Cannabidiol (CBD) for reducing stress and nicotine withdrawal in daily cigarette smokers.

Pharmacological Effects of Cannabidiol on Responses to Stress and Nicotine Withdrawal

This trial tests whether a single dose of CBD can reduce stress responses and nicotine withdrawal symptoms in adults who smoke cigarettes daily.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 21 Years to 70 Years
• Sex: All
• Sponsor: Johns Hopkins University (other)
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT07001930 on ClinicalTrials.gov

What this trial studies

This is a double-blind, placebo-controlled, within-subject crossover trial in which each participant receives three acute oral doses of CBD (0 mg, 200 mg, 400 mg) across separate laboratory visits. Ninety adult daily cigarette smokers will complete three 5-hour lab sessions at least 72 hours apart, with biological and subjective measures collected before and after two challenges: an established psychological stress induction and a 24-hour nicotine abstinence challenge. Participants are randomized, stratified by sex and other tobacco-product use, to either continue nicotine ad libitum or abstain for 24 hours before sessions. The protocol includes one in-person medical screening and three pre-lab phone checks; total participation time for completers is about 2–3 weeks.

Who should consider this trial

Good fit: Ideal candidates are healthy adults aged 21–70 who smoke more than 5 cigarettes per day for at least 2 years, have CO > 8 ppm, are not trying to quit in the next 30 days, and are willing to attend three in-person lab sessions and potentially abstain from nicotine for 24 hours.

Not a fit: People planning to quit or reduce tobacco/cannabis use within 30 days, those meeting DSM-5 criteria for most other substance use disorders, pregnant people, or non-smokers are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, CBD could offer a non-addictive option to reduce stress and ease nicotine withdrawal symptoms during quit attempts or short-term abstinence.

How similar studies have performed: Some small clinical and preclinical studies suggest CBD can reduce cue-induced craving and anxiety, but clinical evidence for nicotine withdrawal is limited and mixed.

Eligibility criteria

Inclusion Criteria:

1. Healthy non-treatment seeking adults aged 21-70 (inclusive).
2. Use of \> 5 cigarettes per day for \> 2 years. (Use of other tobacco/nicotine products in addition to cigarettes will be acceptable).
3. Biological confirmation of cigarette use: have an expired carbon monoxide (CO) level \> 8 ppm.
4. Alcohol Use: \< 2 drinks/day on average (\< 14 drinks/week).
5. Sleep schedule: No graveyard or third shift work (i.e., participants must report a normal nighttime sleep schedule).
6. 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.

Exclusion Criteria:

1. Report current intention to reduce or quit cannabis or tobacco use within the next 30 days
2. Meet Diagnostic and Statistical Manual (DSM-5) criteria for a substance use disorder other than alcohol, cannabis, or nicotine
3. Test positive for illicit drugs other than cannabis
4. Positive breath alcohol test (\>.01 g/210L) at study admission
5. Have a current physical or mental illness or takes a medication judged by the study team to negatively impact participant safety or scientific integrity
6. Have a resting heart rate \>100, systolic blood pressure \>160mmHg or \<100mmHg, or diastolic blood pressure \>100mmHg or \<50mmHg at screening.
7. 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).
8. Are currently pregnant, planning to become pregnant in the next three months, or are currently breastfeeding
9. Have a history of clinically significant cardiac arrhythmias or vasospastic disease (e.g., Prinzmetal's angina, Raynaud's).
10. 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.
11. Are currently enrolled in another clinical trial or have received any drug as part of a research study within 30 days of study participation.

Where this trial is running

Baltimore, Maryland

• Behavioral Pharmacology Research Unit — Baltimore, Maryland, United States (RECRUITING)

Study contacts

• Principal investigator: Dustin C. Lee, PhD — Johns Hopkins University
• Study coordinator: Lauren Brogdon, MHS

Conditions: CBD, Stress, Nicotine Dependence, Tobacco Smoking, Nicotine