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Acute and Short-term Effects of Cannabidiol Admin on Cue-induced Craving in Drug-abstinent Heroin Dependent Humans

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ClinicalTrials.gov Identifier: NCT01605539
Recruitment Status : Completed
First Posted : May 25, 2012
Results First Posted : November 28, 2016
Last Update Posted : November 28, 2016
Sponsor:
Information provided by (Responsible Party):
Yasmin Hurd, Hurd,Yasmin, Ph.D.

Tracking Information
First Submitted Date  ICMJE May 2, 2012
First Posted Date  ICMJE May 25, 2012
Results First Submitted Date  ICMJE September 28, 2015
Results First Posted Date  ICMJE November 28, 2016
Last Update Posted Date November 28, 2016
Study Start Date  ICMJE May 2012
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 5, 2016)
  • Changes in Cue-Induced In-Clinic Craving (From Baseline to Post-cue or Post-neutral - Via the Visual Analog Scale for Craving (VASC) [ Time Frame: VASC: test visits I, II and IV - baseline 1, post cue (PC), baseline 2, post neutral cue (PN) ]
    The VASC will be administered to assess potential variations in the subjective craving effects associated with heroin. Following the administration of the investigational drug, craving induced in response to the cue sessions and neutral cue sessions in the clinic will be measured. In this way, changes in craving from baseline (pre-cue to post-cue and pre-neutral cue to post-neutral cue) within each test visit) will be measured and compared. Scale range: 0 (no craving) - 10 (extreme craving). **For test visits I, II and IV, there will be two cue sessions at each test visit: a neutral cue video (PN) and a drug-related cue video (PC) will be shown in random order at each visit. Before the beginning of each cue session (PN or PC), baseline measures will be taken. The same questionnaires will be administered immediately following the neutral cue video and the drug-related cue video. Thus there will be two sets of baselines and two sets of post cue measurements per test visit for test
  • Changes in Out-of-Clinic Craving (From Pre-Dose to Approximately 6 Hours Post-Dose for Test Visits I and II; and From Pre-Dose Test Visit I to Pre-Cue Test Visit IV) - Via the Heroin Craving Questionnaire (HCQ) [ Time Frame: Test I and II: Change from pre-dose to approx. 6 hours post-dose; Change from pre-dose test visit I to pre-cue test visit IV ]
    Subjects will be asked to complete the short version of the HCQ on their own time at home and bring it with them when they return for their next visit. Upon arrival to the clinic, subjects will also complete an HCQ with the coordinator to assess daily baseline cravings. This questionnaire will help us assess changes in craving generated outside of the clinical laboratory session from test visit 1 through test visit 4. Scale: 1 (strongly disagree) - 7 (strongly agree). Total Score Range: 14 (less cravings) - 98 (more cravings). ** The baseline measure for this outcome will be measured at the beginning of test session I prior to the administration of CBD/Placebo. Test measures will be taken approximately 6 hours following each dose for test sessions I, II and III. The final measure will be taken at test session IV, at the beginning of the session.
Original Primary Outcome Measures  ICMJE
 (submitted: May 21, 2012)
  • In-Clinic Craving Assessment - The Visual Analog Scale for Craving (VASC) [ Time Frame: 0 min, 25min, 45min, 65min where 0 is the beginning of cue-induced craving session in visits 2, 3, and 5 ]
    Questionnaires will be used to measure subjective responses. The VASC will be administered to assess potential variations in the subjective craving effects associated to heroin. In this way, craving will be monitored and measured across the multiple time points to observe if any changes from baseline occur.
  • Out-Clinic Craving Assessment - Heroin Craving Questionnaire [ Time Frame: 4 times in-clinic, pre-dose/craving session and 3 times at home: on average 6-8hrs after end of visits 2, 3, and 4 ]
    Subjects will be asked to complete the short version of the HCQ on their own time at home and bring it with them when they return for their next visit. Upon arrival to the clinic, subjects will also complete an HCQ with the coordinator to assess daily baseline cravings. This questionnaire will help us assess craving generated outside of the clinical laboratory session.
Change History Complete list of historical versions of study NCT01605539 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 5, 2016)
  • Vital Signs - Blood Pressure [ Time Frame: Test sessions 1,2,and 4: baseline 1, post cue (PC), baseline 2, post neutral cue (PN) ]
    Blood pressure (mmHg) will be monitored throughout the time course of the study and changes from baseline will be studied across the various time points. **For test visits I, II and IV, there will be two cue sessions at each test visit: a neutral cue video (PN) and a drug-related cue video (PC) will be shown in random order at each visit. Before the beginning of each cue session (PN or PC), baseline measures will be taken. Blood pressure will be measured again following the neutral cue video and the drug-related cue video. Thus there will be two sets of baselines and two sets of post cue measurements per test visit for test visits I, II and IV.
