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| Name | Class |
|---|---|
| Dalio Foundation | OTHER |
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This pilot study will examine the safety of the cannabinoid cannabidiol (Epidiolex) in a human laboratory model of clinically relevant withdrawal. The study will be a residential within-subject comparison; all participants will receive placebo dosing and active cannabidiol. Results may be used to support an R01 grant application to more closely examine this hypothesis.
Based on preclinical research and emerging human research, cannabidiol (CBD; a major constituent of the cannabis plant) is a promising pharmacotherapy for the treatment of opioid withdrawal. Most recently, CBD decreased cue-induced craving and anxiety (two common withdrawal symptoms) among abstinent heroin-dependent individuals relative to placebo. As of June 2018, Epidiolex, an oral formulation of plant-derived pure CBD, has been approved by the U.S. Food and Drug Administration (FDA) for treating severe forms of epilepsy and can be prescribed for other off-label indications. Epidiolex has a low side effect and high safety profile. Given the recent FDA approval of Epidiolex, and a growing interest to develop existing pharmaceuticals to address issues related to Opioid Use Disorder (OUD) and its recovery, the investigators are proposing a pilot study to examine the safety of Epidiolex in a human laboratory model of clinically relevant withdrawal. The study will be a residential within-subject comparison; methadone-maintained participants will undergo spontaneous withdrawal and receive placebo dosing and active cannabidiol. Data collected for this study will establish: (1) the safety of administering two dosing regimens of Epidiolex within the investigators' withdrawal paradigm and (2) the feasibility of the investigators' withdrawal paradigm for demonstrating clinically meaningful increases in withdrawal. Results may be used to support an R01 grant application to more closely examine this hypothesis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Epidiolex (CBD) Then Placebo | Experimental | Participants first receive 8 mL of Epidiolex (800 mg of cannabidiol) + 16 mL of inactive cherry syrup delivered every 12 hours for 48 hours total (4 doses) during which prescribed methadone is withheld. After 1 week, they receive 20 mL of inactive cherry syrup delivered every 12 hours for 48hours total (4 doses) during which prescribed methadone is withheld. |
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| Placebo Then Epidiolex | Placebo Comparator | Participants first receive 20 mL of inactive cherry syrup delivered every 12 hours for 48hours total (4 doses) during which prescribed methadone is withheld. After 1 week washout, they receive 8 mL of Epidiolex (800 mg of cannabidiol) + 16 mL of inactive cherry syrup delivered every 12 hours for 48 hours total (4 doses) during which prescribed methadone is withheld. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Epidiolex | Drug | Epidiolex 100 mg/mL Oral Solution |
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| Measure | Description | Time Frame |
|---|---|---|
| Safety as Assessed by Number of Adverse Events | Number of Adverse Events reported across sessions with and without study drug. Adverse events were collected for the entire 57 hour session. | through completion of the two study sessions, an average of 17 days |
| Number of Participants Whose Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) Levels >3x Upper Limit of Normal | Number of participants whose AST/ALT levels >3x upper limit of normal (ULN) at the end of a study session when they receive Epidiolex and Placebo. This will be used in the assessment of safety. | End of residential stay, prior to discharge |
| Change in Withdrawal Scores From Baseline AfterReceiving Placebo | Change in withdrawal scores during laboratory evaluation of spontaneous withdrawal. Withdrawal is measured with the Subjective Opiate Withdrawal Scale (SOWS). That has a range of 0-64 where a mild score is represented by a score of 1-10, a moderate score is represented by a score of 11-20 and a severe score is considered anything greater than 21. | Baseline, during residential session up to 57 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Initial Efficacy of Study Drug as Assessed by Area Under the Curve for the Subjective Opiate Withdrawal Scale (SOWS) Scores | Withdrawal symptom suppression during active and placebo conditions. Area Under the Curve (AUC) analyses will be calculated to characterize withdrawal on the Subjective Opiate Withdrawal Scale (SOWS) scores across time. SOWS AUC will be compared between the two conditions. AUC will range from 0 to 3072 where 0 represents no withdrawal during study drug administration and 3072 represents the most severe withdrawal during study drug administration. |
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Inclusion Criteria:
Exclusion Criteria:
Meet Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for alcohol/substance use disorder other than opioid use disorder
Previous adverse reaction to a cannabinoid product
Self-report any illicit drug use or cannabinoid use in the past 7 days
Presence of any clinically significant medical/psychiatric illness judged by the investigators to put subject at elevated risk for experiencing an adverse events
Past year suicidal behavior as assessed via the Columbia Suicide Severity Rating Scale
History of seizure disorder
Past 14 day use of any of the following contraindicated medications:
Breathalyzer that tests positive for alcohol prior to session admission
Self-reported consumption of grapefruit juice within 24 hours of session admission
Have a history of clinically significant cardiac arrhythmias or vasospastic disease
Have circumstances that the study investigators believe are contraindicated with study participation and/or would interfere with study participation (e.g., impending jail).
