Tobacco SmokingEarly Phase 1SED-TUD2NCT05505630
The Effects of Sedatives on Tobacco Use Disorder Version 2
A Early Phase 1 study testing Ketamine, Midazolam and Dexmedetomidine in people with Tobacco Smoking, run by Wake Forest University Health Sciences at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Tobacco Smoking
- What is being tested?
- Ketamine, Midazolam and Dexmedetomidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jan 2023to 10 Dec 2025
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
About this study
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.
Read the 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.
- Conditions
- Tobacco Smoking
- Being tested
- Ketamine, Midazolam, Dexmedetomidine, Saline
- Keywords
- nicotine addiction, smoking, placebo, sedatives
- Medical subject headings
- Tobacco Smoking, Tobacco Use Disorder, Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called a dissociative anesthetic used medically for induction and maintenance of anesthesia
A single dose of IV ketamine will be administered.
MidazolamDrug
Also called benzodiazepine medication
A single dose of IV midazolam will be administered
DexmedetomidineDrug
Also called benzodiazepine medication
A single dose of IV dexmedetomidine will be administered
SalineDrug
A single dose of IV saline will be administered
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Midazolam; Drug: Dexmedetomidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in craving between drug and placebo
difference in self-reported craving for cigarettes after infusions
Measured: 24-hours post infusion
Difference in tobacco withdrawal symptoms
difference in self-reported withdrawal symptoms after infusions
Measured: 24-hours post infusion
Difference in cigarette demand
difference in self-reported cigarette demand after infusions
Measured: 24-hours post infusion
Number of cigarettes smoked ad lib
Measured: 24-hours post infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2022
- Study start31 Jan 2023
- Primary completion10 Dec 2025
- Study completion10 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tobacco SmokingStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Merideth A Addicott, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05505630
- Sponsor's protocol ID
- IRB00081012
- Other IDs
- R21DA053393
- Acronym
- SED-TUD2
- Status last verified
- Dec 2025
- First submitted
- 15 Aug 2022
- Last updated
- 1 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Sedatives on Tobacco Use Disorder Version 2
- ClinicalTrials.gov ID
- NCT05505630
- Acronym / sponsor ID
- SED-TUD2 / IRB00081012
- Conditions
- Tobacco Smoking
- Keywords
- nicotine addiction, smoking, placebo, sedatives
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 31 Jan 2023 (actual)
- Primary completion
- 10 Dec 2025 (actual)
- Study completion
- 10 Dec 2025 (actual)
- First posted
- 18 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, care provider)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Saline first injection; ketamine second injection | Experimental | Drug: Ketamine, Drug: SalineSubjects 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. |
| Saline first injection; midazolam second injection | Experimental | Drug: Midazolam, Drug: SalineSubjects 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 |
| Saline first injection; dexmedetomidine second injection | Experimental | Drug: Dexmedetomidine, Drug: SalineSubjects 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. |
| Ketamine first injection; Saline second injection | Experimental | Drug: Ketamine, Drug: SalineSubjects 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. |
| Ketamine first injection; midazolam second injection | Experimental | Drug: Ketamine, Drug: MidazolamSubjects 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. |
| Ketamine first injection; dexmedetomidine second injection | Experimental | Drug: Ketamine, Drug: DexmedetomidineSubjects 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. |
| Midazolam first injection; Saline second injection | Experimental | Drug: Midazolam, Drug: SalineSubjects 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. |
| Midazolam first injection; ketamine second injection | Experimental | Drug: Ketamine, Drug: MidazolamSubjects 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. |
| Midazolam first injection; dexmedetomidine second injection | Experimental | Drug: Midazolam, Drug: DexmedetomidineSubjects 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. |
| Dexmedetomidine first injection; Saline second injection | Experimental | Drug: Dexmedetomidine, Drug: SalineSubjects 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. |
| Dexmedetomidine first injection; ketamine second injection | Experimental | Drug: Ketamine, Drug: DexmedetomidineSubjects 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. |
| Dexmedetomidine first injection; midazolam second injection | Experimental | Drug: Midazolam, Drug: DexmedetomidineSubjects 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. |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetamineAlso: a dissociative anesthetic used medically for induction and maintenance of anesthesiaA single dose of IV ketamine will be administered. | Drug | 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 |
| MidazolamAlso: benzodiazepine medicationA single dose of IV midazolam will be administered | Drug | 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 |
| DexmedetomidineAlso: benzodiazepine medicationA single dose of IV dexmedetomidine will be administered | Drug | 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 |
| SalineA single dose of IV saline will be administered | Drug | 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 |
Primary outcome
Difference in craving between drug and placebo
Time frame: 24-hours post infusion
difference in self-reported craving for cigarettes after infusions
Difference in tobacco withdrawal symptoms
Time frame: 24-hours post infusion
difference in self-reported withdrawal symptoms after infusions
Difference in cigarette demand
Time frame: 24-hours post infusion
difference in self-reported cigarette demand after infusions
Number of cigarettes smoked ad lib
Time frame: 24-hours post infusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Merideth A Addicott, MD principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Ketamine, Midazolam and Dexmedetomidine in people with Tobacco Smoking, run by Wake Forest University Health Sciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in craving between drug and placebo (time frame: 24-hours post infusion). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2026.