CBDPhase 1CREWSNCT07001930
Effects of Cannabidiol on Stress and Nicotine Withdrawal
A Phase 1 study testing Epidiolex in people with CBD and Stress, run by Johns Hopkins University at 1 site in United States.
Trial summary
The purpose of this study is to examine the effect of doses of cannabidiol (CBD) during exposure to stress and nicotine withdrawal in nicotine users. The main objectives of the study include examining the effect CBD has on stress, tobacco dependence, tobacco withdrawal, and sex differences between these types of… Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- CBD, Stress, Nicotine Dependence
- What is being tested?
- Epidiolex
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Aug 2025to 1 Sep 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Healthy non-treatment seeking adults aged 21-70 (inclusive).
- Use of > 5 cigarettes per day for > 2 years. (Use of other tobacco/nicotine products in addition to cigarettes will be acceptable).
- Biological confirmation of cigarette use: have an expired carbon monoxide (CO) level >= 5 ppm.
- Alcohol Use: < 2 drinks/day on average (< 14 drinks/week).
- Sleep schedule: No graveyard or third shift work (i.e., participants must report a normal nighttime sleep schedule).
- For women of children bearing potential and men with female partners of child-bearing potential, must be willing to use an effective form of contraception during the study and for at least 30 days after the last study drug administration.
Who cannot join
- Report current intention to reduce or quit cannabis or tobacco use within the next 30 days
- Meet Diagnostic and Statistical Manual (DSM-5) criteria for a substance use disorder other than alcohol, cannabis, or nicotine
- Test positive for illicit drugs other than cannabis
- Positive breath alcohol test (>.01 g/210L) at study admission
- Have a current physical or mental illness or takes a medication judged by the study team to negatively impact participant safety or scientific integrity
- Have a resting heart rate >100, systolic blood pressure >160mmHg or <100mmHg, or diastolic blood pressure >100mmHg or <50mmHg at screening.
Show all 11Show fewer
- Have cold intolerance or a medical condition that might be exacerbated by exposure to cold (e.g. Reynaud's, peripheral neuropathy, trigeminal neuralgia, poorly controlled/uncontrolled hypothyroidism).
- Are currently pregnant, planning to become pregnant in the next three months, or are currently breastfeeding
- Have a history of clinically significant cardiac arrhythmias or vasospastic disease (e.g., Prinzmetal's angina, Raynaud's).
- Have a history of and/or current liver disease, or elevated serum liver transaminase (AST or ALT) above 3 x Upper Limit of Normal (ULN), or elevated bilirubin above 2 x ULN at screening.
- Are currently enrolled in another clinical trial or have received any drug as part of a research study within 30 days of study participation.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Behavioral Pharmacology Research Unit
Baltimore, Maryland, 21224
About this study
Official title: Pharmacological Effects of Cannabidiol on Responses to Stress and Nicotine Withdrawal
The purpose of this study is to examine the effect of doses of cannabidiol (CBD) during exposure to stress and nicotine withdrawal in nicotine users. The main objectives of the study include examining the effect CBD has on stress, tobacco dependence, tobacco withdrawal, and sex differences between these types of stress. Participants will be administered CBD and exposed to stress. Biological and subjective measures will be collected. Participants may be asked to stop use for 24 hours. Researchers will also investigate withdrawal effects between participants who have not smoked nicotine in 24 hours and those who have continued to smoke before each session.
Read the detailed description
This study will use a double-blind, placebo-controlled, within-subjects crossover design to examine the effect of acute doses of CBD during exposure to acute stress and nicotine withdrawal using a relevant set of biological and subjective measures that are known to be sensitive to acute stress and to nicotine withdrawal. There will be one in-person medical screening session, 3 pre-laboratory phone sessions, and 3 in-person experimental laboratory sessions separated by at least 72 hrs. Total duration for a study completer is estimated to be 2-3 weeks. Three doses of CBD (0mg, 200mg, and 400mg) will be administered, one at each of three separate laboratory sessions that will last approximately 5 hours each and be separated by at least 72 hours. Two effective induction challenges will be implemented: one is behavioral (an established and well validated acute psychological stress induction) and one is a nicotine withdrawal challenge (24 hours abstinence from all nicotine products). Nicotine users reporting daily cigarette use (N=90) will be recruited. Nicotine users will be randomly assigned to continue nicotine use ad libitum or to abstain for 24 hours before each of three laboratory sessions. Randomization will be stratified based on participant sex and current use of other tobacco products (e.g. e-cigarettes, smokeless tobacco, pouches, cigars/cigarillos). Participants who use other nicotine-related products (e.g., e-cigarettes) will be accepted in the study if they also smoke cigarettes. Use of other nicotine products will be assessed and tracked to account for their effects on the collected measures.
