Cannabidiol for Opioid Addiction

Opioid Use Disorder Clinical Trial

Official title:

Cannabidiol in the Treatment of Opioid Use Disorder

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06206291
• Other study ID #: STUDY-21-00607
• Secondary ID: GCO# 21-0663
• Status: Recruiting
• Phase: Phase 2
• Start date: October 4, 2023
• Est. completion date: October 2024

Study information

• Verified date: January 2024
• Source: Icahn School of Medicine at Mount Sinai
• Contact: Ruthie Perez
• Phone: 212-585-4696
• Email: ruthie.perez[@]mssm.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The long-term goal of the project is to determine whether cannabidiol (CBD) can reduce craving and relapse in individuals with opioid use disorder (OUD). The first phase of our project was an open cross-over design study in healthy individuals to confirm the safety and pharmacokinetic (PK) effects of CBD. This next phase is to determine whether CBD can serve as a potential adjunct treatment to reduce craving and anxiety in individuals with OUD maintained on opioid agonist therapy.

Description:

In this Phase 2 study, the research team will conduct a double-blind (placebo-controlled) randomized controlled trial to evaluate whether 200mg and/or 400mg CBD (BSPG Laboratories) given twice daily (morning and evening), as compared to placebo, reduces cue-induced craving and anxiety in individuals with opioid use disorder who are maintained on methadone or buprenorphine. In addition to in-lab physiological and behavioral assessments of cue-induced craving and anxiety, the research team will also employ ecological momentary assessment to obtain real-world measures of symptoms including craving, anxiety, and mood.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

INCLUSION CRITERIA:

An individual who meets all of the following criteria will be eligible for study

participation:

• Individuals between 18 and 65 years old
• Ability to understand and give informed consent.
• Current opioid use disorder (OUD) or OUD in remission while on maintenance therapy with OAT, as determined by DSM-5 with the M.I.N.I. interview (Mini-International Neuropsychiatric Interview).
• Current opioid agonist maintenance treatment in an opioid treatment program with methadone or buprenorphine for at least 14 days prior to study participation. With the

following more specific criteria for each of these two medications:

• Current methadone maintenance treatment with a dose of = 40mg/day, (maximum:

200mg/day), AND urinary toxicology positive for methadone and EDDP; OR

• Current buprenorphine maintenance treatment with a dose of = 8mg/day (maximum:

24mg/day), AND urinary toxicology positive for buprenorphine. EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation:

• Participants who are non-English speaking.
• Psychiatric conditions under DSM-5 (examined with the MINI) that would make study participation unsafe or which would prevent adherence to study procedure; examples include: suicidal or homicidal ideation requiring immediate attention, inadequately-treated mental health disorder (e.g., active psychosis, uncontrolled bipolar disorder).
• Current diagnosis of a severe substance use disorder (except for opioid and nicotine/tobacco) in the past 3 months, based on the MINI interview, that would preclude safe participation in the study as determined by the study medical clinician.
• Alcohol intoxication when arriving at the study site (i.e., positive alcohol breathalyzer / alcohol salivary strips / urine alcohol).
• Signs of acute drug intoxication when arriving at the study site as determined by clinician assessment.
• Medical or psychiatric contraindications for CBD administration (e.g., history of hypersensitivity to cannabinoids); or any of the ingredients in the product (gelatin or sesame oil).
• Showing signs of acute opioid withdrawal symptoms (as determined by the result of the Clinical Opiate Withdrawal Scale (COWS). A Score of = 5 or as interpreted by the investigator will be considered a positive result for withdrawal symptoms).
• Have a medical condition that would make study participation unsafe, which would make treatment compliance difficult, or would prevent adherence to study procedure. This

includes, but is not limited to the following criteria:

