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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether plant-derived cannabidiol (CBD) can help people who regularly use cannabis concentrates reduce their use, alter the effects of cannabis, or decrease cravings. Participants will take either 200 mg or 400 mg of CBD or a placebo daily for four weeks. The trial seeks individuals who use cannabis concentrates at least four times a week but aren't trying to quit or cut back. Participants should have recently abstained from cannabis for at least three days without severe withdrawal symptoms. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important findings.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that cannabidiol (CBD) has been studied for treating cannabis use disorder, demonstrating promising safety results. One study found that taking 400 mg or 800 mg of CBD was safe and more effective than a placebo in helping people reduce their cannabis use, suggesting that CBD is generally well-tolerated by the body.

Some parents of autistic children have used CBD to help with behavior issues. Although this use is not officially regulated, it indicates that people are using CBD without many reported problems.

In another review of clinical trials, CBD demonstrated various benefits and had some side effects. However, these side effects were usually mild, such as fatigue or changes in appetite. This suggests that while some people might experience minor issues, CBD is considered safe for most.

Overall, evidence suggests that CBD is safe for human use, with only minor side effects reported in clinical studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Broad Spectrum Cannabidiol (bsCBD) is unique because it offers a new approach to treating Cannabis Use Disorder, focusing on cannabidiol, a compound derived from cannabis plants. Unlike current treatments, which may include behavioral therapies or medications like naltrexone, bsCBD provides a non-intoxicating option that might help manage withdrawal symptoms and reduce cannabis use. Researchers are excited because cannabidiol is believed to interact with different pathways in the brain compared to traditional addiction treatments, potentially offering a fresh avenue for those who haven't found success with existing options.

What evidence suggests that this treatment might be an effective treatment for cannabis use disorder?

Research has shown that CBD can help people reduce cannabis use. In one study, 59% of participants reported a significant decrease in illegal cannabis use when taking CBD. Another study found that CBD reduced anxiety in cannabis users. Many cannabis users find CBD helpful in easing symptoms. These findings suggest that CBD might reduce cravings and the amount of cannabis used. Participants in this trial will receive either a 400 mg or 200 mg dose of Broad Spectrum Cannabidiol (bsCBD), or a placebo, to evaluate its effectiveness in treating cannabis use disorder. ^{1 6 7 8 9}

Who Is on the Research Team?

Joseph P Schacht, PhD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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) 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]

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]

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]

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 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]

Citations

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

Cannabidiol for the treatment of cannabis use disorder Compared to placebo, 800mg CBD reduced Beck Anxiety Inventory scores by -1.29 (95% Interval Estimate= -1.97, -0.62) during treatment and by -0.52 (95% Interval ...

2. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1356009/full

Cannabidiol usage, efficacy, and side effects Cannabis users were significantly more likely than non-users to admit that CBD was effective in relieving their symptoms (75% vs.61.5%, Table 4) ...

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/add.16745

Efficacy of cannabidiol alone or in combination with Δ‐9‐ ... We consistently observed positive effects of nabiximols on cannabis withdrawal and cravings across most SRs and particularly in those of high ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06107062

Longitudinal Outpatient Treatment for Cannabis Use Disorder Primary outcomes include reduction in THC exposure [via self-reported amount used and urine THC-COOH (standardized for creatinine)], CUD symptoms, and ...

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

A phase III multisite randomised controlled trial to compare the ... Of these, 59% (61/105) reported that their CBD use led to a large reduction in illegal cannabis consumption, 35% a moderate reduction, 6% no ...

6. 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 ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2772724624000878

Cannabidiol prescribing in the United States: An analysis ... We analyzed 4,127 people who were prescribed Epidiolex®. Epidiolex® recipients often do not have FDA-approved diagnostic indications for cannabidiol.

8. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00063/full

Cannabidiol Drugs Clinical Trial Outcomes and Adverse ... This review aims to present completed clinical trial data surrounding the medicinal benefits and potential side effects of the increasingly popular cannabidiol ...

9. liebertpub.com liebertpub.com/doi/full/10.1089/imr.2022.0081

A Randomized, Multi-Arm, Open-Label Waitlist-Controlled ... Results: Well-being, anxiety, sleep disturbance, and pain significantly improved among those assigned to take a CBD product relative to waitlist ...