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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Wake Forest University Health Sciences

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Drug Abuse (NIDA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 31, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 10, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 10, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 15, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 15, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 18, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 1, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 26, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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