Cannabidiol for Cannabis Use Disorder

(LOTUS Trial)

Overseen By Jonathan Lisano, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Boulder

Must not be taking: Psychotropics, Anti-epileptics, CYP inducers, others

Disqualifiers: Psychotic disorders, Bipolar, Cardiovascular, others

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

Compensation: Varies

Number of Visits: 17

Duration: 8 weeks

165 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if hemp-derived cannabidiol (CBD), with or without THC, can help reduce cannabis use and symptoms of cannabis use disorder (CUD) in adults. Participants will receive either full spectrum CBD, broad spectrum CBD, or a placebo while undergoing psychotherapy for five weeks. Ideal candidates use cannabis concentrates at least four times a week, have CUD, and wish to reduce or stop cannabis use. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires participants to stop using certain medications, including psychotropics (medications affecting mood or behavior), anti-epileptic medications, and those with major interactions with Epidiolex. If you are taking any of these, you may need to stop before joining the trial.

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

Research has shown that cannabidiol (CBD), used in this trial, is generally safe. In one study, doses of 400mg and 800mg of CBD were well-tolerated and reduced cannabis use more effectively than a placebo. Participants did not report any serious side effects.

For both broad spectrum (bsCBD) and full spectrum CBD (fsCBD), common side effects include fatigue, diarrhea, and changes in appetite or weight. These side effects are usually mild and temporary. Another study found that fsCBD had a similar safety profile to bsCBD but was more effective at reducing cravings.

While CBD is often well-tolerated, limited safety data from the FDA exists. Consider possible side effects and consult a healthcare provider if there are any concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Cannabidiol (CBD) for treating Cannabis Use Disorder because it offers a new approach by leveraging its properties without the psychoactive effects of THC. Unlike traditional treatments that often involve behavioral therapy and sometimes medications like N-acetylcysteine, CBD provides a potentially natural alternative that targets the endocannabinoid system directly. The trial investigates two types of CBD: broad spectrum (bsCBD), which contains multiple cannabinoids excluding THC, and full spectrum (fsCBD), which includes all cannabinoids in cannabis, offering different profiles that might benefit patients in unique ways. These features could lead to more personalized and effective treatments for individuals struggling with cannabis dependence.

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

Research has shown that cannabidiol (CBD) may help reduce cannabis use and manage symptoms of cannabis use disorder (CUD). In this trial, participants will receive either full spectrum CBD (fsCBD) or broad spectrum CBD (bsCBD) in separate treatment arms. One study found that fsCBD was more effective than a placebo in helping people reduce cannabis use. Another study found that CBD improved mental health and cognitive skills in cannabis users. Participants using bsCBD reported better sleep and overall well-being. Both types of CBD are considered safe and effective for managing cannabis cravings and withdrawal symptoms. These findings suggest that CBD could support those who want to reduce or stop using cannabis. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults who regularly use cannabis concentrates (at least 4 times a week) for the past year, have at least moderate Cannabis Use Disorder according to DSM5, and are looking to reduce or stop their cannabis use.

Inclusion Criteria

You have used cannabis concentrates at least four times per week for a minimum of one year.

You exhibit the requisite signs and symptoms of a moderate-level Cannabis Use Disorder according to DSM5 criteria.

You are striving to reduce or cease cannabis consumption.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either full spectrum CBD, broad spectrum CBD, or placebo for 8 weeks, along with a five-session psychotherapy treatment for CUD.

8 weeks

5 psychotherapy sessions

Follow-up

Participants are monitored for changes in THC use, CUD symptoms, and withdrawal symptoms through telehealth follow-ups.

8 weeks

Telehealth follow-ups at 12 and 16 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cannabidiol - bsCBD
• Cannabidiol - fsCBD
• Psychotherapy Treatment

Trial Overview

The study compares hemp-derived CBD with THC (fsCBD), without THC (bsCBD), and placebo in reducing cannabis use and symptoms of CUD. Participants will also receive five weeks of psychotherapy and undergo various assessments over an 8-week period with follow-ups.

How Is the Trial Designed?

Group I: 400mg Full Spectrum Cannabidiol (fsCBD) Experimental Treatment 1 Intervention

Group II: 400mg Broad Spectrum Cannabidiol (bsCBD) Experimental Treatment 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

Cannabidiol - bsCBD is already approved in United States, European Union 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

Who Is Running the Clinical Trial?

University of Colorado, Boulder

Lead Sponsor

Trials

128

Recruited

29,600+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

In a study involving 78 adults with moderate to severe cocaine use disorder, daily administration of 800 mg of cannabidiol (CBD) did not significantly reduce drug-cue-induced cravings compared to a placebo.

The study also found no difference in the time to relapse between participants taking CBD and those on placebo, indicating that CBD may not be an effective treatment for preventing relapse in cocaine use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol as a treatment for craving and relapse in individuals with cocaine use disorder: a randomized placebo-controlled trial. Mongeau-Pérusse, V., Brissette, S., Bruneau, J., et al.[2021]

11% of surveyed cannabis users reported using CBD primarily to reduce their cannabis consumption, with significant associations found for those who also smoke tobacco or drink alcohol.

