Opioid Use Disorder
Conditions
Keywords
CBD, Cannabidiol, Methadone, Buprenorphine, Opioid Use Disorder, OUD
Brief 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.
Detailed 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.
Interventions
DRUGPlacebo
Matching placebo twice daily for first 4 weeks
DRUGCannabidiol (CBD) 200mg
First 4 weeks: CBD (200mg)/Placebo twice daily adjunct with opioid agonist treatment.
DRUGCannabidiol (CBD) 400mg
Second 4 weeks: All cohorts receive CBD (400mg) twice daily adjunct with opioid agonist treatment.
Sponsors
Yasmin Hurd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Visual Analog Scale for Craving (VASC) | Baseline and 4 weeks | 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. |
| Change in Visual Analog Scale Anxiety (VASA) | Baseline and 4-weeks | 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. |
| Percentage of Participants With Positive Urine Toxicology | 4-weeks | Percentage of participants with positive urine toxicology for illicit opioid use at 4 weeks. |
| Systematic Assessment for Treatment Emergent Events (SAFTEE) | weekly for 8 weeks (Baseline, Week 1, 2, 3, 4, 5, 6, 7, and 8) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Visual Analog Scale for Craving (VASC) | 4-weeks and 8-weeks | 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. |
| Change in Visual Analog Scale Anxiety (VASA) | 4-weeks and 8-weeks | 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. |
| Change in Percentage of Participants With Positive Urine Toxicology | 4 weeks and 8 weeks | Proportion of percentage with positive urine toxicology for illicit opioid use at 8 weeks as compared to 4 weeks. |
| Change in Heroin Craving Questionnaire Short Form (HCQ-SF-14) | baseline and 4-weeks, 4-weeks and 8-weeks | 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. |
| Change in Generalized Anxiety Disorder Scale (GAD-7) | Baseline and 4-weeks, 4-weeks and 8-weeks | 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. |
| Duration of Participant First Illicit Opioid Abstinence | any time during study, 8 weeks | — |
| Change in Patient Health Questionnaire (PHQ-9) | baseline and 4-weeks, 4-weeks and 8-weeks | 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. |
| Positive and Negative Affect Schedule (PANAS-SF) | baseline, 4-weeks and 8-weeks, post-cue collected within 10 minutes of pre-cue | 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. |
| Change in Heart Rate | baseline and 8-weeks | Heart rate (beats/min) will be monitored throughout the time course of the study and change at Week 8 from baseline will be studied. |
| Change in Blood Pressure | baseline and 8-weeks | Blood pressure (in mmHg) will be monitored throughout the time course of the study and changes at week 8 as compared from baseline will be studied. Both diastolic and systolic pressures will be assessed. |
| Change in Body Temperature | baseline and 8-weeks | Body temperature (in degrees Fahrenheit) will be monitored throughout the time course of the study and changes at week 8 from baseline will be studied. |
| Change in Oxygen Level | baseline and 8-weeks | Oxygen level will be measured by pulse oximetry when vitals are collected. Change in oxygen level at week 8 as compared to baseline |
| Change in Cue-induced Salivary Cortisol Levels | Baseline and 4-weeks, 4-weeks and 8-weeks | 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 neutral cue induced changes from between baseline and 4 weeks, and between 4 weeks and 8 weeks. |
| Sleep Duration in Minutes Per Night | up to 8-weeks | Average sleep duration measured across 8 weeks. |
| Change in Insomnia Severity Index (ISI) | baseline and 8-weeks | 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. |
| Change in The Digit Span Test Subtest of the Wechsler Adult Intelligence Scale 4th Edition | baseline and 8-weeks | 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. |
| Change in The Symptom Check List 90 (SCL-90) | baseline and 8-weeks | 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. |
| Change in Percentage of Participants With THC Positive in Urine. | baseline and 4-weeks, 4-weeks and 8 weeks | Change in percentage of participants with THC positive in Urine - Substance use other than opioids measured in urine. |
| Change in Plasma Level of THC Positive in Blood. | baseline and 4-weeks, 4-weeks and 8 weeks | Change in plasma level THC Positive in - Substance use other than opioids measured in blood. |
| Change in Concentration of Methadone Metabolites in Blood | baseline and 4-weeks, 4-weeks and 8-weeks | Concentration of methadone metabolites measured in blood. |
| Change in Concentration of Buprenorphine Metabolites in Blood | baseline and 4-weeks, 4-weeks and 8 weeks | Concentration of buprenorphine metabolites measured in blood. |
| Number of Participants Remaining in Treatment | up to 8 weeks | Retention in treatment as measured by number of participants remaining in treatment. |
| Change Methadone Dosage of Opioid Agonist Treatment | baseline and 8 weeks | Change in the methadone dosage at Week 8 as compared to baseline. |
| Number of CBD-COOH Positive Blood Toxicology | 4 weeks | The number of CBD-COOH positive blood toxicology to measure adherence |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORYasmin Hurd, PhD
Icahn School of Medicine at Mount Sinai
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 45.74 years STANDARD_DEVIATION 11.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 25 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 30 | 0 / 55 | 0 / 8 | 0 / 6 | 0 / 13 |
| other Total, other adverse events | 12 / 32 | 21 / 30 | 38 / 55 | 5 / 8 | 4 / 6 | 6 / 13 |
| serious Total, serious adverse events | 0 / 32 | 0 / 30 | 0 / 55 | 0 / 8 | 0 / 6 | 0 / 13 |
Outcome results
None listed