Cannabidiol for Cannabis Use Disorder

Overseen By Ashlyn Summersett

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Medical University of South Carolina

Must not be taking: Antidepressants, Heart medications, others

Disqualifiers: Pregnancy, Severe substance use, others

Compensation: Varies

Number of Visits: Unknown

148 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The interface between cannabis use and stress is a particularly important focus for sex differences research in emerging adults. Given the dynamics at play in this critical stage when cannabis use is most prevalent, developmentally informed research is needed to guide tailored clinical interventions. This study will apply rigorous and innovative methods to elucidate sex differences in the nexus of cannabis use and stress among emerging adults with cannabis use disorder to guide the development of tailored treatments.

Will I have to stop taking my current medications?

You may need to stop taking certain medications if they have significant interactions with cannabidiol. The trial excludes participants taking specific medications like Citalopram, Digoxin, and others that could interact with the study drug.

Is cannabidiol (CBD) safe for human use?

Cannabidiol (CBD), particularly in the form of Epidiolex, has been studied for safety in humans and is generally well tolerated, with no serious adverse events reported in trials. It has a very low potential for abuse and is unlikely to cause physical dependence, but dose adjustments may be needed for people with liver issues. ^{1 2 3 4 5}

How is the drug Cannabidiol oral solution unique for treating cannabis use disorder?

Cannabidiol (CBD) oral solution, known as Epidiolex, is unique because it is a non-psychoactive component of cannabis that has shown potential in reducing withdrawal symptoms and cravings in cannabis use disorder without the risk of abuse or physical dependence, unlike other treatments that may have higher abuse potential. ^{2 3 4 6 7}

What data supports the effectiveness of the drug Cannabidiol oral solution for treating Cannabis Use Disorder?

Cannabidiol (CBD) has been approved for treating certain types of epilepsy, showing its potential as a therapeutic drug. While specific studies on CBD for Cannabis Use Disorder are limited, ongoing research is exploring its use for various substance use disorders, suggesting it may help reduce withdrawal symptoms and drug use. ^{2 3 4 7 8}

Who Is on the Research Team?

Kevin Gray, MD

Principal Investigator

Medical University of South Carolina

Are You a Good Fit for This Trial?

This trial is for young adults aged 18-25 with Cannabis Use Disorder (CUD), using cannabis at least five times a week. They must see cannabis as their main substance, have normal liver function tests, and agree to use birth control if applicable. Participants can't be pregnant or on certain medications that interact with CBD, and should not have severe mental health issues or other serious substance abuse problems.

Inclusion Criteria

Consent to random assignment to CBD versus placebo

Consent to alcohol abstinence for 12 hours prior to study visits, three days of cannabis abstinence as part of study procedures, and abstinence from all substances aside from cannabis, alcohol, and nicotine for the duration of the study

Meet DSM-5 criteria for CUD and report using cannabis at least five times weekly over the past month. Individuals may also meet criteria for other mild substance use disorders, but must identify cannabis as their primary substance

Exclusion Criteria

Current moderate or severe substance use disorder other than cannabis

I am not pregnant, nursing, or planning to become pregnant during the study.

Current unstable psychiatric or medical disorder that would interfere with safety, compromise data integrity, or preclude reliable participation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Abstinence

Participants undergo 3 days of reinforced abstinence with ecological momentary assessment monitoring of cannabis withdrawal and stress-related symptoms

3 days

Laboratory Session

Participants undergo a standardized laboratory stress induction paradigm with double-blind cannabidiol versus placebo dosing, and collection of self-report measures and biomarkers of stress reactivity

1 day

Follow-up

Ecological momentary assessment monitoring resumes as participants return to ad libitum cannabis use, testing associations between stress reactivity and time to resumption of use

10 days

What Are the Treatments Tested in This Trial?