Moderate-severe hepatic impairment as indicated by ALT or AST levels > 3x ULN and/or Bilirubin levels >2x ULN as evidenced by a blood test.
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| Name | Affiliation | Role |
|---|---|---|
| Cecilia L Bergeria, PhD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins University | Baltimore | Maryland | 21224 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42113179 | Derived | Srungaram D, Rincon N, Durgin CJ, Dunn KE, Bergeria CL. Feasibility data from a novel laboratory model of spontaneous opioid withdrawal. Exp Clin Psychopharmacol. 2026 May 11. doi: 10.1037/pha0000850. Online ahead of print. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Epidiolex Then Placebo | Participants first receive 8 mL of Epidiolex (800 mg of cannabidiol) + 16 mL of inactive cherry syrup delivered every 12 hours for 48 hours total (4 doses) during which prescribed methadone is withheld. After 1 week, they receive 20 mL of inactive cherry syrup delivered every 12 hours for 48hours total (4 doses) during which prescribed methadone is withheld. |
| FG001 | Placebo Then Epidiolex | Participants first receive 20 mL of inactive cherry syrup delivered every 12 hours for 48hours total (4 doses) during which prescribed methadone is withheld. After 1 week washout, they receive 8 mL of Epidiolex (800 mg of cannabidiol) + 16 mL of inactive cherry syrup delivered every 12 hours for 48 hours total (4 doses) during which prescribed methadone is withheld. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention |
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| Washout - 1 Week |
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| Second Intervention |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | Each participant will receive Epidiolex oral solution and Cherry syrup oral solution (placebo) in a randomized fashion. Epidiolex 100 mg/mL Oral Solution: 8 mL of Epidiolex (800 mg of cannabidiol) + 16 mL of inactive cherry syrup delivered every 12 hours for 48 hours total (4 doses) Cherry Syrup Oral Solution: 20 mL of inactive cherry syrup delivered every 12 hours for 48 hours total (4 doses) |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Safety as Assessed by Number of Adverse Events | Number of Adverse Events reported across sessions with and without study drug. Adverse events were collected for the entire 57 hour session. | Posted | Number | Adverse Events | through completion of the two study sessions, an average of 17 days |
|
through completion of the two study sessions, an average of 17 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Epidiolex | Epidiolex 100 mg/mL oral solution: 8 mL of Epidiolex (800 mg of cannabidiol) + 16 mL of inactive cherry syrup delivered every 12 hours for 48 hours total (4 doses) |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Drowsiness | Nervous system disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Cecilia Bergeria | Johns Hopkins Univeristy | 410-550-1979 | cberge21@jhmi.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 28, 2021 | Jun 15, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009293 | Opioid-Related Disorders |
| ID | Term |
|---|---|
| D000079524 | Narcotic-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D002185 | Cannabidiol |
| ID | Term |
|---|---|
| D002186 | Cannabinoids |
| D013729 | Terpenes |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
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Within subject comparison of Epidiolex to placebo. The order of study drug (active Epidiolex or placebo) is randomized across participants. Epidiolex is flavor masked with cherry syrup.
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Epidiolex is flavor masked with cherry syrup.