• History of impaired renal function or elevated liver enzymes at prescreening. The exclusionary lab values are: >4x the upper limit of normal (ULN) per laboratory criteria for AST or ALT, >1.5x ULN for bilirubin or <30mL/min/1.73m2 eGFR
• QTc Frederica > 500ms
• Participating in another pharmacotherapeutic trial in the past 3 months.
• Participants who have used any medication, dietary supplements (and/or grapefruit juice), or combination of medications and supplements known to alter the metabolism of, or interact with CBD (buproprion, rifampin, barbiturates, phenothiazines, cimetidine, etc.) 14 days prior to and during the duration of the study
• For women: being pregnant (positive urine test for pregnancy) or breastfeeding.
• Not using an appropriate method of contraception such as hormonal contraception (oral hormonal contraceptives, Depo-Provera, Nuva-Ring), intrauterine device (IUD), sterilization, or double barrier method (combination of any two barrier methods used simultaneously, i.e. condom, spermicide, diaphragm).
• Participants who have been court mandated to attend treatment centers.

Related Conditions & MeSH terms

• Opioid Use Disorder
• Opioid-Related Disorders
• Substance-Related Disorders

Intervention

Drug:
• Placebo
Matching placebo twice daily for first 4 weeks
• Cannabidiol (CBD) 200mg
First 4 weeks: CBD (200mg)/Placebo twice daily adjunct with opioid agonist treatment.
• Cannabidiol (CBD) 400mg
Second 4 weeks: All cohorts receive CBD (400mg) twice daily adjunct with opioid agonist treatment.