- Conditions
- CBD, Stress, Nicotine Dependence, Tobacco Smoking
- Being tested
- Epidiolex
- Keywords
- CBD, Stress, Nicotine, Tobacco Smoking
- Medical subject headings
- Tobacco Use Disorder, Tobacco Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EpidiolexDrug
Oral cannabidiol
| Study group | Role | What they receive |
|---|---|---|
| Ad Lib (first) | Experimental | Participants who use tobacco cigarettes and will be randomly assigned to smoking ab lib. Each participant will receive 0, 200, 400 mg of CBD in this arm. Receives: Drug: Epidiolex |
| Abstinence (first) | Experimental | Participants who use tobacco cigarettes and will be randomly assigned to smoking abstinence for 24 hours before each session. Each participant will receive 0, 200, 400 mg of CBD in this arm. Receives: Drug: Epidiolex |
What is being measured
The primary outcome is the main question the study is designed to answer.
Negative Affect as assessed by the Subjective State Scale
Negative affect is measured using the Subjective State Scale which includes 4 items measuring negative affect. The scale has a range of 0 to 28 with higher scores indicating greater negative affect.
Measured: 20 minutes, 70 minutes, 120 minutes, 170 minutes, 190 minutes, 200 minutes, 220 minutes timepoints
Positive Affect as assessed by the Subjective State Scale
Positive affect is measured using the Subjective State Scale which includes 5 items measuring positive affect. The scale has a range of 0 to 35 with higher scores indicating greater positive affect.
Measured: 20 minutes, 70 minutes, 120 minutes, 170 minutes, 190 minutes, 200 minutes, 220 minutes timepoints
Blood Plasma Cortisol level
Blood plasma cortisol will be collected during laboratory stress testing sessions using a 20-gauge IV Teflon catheter inserted in a non-dominant forearm vein.
Measured: 20 minutes, 70 minutes, 120 minutes, 170 minutes, 190 minutes, 200 minutes, 220 minutes timepoints
Salivary Cortisol level
Salivary cortisol will be collected during laboratory stress sessions using Salivette tubes and assayed using time-resolved fluorescence immunoassay.
Measured: 20 minutes, 70 minutes, 120 minutes, 170 minutes, 190 minutes, 200 minutes, 220 minutes timepoints
Plasma Concentration of Endocannabinoids
Blood plasma endocannabinoids will be collected during laboratory stress testing sessions using a 20-gauge IV Teflon catheter inserted in a non-dominant forearm vein.
Measured: 20 minutes, 70 minutes, 120 minutes, 170 minutes, 190 minutes, 200 minutes, 220 minutes timepoints
Heart Rate (beats per minutes)
Heart rate will be collected during laboratory stress testing sessions.
Measured: 20 minutes, 70 minutes, 120 minutes, 170 minutes, 190 minutes, 200 minutes, 220 minutes timepoints
Systolic Blood Pressure (mmHg)
Systolic blood pressure will be collected during laboratory stress testing sessions.
Measured: 20 minutes, 70 minutes, 120 minutes, 170 minutes, 190 minutes, 200 minutes, 220 minutes timepoints
Diastolic Blood Pressure (mmHg)
Diastolic blood pressure will be collected during laboratory stress testing sessions.
Measured: 20 minutes, 70 minutes, 120 minutes, 170 minutes, 190 minutes, 200 minutes, 220 minutes timepoints
Secondary outcomes (6)
Subjective Pain as assessed by the McGill Pain Questionnaire short form (MPQ)
Subjective pain will be measured immediately after the cold pressor task (CPT) at each stress session using the McGill Pain Questionnaire short form, with a score range of 0 to 78, with higher values indicating more significant pain.
Measured: 170 minute timepoint
Nicotine urge as assessed by the Questionnaire on Smoking Urges (QSU-brief)
Nicotine urge will be measured using the Questionnaire on Smoking Urges (QSU-brief) includes 10 items on a likert scale from 1 to 7. Total score range is 7 to 70, higher scores more nicotine urge.
Measured: 20 minutes, 70 minutes, 120 minutes, 170 minutes, 190 minutes, 200 minutes, 220 minutes timepoints
Craving for Sweet and Rich Foods as assessed by the Questionnaire on Craving for Sweet and Rich Food,
Craving for sweet and rich foods will be measured using the Questionnaire on Craving for Sweet and Rich Food, which includes one question assessing craving sweet or rich foods at the current moment, with scores ranging from 1 to 7, with higher scores indicating greater craving.
