Endocannabinoids, Stress, Craving And Pain Effects Study

NCT ID: NCT05480072

Last Updated: 2025-10-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-01
• Study Completion Date: 2025-01-14

Brief Summary

Opioid use disorder (OUD) represents one of the most severe public health crises, with more than 2 million individuals affected in the United States. Existing treatments do not target and restore several key alterations triggering opioid craving and relapse, including increased response to stress, mood disturbances and greater sensitivity to pain, which are caused by prolonged exposure to opioids. This double-blind, randomized, placebo-controlled study will investigate the effects that palmitoylethanolamide (PEA), an endogenous molecule part of the endocannabinoid system available as a dietary supplement, exerts on these alterations and their underlying mechanisms, with the goal of identifying a novel therapeutic approach to reduce craving and prevent relapse in patients with OUD.

Conditions

Opioid Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

PEA 600 mg

PEA capsules (600 mg twice a day) will be administered for 21 days

Group Type: ACTIVE_COMPARATOR

Palmitoylethanolamide

Intervention Type: DRUG

Palmitoyethanolamide (PEA) s a dietary supplement with anti-inflammatory and analgesic properties. Subjects will receive PEA (Levagen+) 600 capsules mg twice daily (BID) orally from Day 1 to Day 21

Placebo

Placebo capsules (600 mg twice a day) will be administered for 21 days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Participants will receive placebo matched to 600 mg PEA (Levagen+) capsules BID orally from Day 1 to Day 21

Interventions

Palmitoylethanolamide

Palmitoyethanolamide (PEA) s a dietary supplement with anti-inflammatory and analgesic properties. Subjects will receive PEA (Levagen+) 600 capsules mg twice daily (BID) orally from Day 1 to Day 21

Intervention Type: DRUG

Placebo

Participants will receive placebo matched to 600 mg PEA (Levagen+) capsules BID orally from Day 1 to Day 21

Intervention Type: OTHER

Other Intervention Names

Levagen+

Eligibility Criteria

Inclusion Criteria

• Age 18 to 65
• DSM-5 diagnosis of OUD
• English speaking
• Receiving either buprenorphine or methadone for treatment of opioid use disorder for at least 3 consecutive months prior to enrollment
• Receiving a stable dose of buprenorphine or methadone for the duration of the study
• Agreeable to abstaining from using any cannabis or CBD products two weeks prior to enrollment in the study, and for the duration of the trial
• For women of childbearing potential: agreeable to use one of the following:

• hormonal methods, such as birth control pills, patches, injections, vaginal rings, or implants
• barrier methods (such as a condom or diaphragm) used with a spermicide (a foam, cream, or gel that kills sperm)
• intrauterine device (IUD)
• abstinence (no sex)

Exclusion Criteria

• DSM-5 diagnosis of moderate-to-severe cannabis use disorder, alcohol use disorder, and/or psychostimulant use disorder [medical record review and health history form]
• Active, recurrent substance use within the last 3 months that will interfere with study participation and completion of study procedures [medical record review and health history form]
• History of psychotic, bipolar and schizoaffective disorders [medical record review and health history form]
• Lifetime psychiatric hospitalization or suicide attempt, as assessed by the health history form
• Recent history (within 2 years) of major depressive disorder [health history form and clinical interview]
• Currently pregnant or breastfeeding (female only) [pregnancy test/ self-reported]
• History of autoimmune or chronic inflammatory diseases [health history form] Current use of medications known to alter inflammatory and immune response [health history form] Raynaud's disease [health history form]
• BMI >45
• Hepatic liver enzymes greater than 3x upper normal limit
• Vital signs: HR ≤60 or ≥100, SBP ≤90 or ≥160, DBP ≤50 or ≥100, RR < 12 or > 20
• Recent history of clinically significant medical conditions including, but not limited to, malignancy (and treatment for malignancy), HIV, immunological, endocrine (including uncontrolled diabetes or thyroid disease), renal, GI, or hematological abnormalities that are uncontrolled* [health history form and medical record review]

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Primavera A. Spagnolo, MD, PhD

Assistant Professor/Research Scientist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

2022P001440

Identifier Type: -

Identifier Source: org_study_id