Dronabinol + Epidiolex for Opioid Use Disorder

(DEMURE Trial)

Overseen By Deepika Slawek, MD, MPH, MS

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Montefiore Medical Center

Must be taking: Buprenorphine

Must not be taking: Cannabinoids

Disqualifiers: Liver disease, Pregnancy, Cardiac disease, Psychotic disorder, Alcohol use disorder, others

Stay on Your Current Meds You can continue your current medications while participating

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether two FDA-approved cannabis-based medications, dronabinol (synthetic THC) and Epidiolex (CBD), can help individuals new to buprenorphine treatment for opioid use disorder (OUD) remain in treatment and reduce opioid use. The study focuses on those who began buprenorphine within the last 21 days and remain at risk of returning to opioid use. Suitable candidates for this trial include individuals who have recently started buprenorphine, have used cannabis after age 18, and have experienced recent opioid-related issues or symptoms. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment for OUD.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you must not have cannabinoids in your system, and certain medical conditions may prevent participation.

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

A previous study showed that dronabinol at doses of 20 mg and higher increased heart rate in healthy adults during opioid withdrawal, raising concerns about its safety in this context. However, the trial carefully doses treatments to minimize potential side effects, gradually increasing doses over time. Both dronabinol and Epidiolex have FDA approval for other uses, indicating they have passed safety checks for those conditions. This suggests they are generally well-tolerated, but monitoring for side effects, especially related to heart rate with dronabinol, remains important. Participants should consult their doctor if they have concerns about joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Dronabinol and Epidiolex for opioid use disorder because it offers a novel approach by targeting the endocannabinoid system. Unlike traditional treatments like methadone and buprenorphine, which mainly focus on opioid receptors, this combination uses THC (from Dronabinol) and CBD (from Epidiolex) to potentially modulate mood and reduce cravings via different pathways. This unique mechanism of action could provide an alternative for those who do not respond well to existing therapies, offering a new hope in managing opioid dependency.

What evidence suggests that the combination of dronabinol and Epidiolex could be effective for opioid use disorder?

This trial will evaluate the combination of dronabinol (a synthetic form of THC) and Epidiolex (CBD) for opioid use disorder (OUD). Research has shown that THC and CBD can ease symptoms of multiple sclerosis, such as tremors and muscle stiffness, suggesting they might calm the nervous system. Studies have also found that CBD can control epilepsy, indicating it might stabilize mood and behavior. Combining THC with CBD could reduce side effects and improve treatment outcomes. This trial studies these substances as a way to help individuals remain in buprenorphine treatment and reduce opioid use if they have OUD. ^{1 2 6 7 8}

Who Is on the Research Team?

Deepika Slawek, MD, MPH, MS

Principal Investigator

Montefiore Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with opioid use disorder who have started buprenorphine treatment. It's designed to help those at risk of overdose or other complications early in their recovery process.

Inclusion Criteria

Positive urine toxicology for opioids other than buprenorphine in the past week OR opioid withdrawal symptoms in the past week based on the Clinical Opioid Withdrawal Scale (COWS) >=5

I am fluent in both English and Spanish.

I started taking buprenorphine less than 21 days ago.

Exclusion Criteria

I do not have unstable heart conditions or a history of fainting.

I have a progressive neurological condition, frequent falls, or a history of seizures.

Urine toxicology positive for cannabinoids

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dronabinol and Epidiolex as adjuncts to buprenorphine for 8 weeks

8 weeks

Visits at enrollment, and weeks 1, 2, 4, 8, and 12

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dronabinol
• Epidiolex

Trial Overview The study tests the effectiveness of dronabinol (synthetic THC) and Epidiolex (CBD), both FDA-approved, as additional treatments to improve retention in buprenorphine therapy and reduce opioid use among participants.

How Is the Trial Designed?

Group I: Dronabinol + Epidiolex Arm Experimental Treatment 2 Interventions

Dronabinol (THC) will be dosed every 12 hours. To limit potential adverse effects, the dose of dronabinol will be titrated up gradually over 15 days to a final daily dose of 20 mg (10 mg every 12 hours). This final dosage will be administered twice daily from Day 16 to Week 8. Epidiolex (CBD) will also be dosed every 12 hours. To limit potential adverse effects, the dose of Epidiolex will be titrated up gradually over 15 days to a final dose of 400 mg every 12 hours. Participants will start off taking 200 mg daily (100 mg every 12 hours) for 5 days, then uptitrate to 400 mg (200 mg every 12 hours) for 5 days, then uptitrate to 600 mg for 5 days (300 mg every 12 hours), and finally 800 mg from day 16 through week 8 (400 mg every 12 hours).

Group II: Placebo Arm Placebo Group 2 Interventions

Placebo Dronabinol capsules will be labeled and identical in appearance to dronabinol capsules. They will be made of pearl capsules filled with lactose by Montefiore's Investigational Drug Pharmacy team. Placebo Epidiolex oral solution will be made up of ethanol (79.0 mg/mL), sucralose (0.5 mg/mL), strawberry flavor (0.2 mg/mL), and refined sesame oil (to a volume of 1 mL). This mixture will be identical in appearance, taste, and composition of Epidiolex, except for the active ingredient of pure CBD.

Who Is Running the Clinical Trial?

Montefiore Medical Center

Lead Sponsor

Trials

468

Recruited

599,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07148206

Study Details | NCT07148206 | Dronabinol and Epidiolex ... The overarching hypothesis of this study is that adjunctive dronabinol + Epidiolex improves buprenorphine retention and opioid use in POUD through reducing ...

2. canada.ca canada.ca/en/health-canada/services/drugs-medication/cannabis/information-medical-practitioners/information-health-care-professionals-cannabis-cannabinoids.html

For health care professionals: Cannabis and cannabinoids Evidence from pre-clinical studies suggests THC, CBD and nabiximols improve multiple sclerosis (MS) associated symptoms of tremor, spasticity and inflammation.

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK556048/

Cannabidiol (CBD) in Clinical Care - StatPearls - NCBI - NIH This activity focuses on cannabidiol's (CBD) role in managing refractory epilepsy. Participants will explore indications, actions, and contraindications.

4. aafp.org aafp.org/about/policies/all/cannabis-position-paper.html

Cannabis: Health, Research and Regulatory ... A number of systematic reviews and meta-analyses have reported on the uses, efficacy and safety of cannabis and cannabinoid-containing products, including ...

5. uptodate.com uptodate.com/contents/medical-use-of-cannabis-and-cannabinoids-in-adults

Medical use of cannabis and cannabinoids in adults - UpToDate Another strategy to limit adverse effects is to combine THC with cannabidiol (CBD), which is associated with fewer adverse events and can dampen ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4663169/

Safety of Oral Dronabinol During Opioid Withdrawal in Humans Dronabinol 20mg and higher increased heart rate among healthy adults at rest who were in a state of opioid withdrawal, raising concern about its safety.

7. link.springer.com link.springer.com/article/10.1007/s40122-024-00599-1

The Role of Medicinal Cannabis as an Emerging Therapy ... This narrative review explores current insights into the potential use of medicinal cannabis-related products as an emerging therapy for opioid use disorder.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0924977X20300651

Therapeutic potential of opioid/cannabinoid combinations ... The extant controlled clinical data do not support the role of cannabinoids for opioid replacement or opioid-sparing effects when treating opioid use disorder ...