Cannabidiol added to methadone or buprenorphine for opioid recovery

Adjunctive Cannabidiol for Recovery From Opioid Study (ACROS)

This trial will test whether adding cannabidiol (CBD) to methadone or buprenorphine helps people with opioid use disorder reduce craving and stop using illicit opioids.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 450 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Icahn School of Medicine at Mount Sinai (Academic / other)
• Locations: 2 sites (New York, New York and 1 other locations)
• Trial ID: NCT06940674 on ClinicalTrials.gov

What this trial studies

This Phase 3, randomized, double-blind, placebo-controlled trial will give adults with opioid use disorder who are maintained on methadone or buprenorphine either oral cannabidiol (BSPG CBD) or placebo alongside their usual opioid agonist therapy. Participants will be followed for illicit opioid use, craving, anxiety, and safety outcomes, building on prior Phase 1 pharmacokinetic work and Phase 2 human trials. The protocol is informed by preclinical data showing CBD reduces cue-induced heroin seeking and earlier human trials where acute CBD decreased craving and anxiety. Study sites include Icahn School of Medicine at Mount Sinai (New York) and CODA Treatment Recovery (Portland, Oregon).

Who should consider this trial

Good fit: Adults (18–65) with opioid use disorder who have been on a stable dose of methadone (≥10 mg/day) or buprenorphine (≥2 mg/day) for at least 14 days and can attend one of the study sites are ideal candidates.

Not a fit: People who are not on opioid agonist maintenance, are outside the 18–65 age range, are non-English-speaking, or have disqualifying psychiatric conditions are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, CBD could help people on methadone or buprenorphine reduce craving and lower the chance of relapse to illicit opioid use.

How similar studies have performed: Prior randomized, double-blind human trials and animal studies reported that acute CBD reduced heroin cue-induced craving and anxiety and was safe with opioids, so this approach has promising but not yet definitive support.

Eligibility criteria

Inclusion Criteria:

* Individuals between 18 and 65 years old.
* Ability to understand and give informed consent.
* Current opioid use disorder (OUD) or OUD in remission while on maintenance therapy with OAT, as determined by DSM-5 with the M.I.N.I. interview (Mini-International Neuropsychiatric Interview).
* Current opioid agonist maintenance treatment with methadone or buprenorphine for at least 14 days prior to consent. With the following more specific criteria for each of these two medications:

  * Current methadone maintenance treatment with a dose of ≥ 10mg/day, (maximum: 250mg/day), AND urinary toxicology positive for methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP).
  * Current buprenorphine maintenance treatment with a dose of ≥ 2mg/day (maximum: 32mg/day), AND urinary toxicology positive for buprenorphine.

Exclusion Criteria:

* Participants who are non-English speaking.
* Psychiatric conditions under DSM-5 (examined with the MINI) that would make study participation unsafe, or which would prevent adherence to study procedure; examples include: suicidal (i.e. high risk for suicide on the Columbia suicide severity rating scale (C-SSRS) screen version) or homicidal ideation requiring immediate attention, inadequately-treated mental health disorder (e.g., active psychosis, uncontrolled bipolar disorder).
* Current diagnosis of a severe substance use disorder (except for opioid and nicotine/tobacco) in the past 3 months, based on the MINI interview, that would preclude safe participation in the study as determined by the study medical clinician.
* Signs of acute drug intoxication when arriving at the study site as determined by clinician assessment.
* Medical or psychiatric contraindications for CBD administration (e.g., history of hypersensitivity to cannabinoids); or any of the ingredients in the product (gelatin or sesame oil).
* Showing signs of acute opioid withdrawal symptoms (as determined by the result of the Clinical Opiate Withdrawal Scale (COWS). A Score of ≥ 5 or as interpreted by the investigator will be considered a positive result for withdrawal symptoms).
* Have a medical condition that would make study participation unsafe, which would make treatment compliance difficult, or would prevent adherence to study procedure. This includes but is not limited to the following criteria: • \< 30mL/min/1.73m2 eGFR. •QTc Fridericia \> 500ms at screening. •Elevated liver enzymes at screening. The exclusionary lab values are: \>4x the upper limit of normal (ULN) per laboratory criteria for AST or ALT or \>1.5x ULN for bilirubin.
* Participating in another pharmacotherapeutic trial in the past 3 months.
* Participants who have used (within 14 days prior to consent) or plan to use (during the 24-week treatment period) any medications, dietary supplements (and/or grapefruit juice), or combination of medications and supplements known to alter the metabolism of, or interact with CBD (buproprion, rifampin, barbiturates, phenothiazines, cimetidine, anticoagulants, antiplatelets, etc.).
* For women: being pregnant (positive urine test for pregnancy) or breastfeeding.
* Not using an appropriate method of contraception such as hormonal contraception (oral hormonal contraceptives, Depo-Provera, Nuva-Ring), intrauterine device (IUD), sterilization, or double barrier method (combination of any two barrier methods used simultaneously, i.e. condom, spermicide, diaphragm).
* Participants who have been court mandated to attend treatment centers

Where this trial is running

New York, New York and 1 other locations

• Icahn School of Medicine at Mount Sinai — New York, New York, United States (Recruiting)
• CODA Treatment Recovery — Portland, Oregon, United States (Recruiting)

Study contacts

• Principal investigator: Yasmin Hurd, PhD — Icahn School of Medicine at Mount Sinai
• Study coordinator: Zoe Spieler

Conditions Opioid Use Disorder