Cannabidiol for Cannabis Use Disorder

Overseen By Kristen M Raymond, BA

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

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

Disqualifiers: Psychotic disorders, Bipolar, Major depression, others

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

Compensation: Varies

Number of Visits: 5

Duration: 8 weeks

200 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators will study the harm-reducing effect of hemp-derived CBD in non-treatment-seeking emerging adults who use cannabis regularly. The study will use a novel naturalistic cannabis administration approach, which examines ecologically valid cannabis use utilizing a mobile lab setting to assess the effects of the cannabis products the participants regularly use. The investigators will recruit a sample of emerging adults, half of whom primarily use flower products and half of whom primarily use concentrate products. Individuals will be randomly assigned to hemp-derived CBD or placebo.

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 data supports the effectiveness of the drug Cannabidiol for Cannabis Use Disorder?

Research shows that Cannabidiol (CBD) has potential therapeutic uses for substance use disorders, including cannabis use disorder, with ongoing studies improving outcome measures and biomarkers to predict treatment response. Additionally, CBD is approved for treating seizures in epilepsy, indicating its safety and therapeutic potential. ^{1 2 3 4 5}

Is cannabidiol (CBD) generally safe for human use?

Cannabidiol (CBD) is generally considered safe for human use, with studies showing it has very low abuse potential and is unlikely to cause 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. ^{4 6 7 8 9}

How is the drug Broad Spectrum Cannabidiol (bsCBD) unique for treating cannabis use disorder?

Broad Spectrum Cannabidiol (bsCBD) is unique for treating cannabis use disorder because it is derived from the cannabis plant but does not have the mind-altering effects associated with THC, the main psychoactive component of cannabis. Unlike other treatments, bsCBD has a very low potential for abuse and physical dependence, making it a safer option for individuals with substance use disorders. ^{1 4 6 7 10}

Research Team

Christian J Hopfer, MD

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

This trial is for young adults who regularly use cannabis but aren't seeking treatment. Participants must be users of either flower or concentrate cannabis products and will be randomly assigned to receive either hemp-derived CBD or a placebo.

Inclusion Criteria

Currently not seeking to cut down or stop cannabis use

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

Must have used cannabis flower or concentrates at least five days per week for the past year

Exclusion Criteria

I am currently taking medication that strongly affects liver enzyme CYP2C19.

I am not pregnant nor trying to become pregnant.

I am currently breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomly assigned to receive either hemp-derived CBD or placebo over 8 weeks to assess the harm-reducing effects on cannabis use

8 weeks

Visits at baseline, Week 4, and Week 8

Follow-up

Participants are monitored for the persistence of treatment effects on cannabis use, mood, and cognitive function

4 weeks

1 visit (in-person) at 12 weeks

Treatment Details

Interventions

• Broad Spectrum Cannabidiol (bsCBD)
• Placebo

Trial Overview The study is testing the effects of Broad Spectrum Cannabidiol (bsCBD) at a dose of 400 mg compared to a placebo in reducing harm from regular cannabis use. The research involves using a mobile lab to monitor real-world consumption patterns.

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: 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 phase 2a trial involving 82 participants, cannabidiol (CBD) at doses of 400 mg and 800 mg was found to be safe and significantly more effective than placebo in reducing cannabis use, as measured by lower THC-COOH levels and increased days of abstinence.

The study eliminated the 200 mg dose as ineffective, demonstrating that higher doses of CBD (400 mg and 800 mg) are more beneficial for individuals with cannabis use disorder, with no severe adverse events reported during the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol for the treatment of cannabis use disorder: a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial. Freeman, TP., Hindocha, C., Baio, G., 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]

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]

High doses of CBD can be effectively vaporized, with a maximum of 200 mg yielding about 40% availability in the vapor phase, which is significant for achieving faster therapeutic effects.

The study found that the vaporization efficiency of THC and CBD is dynamic and dose-dependent, meaning that the presence of one cannabinoid can affect the availability of the other, which is important for optimizing their combined therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A protocol for the delivery of cannabidiol (CBD) and combined CBD and ∆9-tetrahydrocannabinol (THC) by vaporisation. Solowij, N., Broyd, SJ., van Hell, HH., 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]

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 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]

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]

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]

References

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

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

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

Cannabidiol for the treatment of cannabis use disorder: a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial. [2021]

3. England pubmed.ncbi.nlm.nih.gov

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

4. 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]

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

A protocol for the delivery of cannabidiol (CBD) and combined CBD and ∆9-tetrahydrocannabinol (THC) by vaporisation. [2022]

6. 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]

7. Italy pubmed.ncbi.nlm.nih.gov

Pharmacology and legal status of cannabidiol. [2021]

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

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

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

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

10. Netherlands pubmed.ncbi.nlm.nih.gov

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