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| Placebo | Drug | Cherry syrup oral solution |
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| After first administration of study drug and up to 48 hours |
| Acceptability Assessed by Number of Participants Who Would Recommend the Medication to a Family Member or Friend | Number of participants who would recommend the medication to a family member or friend trying to taper down from opioid medications. | at the end of the 57-hour residential session, prior to discharge |
| Acceptability Assessed by Visual Analog Ratings | Visual analog ratings of the degree to which the medication suppressed opioid withdrawal symptoms. The visual analog ratings will be scored on a scale from 0-100 where 0 represents no suppression of withdrawal and 100 represents complete suppression of withdrawal. | at the end of the 57-hour residential session, prior to discharge |
| Acceptability Assessed by Rating of Medication Acceptance on a 5-point Acceptance Rating Scale | Participant rating of medication acceptance on a 5-point acceptance rating scale. The acceptance rating scale will range from 0-4 where 0 represents no acceptance of the medication and 4 represents complete acceptance of the medication. | at the end of the 57-hour residential session, prior to discharge |
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| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Units |
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| Counts |
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| Participants |
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| Primary | Number of Participants Whose Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) Levels >3x Upper Limit of Normal | Number of participants whose AST/ALT levels >3x upper limit of normal (ULN) at the end of a study session when they receive Epidiolex and Placebo. This will be used in the assessment of safety. | Posted | Count of Participants | Participants | End of residential stay, prior to discharge |
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| Primary | Change in Withdrawal Scores From Baseline AfterReceiving Placebo | Change in withdrawal scores during laboratory evaluation of spontaneous withdrawal. Withdrawal is measured with the Subjective Opiate Withdrawal Scale (SOWS). That has a range of 0-64 where a mild score is represented by a score of 1-10, a moderate score is represented by a score of 11-20 and a severe score is considered anything greater than 21. | Posted | Mean | Standard Deviation | score on a scale | Baseline, during residential session up to 57 hours |
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| Secondary | Initial Efficacy of Study Drug as Assessed by Area Under the Curve for the Subjective Opiate Withdrawal Scale (SOWS) Scores | Withdrawal symptom suppression during active and placebo conditions. Area Under the Curve (AUC) analyses will be calculated to characterize withdrawal on the Subjective Opiate Withdrawal Scale (SOWS) scores across time. SOWS AUC will be compared between the two conditions. AUC will range from 0 to 3072 where 0 represents no withdrawal during study drug administration and 3072 represents the most severe withdrawal during study drug administration. | Posted | Mean | Standard Deviation | scores on SOWS scale X hour | After first administration of study drug and up to 48 hours |
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| Secondary | Acceptability Assessed by Number of Participants Who Would Recommend the Medication to a Family Member or Friend | Number of participants who would recommend the medication to a family member or friend trying to taper down from opioid medications. | Posted | Count of Participants | Participants | at the end of the 57-hour residential session, prior to discharge |
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| Secondary | Acceptability Assessed by Visual Analog Ratings | Visual analog ratings of the degree to which the medication suppressed opioid withdrawal symptoms. The visual analog ratings will be scored on a scale from 0-100 where 0 represents no suppression of withdrawal and 100 represents complete suppression of withdrawal. | Posted | Mean | Standard Deviation | units on a scale | at the end of the 57-hour residential session, prior to discharge |
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| Secondary | Acceptability Assessed by Rating of Medication Acceptance on a 5-point Acceptance Rating Scale | Participant rating of medication acceptance on a 5-point acceptance rating scale. The acceptance rating scale will range from 0-4 where 0 represents no acceptance of the medication and 4 represents complete acceptance of the medication. | Posted | Mean | Standard Deviation | score on a scale | at the end of the 57-hour residential session, prior to discharge |
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| 0 |
| 3 |
| 0 |
| 3 |
| 2 |
| 3 |
| EG001 | Placebo | Cherry Syrup Oral Solution: 20 mL of inactive cherry syrup delivered every 12 hours for 48 hours total (4 doses) | 0 | 3 | 0 | 3 | 1 | 3 |
| Abdominal Pain | Gastrointestinal disorders | Non-systematic Assessment |
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| Back Pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Headache | Nervous system disorders | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | Non-systematic Assessment |
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