Cannabidiol for Cannabis Use Disorder

Overseen By L. Cinnamon Bidwell, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must not be taking: Antidepressants, Anxiogenics, Anti-epileptics, others

Disqualifiers: Illicit drugs, Alcohol, Nicotine, Psychotic disorders, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

120 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications. The trial excludes participants who are currently using psychotropic or hepatotoxic medications, anti-epileptic medications, and those with major interactions with Epidiolex. It also excludes those using strong or moderate CYP3A4 or CYP2C19 inhibitors or inducers.

What evidence supports the effectiveness of the drug Cannabidiol (CBD) for treating cannabis use disorder?

Research shows that Cannabidiol (CBD) has been studied for its potential to treat substance use disorders, including cannabis use disorder. Although specific data on cannabis use disorder is limited, CBD is known to help reduce withdrawal symptoms and drug cravings in other substance use disorders, which suggests it might be beneficial for cannabis use disorder as well. ^{1 2 3 4 5}

How is the drug Cannabidiol (CBD) unique for treating Cannabis Use Disorder?

Cannabidiol (CBD) is unique because it is a non-psychoactive component of cannabis that can reduce the effects of THC, the compound responsible for the 'high' in cannabis. Unlike other treatments, CBD is already approved for certain types of epilepsy, showing its potential for treating conditions related to cannabis use without causing a high. ^{4 5 6 7 8}

What is the purpose of this trial?

This study is a randomized, placebo-controlled, dose-ranging trial of plant-derived cannabidiol (CBD) among people who regularly use cannabis concentrates but are not trying to stop or cut down on their use. The main questions it aims to answer are whether CBD, relative to placebo, reduces cannabis concentrate use, the subjective effects of cannabis, or cannabis craving. Participants will take CBD (200 mg or 400 mg per day) or placebo for 4 weeks and will complete three visits during the study medication period, all conducted using a mobile laboratory.

Research Team

Joseph P Schacht, PhD

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

This trial is for individuals who regularly use cannabis concentrates but aren't looking to reduce their usage. Participants must be willing to take CBD or a placebo and attend three study visits using a mobile lab.

Inclusion Criteria

At least one episode of 3 consecutive days of cannabis abstinence with no experience of severe withdrawal symptoms in the last 90 days

At least two symptoms of a DSM-5 cannabis use disorder

Regular use (at least 4 times per week) of cannabis concentrates for the last year

Exclusion Criteria

Alcohol use on 3 or more days per week, and/or > 3 drinks per drinking day in the past 60 days

Daily nicotine use

Use of any illicit substance besides alcohol, nicotine, or cannabis in the past 60 days

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants take CBD (200 mg or 400 mg per day) or placebo for 4 weeks and complete three visits in a mobile laboratory

4 weeks

3 visits (mobile laboratory)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Broad Spectrum Cannabidiol (bsCBD)

Trial Overview The study tests if plant-derived CBD at doses of 200 mg or 400 mg per day can lower the use, effects, or craving of cannabis compared to a placebo. It's randomized and controlled, meaning participants are put into groups by chance.

Participant Groups

Group I: Broad Spectrum Cannabidiol (bsCBD) 400 mg Active Control 1 Intervention

bsCBD in a 400 mg dose will be used as described in the study arms.

Group II: Broad Spectrum Cannabidiol (bsCBD) 200 mg Active Control 1 Intervention

bsCBD in a 200 mg dose will be used as described in the study arms.

Group III: Placebo Placebo Group 1 Intervention

A medically inert placebo medication will be used as described in the study arms.

Broad Spectrum Cannabidiol (bsCBD) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Epidiolex for:

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

Approved in Canada as Sativex for:

• Symptomatic relief of spasticity in adult patients with multiple sclerosis
• Adjunctive analgesic treatment in adult patients with advanced cancer who experience moderate to severe pain

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

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 of 47 patients with refractory epilepsy, highly purified cannabidiol (CBD) was found to be effective in reducing seizure frequency, regardless of whether it was used with clobazam (CLB) or not.

Patients taking CBD alongside CLB had a significantly higher responder rate (more than 50% reduction in seizures) at the point of best seizure control within the first year, indicating that combining these treatments may enhance efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of cannabidiol in subjects with refractory epilepsy relative to concomitant use of clobazam. Savage, TE., Sourbron, J., Bruno, PL., 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]

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 45 children with treatment-resistant epilepsy, cannabidiol (CBD) significantly reduced major seizure frequency by 54-72% and increased seizure-free days by an average of 7.52 days over 36 months, demonstrating its efficacy as an adjunctive treatment.

CBD was well tolerated at doses up to 50 mg/kg/day, although children who increased their dose beyond 25 mg/kg/day initially reported more adverse events; however, the overall rate of adverse events decreased after transitioning to higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of cannabidiol (CBD) in children with treatment-resistant epilepsy: Results from a state-based expanded access program. Park, YD., Linder, DF., Pope, J., et al.[2021]

Cannabidiol (CBD) has strong evidence supporting its effectiveness in controlling refractory seizures, but for other conditions, the evidence is generally weak or very weak, highlighting the need for more research.

While CBD products vary widely in quality and consistency, non-FDA-approved products may not accurately reflect their labeled dosages or purity, and CBD can cause adverse effects such as somnolence and gastrointestinal issues, as well as potential drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Human Studies Assessing Cannabidiol's (CBD) Therapeutic Actions and Potential. White, CM.[2020]

In a survey of 239 young adults using cannabis, those who preferred CBD-dominant products were more likely to be female, use cannabis less frequently, and report using it primarily for medical reasons such as pain and psychological issues.

The study found a concerning association between CBD use and increased illicit drug use, suggesting that some individuals may be using CBD as a form of self-medication for underlying psychological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol (CBD) and other drug use among young adults who use cannabis in Los Angeles. Fedorova, EV., Wong, CF., Ataiants, J., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

2. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of cannabidiol in subjects with refractory epilepsy relative to concomitant use of clobazam. [2021]

3. 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]

4. Italy pubmed.ncbi.nlm.nih.gov

Pharmacology and legal status of cannabidiol. [2021]

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

Long-term efficacy and safety of cannabidiol (CBD) in children with treatment-resistant epilepsy: Results from a state-based expanded access program. [2021]

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

A Review of Human Studies Assessing Cannabidiol's (CBD) Therapeutic Actions and Potential. [2020]

8. Ireland pubmed.ncbi.nlm.nih.gov

Cannabidiol (CBD) and other drug use among young adults who use cannabis in Los Angeles. [2022]