  • Visual Analog Scale for Anxiety (VASA) [ Time Frame: Test visit I, II and IV: baseline 1, post cue (PC), baseline 2, post neutral cue (PN) ]
    Questionnaires will be used to measure subjective responses. Anxiety will be assessed using a visual analog scale for anxiety (VASA). Scale: 0 (not at all anxious) - 10 (extremely anxious). **For test visits I, II and IV, there will be two cue sessions at each test visit: a neutral cue video (PN) and a drug-related cue video (PC) will be shown in random order at each visit. Before the beginning of each cue session (PN or PC), baseline measures will be taken for each variable. The same variables will be measured following the neutral cue video and the drug-related cue video. Thus there will be two sets of baselines and two sets of post cue measurements per test visit for test visits I, II and IV.
  • The Positive and Negative Affect Schedule (PANAS) - Positive Affect Schedule (PAS) Data [ Time Frame: Test session 1, 2, and 4: baseline 1, post cue (PC), baseline 2, post neutral cue (PN) ]
    Questionnaires will be used to measure subjective responses. The Positive and Negative Affect Schedule will allow us to obtain positive and negative affect measures and observe their changes from baseline over the course of the cue-induced craving session. Scale: 0 (only slightly or not at all) - 5 (extremely). Total Score Range for Positive Affect Assessment (PAS): 10 (minimum) - 50 (maximum). Higher score reflects stronger positive affect. **For test visits I, II and IV, there will be two cue sessions at each test visit: a neutral cue video (PN) and a drug-related cue video (PC) will be shown in random order at each visit. Before the beginning of each cue session (PN or PC), baseline measures will be taken for each variable. The same variables will be measured following the neutral cue video and the drug-related cue video. Thus there will be two sets of baselines and two sets of post cue measurements per test visit for test visits I, II and IV.
  • The Positive and Negative Affect Schedule (PANAS) - Negative Affect Schedule (NAS) Data [ Time Frame: Test session 1, 2, and 4: baseline 1, post cue (PC), baseline 2, post neutral cue (PN) ]
    Questionnaires will be used to measure subjective responses. The Positive and Negative Affect Schedule will allow us to obtain positive and negative affect measures and observe their changes from baseline over the course of the cue-induced craving session. Scale: 0 (only slightly or not at all) - 5 (extremely). Total Score Range for Negative Affect Assessment (NAS): 10 (minimum) - 50 (maximum). Higher score reflects stronger negative affect. **For test visits I, II and IV, there will be two cue sessions at each test visit: a neutral cue video (PN) and a drug-related cue video (PC) will be shown in random order at each visit. Before the beginning of each cue session (PN or PC), baseline measures will be taken for each variable. The same variables will be measured following the neutral cue video and the drug-related cue video. Thus there will be two sets of baselines and two sets of post cue measurements per test visit for test visits I, II and IV.
  • Vital Signs - Heart Rate [ Time Frame: Test sessions 1,2,and 4: baseline 1, post cue (PC), baseline 2, post neutral cue (PN) ]
    Heart rate (in beats/min) will be monitored throughout the time course of the study and changes from baseline will be studied across the various time points. **For test visits I, II and IV, there will be two cue sessions at each test visit: a neutral cue video (PN) and a drug-related cue video (PC) will be shown in random order at each visit. Before the beginning of each cue session (PN or PC), baseline measures will be taken. Heart rate will be measured again following the neutral cue video and the drug-related cue video. Thus there will be two sets of baselines and two sets of post cue measurements per test visit for test visits I, II and IV.
  • Vital Signs - Respiratory Rate [ Time Frame: Test sessions 1,2,and 4: baseline 1, post cue (PC), baseline 2, post neutral cue (PN) ]
    Respiratory rate (in breaths/min) will be monitored throughout the time course of the study and changes from baseline will be studied across the various time points. **For test visits I, II and IV, there will be two cue sessions at each test visit: a neutral cue video (PN) and a drug-related cue video (PC) will be shown in random order at each visit. Before the beginning of each cue session (PN or PC), baseline measures will be taken. Respiratory rate will be measured again following the neutral cue video and the drug-related cue video. Thus there will be two sets of baselines and two sets of post cue measurements per test visit for test visits I, II and IV.
