Opioid Use DisorderPhase 3DEMURENCT07148206
Dronabinol and Epidiolex to Manage Uncontrolled Residual Symptoms of Buprenorphine Initiation Trial
A Phase 3 study testing Dronabinol Capsules and Epidiolex 100 mg/mL Oral Solution in people with Opioid Use Disorder, run by Montefiore Medical Center at 1 site in United States.
Trial summary
The goal of this pilot study is to test novel, adjunctive pharmacotherapy for patients with opioid use disorder (POUD) who may be at risk for overdose and other poor opioid use disorder (OUD) outcomes even after initiating buprenorphine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Opioid Use Disorder
- What is being tested?
- Dronabinol Capsules and Epidiolex 100 mg/mL Oral Solution
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2026to May 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Fluency in English and Spanish
- The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of OUD
- Newly initiated on buprenorphine within 21 days
- 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
- Any cannabis use in the past at or after the age of 18 years based on self-report
Who cannot join
- Urine toxicology positive for cannabinoids
- Inability to provide informed consent
- Liver tests (AST or ALT) >3 times the upper limit of normal, or a history of liver disease
- Pregnancy or breast/chest feeding
- Unstable cardiac disease, history of hypotension or syncope
- Psychotic disorder, or history of suicidal behavior and/or ideation
Show all 9Show fewer
- Progressive neurological conditions, frequent falls, or history of epileptic seizures
- Severe alcohol use disorder, benzodiazepine use disorder or stimulant use disorder
- Other serious medical conditions that would be a contraindication to THC or CBD use
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Deepika Slawek contact
United States1 site
Montefiore Health System (Montefiore) Buprenorphine Treatment Network
The Bronx, New York, 10467
Deepika Slawek, MD, MPH, MS, 718-920-3786, dslawek@montefiore.org
About this study
The goal of this pilot study is to test novel, adjunctive pharmacotherapy for patients with opioid use disorder (POUD) who may be at risk for overdose and other poor opioid use disorder (OUD) outcomes even after initiating buprenorphine. The investigator team proposes to test the effectiveness of combined dronabinol (synthetic delta-9-tetrahydrocannabinol [THC]) and Epidiolex (cannabidiol [CBD]) - two FDA-approved cannabinoids - to improve retention in buprenorphine treatment and reduce opioid use among POUD who are early in treatment. POUD who are early in treatment are at a critical juncture-a moment of opportunity and motivation, but also of high risk of return to opioid use and loss to follow up.
Read the detailed description
OUD and opioid overdose death rates remain shockingly high in the United States fueled by high potency opioids like fentanyl. Buprenorphine is an evidence-based therapy for OUD that reduces mortality, improves OUD outcomes, and is increasingly available. Three-month buprenorphine retention halves all-cause mortality; however, only 40-60% of POUD are retained in buprenorphine treatment for 3 or more months. Further, POUD who use fentanyl report protracted opioid withdrawal symptoms including anxiety, pain, insomnia, and opioid cravings, even months after reaching maximum doses of buprenorphine. Nearly 50% of POUD who use fentanyl return to use within 3 months.12 To improve success of buprenorphine treatment, new strategies for starting buprenorphine have emerged, such as low-dose initiation with ongoing opioid agonists, however, few interventions exist to improve treatment after starting buprenorphine, and those that exist are non-pharmacologic. Alpha-2-agonists (e.g., clonidine) reduce some withdrawal symptoms but can only be given for a short time without cardiac side effects. Pharmacologic adjuncts to buprenorphine are desperately needed to improve OUD outcomes in the fentanyl era.
Cannabis, the two key ingredients of which are THC and CBD, reduces opioid withdrawal in observational studies and thus has biologic plausibility for improving buprenorphine treatment retention. In two randomized trials, THC improved acute opioid withdrawal symptoms (e.g., muscle aches, muscle tension, and flu-like prodrome) a common driver of ongoing opioid use. THC is also effective in reducing acute and chronic pain in POUD another driver of ongoing use; however, patients receiving THC alone may experience adverse effects, such as panic, anxiety, and poor cognition. Co-administration with CBD may counteract these effects and maximize THC's benefits. In pre-clinical and clinical trials CBD reduces anxiety, pain, cue-induced opioid cravings, and attentional bias to drug-induced cues. When THC and CBD are co-administered, patients experience improved analgesic effects and reduced adverse effects. The overarching hypothesis of this study is that adjunctive dronabinol + Epidiolex improves buprenorphine retention and opioid use in POUD through reducing opioid withdrawal (including cravings, and pain).