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Yasmin Hurd

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Visual Analog Scale for Craving (VASC)	Cue-induced Visual Analog Scale for craving is used to measure subjective craving responses to a drug and neutral video cues evaluated in the clinic. Changes in craving from baseline (pre-cue to post-cue and pre-neutral cue to post-neutral cue) will be measured and compared. Total scale ranges from 0-10, with higher scores indicating extreme cravings.	Baseline and 4 weeks
Primary	Change in Visual Analog Scale Anxiety (VASA)	Cue-induced Visual Analog Scale Anxiety is used to measure subjective anxiety responses to a drug and neutral video cue evaluated in the clinic. Changes in anxiety from baseline (pre-cue to post-cue and pre-neutral cue to post-neutral cue) will be measured and compared. Total scale from 0-10, with higher score indicating extreme anxiety.	Baseline and 4-weeks
Primary	Proportion of participants with positive urine toxicology	Proportion of participants with positive urine toxicology for illicit opioid use at 4 weeks.	4-weeks
Primary	Systematic Assessment for Treatment Emergent Events (SAFTEE)	Systematic Assessment for Treatment Emergent Events (SAFTEE) is used to measure safety and tolerability. SAFTEE is a side effect self-report assessment scale that consists of 56 potential side effects. Participants rate how bothersome each side effect is on a scale of "none" (0), "mild" (1), "moderate" (2), "severe" (3). Total score ranges 0 - 168, higher scores indicate a higher level of side effect burden.	weekly for 8 weeks
Secondary	Change in Visual Analog Scale for craving (VASC)	Cue-induced Visual Analog Scale for craving is used to measure subjective craving responses to a drug and neutral video cues evaluated in the clinic. Changes in craving at 4 weeks compared to baseline (pre-cue to post-cue and pre-neutral cue to post-neutral cue) will be measured and compared. Scale range: 0 (no craving) - 10 (extreme craving). Higher score indicates more extreme craving.	baseline and 4-weeks
Secondary	Change in Visual Analog Scale for craving (VASC)	Cue-induced Visual Analog Scale for craving is used to measure subjective craving responses to a drug and neutral video cues evaluated in the clinic. Changes in craving at 8 weeks as compared to 4 weeks (pre-cue to post-cue and pre-neutral cue to post-neutral cue) will be measured and compared. Scale range: 0 (no craving) - 10 (extreme craving). Higher score indicates more extreme craving.	4-weeks and 8-weeks
Secondary	Change in Visual Analog Scale Anxiety (VASA)	Cue-induced Visual Analog Scale Anxiety is used to measure subjective anxiety responses to a drug and neutral video cue evaluated in the clinic. Changes in anxiety at 4 weeks compared to baseline (pre-cue to post-cue and pre-neutral cue to post-neutral cue) will be measured and compared. Scale: 0 (not at all anxious) - 10 (extremely anxious). Higher score indicates more extreme anxiety.	baseline and 4-weeks
Secondary	Change in Visual Analog Scale Anxiety (VASA)	Cue-induced Visual Analog Scale Anxiety is used to measure subjective anxiety responses to a drug and neutral video cue evaluated in the clinic. Changes in anxiety at 8 weeks as compared to 4 weeks (pre-cue to post-cue and pre-neutral cue to post-neutral cue) will be measured and compared. Scale: 0 (not at all anxious) - 10 (extremely anxious). Higher score indicates more extreme anxiety.	4-weeks and 8-weeks
Secondary	Change in proportion of participants with positive urine toxicology	Proportion of participants with positive urine toxicology for illicit opioid use at 8 weeks as compared to 4 weeks.	4 weeks and 8 weeks
Secondary	Change in Heroin Craving Questionnaire Short Form (HCQ-SF-14)	Heroin Craving Questionnaire Short Form (HCQ-SF-14): A 15 minute, 14 item self-administered to measure general heroin craving. Each item is rated on a 7-point Likert scale (1= strongly disagree, 7= strongly agree). Full scale ranges from 14-98, with higher scores indicating more severe heroin craving.	baseline and 4-weeks
Secondary	Change in Heroin Craving Questionnaire Short Form (HCQ-SF-14)	Heroin Craving Questionnaire Short Form (HCQ-SF-14): A 15 minute, 14 item self-administered to measure general heroin craving. Each item is rated on a 7-point Likert scale (1= strongly disagree, 7= strongly agree). Full scale ranges from 14-98, with higher scores indicating more severe heroin craving.	4-weeks and 8-weeks
Secondary	Change in Generalized Anxiety Disorder Scale (GAD-7)	The General Anxiety Disorder 7-item questionnaire (GAD-7) assesses seven problem items potentially experienced over the past two weeks from "0" (not at all) to "3" (nearly every day). Individuals rank their levels of nervousness, anxiousness, relaxing, restlessness, irritability and fearfulness. Full scale from 0-21, with higher score indicating more anxiety symptoms.	baseline and 4-weeks
Secondary	Change in Generalized Anxiety Disorder Scale (GAD-7)	The General Anxiety Disorder 7-item questionnaire (GAD-7) assesses seven problem items potentially experienced over the past two weeks from "0" (not at all) to "3" (nearly every day). Individuals rank their levels of nervousness, anxiousness, relaxing, restlessness, irritability and fearfulness. Full scale from 0-21, with higher score indicating more anxiety symptoms.	4-weeks and 8-weeks
Secondary	Duration of participant first illicit opioid abstinence		any time during study, 8 weeks
Secondary	Change in Patient Health Questionnaire (PHQ-9)	The Questionnaire Type 9 for Depression (PHQ-9) measures depression severity with the nine DSM-IV criteria scored as "0" (not at all) to "3" (nearly every day). Full scale ranges from 0-27, with higher score indicating more severe symptoms.	baseline and 4-weeks
