Cannabidiol Effects on Craving and Relapse Prevention in Opioid Use Disorder

NCT03787628 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 18-0017485UG3DA048388-03
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This research aims to determine the effects and safety of cannabidiol (CBD) (ATL5 softgel capsules) as an adjunctive therapy for patients who have Opioid Use Disorder and are taking buprenorphine + naloxone or methadone. Buprenorphine + naloxone and methadone is an approved treatment for Opioid Use Disorder, but relapse to opioid misuse is common among patients who receive this treatment. Finding an adjunctive treatment for these patients would be helpful. We will recruit participants from the Tarzana Treatment Center (TTC) in the San Fernando Valley. They will be receiving buprenorphine + naloxone or methadone as part of residential therapy. Potential participants who pass initial screening and wish to continue in the study will provide written, informed consent and will complete a 2-day evaluation, including blood and urine tests, questionnaires about their mood, medical, psychiatric and drug use history and physical exam. Up to 60 participants who meet all eligibility criteria will be invited to complete baseline assessments (blood and urine tests, questionnaires), and will be assigned randomly to receive CBD (600 mg/day) or placebo, corresponding to two groups of up to 30 participants each. After the baseline measurements, participants will take part in a 28-day treatment phase for 4 weeks. They will take the study medication under supervision (CBD 300 mg twice daily or placebo). Questionnaires on opioid craving, withdrawal, and mood symptoms will be administered daily during the treatment period, excluding weekends. After the 28-day intervention, participants will complete the questionnaires and undergo urine drug tests in 4 weekly follow-up visits. The study will last \~10 weeks, comprising three periods: a screening period (2-weeks when participants are stabilized on buprenorphine + naloxone or methadone in residential treatment at the Tarzana Treatment Center), a treatment period (4 weeks when study CBD or placebo is administered at Tarzana Treatment Center), and a follow-up period (4 weeks after termination of the test intervention).

Conditions

Opioid-use Disorder

Keywords

Buprenorphine; Cannabidiol; Opioid Use disorder

Outcome Measures

Primary Outcomes (1)

• The Primary Endpoint Will be Safety and Tolerability of CBD.

  Number of participants with treatment-emergent adverse events (n/% per treatment group).

  Days 1-56

Secondary Outcomes (1)

• The Extent to Which CBD Reduces Cue-induced Craving for Opioids.

  Before dosing on Day 0 (baseline without CBD) and on Days 7 and 28 after treatment with CBD. The group means below reflect the overall group means across time points as reported from descriptive statistics in the Generalized Linear Mixed Model (GLMM).

Other Outcomes (3)

• Spontaneous Opioid Craving Using the Penn Alcohol Craving Scale (PACS), Adapted for Opioid Craving.

  Before dosing (Day 0), daily during treatment period (28 days), and weekly during follow-up (up to 4 weeks). Group means below reflect overall group means across time points as reported from descriptive statistics in the Generalized Linear Mixed Model.

• State Anxiety Subscale of the Spielberger State-Trait Anxiety Inventory (STAI).

  Before dosing (Day 0), daily during treatment period (28 days), and weekly during follow-up (up to 4 weeks). Group means below reflect overall group means across time points as reported from descriptive statistics in the Generalized Linear Mixed Model.

• Negative Affect Subscale From the Positive and Negative Affect Schedule (PANAS).

  Before dosing (Day 0), daily during treatment period (28 days), and weekly during follow-up (up to 4 weeks). Group means reflect overall group means across time points as reported from descriptive statistics in the Generalized Linear Mixed Model.

Study Arms (2)

Cannabidiol (CBD) 600 mg

ACTIVE COMPARATOR

Thirty participants who meet all eligibility criteria will be randomized to receive CBD (ATL5; Ananda Scientific) at a dose of 600 mg.

Drug: Cannabidiol (CBD) 600 mg

Placebo

PLACEBO COMPARATOR

Thirty participants who meet all eligibility criteria will be randomized to receive placebo.

Drug: Placebo

Interventions

Cannabidiol (CBD) 600 mg DRUG

CBD (300 mg) will be administered orally twice daily in the morning and again in the afternoon. The active ingredient in the Ananda investigational new drug, ATL5, is cannabidiol (CBD), extracted from hemp, at a 10% strength (softgel capsules with 100 mg/ml of CBD per capsule). The novel formulation is based on the principle that a water-free mixture of some concentrated inactive ingredients (excipients) self-assemble spontaneously into liquid nanodomains that contain the active component CBD. ATL5 Softgel Capsules will be manufactured by Baxco Pharmaceutical Inc. (California, USA) under cGMP conditions.