Among those using CBD for reduction, 58.7% reported a large decrease in cannabis use, particularly linked to non-daily cannabis use and daily CBD consumption, with many citing reduced withdrawal symptoms as a key benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A "Good" Smoke? The Off-Label Use of Cannabidiol to Reduce Cannabis Use. Fortin, D., Di Beo, V., Massin, S., et al.[2022]

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]

Serious suspected adverse reactions (SARs) to unlicensed cannabidiol (CBD) products were found to be 18.9% of all adverse events, with a higher frequency in men and adults, indicating a need for careful monitoring of its use.

The most common adverse effects associated with unlicensed CBD included mental disorders, hepatic disorders, and worsening of pre-existing epilepsy, particularly in patients also taking antiepileptic medications like clobazam and valproic acid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacovigilance of unlicensed cannabidiol in European countries. Calapai, F., Esposito, E., Ammendolia, I., et al.[2023]

In a study involving 20 patients with severe behavioral and psychological symptoms of dementia (BPSD), those treated with 3% cannabidiol (CBD) showed significant improvement compared to those receiving usual medical treatment over a six-month period.

The results suggest that CBD may be a safer and more effective option for managing BPSD, indicating a need for larger randomized clinical trials to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Cannabidiol 3% on Neuropsychiatric Symptoms in Dementia - Six-Month Follow-Up. Alexandri, F., Papadopoulou, L., Tsolaki, A., et al.[2023]

A systematic review of 4186 studies on cannabidiol (CBD) revealed that most research focuses on neurological outcomes, with significant adverse events reported in this area, highlighting the need for careful assessment of CBD's safety.

There is a notable gap in research regarding the reproductive and developmental toxicity of CBD, suggesting that future studies should prioritize these areas to establish safe intake levels for consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol Safety Data: A Systematic Mapping Study. Henderson, RG., Franke, KS., Payne, LE., et al.[2023]

A systematic review of 51 clinical studies indicates that cannabidiol (CBD) is generally well tolerated in humans, with most adverse events (AEs) being mild to moderate, such as diarrhea and sedation.

While serious AEs are rare, they can occur, particularly when CBD is taken with other medications, highlighting the need for careful monitoring of drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on Cannabidiol Clinical Toxicity and Adverse Effects: A Systematic Review. Madeo, G., Kapoor, A., Giorgetti, R., et al.[2023]

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]

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 involving 20 patients with cannabis use disorder, 30% of participants reduced their daily cannabis consumption by at least 50% after 12 weeks of using inhaled CBD, indicating potential efficacy in treating this condition.

The study suggests that inhalation of CBD allows users to adjust their dosage based on withdrawal symptoms and cravings, highlighting a flexible and user-friendly method of administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficiency of Inhaled Cannabidiol in Cannabis Use Disorder: The Pilot Study Cannavap. Cleirec, G., Desmier, E., Lacatus, C., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

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

Cannabidiol for the treatment of cannabis use disorder

A 10-week open-label trial found that CBD administration was associated with improvements in psychological wellbeing and cognition in regular cannabis users who ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10938386/

Cannabidiol usage, efficacy, and side effects

The top five reasons for using CBD were self-reported stress (65.3%), sleep problems (51.7%), overall improvement in well-being (52.5%), ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05613608

NCT05613608 | Alcohol Use Disorder and Cannabidiol

The current study will test the hypothesis that a moderate dose of CBD leads to a reduction in alcohol consumption, alcohol craving, peripheral markers of ...

4.

health.harvard.edu

health.harvard.edu/blog/cannabidiol-cbd-what-we-know-and-what-we-dont-201808242496

Cannabidiol (CBD): What we know and what we don't

We need more research, but CBD is proving to be a helpful, relatively nontoxic option for managing anxiety, insomnia, and chronic pain.

5.

bmcpsychiatry.biomedcentral.com

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

A phase III multisite randomised controlled trial to compare the ...

This study examines the efficacy, safety and quality of life of longer-term CBD treatment for patients with moderate-to-severe CUD.

6.

library.samhsa.gov

library.samhsa.gov/sites/default/files/pep22-06-04-003.pdf

Cannabidiol (CBD) – Potential Harms, Side Effects, and ...

Non-FDA-approved CBD products lack safety standards, may have contaminants, and may contain THC. Limited evidence supports their safety.

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5569602/

An Update on Safety and Side Effects of Cannabidiol

The most commonly reported side effects were tiredness, diarrhea, and changes of appetite/weight. In comparison with other drugs, used for the treatment of ...

8.

frontiersin.org

frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2025.1516351/full

A preliminary randomized trial of the safety, tolerability, and ...

In this pilot study, safety profiles fsCBD and bsCBD were similar, and fsCBD was associated with a greater reduction in craving and AUD symptoms relative to ...

9.

cdc.gov

cdc.gov/cannabis/about/about-cbd.html

About CBD | Cannabis and Public Health

Using CBD products is not risk free. The FDA has limited data on CBD safety. Please consider these possible side effects and risks before using ...