Cannabidiol for Tobacco Addiction

Overseen By Edythe D London, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Los Angeles

Must not be taking: Opioids, Antivirals, CYP3A4 inducers

Disqualifiers: Alcohol dependence, Schizophrenia, Bipolar, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 8 weeks

120 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this research is to evaluate the efficacy of cannabidiol (CBD) in reducing cigarette smoking. Although there are safe and effective treatments for smoking cessation, not everyone who attempts smoking cessation is successful, even with these treatments. Relapse rates are high, leaving a need for new approaches. Despite justification to evaluate CBD for this indication, human research on the topic is scant. Larger, more extended studies are warranted and essential. The investigators will recruit participants from CRI-Help, Inc., a substance abuse treatment program in North Hollywood, where residents who indicate the desire to stop smoking are prohibited from using other cannabis products which would affect recruitment. The aims of this study are: 1. Evaluate the effects of CBD on changes in cigarette use throughout and following the trial. 2. Exploratory Aims. Measure plasma concentrations of CBD, N-arachidonoyl-ethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG) throughout the trial. Participants who meet eligibility criteria will take part in a 56-day treatment phase during which they receive the study medication under supervision (CBD or placebo twice daily) and complete questionnaires on side effects, withdrawal, craving and mood symptoms. Blood, breath, and urine tests will also be performed throughout the study. Participants who complete the treatment will also be assessed at 1-month and 3-month follow up visits.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications that interact with CBD, such as strong inducers of CYP3A4 or CYP2C19, and substrates of UGT1A9, UGT2B7, CYP2B6, CYP2C19. If you are on these medications, you may need to stop them to participate.

What data supports the effectiveness of the drug Cannabidiol (CBD) for tobacco addiction?

Research shows that CBD can help reduce cigarette consumption by about 40% in smokers who want to quit, and it may also lessen withdrawal symptoms and anxiety during nicotine abstinence. These findings suggest that CBD could be a promising option for those trying to quit smoking. ^{1 2 3 4 5}

Is cannabidiol (CBD) safe for human use?

Cannabidiol (CBD) is generally considered safe for human use, with studies showing it has a low potential for abuse and physical dependence. However, some users may experience side effects like sleep disturbances, sedation, and potential interactions with other medications, so it's important to monitor for these and consult with a healthcare provider. ^{1 2 6 7 8}

How does the drug Cannabidiol (CBD) differ from other treatments for tobacco addiction?

Cannabidiol (CBD) is unique because it is derived from the cannabis plant and does not have the addictive or psychoactive effects associated with other substances. Unlike traditional treatments for tobacco addiction, CBD may help reduce withdrawal symptoms and anxiety without the risk of abuse or dependence. ^{2 4 6 9 10}

Research Team

Edythe D London, PhD

Principal Investigator

University of California, Los Angeles

Eligibility Criteria

This trial is for individuals seeking to quit smoking and are currently in a substance abuse treatment program. Participants must desire to stop smoking, be willing to take CBD or placebo twice daily, and complete various tests and questionnaires. They cannot use other cannabis products during the study.

Inclusion Criteria

All racial and ethnic groups are included, with anticipated percentages aligning with recent studies

Participants will not be recruited from the general population due to potential confounding effects of cannabis use in the greater Los Angeles area

I am 18-65, smoke cigarettes, and am in treatment at Cri-Help in North Hollywood.

Exclusion Criteria

I have been diagnosed with schizophrenia, bipolar I, or another psychotic disorder, or I've had thoughts of or attempted suicide in the past year.

I am not on medication that affects certain liver enzymes.

Pregnancy and/or lactation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline

Baseline assessments including blood plasma cotinine assay and self-reports of smoking-related behaviors

1 day

1 visit (in-person)

Treatment

Participants receive CBD or placebo for 56 days with daily and weekly assessments

8 weeks

Daily assessments, weekly in-person visits

Follow-up

Participants are monitored for safety and effectiveness after treatment with assessments at 1 and 3 months

16 weeks

2 visits (in-person)

Treatment Details

Interventions

• Cannabidiol (CBD)

Trial Overview The study is testing whether cannabidiol (CBD) can help reduce cigarette use. Participants will receive either a placebo or CBD at doses of 400 mg or 800 mg under supervision for 56 days, with follow-up visits at one and three months after treatment ends.

Participant Groups

Group I: Cannabidiol (CBD) 800 mg Active Control 1 Intervention

Sixty participants who meet all eligibility criteria will be randomized to receive CBD (ATL5; Ananda Scientific) at a dose of 800 mg.

Group II: Placebo Placebo Group 1 Intervention

Sixty participants who meet all eligibility criteria will be randomized to receive placebo.

Cannabidiol (CBD) is already approved in United States, European Union for the following indications:

Approved in United States as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in European Union as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Findings from Research

In a pilot study involving 24 smokers, those using cannabidiol (CBD) inhalers reduced their cigarette consumption by approximately 40% over one week, while the placebo group showed no change.

The positive effects of CBD on reducing smoking urges appeared to persist even after the treatment period, suggesting its potential as a therapeutic option for nicotine addiction that deserves further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol reduces cigarette consumption in tobacco smokers: preliminary findings. Morgan, CJ., Das, RK., Joye, A., et al.[2022]

Cannabidiol (CBD) has shown promise in preclinical and clinical studies for its ability to inhibit the rewarding effects of addictive substances like cocaine, methamphetamine, and opioids, suggesting its potential as a treatment for substance use disorders.