The investigator team has developed an innovative 12-week pilot randomized trial of dronabinol + Epidiolex (versus placebo) as an adjunct to buprenorphine for OUD outcomes. 40 POUD participants within 21 days of buprenorphine initiation who are continuing either to use illicit opioids or to experience opioid withdrawal symptoms will be enrolled. Participants will be randomized to one of two arms as described in this registration. Study visits will occur at enrollment, and weeks 1, 2, 4, 8, and 12.
There are two overarching Aims in this study.
Aim 1: To determine the effectiveness and safety of 8- weeks of dronabinol + Epidiolex (vs. placebo) as an adjunct to buprenorphine in improving retention in OUD treatment and reducing opioid use. Hypothesis 1a: The dronabinol + Epidiolex (vs. placebo) group will have better 12-week retention in OUD treatment. Hypothesis 1b: The dronabinol + Epidiolex (vs. placebo) group will report less illicit opioid use. Hypothesis 2: The dronabinol + Epidiolex (vs. placebo) group will have no difference in significant adverse events or treatment limiting adverse events.
Aim 2: To explore the mechanism by which cannabinoids may improve OUD outcomes after buprenorphine initiation in POUD. The investigator team will explore how dronabinol + Epidiolex use are associated with change in opioid withdrawal symptoms, opioid cravings, and pain and whether these changes are associated with OUD outcomes. Hypothesis 3: The dronabinol + Epidiolex (vs. placebo) group will have fewer withdrawal symptoms, opioid cravings and pain, which will mediate the impact of cannabinoids on OUD outcomes.
- Conditions
- Opioid Use Disorder
- Being tested
- Dronabinol Capsules, Epidiolex 100 mg/mL Oral Solution, Placebo Dronabinol, Placebo Epidiolex
- Keywords
- Buprenorphine, delta-9-Tetrahydrocannabinol (THC), Cannabidiol (CBD), Cannabinoids, Opioid Use, Opioid Withdrawal, Retention to Treatment
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dronabinol CapsulesDrug
Also called Marinol
Dronabinol is a synthetic form of THC. Dronabinol is eliminated in a biphasic manner, with an initial half-life of 25-36 hours.
Epidiolex 100 mg/mL Oral SolutionDrug
Also called Cannabidiol (CBD)
Epidiolex is an oral solution (100 mg/mL) which rapidly appears in plasma, reaches peak plasma concentration in 3-4 hours and has a half-life of 18-32 hours.
Placebo DronabinolOther
Placebo capsules
Placebo EpidiolexOther
Placebo oral solution
| Study group | Role | What they receive |
|---|---|---|
| Dronabinol + Epidiolex Arm | Experimental | 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). Receives: Drug: Dronabinol Capsules; Drug: Epidiolex 100 mg/mL Oral Solution |
| Placebo Arm | Placebo comparator | 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. Receives: Other: Placebo Dronabinol; Other: Placebo Epidiolex |
What is being measured
The primary outcome is the main question the study is designed to answer.
Retention in OUD Treatment
Retention in OUD Treatment will be assessed as a dichotomous measure and will be based on the number of participants maintaining both an active buprenorphine prescription AND urine toxicology positive for buprenorphine at 12 weeks. The number/percentage of participants will be summarized by study arm.
Measured: ~12 weeks following initiation of intervention
Secondary outcomes (10)
Retention in OUD Treatment
Retention in OUD Treatment will be assessed as a dichotomous measure and will be based on the number of participants maintaining both an active buprenorphine prescription AND urine toxicology positive for buprenorphine at 12 weeks. The number/percentage of participants will be summarized by study arm.
Measured: Baseline and ~1-week, 2-weeks, 4-weeks, and 8-weeks following initiation of intervention
Opioid Use - Self Reported
Self-reported opioid use will be assessed using the Timeline Follow-back (TLFB) calendar-based research tool. Using the TLFB methodology, participants will be provided with a calendar and asked to record, using a binary "Yes" or "No" response, whether opioid was used during each day over the prior 30-day period. Participants will be guided by a trained assessor during this process to help facilitate recall. If a participant's most recent study visit was within 30 days, then opioid use will be limited to the period of time since the last study visit. The number of days using opioids over the prior 30-day period will be summarized by study arm.
