will be administered
Experimental: Saline first injection; dexmedetomidine second injection
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
A single dose of IV dexmedetomidine will be administered
Other Names:
  • benzodiazepine medication
Drug: Saline
A single dose of IV saline will be administered
Experimental: Ketamine first injection; Saline second injection
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
A single dose of IV ketamine will be administered.
Other Names:
  • a dissociative anesthetic used medically for induction and maintenance of anesthesia
Drug: Saline
A single dose of IV saline will be administered
Experimental: Midazolam first injection; Saline second injection
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
A single dose of IV midazolam will be administered
Other Names:
  • benzodiazepine medication
Drug: Saline
A single dose of IV saline will be administered
Experimental: Dexmedetomidine first injection; Saline second injection
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
A single dose of IV dexmedetomidine will be administered
Other Names:
  • benzodiazepine medication
Drug: Saline
A single dose of IV saline will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in craving between drug and placebo
Time Frame: 24-hours post infusion
difference in self-reported craving for cigarettes after infusions
24-hours post infusion
Difference in tobacco withdrawal symptoms
Time Frame: 24-hours post infusion
difference in self-reported withdrawal symptoms after infusions
24-hours post infusion
Difference in cigarette demand
Time Frame: 24-hours post infusion
difference in self-reported cigarette demand after infusions
24-hours post infusion
Number of cigarettes smoked ad lib
Time Frame: 24-hours post infusion
24-hours post infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wake Forest University Health Sciences

Collaborators

National Institute on Drug Abuse (NIDA)

Investigators

  • Principal Investigator: Merideth A Addicott, MD, Wake Forest University Health Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 31, 2023

Primary Completion (Actual)

December 10, 2025

Study Completion (Actual)

December 10, 2025

Study Registration Dates

First Submitted

August 15, 2022

First Submitted That Met QC Criteria

August 15, 2022

First Posted (Actual)

August 18, 2022

Study Record Updates

Last Update Posted (Actual)

April 1, 2026

Last Update Submitted That Met QC Criteria

March 26, 2026

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00081012
  • R21DA053393 (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.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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