Secondary	Change in Patient Health Questionnaire (PHQ-9)	The Questionnaire Type 9 for Depression (PHQ-9) measures depression severity with the nine DSM-IV criteria scored as "0" (not at all) to "3" (nearly every day). Full scale ranges from 0-27, with higher score indicating more severe symptoms.	4-weeks and 8-weeks
Secondary	Positive and Negative Affect Schedule (PANAS-SF)	A 20 item self-administered questionnaire evaluating current positive and negative affect. Each item is rated on a 5-point scale (0= Very slightly or not at all, 5= Extremely). Scores range from 10 - 50 for both sets of items. For the total positive score, a higher score indicates more of a positive affect. For the total negative score, a lower score indicates less of a negative affect.	baseline and 4-weeks
Secondary	Positive and Negative Affect Schedule (PANAS-SF)	A 20 item self-administered questionnaire evaluating current positive and negative affect. Each item is rated on a 5-point scale (0= Very slightly or not at all, 5= Extremely). Scores range from 10 - 50 for both sets of items. For the total positive score, a higher score indicates more of a positive affect. For the total negative score, a lower score indicates less of a negative affect.	4-weeks and 8-weeks
Secondary	Change in Heart rate	Heart rate (beats/min) will be monitored throughout the time course of the study and changes from baseline will be studied.	baseline and 8-weeks
Secondary	Change in Blood pressure	Blood pressure (in mmHg) will be monitored throughout the time course of the study and changes from baseline will be studied. Both diastolic and systolic pressures will be assessed.	baseline and 8-weeks
Secondary	Change in Body Temperature	Body temperature (in degrees Fahrenheit) will be monitored throughout the time course of the study and changes from baseline will be studied.	baseline and 8-weeks
Secondary	Change in Oxygen level	Oxygen level will be measured by pulse oximetry when vitals are collected for each participant throughout the study.	baseline and 8-weeks
Secondary	Change in Cue-induced salivary cortisol levels	Study participant will chew on a cotton swab providing a saliva sample from which free cortisol levels will be measured as an indicator of stress response in association with video cues. Thus, the stress of craving will be monitored and measured to observe any changes from baseline.	baseline and 4-weeks
Secondary	Change in Cue-induced salivary cortisol levels	Study participant will chew on a cotton swab providing a saliva sample from which free cortisol levels will be measured as an indicator of stress response in association with video cues. Thus, the stress of craving will be monitored and measured to observe any changes from 4-weeks.	4-weeks and 8-weeks
Secondary	Sleep duration	Average sleep duration measured across 8 weeks.	up to 8-weeks
Secondary	Change in Insomnia Severity Index (ISI)	A 5-10 minute, 7 question self-administered screening tool for insomnia. Each item rates the nature and symptoms of potential sleep problems using a 5-point Likert-type scale. Minimum score of 0 and maximum score of 28, with the highest score indicating prevalence and severity of insomnia.	baseline and 8-weeks
Secondary	Change in The Digit Span Test subtest of the Wechsler Adult Intelligence Scale 4th edition	A 10-15 minute 30-item assessment that includes Digit Span Forward (DSF) and Digit Span Backward (DSB). DSF measures short-term memory, not working memory. DSB measures auditory working memory. Full scale from a minimum score of 0 and maximum score of 30, with the highest score indicating the total number of points achieved for correct responses.	baseline and 8-weeks
Secondary	Change in The Symptom Check List 90 (SCL-90)	The Symptom Check List 90 (SCL-90): A 12-15 minute, 90 item self-administered psychometric instrument yielding nine scores of primary symptom dimensions (5-point rating scale; 1= Not at all, 5= Extremely), along with three scores based on global distress measures. Full scale ranges from a minimum score of 90 and maximum score of 450, with higher scores indicating more severe psychological distress.	baseline and 8-weeks
Secondary	Change in Substance use other than opioids in urine	Substance use other than opioids measured in urine.	baseline and 4-weeks
Secondary	Change in Substance use other than opioids in urine	Substance use other than opioids measured in urine.	4-weeks and 8 weeks
Secondary	Change in Substance use other than opioids in blood	Substance use other than opioids measured in blood.	baseline and 4-weeks
Secondary	Change in Substance use other than opioids in blood	Substance use other than opioids measured in blood.	4-weeks and 8 weeks
Secondary	Change in Concentration of methadone or buprenorphine metabolites in urine	Concentration of methadone or buprenorphine metabolites measured in urine.	baseline and 4-weeks
Secondary	Change in Concentration of methadone or buprenorphine metabolites in urine	Concentration of methadone or buprenorphine metabolites measured in urine.	4-weeks and 8-weeks
Secondary	Change in Concentration of methadone or buprenorphine metabolites in blood	Concentration of methadone or buprenorphine metabolites measured in blood.	baseline and 4-weeks
Secondary	Change in Concentration of methadone or buprenorphine metabolites in blood	Concentration of methadone or buprenorphine metabolites measured in blood.	4-weeks and 8-weeks
Secondary	Number of participants remaining in treatment	Retention in treatment	up to 8 weeks
Secondary	Change in Change in dosage of opioid agonist treatment		baseline and 8 weeks
Secondary	Number of positive urine toxicology	The number of positive urine toxicology to measure adherence	4 weeks
Secondary	Number of positive blood toxicology	The number of positive blood toxicology to measure adherence	4 weeks