Interventions

• Cannabidiol oral solution
• Placebo

Trial Overview The study is testing the effects of Cannabidiol (CBD) oral solution versus a placebo in managing stress related to cannabis use in emerging adults. It aims to understand sex differences in this context to develop better treatments for CUD.

How Is the Trial Designed?

Group I: cannabidiol 800 mg Experimental Treatment 1 Intervention

Cannabidiol 800 mg will be administered orally once in the laboratory prior to a stress induction paradigm.

Group II: placebo Placebo Group 1 Intervention

Placebo (formulated to appear identical to active condition) administered orally once in the laboratory prior to a stress induction paradigm.

Cannabidiol oral solution is already approved in United States, European Union, Canada 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 Epidyolex for:

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

Approved in Canada as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Published Research Related to This Trial

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]

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]

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]

Acute administration of THC significantly increases psychiatric symptoms, including psychotic and negative symptoms, with large effect sizes in healthy individuals, indicating potential risks associated with cannabis use.

There is limited evidence that CBD effectively reduces THC-induced psychiatric symptoms, suggesting that while THC can exacerbate mental health issues, CBD may not consistently mitigate these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychiatric symptoms caused by cannabis constituents: a systematic review and meta-analysis. Hindley, G., Beck, K., Borgan, F., et al.[2023]

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]

In a study involving 18 healthy adults, vaporized CBD and CBD-dominant cannabis produced noticeable subjective effects, such as increased enjoyment, while oral CBD did not show any significant effects compared to placebo.

Importantly, neither vaporized CBD nor CBD-dominant cannabis caused cognitive or psychomotor impairment, suggesting that these forms of CBD may be safer alternatives to THC-dominant products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamic effects of vaporized and oral cannabidiol (CBD) and vaporized CBD-dominant cannabis in infrequent cannabis users. Spindle, TR., Cone, EJ., Goffi, E., et al.[2022]

A study involving 30 subjects with varying degrees of hepatic impairment showed that a single 200-mg dose of cannabidiol (CBD) was rapidly absorbed, with the time to maximum plasma concentration ranging from 2 to 2.8 hours across all groups.

Significantly increased exposure to CBD was observed in subjects with moderate (2.45 times) and severe (5.15 times) hepatic impairment compared to those with normal liver function, indicating that dose adjustments are necessary for these patients, while CBD was well tolerated with no serious adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1, Open-Label, Parallel-Group, Single-Dose Trial of the Pharmacokinetics and Safety of Cannabidiol (CBD) in Subjects With Mild to Severe Hepatic Impairment. Taylor, L., Crockett, J., Tayo, B., et al.[2023]

Current treatments for cannabis use disorders are not very effective, highlighting a significant health issue worldwide.

Preliminary evidence suggests that cannabidiol (CBD) may help reduce cannabis use, withdrawal symptoms, and cravings, but more extensive trials with larger patient groups and longer durations are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol pharmacotherapy for delta-9-tetrahidrocannabinol dependence Pavlovsky, F., Groisman, R., Hurtado, AK., et al.[2022]

Citations

1. 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]

2. Italy pubmed.ncbi.nlm.nih.gov

Pharmacology and legal status of cannabidiol. [2021]

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

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

4. England pubmed.ncbi.nlm.nih.gov

Psychiatric symptoms caused by cannabis constituents: a systematic review and meta-analysis. [2023]

5. 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]

6. Ireland pubmed.ncbi.nlm.nih.gov

Pharmacodynamic effects of vaporized and oral cannabidiol (CBD) and vaporized CBD-dominant cannabis in infrequent cannabis users. [2022]

7. England pubmed.ncbi.nlm.nih.gov

A Phase 1, Open-Label, Parallel-Group, Single-Dose Trial of the Pharmacokinetics and Safety of Cannabidiol (CBD) in Subjects With Mild to Severe Hepatic Impairment. [2023]

8. Argentina pubmed.ncbi.nlm.nih.gov

Cannabidiol pharmacotherapy for delta-9-tetrahidrocannabinol dependence [2022]