  • Vital Signs - Temperature [ Time Frame: Test sessions 1,2,and 4: baseline 1, post cue (PC), baseline 2, post neutral cue (PN) ]
    Temperature (in degrees Fahrenheit) will be monitored throughout the time course of the study and changes from baseline will be studied across the various time points. **For test visits I, II and IV, there will be two cue sessions at each test visit: a neutral cue video (PN) and a drug-related cue video (PC) will be shown in random order at each visit. Before the beginning of each cue session (PN or PC), baseline measures will be taken. Temperature will be measured again following the neutral cue video and the drug-related cue video. Thus there will be two sets of baselines and two sets of post cue measurements per test visit for test visits I, II and IV.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 21, 2012)
  • Vital Signs [ Time Frame: 23 time points over the course of 5 visits in 2 weeks: pre-dose, (-60min, -40min, -20min), 0min, 25min, {30min} 45min, 65min, [90min] on visits 2, 3, 4, and 5 (where 0 minutes is the onset of cue-inducing session) ]
    Blood pressure (in mmHg), heart rate (in beats/min), temperature (in degrees Fahrenheit), respiratory rate (in breaths/min), and O2 saturation will be monitored throughout the time course of the study and changes from baseline will be studied across the various time points. Key: (time point) = included with other time points for ONLY Test Session 1 Key: [time point] = included with other time points for ONLY Test Session 2 Key: {time point} = only time point taken on Test Session 3 along with pre-dose and zero
  • CBD Effects on Cognitive Behavior [ Time Frame: 1 time, 30-35 minutes into fourth visit ]
    Subjects will be asked to complete a battery of performance tests conducted to examine subtle changes in mental acuity, learning and memory, and other aspects of performance that will provide insight about cannabidiol's effects on cognitive behavior. The battery will comprised of the Divided Attention, Rapid Information Processing, Repeated Acquisition, and Digit-Symbol Substitution tasks.
  • Diagnostic Measure - EKG [ Time Frame: 25min (pre-screening visit only) ]
    EKG will be administered and assessed to confirm normal functionality of subject's heart.
  • Visual Analog Scale for Anxiety (VASA) [ Time Frame: 5 time points: pre-dose [on visits 2 and visit 4], -20min [visit 3], 0min, 20min, 40min, 65 min (where 0 minutes is the onset of cue-induced craving session) ]
    Questionnaires will be used to measure subjective responses. Anxiety will be assessed using a visual analog scale for anxiety (VASA).
  • The Positive and Negative Affect Schedule(PANAS) [ Time Frame: 4 times during visit 2, visit 3, and visit 5: 0min, 25, min, 45min, 65min (where 0 is the onset of the cue-induced craving session) ]
    Questionnaires will be used to measure subjective responses. The Positive and Negative Affect Schedule will allow us to obtain positive and negative affect measures and observe their changes from baseline over the course of the cue-induced craving session.
  • Physiological Response to Stress - Salivary Cortisol Measures [ Time Frame: 4 times per visit at 0min, 25min, 45min, and 65min (where 0 is the beginning of the video cue session) during visits 2, 3, and 5. ]
    Subjects will be asked to chew on a cotton swab, each time providing us with a saliva sample from which we can detect free cortisol levels and extrapolate serum levels of the stress indicator affected by the video cues. Thus, the stress of craving will be monitored and measured across the multiple time points to observe any changes from baseline.
  • Adverse Effects - SAFTEE [ Time Frame: 3 times: 135min (at the end of visit 2), 100min (at the end of visit 3), and 55min (at the end of visit 4) ]
    Before being sent home, subjects will be asked to complete the Systematic Assessment for Treatment of Emergent Events (SAFTEE) to ensure that they are not experiencing any negative effects of the treatment. There will also be a debriefing period at the end of each session aimed to minimize any potential increase in craving beyond the clinical laboratory session. At the end of the last study, subjects will be assessed and offered appropriate resources and guidance for seeking help for substance abuse or cravings should they need it after participation in the study has concluded.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Acute and Short-term Effects of Cannabidiol Admin on Cue-induced Craving in Drug-abstinent Heroin Dependent Humans
Official Title  ICMJE Cannabidiol as Treatment Intervention for Opioid Relapse
Brief Summary Despite the current available therapies for opioid-dependent patients, most patients relapse. This research project focuses on the development of a novel compound, cannabidiol, to modulate opioid craving in humans based on animal models showing its selective effectiveness to inhibit drug-seeking behavior. The development of a targeted treatment for opioid relapse would be of tremendous medical and public health value.