Measured: 200 minute timepoint
Hypothetical Tobacco Demand
Hypothetical tobacco demand will be measured using a cigarette purchase task after each laboratory stress session. Change in demand (amplitude and persistence) will be assessed to create an overall demand curve.
Measured: 200 minute timepoint
Sustained Attention to Response Task
Sustained attention will be measured using the Sustained Attention to Response Task. Errors of commission and errors of omission will be assessed during the recovery period at each laboratory stress session.
Measured: 200 minute timepoint
Reaction time on the N-Back Cognitive test
N-back task (0 back and 1 back) accuracy will be used to measure working memory during the recovery period at each laboratory stress session. Participants will be exposed to a series of numbers and will be asked to respond on a keypad when the current number matches a number presented "n" trials back.
Measured: 200 minute timepoint
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2025
- Study start25 Aug 2025
- Primary completion1 Sep 2029 (estimated)
- Study completion1 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CBDStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe 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
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- double-blind, placebo-controlled, within-subjects crossover design
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), University of Minnesota
- Responsible party
- Sponsor
- Investigators
- Dustin C. Lee, PhD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07001930
- Sponsor's protocol ID
- IRB00440948
- Other IDs
- R01DA027232-09A1
- Acronym
- CREWS
- Status last verified
- Aug 2026
- First submitted
- 23 May 2025
- Last updated
- 10 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacological Effects of Cannabidiol on Responses to Stress and Nicotine Withdrawal
- ClinicalTrials.gov ID
- NCT07001930
- Acronym / sponsor ID
- CREWS / IRB00440948
- Conditions
- CBD, Stress, Nicotine Dependence, Tobacco Smoking
- Keywords
- CBD, Stress, Nicotine, Tobacco Smoking
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), University of Minnesota
- Study start
- 25 Aug 2025 (actual)
- Primary completion
- 1 Sep 2029 (estimated)
- Study completion
- 1 Sep 2029 (estimated)
- First posted
- 3 Jun 2025 (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.
The purpose of this study is to examine the effect of doses of cannabidiol (CBD) during exposure to stress and nicotine withdrawal in nicotine users. The main objectives of the study include examining the effect CBD has on stress, tobacco dependence, tobacco withdrawal, and sex differences between these types of stress. Participants will be administered CBD and exposed to stress. Biological and subjective measures will be collected. Participants may be asked to stop use for 24 hours. Researchers will also investigate withdrawal effects between participants who have not smoked nicotine in 24 hours and those who have continued to smoke before each session.
Detailed description
This study will use a double-blind, placebo-controlled, within-subjects crossover design to examine the effect of acute doses of CBD during exposure to acute stress and nicotine withdrawal using a relevant set of biological and subjective measures that are known to be sensitive to acute stress and to nicotine withdrawal. There will be one in-person medical screening session, 3 pre-laboratory phone sessions, and 3 in-person experimental laboratory sessions separated by at least 72 hrs. Total duration for a study completer is estimated to be 2-3 weeks. Three doses of CBD (0mg, 200mg, and 400mg) will be administered, one at each of three separate laboratory sessions that will last approximately 5 hours each and be separated by at least 72 hours. Two effective induction challenges will be implemented: one is behavioral (an established and well validated acute psychological stress induction) and one is a nicotine withdrawal challenge (24 hours abstinence from all nicotine products). Nicotine users reporting daily cigarette use (N=90) will be recruited. Nicotine users will be randomly assigned to continue nicotine use ad libitum or to abstain for 24 hours before each of three laboratory sessions. Randomization will be stratified based on participant sex and current use of other tobacco products (e.g. e-cigarettes, smokeless tobacco, pouches, cigars/cigarillos). Participants who use other nicotine-related products (e.g., e-cigarettes) will be accepted in the study if they also smoke cigarettes. Use of other nicotine products will be assessed and tracked to account for their effects on the collected measures.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- double-blind, placebo-controlled, within-subjects crossover design
| Arm | Type | Receives |
|---|---|---|
| Ad Lib (first) | Experimental | Drug: EpidiolexParticipants who use tobacco cigarettes and will be randomly assigned to smoking ab lib. Each participant will receive 0, 200, 400 mg of CBD in this arm. |
| Abstinence (first) | Experimental | Drug: EpidiolexParticipants who use tobacco cigarettes and will be randomly assigned to smoking abstinence for 24 hours before each session. Each participant will receive 0, 200, 400 mg of CBD in this arm. |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Healthy non-treatment seeking adults aged 21-70 (inclusive).
- Use of > 5 cigarettes per day for > 2 years. (Use of other tobacco/nicotine products in addition to cigarettes will be acceptable).