Despite the encouraging evidence supporting CBD's efficacy in reducing drug addiction behaviors, further research is necessary to fully establish its therapeutic role in addiction treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol and substance use disorder: Dream or reality. Karimi-Haghighi, S., Razavi, Y., Iezzi, D., et al.[2023]

A review of 207 studies identified only 3 randomized clinical trials (RCTs) specifically focused on using cannabidiol (CBD) for cannabis use disorder, highlighting a significant gap in research for CBD's efficacy in treating substance use disorders.

Ongoing trials are enhancing outcome measures by incorporating peripheral biomarkers from the endocannabinoid system, which may help predict how well individuals respond to CBD treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Trials of Cannabidiol for Substance Use Disorders: Outcome Measures, Surrogate Endpoints, and Biomarkers. Morel, A., Lebard, P., Dereux, A., et al.[2021]

In a study involving 20 daily nicotine-containing e-cigarette users, oral administration of 320 mg of CBD significantly reduced self-reported nicotine withdrawal symptoms and anxiety after a 4-hour abstinence period.

These promising results suggest that CBD could be a helpful aid for individuals trying to quit e-cigarettes, indicating further research on its effectiveness in cessation efforts is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol Reduces Nicotine Withdrawal Severity and State Anxiety During an Acute E-cigarette Abstinence Period: A Novel, Open-Label Study. Gournay, LR., Petry, J., Bilsky, S., et al.[2023]

In a study involving 30 dependent cigarette smokers, a single 800 mg dose of cannabidiol (CBD) significantly reduced the attentional bias and pleasantness ratings towards cigarette-related cues after overnight abstinence, compared to a placebo.

CBD did not affect craving or withdrawal symptoms, indicating it may help reduce the appeal of smoking cues without causing side effects, making it a potential aid for smoking cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol reverses attentional bias to cigarette cues in a human experimental model of tobacco withdrawal. Hindocha, C., Freeman, TP., Grabski, M., et al.[2021]

Cannabidiol (CBD), specifically in its oral formulation Epidiolex, has been shown to have very low abuse potential and is unlikely to cause physical dependence, as demonstrated by studies in rats and nonhuman primates that showed no significant self-administration or withdrawal signs after chronic treatment.

The pharmacokinetic studies confirmed that the doses used in the experiments resulted in therapeutically relevant plasma levels, supporting the safety and efficacy of CBD for treating seizures in severe forms of epilepsy without the risks associated with addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Assessment of the Abuse Potential of Purified Botanical Cannabidiol: Self-Administration, Drug Discrimination, and Physical Dependence. Gray, RA., Heal, DJ., Maguire, DR., et al.[2022]

Nearly 50% of CBD users experienced adverse drug events (ADEs), with common issues including elevated liver enzymes, sedation, and sleep disturbances, indicating a significant safety concern.

CBD has a high potential for drug-drug interactions (DDIs) due to its effects on drug metabolism, particularly with enzymes like CYP3A4 and CYP2C19, suggesting that careful monitoring and dose adjustments may be necessary for patients on multiple medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. Brown, JD., Winterstein, AG.[2020]

A single oral dose of 750 mg of cannabidiol (CBD) showed significantly increased exposure when taken with a high-fat/calorie meal, with a 3.8-fold increase in overall exposure (AUC0-∞) and a 5.2-fold increase in maximum concentration (Cmax) compared to fasting.

CBD was well-tolerated with no severe adverse events reported, indicating its safety in healthy adults, while its absorption was also enhanced by low-fat meals, whole milk, and alcohol, albeit to a lesser extent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1, randomized, pharmacokinetic trial of the effect of different meal compositions, whole milk, and alcohol on cannabidiol exposure and safety in healthy subjects. Crockett, J., Critchley, D., Tayo, B., et al.[2021]

Epidiolex, the only FDA-approved CBD-based drug, has been studied for its medicinal benefits and potential side effects across various clinical trials, focusing on both physiological and neurological conditions.

The review highlights that the outcomes of these trials can vary significantly based on the funding source, which may influence the reported efficacy and safety of Epidiolex and other CBD formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol Drugs Clinical Trial Outcomes and Adverse Effects. Pauli, CS., Conroy, M., Vanden Heuvel, BD., et al.[2020]

Cannabidiol (CBD) is a non-psychoactive compound from cannabis that can counteract the psychotropic effects of THC and has gained popularity in various therapeutic products, especially after the FDA approved Epidiolex® for treating severe epilepsy in children.

Despite its therapeutic potential, there is a lack of consistent international regulations governing the marketing and authorization of CBD products, which raises concerns about product safety and efficacy for consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology and legal status of cannabidiol. Brunetti, P., Lo Faro, AF., Pirani, F., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Cannabidiol reduces cigarette consumption in tobacco smokers: preliminary findings. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Cannabidiol and substance use disorder: Dream or reality. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Trials of Cannabidiol for Substance Use Disorders: Outcome Measures, Surrogate Endpoints, and Biomarkers. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Cannabidiol Reduces Nicotine Withdrawal Severity and State Anxiety During an Acute E-cigarette Abstinence Period: A Novel, Open-Label Study. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Cannabidiol reverses attentional bias to cigarette cues in a human experimental model of tobacco withdrawal. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Preclinical Assessment of the Abuse Potential of Purified Botanical Cannabidiol: Self-Administration, Drug Discrimination, and Physical Dependence. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

A phase 1, randomized, pharmacokinetic trial of the effect of different meal compositions, whole milk, and alcohol on cannabidiol exposure and safety in healthy subjects. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Cannabidiol Drugs Clinical Trial Outcomes and Adverse Effects. [2020]

10. Italy pubmed.ncbi.nlm.nih.gov

Pharmacology and legal status of cannabidiol. [2021]