Measured: Baseline and ~1-week, 2-weeks, 4-weeks, 8-weeks, and 12 weeks following initiation of intervention
Opioid Use - Urine Toxicology
Opioid use will also be assessed using a urine toxicology immunoassay. Unobserved urine sample collection will be conducted at defined visits and samples will be analyzed to detect for the presence opioids and their metabolites. Results above the laboratory threshold for opiates will be reported as Either "Positive" or "Negative" and summarized by study arm at each timepoint.
Measured: Baseline and ~2-weeks, 4-weeks, 8-weeks, and 12 weeks following initiation of intervention
Opioid Use Disorder Symptoms - Subjective Opiate Withdrawal Scale
Opioid Use Disorder Symptoms will be assessed using the Subjective Opiate Withdrawal Scale (SOWS). The SOWS is a 16-item clinician administered scale designed to reproducibly rate the severity of opiate withdrawal symptoms. Participants rate each symptom on a 5-point scale ranging from 0 ("Not at all") to 4 ("Extremely") based on the intensity they are experiencing at the moment, yielding an overall possible range from 0-64, wherein higher scores are associated with more severe withdrawal symptoms. Specific scoring guideline categories include 1-10 = mild withdrawal; 11-20 = moderate withdrawal; 21-30+ = severe withdrawal. Mean scores will be summarized by study arm at each timepoint using basic descriptive statistics.
Measured: Baseline and ~4-weeks, 8-weeks, and 12 weeks following initiation of intervention
Opioid Use Disorder Symptoms - Opiate Craving Scale
Opioid Use Disorder Symptoms will also be assessed using the 3-item Opiate Craving Scale. The Opiate Craving Scale is a clinician administered scale designed to evaluate opiate cravings over the prior week. Participants are asked to (1) "Please rate how strong your desire was to use in the past 24 hours." (2) "Please imagine yourself in the environment in which you previously used drugs or alcohol. If you were in this environment today, what is the likelihood you would use?" and (3) "Please rate how strong your urges are for drugs or alcohol when something in the environment reminds you of it." Each item is rated on a scale ranging from 0 to 9 and an average score from the 3 items is calculated. Higher scores are indicative of greater craving. Mean scores will be summarized by study arm using basic descriptive statistics.
Measured: Baseline and ~4-weeks, 8-weeks, and 12 weeks following initiation of intervention
Pain Severity
Pain Severity will be assessed by administration of the Pain Severity questions within the Brief Pain Inventory-Short Form (BPI-SF). Pain severity over the prior 24 hours is calculated by averaging the ratings for worst, least, and average pain for the past week as well as current pain (four individual items on the BPI-SF). This results in a Pain Severity score ranging from 0-10, with higher scores being indicative of more severe pain. A score of 0 means "No pain" and a score of 10 means "Pain as bad as you can imagine." Scores will be summarized by study arm at each timepoint using basic descriptive statistics.
Measured: Baseline and ~1-week, 2-weeks, 4-weeks, 8-weeks, and 12 weeks following initiation of intervention
Pain Interference
Pain Interference will be assessed using the corresponding Pain Interference questions within the Brief Pain Inventory-Short Form (BPI-SF). Pain interference over the prior 24 hours is calculated by averaging the ratings of the corresponding 7 items on the questionnaire to determine how much pain interferes with general activity, mood, walking, work, relations, sleep, and enjoyment of life. This results in a Pain Interference score ranging from 0-10, with higher scores indicating that the pain is more significantly interfering with daily activities. A score of 0 means "No Interference" and a score of 10 means "Pain completely interferes with daily activities." Scores will be summarized by study arm at each timepoint using basic descriptive statistics.
Measured: Baseline and ~1-week, 2-weeks, 4-weeks, 8-weeks, and 12 weeks following initiation of intervention
Panic Symptoms
Panic symptoms will be assessed by administration of the Panic Disorder Severity Scale (PDSS). The PDSS is a seven-item self-report scale that measures the severity of panic attacks and panic disorder symptoms. Each of the 7 items is rated on a 5-point Likert scale ranging from 0 ("No/None/Not at all") to 4 ("Extreme/Extremely/Nearly constantly") yielding an overall possible scoring range of 0-28, such that higher scores are indicative of greater severity of panic disorder. Scores will be summarized by study arm at each timepoint using basic descriptive statistics.