Detailed Description Opioid abuse is a significant global public health problem. Of the more than one million people suffering today from opiate dependency, less than a quarter of such individuals receive treatment. Pharmacotherapeutic approaches traditionally have targeted mu opioid receptors since heroin and its metabolites bind with highest affinity to this receptor subtype. Although such treatment strategies have improved substance abuse outcomes, they do not effectively block opiate craving and thus are still associated with high rates of relapse. Using a strategy of indirectly regulating neural systems to modulate opioid-related behavior, our preclinical rodent studies consistently demonstrated that cannabidiol (CBD), a nonpsychoactive component of cannabis, specifically inhibited cue-induced heroin-seeking behavior. CBD's selective effect on drug-seeking behavior was pronounced after 24 hrs and endured even two weeks after the last drug administration following short-term CBD exposure. The fact that drug craving is generally triggered by exposure to conditioned cues suggests that CBD might be an effective treatment for heroin craving, specially given its protracted impact on behavior. CBD has already been shown in Phase I of our study and in various clinical studies to be well tolerated with a wide safety margin in human subjects. CBD thus represents a strong candidate for the development as a potential therapeutic agent in humans for opioid craving and relapse prevention. It is the goal of this second exploratory phase of the project to characterize the effects of CBD administration on cue-induced craving in drug-abstinent heroin-dependent subjects using a random double blind design during a post-acute (greater than 6 days since last use) heroin withdrawal period. Study participants will be administered CBD during 3 test sessions and studied for the effects on cue-induced craving during those sessions as well as one week after the final CBD administration on the final test day (session 4).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Opiate Addiction
Intervention  ICMJE
  • Drug: Cannabidiol 400
    Subjects in Arm CBD 400 will receive 400mg of Cannabidiol in each of the three test sessions
    Other Name: CBD
  • Drug: Cannabidiol 800
    Subjects in Arm CBD 800 will receive 800mg of Cannabidiol in each of the three test sessions
    Other Name: CBD
  • Drug: Control
    Subjects will receive a harmless, inactive pill to compare and validate the results of the other arms of the study
    Other Name: CBD
Study Arms  ICMJE
  • Placebo Comparator: Control
    Subjects will receive pills that resemble the Cannabidiol capsule but do not have have its properties.
    Intervention: Drug: Control
  • Experimental: Cannabidiol 400
    Subjects in Arm Cannabidiol 400 will receive 400 mg of cannabidiol
    Intervention: Drug: Cannabidiol 400
  • Experimental: Cannabidiol 800
    Subjects in Arm Cannabidiol 800 will receive 800mg of cannabidiol
    Intervention: Drug: Cannabidiol 800
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 3, 2014)
10
Original Estimated Enrollment  ICMJE
 (submitted: May 21, 2012)
45
Actual Study Completion Date  ICMJE October 2013
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Must be between 21 and 65 years old
  • Must have an opiate dependence that meets criteria set in the Structured Clinical Interview for DSM-IV(SCID-IV) over the last three months
  • No opioid use in the past 7 days (will be verified via urine drug screen and opiate metabolite test)

Exclusion Criteria:

  • Using any psychoactive drug (other than nicotine) any time up to test session 3
  • Having a diagnosis of drug dependence (except for heroin or nicotine) in the past 3 months, based on the SCID-IV interview criteria
  • Being maintained on methadone or buprenorphine, or taking opioid antagonists such as naltrexone
  • Having a positive a drug screen
  • Showing signs of acute heroin withdrawal symptoms
  • Having medical conditions, including Axis I psychiatric conditions under DSM-IV (examined using the Mini International Neuropsychiatric Interview [MINI])
  • Having a a history of cardiac disease, arrhythmias, head trauma, and seizures
  • Having a history of hypersensitivity to cannabinoids
  • Arriving to the study site visibly intoxicated as determined by a clinical evaluation for signs and symptoms of intoxication and as verified by a drug screen
  • Participating in a another pharmacotherapeutic trial in the past 3 months
  • Being pregnant of breastfeeding
  • Not using or irregularly using appropriate methods of contraception such as hormonal contraceptives (e.g., Depo-Provera, Nuva-Ring), an intrauterine device (IUD), or double barrier method (combination of any two barrier methods used simultaneously, e.g., condoms, spermicide, diaphragms)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01605539
Other Study ID Numbers  ICMJE R21 DA027781(2)
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yasmin Hurd, Hurd,Yasmin, Ph.D.
Study Sponsor  ICMJE Hurd,Yasmin, Ph.D.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Yasmin Hurd, Ph.D. Icahn School of Medicine at Mount Sinai
PRS Account Hurd,Yasmin, Ph.D.
Verification Date October 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP