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?

This trial aims to explore how cannabidiol (CBD), a compound from the cannabis plant, affects stress levels in young adults with cannabis use disorder (CUD). Researchers seek to understand the differences in stress and cannabis use between males and females. Participants will receive either a CBD oral solution or a placebo to compare results. Those who use cannabis at least five times weekly and consider it their main substance may find this trial suitable. As a Phase 1 and Phase 2 trial, the study focuses on understanding how CBD works in people and measuring its effectiveness in a smaller group, offering participants a chance to contribute to groundbreaking research.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that cannabidiol (CBD), the treatment being tested in this trial, is generally safe. The FDA has approved CBD for treating certain seizure disorders, indicating it is usually well-tolerated.

Some studies report common side effects such as sleepiness, reduced appetite, or diarrhea. Increases in liver enzymes, which help the liver function properly, have also been noted. These side effects have appeared in more than 10% of people taking the medication, but they are usually mild to moderate.

Overall, many people have used CBD safely, but monitoring for any side effects remains important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cannabis use disorder?

Researchers are excited about cannabidiol for cannabis use disorder because it offers a novel approach compared to traditional treatments like behavioral therapies and medications that target withdrawal symptoms. Unlike these conventional options, cannabidiol (CBD) is derived from cannabis itself but does not produce a high, which makes it potentially effective without the risk of addiction. Additionally, CBD may work by reducing anxiety and stress, which are often triggers for cannabis use. This unique mechanism of action sets it apart and could provide a promising alternative for those struggling to reduce or quit cannabis use.

What evidence suggests that this trial's treatments could be effective for cannabis use disorder?

This trial will compare the effects of cannabidiol (CBD) with a placebo for treating cannabis use disorder. Research has shown that CBD may help reduce cannabis use. In one study, taking either 400 mg or 800 mg of CBD reduced cannabis use during treatment. Another study found that CBD significantly decreased cannabis consumption, with some participants cutting their use by at least half. Although more research is needed, these findings suggest that CBD could be a helpful option for reducing cannabis use. Participants in this trial will receive either 800 mg of CBD or a placebo to further evaluate its effectiveness. ^{6 7 8 9 10}

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

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

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

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

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7116091/

Cannabidiol for the treatment of cannabis use disorder Both 400mg CBD and 800mg CBD exceeded primary endpoint criteria (Pr = 0.9) for reducing cannabis use during treatment, with converging evidence from biological ...

2. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.899221/full

Efficiency of Inhaled Cannabidiol in Cannabis Use Disorder The primary endpoint was a reduction of at least 50% in reported cannabis consumption, measured in terms of number of joints per day after 12 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S092012112300205X

Caregiver-reported outcomes with real-world use of ... Overall, 93% of caregivers reported planning to continue CBD treatment, primarily because of reduced seizure burden but also because of improvements in ...

4. bmcpsychiatry.biomedcentral.com bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-024-05616-3

A phase III multisite randomised controlled trial to compare the ... Results from a Phase IIa randomised clinical trial suggest that treatment with CBD for four weeks reduced non-prescribed cannabis use in people ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04517799

Trial of Cannabidiol to Treat Severe Behavior Problems in ... Parents of autistic children have been using CBD products in an unregulated fashion with unknown dosing with anecdotal reports of improved behavior. This study ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/210365lbl.pdf

EPIDIOLEX (cannabidiol) oral solution - accessdata.fda.gov most common adversereactions (10% or more for EPIDIOLEX and greater than placebo) are: somnolence; decreased appetite; diarrhea; transaminase elevations; ...

7. epidiolexhcp.com epidiolexhcp.com/resources/frequently-asked-questions

Frequently Asked Questions | EPIDIOLEX® (cannabidiol) EPIDIOLEX is the first and only FDA-approved prescription cannabidiol and the only cannabidiol formulation demonstrated in well-controlled clinical trials to ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/cannabidiol-oral-route/description/drg-20443842

Cannabidiol (oral route) - Side effects & dosage Cannabidiol is used to treat seizures in patients with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex.

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1876201823003854

Adverse events of epidiolex: A real-world drug safety ... Epidiolex mainly includes drowsiness, reduced appetite, diarrhea, increased transaminases, fatigue, rash, sleep disorders, and infections.

10. epidiolex.com epidiolex.com/

EPIDIOLEX® (cannabidiol) - FDA-Approved Seizure ... EPIDIOLEX® (cannabidiol) is the only FDA-approved CBD medication for seizures associated with LennoxGastaut Syndrome, Dravet complex, or tuberous sclerosis ...