Also known as: ATL5 (Ananda Scientific)

Cannabidiol (CBD) 600 mg

Placebo DRUG

The placebo softgel capsule formulation will have a composition with the same relative proportions as the CBD ATL5 Softgel Capsules. This formulation will be manufactured by Baxco Pharmaceutical Inc. under cGMP conditions. The amount (number of softgel capsules) of placebo will be administered to match that of the active compound, daily in the morning and afternoon for each of 28 days.

Also known as: Placebo for ATL5 (Ananda Ccientific)

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to read and speak English and has provided written informed consent.
• Age of 18-65 years (inclusive).
• Meeting criteria for an OUD according to the MINI for ≥ 3 months before screening.
• Self-report of opioid use in the 60 days before screening; verified by treatment center records.
• On a stable dose of ≥12 mg buprenorphine, either alone, or in combination with naloxone (buprenorphine/naloxone ratio of 4/1) for at least 7 days prior to starting and for the duration of the treatment phase of the study. OR, receiving methadone maintenance therapy for at least 7 days prior to starting and for the duration of the treatment phase of the study.
• If female, being surgically sterile or willing to use birth control (e.g., oral contraceptives, condoms, intrauterine device) or willingness to abstain from sex throughout the study.
• Body Mass Index (BMI) between 17.5 and 35 kg/m2; total body weight \> 110 lb (50 kg).
• Currently in residential treatment at the Tarzana Treatment Center.

You may not qualify if:

• History of sensitivity to a CBD product or any of the ingredients in the study drug, including glycerin or gelatin.
• A condition that may affect drug absorption (e.g., gastrectomy).
• Taking a medications that has clinically significant interactions with CBD or are contraindicated for the study (check with study physician).
• Positive urine test for THC at screening.
• Self-report of using CBD at screening.
• PK analysis at screening showing evidence of CBD use (a signal that is ≥ three times the background noise at the corresponding CBD retention time and MS2 transition).
• Physiological dependence on alcohol or a sedative-hypnotic benzodiazepine drug.
• Current medication-assisted treatment with naltrexone.
• Acute opioid withdrawal symptoms, as defined by a score on the COWS \> 4.
• Clinical laboratory finding of AST or ALT \> 3 times the upper limit of normal (ULN) or bilirubin \> 1.5 times ULN.
• AIDS or HIV positive status (because treatment medications have potential interactions with CBD).
• Pregnancy or lactation.
• Clinically significant EKG abnormalities, as determined by the study physician, including the following: QTc \>450 msec (men) or \>470 (women) or QRS interval \>120 msec (If QTc or QRS interval exceed these cutoff points, EKG will be repeated twice and the average of the three QTc values used to determine eligibility.), congenital long QT syndrome, history of prolonged QT in the 3 months before screening, corrected QT interval (Fridericia's - QTcF) \>450 msec (male) or \>470 msec (female) or history of risk factors for Torsades de Pointes.
• For women: any value outside reference ranges on a hormonal battery \[estradiol, follicle-stimulating hormone, free thyroxine index, luteinizing hormone, prolactin, T3 uptake, thyroid-stimulating hormone, and thyroxine\], followed by an abnormal ovarian ultrasound finding.
• Clinically significant cardiovascular, hematologic, hepatic, renal, or endocrine abnormalities, as determined by the study physician.

Sponsors & Collaborators

• University of California, Los Angeles: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Tarzana Treatment Centers

Tarzana, California, 91356, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Dr. Edythe London
• Organization: UCLA David Geffen School of Medicine

elondon@mednet.ucla.edu

3106142150

Study Officials

• Edythe London, PhD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Distinguished Professor in Residence

Study Record Dates

• First Submitted: December 17, 2018
• First Posted: December 26, 2018
• Study Start: May 19, 2022
• Primary Completion: March 12, 2024
• Study Completion: March 12, 2024
• Last Updated: April 22, 2026
• Results First Posted: August 1, 2025

Record last verified: 2025-07

Locations

US (1)