Measured: Baseline and ~1-week, 2-weeks, 4-weeks, 8-weeks, and 12 weeks following initiation of intervention
Anxiety Symptoms
Anxiety will be assessed by administration of the Generalized Anxiety Disorder 7-item (GAD-7) questionnaire. The GAD-7 is a seven-item screening tool used to assess the severity of generalized anxiety disorder over the prior two-week period. Each item on the questionnaire is rated on a 4-point Likert scale ranging from 0 ("Not at all") to 3 ("Nearly every day") yielding an overall possible scoring range of 0-21, such that higher scores are indicative of greater anxiety. Scores will be summarized by study arm at each timepoint using basic descriptive statistics.
Measured: Baseline and ~4-weeks, 8-weeks, and 12 weeks following initiation of intervention
Cognitive Function
Cognitive Function will be assessed by administration of the Patient-Reported Outcomes Measurement Information System Cognitive Function (PROMIS-CF) questionnaire. The PROMIS-CF questionnaire is a 4-item patient-reported outcome measures that assesses self-perceived cognitive abilities in the domains of memory (2 items) and concentration (2 items). Responses are scored on a 5-point Likert scale ranging from 1-5, yielding a scoring range of 4-20. Using item-level calibrations, raw scores are then converted to T-scores. T-scores are standardized to a metric with a mean of 50 and a standard deviation of 10 for reference to a population. Higher scores on the PROMIS-CF indicate better perceived cognitive function. Scores will be summarized by study arm at each timepoint using basic descriptive statistics.
Measured: Baseline and ~1-week, 2-weeks, 4-weeks, 8-weeks, and 12 weeks following initiation of intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2025
- Study startOct 2026 (estimated)
- Primary completionMay 2028 (estimated)
- Study completionMay 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (46)Papers the sponsor has linked to this study.
- Other trials for Opioid Use DisorderStudies of the same condition, open and under way.
- More trials run by Montefiore Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 1:1 randomization
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Montefiore Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Deepika Slawek, MD, MPH, MS, Principal investigator, Montefiore Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07148206
- Sponsor's protocol ID
- 2025-17060
- Other IDs
- R34DA063987, 2025
- Acronym
- DEMURE
- Status last verified
- Jun 2026
- First submitted
- 21 Aug 2025
- Last updated
- 9 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual Participant Data (IPD) Sharing Statement will be completed upon receipt of Notice of Award.
Publications
The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update. J Addict Med. 2020 Mar/Apr;14(2S Suppl 1):1-91. doi: 10.1097/ADM.0000000000000633. No abstract available.
PubMed 32511106Schwartz RP, Gryczynski J, O'Grady KE, Sharfstein JM, Warren G, Olsen Y, Mitchell SG, Jaffe JH. Opioid agonist treatments and heroin overdose deaths in Baltimore, Maryland, 1995-2009. Am J Public Health. 2013 May;103(5):917-22. doi: 10.2105/AJPH.2012.301049. Epub 2013 Mar 14.
PubMed 23488511Samples H, Williams AR, Crystal S, Olfson M. Impact Of Long-Term Buprenorphine Treatment On Adverse Health Care Outcomes In Medicaid. Health Aff (Millwood). 2020 May;39(5):747-755. doi: 10.1377/hlthaff.2019.01085.
PubMed 32364847Krawczyk N, Mojtabai R, Stuart EA, Fingerhood M, Agus D, Lyons BC, Weiner JP, Saloner B. Opioid agonist treatment and fatal overdose risk in a state-wide US population receiving opioid use disorder services. Addiction. 2020 Sep;115(9):1683-1694. doi: 10.1111/add.14991. Epub 2020 Feb 24.
PubMed 32096302Nunes EV, Comer SD, Lofwall MR, Walsh SL, Peterson S, Tiberg F, Hjelmstrom P, Budilovsky-Kelley NR. Extended-Release Injection vs Sublingual Buprenorphine for Opioid Use Disorder With Fentanyl Use: A Post Hoc Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024 Jun 3;7(6):e2417377. doi: 10.1001/jamanetworkopen.2024.17377.
PubMed 38916892Mariani JJ, Dobbins RL, Heath A, Gray F, Hassman H. Open-label investigation of rapid initiation of extended-release buprenorphine in patients using fentanyl and fentanyl analogs. Am J Addict. 2024 Jan;33(1):8-14. doi: 10.1111/ajad.13484. Epub 2023 Nov 8.