- Biological confirmation of cigarette use: have an expired carbon monoxide (CO) level >= 5 ppm.
- Alcohol Use: < 2 drinks/day on average (< 14 drinks/week).
- Sleep schedule: No graveyard or third shift work (i.e., participants must report a normal nighttime sleep schedule).
Key exclusion criteria (11 listed)
- Report current intention to reduce or quit cannabis or tobacco use within the next 30 days
- Meet Diagnostic and Statistical Manual (DSM-5) criteria for a substance use disorder other than alcohol, cannabis, or nicotine
- Test positive for illicit drugs other than cannabis
- Positive breath alcohol test (>.01 g/210L) at study admission
- Have a current physical or mental illness or takes a medication judged by the study team to negatively impact participant safety or scientific integrity
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 |
|---|---|---|
| EpidiolexOral cannabidiol | Drug | Abstinence (first), Ad Lib (first) |
Primary outcome
Negative Affect as assessed by the Subjective State Scale
Time frame: 20 minutes, 70 minutes, 120 minutes, 170 minutes, 190 minutes, 200 minutes, 220 minutes timepoints
Negative affect is measured using the Subjective State Scale which includes 4 items measuring negative affect. The scale has a range of 0 to 28 with higher scores indicating greater negative affect.
Positive Affect as assessed by the Subjective State Scale
Time frame: 20 minutes, 70 minutes, 120 minutes, 170 minutes, 190 minutes, 200 minutes, 220 minutes timepoints
Positive affect is measured using the Subjective State Scale which includes 5 items measuring positive affect. The scale has a range of 0 to 35 with higher scores indicating greater positive affect.
Blood Plasma Cortisol level
Time frame: 20 minutes, 70 minutes, 120 minutes, 170 minutes, 190 minutes, 200 minutes, 220 minutes timepoints
Blood plasma cortisol will be collected during laboratory stress testing sessions using a 20-gauge IV Teflon catheter inserted in a non-dominant forearm vein.
Salivary Cortisol level
Time frame: 20 minutes, 70 minutes, 120 minutes, 170 minutes, 190 minutes, 200 minutes, 220 minutes timepoints
Salivary cortisol will be collected during laboratory stress sessions using Salivette tubes and assayed using time-resolved fluorescence immunoassay.
Plasma Concentration of Endocannabinoids
Time frame: 20 minutes, 70 minutes, 120 minutes, 170 minutes, 190 minutes, 200 minutes, 220 minutes timepoints
Blood plasma endocannabinoids will be collected during laboratory stress testing sessions using a 20-gauge IV Teflon catheter inserted in a non-dominant forearm vein.
Heart Rate (beats per minutes)
Time frame: 20 minutes, 70 minutes, 120 minutes, 170 minutes, 190 minutes, 200 minutes, 220 minutes timepoints
Heart rate will be collected during laboratory stress testing sessions.
Systolic Blood Pressure (mmHg)
Time frame: 20 minutes, 70 minutes, 120 minutes, 170 minutes, 190 minutes, 200 minutes, 220 minutes timepoints
Systolic blood pressure will be collected during laboratory stress testing sessions.
Diastolic Blood Pressure (mmHg)
Time frame: 20 minutes, 70 minutes, 120 minutes, 170 minutes, 190 minutes, 200 minutes, 220 minutes timepoints
Diastolic blood pressure will be collected during laboratory stress testing sessions.
6 secondary outcomes
Subjective Pain as assessed by the McGill Pain Questionnaire short form (MPQ)
Time frame: 170 minute timepoint
Nicotine urge as assessed by the Questionnaire on Smoking Urges (QSU-brief)
Time frame: 20 minutes, 70 minutes, 120 minutes, 170 minutes, 190 minutes, 200 minutes, 220 minutes timepoints
Craving for Sweet and Rich Foods as assessed by the Questionnaire on Craving for Sweet and Rich Food,
Time frame: 200 minute timepoint
Hypothetical Tobacco Demand
Time frame: 200 minute timepoint
Sustained Attention to Response Task
Time frame: 200 minute timepoint
Reaction time on the N-Back Cognitive test
Time frame: 200 minute timepoint
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2026.
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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.
Dustin C. Lee, PhD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Epidiolex in people with CBD and Stress, run by Johns Hopkins University 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 6 inclusion and 11 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: looking for participants now, as of the sponsor's last update on 10 Aug 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lauren Brogdon, MHS (410-550-6953, lmorri20@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Negative Affect as assessed by the Subjective State Scale (time frame: 20 minutes, 70 minutes, 120 minutes, 170 minutes, 190 minutes, 200 minutes, 220 minutes timepoints). The study lists 8 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 10 Aug 2026.