Opioid WithdrawalPhase 1/2NCT04238754
Oral Cannabidiol for Opioid Withdrawal
A Phase 1/2 study testing Epidiolex in people with Opioid Withdrawal and Opioid Craving, run by Johns Hopkins University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Opioid Withdrawal, Opioid Craving, Opioid Use Disorder
- What is being tested?
- Epidiolex
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2020to 30 Jun 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Medically cleared to take study medication
- Are not pregnant or breast feeding
- Willing to comply with the study protocol
- Provides urine that tests positive for methadone
- Maintained on 80-120 mg of daily methadone with no dose changes in the past 2 weeks (verified through a medical release with the participant's provider)
Who cannot join
- 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
Show all 17Show fewer
- Past 14 day use of any of the following contraindicated medications:
- Clobazam, Valproate
- Moderate or strong inhibitors of CYP3A4 or CYPC19 (with the exception of methadone, as outlined in the Protection Against CBD Risks section).
- Strong CYP3A4 or CYP2C19 inducers
- UGT1A9, UGT2B7, CYP1A2, CYP2C8, CYP2C9 and CYP2C19 substrates (with the exclusion of caffeine).
- Central nervous system (CNS) depressants that are contraindicated with Epidiolex
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Placebo-Controlled Evaluation of the Safety of Oral Cannabidiol in a Clinically Relevant Model of Opioid Withdrawal
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.
Read the detailed description
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.
- Conditions
- Opioid Withdrawal, Opioid Craving, Opioid Use Disorder
- Being tested
- Epidiolex, Placebo
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EpidiolexDrug
Also called Cannabidiol
Epidiolex 100 mg/mL Oral Solution
PlaceboDrug
Cherry syrup oral solution
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Epidiolex; Drug: Placebo |
| 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. Receives: Drug: Epidiolex; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Baseline, during residential session up to 57 hours
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: at the end of the 57-hour residential session, prior to discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2020
- Study start1 Nov 2020
- Primary completion30 Jun 2022
- Study completion30 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Opioid WithdrawalStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- Dalio Foundation
- Responsible party
- Sponsor
- Investigators
- Cecilia L Bergeria, PhD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04238754
- Sponsor's protocol ID
- IRB00232412
- Status last verified
- Aug 2023
- First submitted
- 17 Jan 2020
- Last updated
- 29 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 42113179
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Placebo-Controlled Evaluation of the Safety of Oral Cannabidiol in a Clinically Relevant Model of Opioid Withdrawal
- ClinicalTrials.gov ID
- NCT04238754
- Acronym / sponsor ID
- IRB00232412
- Conditions
- Opioid Withdrawal, Opioid Craving, Opioid Use Disorder
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- Dalio Foundation
- Study start
- 1 Nov 2020 (actual)
- Primary completion
- 30 Jun 2022 (actual)
- Study completion
- 30 Jun 2022 (actual)
- First posted
- 23 Jan 2020 (actual)
- Results
- Posted 29 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Epidiolex (CBD) Then Placebo | Experimental | Drug: Epidiolex, Drug: PlaceboParticipants 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. |
| Placebo Then Epidiolex | Placebo comparator | Drug: Epidiolex, Drug: PlaceboParticipants 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Medically cleared to take study medication
- Are not pregnant or breast feeding
- Willing to comply with the study protocol
- Provides urine that tests positive for methadone
- Maintained on 80-120 mg of daily methadone with no dose changes in the past 2 weeks (verified through a medical release with the participant's provider)
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EpidiolexAlso: CannabidiolEpidiolex 100 mg/mL Oral Solution | Drug | Epidiolex (CBD) Then Placebo, Placebo Then Epidiolex |
| PlaceboCherry syrup oral solution | Drug | Epidiolex (CBD) Then Placebo, Placebo Then Epidiolex |
Primary outcome
Safety as Assessed by Number of Adverse Events
Time frame: through completion of the two study sessions, an average of 17 days
Number of Adverse Events reported across sessions with and without study drug. Adverse events were collected for the entire 57 hour session.
Number of Participants Whose Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) Levels >3x Upper Limit of Normal
Time frame: End of residential stay, prior to discharge
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.
Change in Withdrawal Scores From Baseline AfterReceiving Placebo
Time frame: Baseline, during residential session up to 57 hours
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.
4 secondary outcomes
Initial Efficacy of Study Drug as Assessed by Area Under the Curve for the Subjective Opiate Withdrawal Scale (SOWS) Scores
Time frame: 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
Time frame: at the end of the 57-hour residential session, prior to discharge
Acceptability Assessed by Visual Analog Ratings
Time frame: 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
Time frame: at the end of the 57-hour residential session, prior to discharge
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42113179Srungaram 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cecilia L Bergeria, PhD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Epidiolex in people with Opioid Withdrawal and Opioid Craving, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety as Assessed by Number of Adverse Events (time frame: through completion of the two study sessions, an average of 17 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04238754, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2023.