PubMed 37936553Santo T Jr, Clark B, Hickman M, Grebely J, Campbell G, Sordo L, Chen A, Tran LT, Bharat C, Padmanathan P, Cousins G, Dupouy J, Kelty E, Muga R, Nosyk B, Min J, Pavarin R, Farrell M, Degenhardt L. Association of Opioid Agonist Treatment With All-Cause Mortality and Specific Causes of Death Among People With Opioid Dependence: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2021 Sep 1;78(9):979-993. doi: 10.1001/jamapsychiatry.2021.0976.
PubMed 34076676Wyse JJ, Eckhardt A, Waller D, Gordon AJ, Shull S, Lovejoy TI, Mackey K, Morasco BJ. Patients' Perspectives on Discontinuing Buprenorphine for the Treatment of Opioid Use Disorder. J Addict Med. 2024 May-Jun 01;18(3):300-305. doi: 10.1097/ADM.0000000000001292. Epub 2024 Mar 18.
PubMed 38498620Reddon H, Lake S, Socias ME, Hayashi K, DeBeck K, Walsh Z, Milloy MJ. Cannabis use to manage opioid cravings among people who use unregulated opioids during a drug toxicity crisis. Int J Drug Policy. 2023 Sep;119:104113. doi: 10.1016/j.drugpo.2023.104113. Epub 2023 Jul 21.
PubMed 37481875Spadaro A, Sarker A, Hogg-Bremer W, Love JS, O'Donnell N, Nelson LS, Perrone J. Reddit discussions about buprenorphine associated precipitated withdrawal in the era of fentanyl. Clin Toxicol (Phila). 2022 Jun;60(6):694-701. doi: 10.1080/15563650.2022.2032730. Epub 2022 Feb 4.
PubMed 35119337Wakeman SE, Chang Y, Regan S, Yu L, Flood J, Metlay J, Rigotti N. Impact of Fentanyl Use on Buprenorphine Treatment Retention and Opioid Abstinence. J Addict Med. 2019 Jul/Aug;13(4):253-257. doi: 10.1097/ADM.0000000000000486.
PubMed 30550392Randhawa PA, Brar R, Nolan S. Buprenorphine-naloxone "microdosing": an alternative induction approach for the treatment of opioid use disorder in the wake of North America's increasingly potent illicit drug market. CMAJ. 2020 Jan 20;192(3):E73. doi: 10.1503/cmaj.74018. No abstract available.
PubMed 31959660Klaire S, Zivanovic R, Barbic SP, Sandhu R, Mathew N, Azar P. Rapid micro-induction of buprenorphine/naloxone for opioid use disorder in an inpatient setting: A case series. Am J Addict. 2019 Jul;28(4):262-265. doi: 10.1111/ajad.12869. Epub 2019 Mar 22.
PubMed 30901127Azar P, Schneiderman H, Barron H, Wong JSH, Meyer M, Newman-Azar D, Narimani M, Ignaszewski MJ, Mathew N, Mullen R, Krausz RM, Maharaj AR. Rapid induction of transdermal buprenorphine to subcutaneous extended-release buprenorphine for the treatment of opioid use disorder. Addict Sci Clin Pract. 2024 Jun 18;19(1):50. doi: 10.1186/s13722-024-00479-1.
PubMed 38886826D'Onofrio G, Perrone J, Hawk KF, Cowan E, McCormack R, Coupet E Jr, Owens PH, Martel SH, Huntley K, Walsh SL, Lofwall MR, Herring A; ED-INNOVATION Investigators. Early emergency department experience with 7-day extended-release injectable buprenorphine for opioid use disorder. Acad Emerg Med. 2023 Dec;30(12):1264-1271. doi: 10.1111/acem.14782. Epub 2023 Aug 22.
PubMed 37501652
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dronabinol and Epidiolex to Manage Uncontrolled Residual Symptoms of Buprenorphine Initiation Trial
- ClinicalTrials.gov ID
- NCT07148206
- Acronym / sponsor ID
- DEMURE / 2025-17060
- Conditions
- Opioid Use Disorder
- Keywords
- Buprenorphine, delta-9-Tetrahydrocannabinol (THC), Cannabidiol (CBD), Cannabinoids, Opioid Use, Opioid Withdrawal, Retention to Treatment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Montefiore Medical CenterUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Oct 2026 (estimated)
- Primary completion
- May 2028 (estimated)
- Study completion
- May 2028 (estimated)
- First posted
- 29 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this pilot study is to test novel, adjunctive pharmacotherapy for patients with opioid use disorder (POUD) who may be at risk for overdose and other poor opioid use disorder (OUD) outcomes even after initiating buprenorphine. The investigator team proposes to test the effectiveness of combined dronabinol (synthetic delta-9-tetrahydrocannabinol [THC]) and Epidiolex (cannabidiol [CBD]) - two FDA-approved cannabinoids - to improve retention in buprenorphine treatment and reduce opioid use among POUD who are early in treatment. POUD who are early in treatment are at a critical juncture-a moment of opportunity and motivation, but also of high risk of return to opioid use and loss to follow up.
Detailed description
OUD and opioid overdose death rates remain shockingly high in the United States fueled by high potency opioids like fentanyl. Buprenorphine is an evidence-based therapy for OUD that reduces mortality, improves OUD outcomes, and is increasingly available. Three-month buprenorphine retention halves all-cause mortality; however, only 40-60% of POUD are retained in buprenorphine treatment for 3 or more months. Further, POUD who use fentanyl report protracted opioid withdrawal symptoms including anxiety, pain, insomnia, and opioid cravings, even months after reaching maximum doses of buprenorphine. Nearly 50% of POUD who use fentanyl return to use within 3 months.12 To improve success of buprenorphine treatment, new strategies for starting buprenorphine have emerged, such as low-dose initiation with ongoing opioid agonists, however, few interventions exist to improve treatment after starting buprenorphine, and those that exist are non-pharmacologic. Alpha-2-agonists (e.g., clonidine) reduce some withdrawal symptoms but can only be given for a short time without cardiac side effects. Pharmacologic adjuncts to buprenorphine are desperately needed to improve OUD outcomes in the fentanyl era.
Cannabis, the two key ingredients of which are THC and CBD, reduces opioid withdrawal in observational studies and thus has biologic plausibility for improving buprenorphine treatment retention. In two randomized trials, THC improved acute opioid withdrawal symptoms (e.g., muscle aches, muscle tension, and flu-like prodrome) a common driver of ongoing opioid use. THC is also effective in reducing acute and chronic pain in POUD another driver of ongoing use; however, patients receiving THC alone may experience adverse effects, such as panic, anxiety, and poor cognition. Co-administration with CBD may counteract these effects and maximize THC's benefits. In pre-clinical and clinical trials CBD reduces anxiety, pain, cue-induced opioid cravings, and attentional bias to drug-induced cues. When THC and CBD are co-administered, patients experience improved analgesic effects and reduced adverse effects. The overarching hypothesis of this study is that adjunctive dronabinol + Epidiolex improves buprenorphine retention and opioid use in POUD through reducing opioid withdrawal (including cravings, and pain).
The investigator team has developed an innovative 12-week pilot randomized trial of dronabinol + Epidiolex (versus placebo) as an adjunct to buprenorphine for OUD outcomes. 40 POUD participants within 21 days of buprenorphine initiation who are continuing either to use illicit opioids or to experience opioid withdrawal symptoms will be enrolled. Participants will be randomized to one of two arms as described in this registration. Study visits will occur at enrollment, and weeks 1, 2, 4, 8, and 12.
There are two overarching Aims in this study.
Aim 1: To determine the effectiveness and safety of 8- weeks of dronabinol + Epidiolex (vs. placebo) as an adjunct to buprenorphine in improving retention in OUD treatment and reducing opioid use. Hypothesis 1a: The dronabinol + Epidiolex (vs. placebo) group will have better 12-week retention in OUD treatment. Hypothesis 1b: The dronabinol + Epidiolex (vs. placebo) group will report less illicit opioid use. Hypothesis 2: The dronabinol + Epidiolex (vs. placebo) group will have no difference in significant adverse events or treatment limiting adverse events.
Aim 2: To explore the mechanism by which cannabinoids may improve OUD outcomes after buprenorphine initiation in POUD. The investigator team will explore how dronabinol + Epidiolex use are associated with change in opioid withdrawal symptoms, opioid cravings, and pain and whether these changes are associated with OUD outcomes. Hypothesis 3: The dronabinol + Epidiolex (vs. placebo) group will have fewer withdrawal symptoms, opioid cravings and pain, which will mediate the impact of cannabinoids on OUD outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- 1:1 randomization
| Arm | Type | Receives |
|---|---|---|
| Dronabinol + Epidiolex Arm | Experimental | Drug: Dronabinol Capsules, Drug: Epidiolex 100 mg/mL Oral SolutionDronabinol (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). |
| Placebo Arm | Placebo comparator | Other: Placebo Dronabinol, Other: Placebo EpidiolexPlacebo 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 may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Fluency in English and Spanish
- The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of OUD
- Newly initiated on buprenorphine within 21 days
- 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
- Any cannabis use in the past at or after the age of 18 years based on self-report
Key exclusion criteria (9 listed)
- Urine toxicology positive for cannabinoids
- Inability to provide informed consent
- Liver tests (AST or ALT) >3 times the upper limit of normal, or a history of liver disease
- Pregnancy or breast/chest feeding
- Unstable cardiac disease, history of hypotension or syncope
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dronabinol CapsulesAlso: MarinolDronabinol is a synthetic form of THC. Dronabinol is eliminated in a biphasic manner, with an initial half-life of 25-36 hours. | Drug | Dronabinol + Epidiolex Arm |
| Epidiolex 100 mg/mL Oral SolutionAlso: Cannabidiol (CBD)Epidiolex is an oral solution (100 mg/mL) which rapidly appears in plasma, reaches peak plasma concentration in 3-4 hours and has a half-life of 18-32 hours. | Drug | Dronabinol + Epidiolex Arm |
| Placebo DronabinolPlacebo capsules | Other | Placebo Arm |
| Placebo EpidiolexPlacebo oral solution | Other | Placebo Arm |
Primary outcome
Retention in OUD Treatment
Time frame: ~12 weeks following initiation of intervention
Retention in OUD Treatment will be assessed as a dichotomous measure and will be based on the number of participants maintaining both an active buprenorphine prescription AND urine toxicology positive for buprenorphine at 12 weeks. The number/percentage of participants will be summarized by study arm.
10 secondary outcomes
Retention in OUD Treatment
Time frame: Baseline and ~1-week, 2-weeks, 4-weeks, and 8-weeks following initiation of intervention
Opioid Use - Self Reported
Time frame: Baseline and ~1-week, 2-weeks, 4-weeks, 8-weeks, and 12 weeks following initiation of intervention
Opioid Use - Urine Toxicology
Time frame: Baseline and ~2-weeks, 4-weeks, 8-weeks, and 12 weeks following initiation of intervention
Opioid Use Disorder Symptoms - Subjective Opiate Withdrawal Scale
Time frame: Baseline and ~4-weeks, 8-weeks, and 12 weeks following initiation of intervention
Opioid Use Disorder Symptoms - Opiate Craving Scale
Time frame: Baseline and ~4-weeks, 8-weeks, and 12 weeks following initiation of intervention
Pain Severity
Time frame: Baseline and ~1-week, 2-weeks, 4-weeks, 8-weeks, and 12 weeks following initiation of intervention
Pain Interference
Time frame: Baseline and ~1-week, 2-weeks, 4-weeks, 8-weeks, and 12 weeks following initiation of intervention
Panic Symptoms
Time frame: Baseline and ~1-week, 2-weeks, 4-weeks, 8-weeks, and 12 weeks following initiation of intervention
Anxiety Symptoms
Time frame: Baseline and ~4-weeks, 8-weeks, and 12 weeks following initiation of intervention
Cognitive Function
Time frame: Baseline and ~1-week, 2-weeks, 4-weeks, 8-weeks, and 12 weeks following initiation of intervention
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2026.
- Background: PubMed 32511106The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update. J Addict Med. 2020 Mar/Apr;14(2S Suppl 1):1-91. doi: 10.1097/ADM.0000000000000633. No abstract available.
- Background: PubMed 23488511Schwartz RP, Gryczynski J, O'Grady KE, Sharfstein JM, Warren G, Olsen Y, Mitchell SG, Jaffe JH. Opioid agonist treatments and heroin overdose deaths in Baltimore, Maryland, 1995-2009. Am J Public Health. 2013 May;103(5):917-22. doi: 10.2105/AJPH.2012.301049. Epub 2013 Mar 14.
- Background: PubMed 32364847Samples H, Williams AR, Crystal S, Olfson M. Impact Of Long-Term Buprenorphine Treatment On Adverse Health Care Outcomes In Medicaid. Health Aff (Millwood). 2020 May;39(5):747-755. doi: 10.1377/hlthaff.2019.01085.
- Background: PubMed 32096302Krawczyk N, Mojtabai R, Stuart EA, Fingerhood M, Agus D, Lyons BC, Weiner JP, Saloner B. Opioid agonist treatment and fatal overdose risk in a state-wide US population receiving opioid use disorder services. Addiction. 2020 Sep;115(9):1683-1694. doi: 10.1111/add.14991. Epub 2020 Feb 24.
- Background: PubMed 38916892Nunes EV, Comer SD, Lofwall MR, Walsh SL, Peterson S, Tiberg F, Hjelmstrom P, Budilovsky-Kelley NR. Extended-Release Injection vs Sublingual Buprenorphine for Opioid Use Disorder With Fentanyl Use: A Post Hoc Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024 Jun 3;7(6):e2417377. doi: 10.1001/jamanetworkopen.2024.17377.
- Background: PubMed 37936553Mariani JJ, Dobbins RL, Heath A, Gray F, Hassman H. Open-label investigation of rapid initiation of extended-release buprenorphine in patients using fentanyl and fentanyl analogs. Am J Addict. 2024 Jan;33(1):8-14. doi: 10.1111/ajad.13484. Epub 2023 Nov 8.
- Background: PubMed 34076676Santo T Jr, Clark B, Hickman M, Grebely J, Campbell G, Sordo L, Chen A, Tran LT, Bharat C, Padmanathan P, Cousins G, Dupouy J, Kelty E, Muga R, Nosyk B, Min J, Pavarin R, Farrell M, Degenhardt L. Association of Opioid Agonist Treatment With All-Cause Mortality and Specific Causes of Death Among People With Opioid Dependence: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2021 Sep 1;78(9):979-993. doi: 10.1001/jamapsychiatry.2021.0976.
- Background: PubMed 38498620Wyse JJ, Eckhardt A, Waller D, Gordon AJ, Shull S, Lovejoy TI, Mackey K, Morasco BJ. Patients' Perspectives on Discontinuing Buprenorphine for the Treatment of Opioid Use Disorder. J Addict Med. 2024 May-Jun 01;18(3):300-305. doi: 10.1097/ADM.0000000000001292. Epub 2024 Mar 18.
- Background: PubMed 37481875Reddon H, Lake S, Socias ME, Hayashi K, DeBeck K, Walsh Z, Milloy MJ. Cannabis use to manage opioid cravings among people who use unregulated opioids during a drug toxicity crisis. Int J Drug Policy. 2023 Sep;119:104113. doi: 10.1016/j.drugpo.2023.104113. Epub 2023 Jul 21.
- Background: PubMed 35119337Spadaro A, Sarker A, Hogg-Bremer W, Love JS, O'Donnell N, Nelson LS, Perrone J. Reddit discussions about buprenorphine associated precipitated withdrawal in the era of fentanyl. Clin Toxicol (Phila). 2022 Jun;60(6):694-701. doi: 10.1080/15563650.2022.2032730. Epub 2022 Feb 4.
- Background: PubMed 30550392Wakeman SE, Chang Y, Regan S, Yu L, Flood J, Metlay J, Rigotti N. Impact of Fentanyl Use on Buprenorphine Treatment Retention and Opioid Abstinence. J Addict Med. 2019 Jul/Aug;13(4):253-257. doi: 10.1097/ADM.0000000000000486.
- Background: PubMed 31959660Randhawa PA, Brar R, Nolan S. Buprenorphine-naloxone "microdosing": an alternative induction approach for the treatment of opioid use disorder in the wake of North America's increasingly potent illicit drug market. CMAJ. 2020 Jan 20;192(3):E73. doi: 10.1503/cmaj.74018. No abstract available.
- Arnsten JH. Does Medical Cannabis Reduce Opioid Use in Adults With PainLink provided by the sponsor.
- Slawek DE. Pain, Inflammation, and Cannabis in HIVLink provided by the sponsor.
- Withdrawal Management. In: Clinical Guidelines for Withdrawal Management and Treatment of Drug Dependence in Closed Settings. World Health Organization; 2009.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual Participant Data (IPD) Sharing Statement will be completed upon receipt of Notice of Award.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Deepika Slawek contact
Deepika Slawek, MD, MPH, MS principal investigator
Montefiore Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dronabinol Capsules and Epidiolex 100 mg/mL Oral Solution in people with Opioid Use Disorder, run by Montefiore Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 9 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Deepika Slawek, MD, MPH, MS (718-920-3786, dslawek@montefiore.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Retention in OUD Treatment (time frame: ~12 weeks following initiation of intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07148206, which also lists 46 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2026.