Endocannabinoids, Stress, Craving And Pain Effects Study

NCT05480072 | Completed Early Phase 1 FDA Drug

• 1 other identifier: 2022P001440
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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

Keywords

palmitoylethanolamide; stress; craving; pain

Outcome Measures

Primary Outcomes (1)

• stress-induced opioid craving visual analog scale (VAS)

  decrease from baseline in experimentally-provoked stress-induced craving ratings as measured via the visual analog scale (0= no craving to 100= extremely strong craving). Lower scores indicate reduced craving

  day 21

Study Arms (2)

PEA 600 mg

ACTIVE COMPARATOR

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

Drug: Palmitoylethanolamide

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Palmitoylethanolamide 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

Also known as: Levagen+

PEA 600 mg

Placebo OTHER

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

Placebo

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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\* \[health history form and medical record review\]

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders; Pain

Interventions

palmidrol

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: early phase 1
• 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: Assistant Professor/Research Scientist

Study Record Dates

• First Submitted: July 27, 2022
• First Posted: July 29, 2022
• Study Start: November 1, 2022
• Primary Completion: January 14, 2025
• Study Completion: January 14, 2025
• Last Updated: October 20, 2025

Record last verified: 2025-09

Locations

US (1)