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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Yasmin Hurd, Hurd,Yasmin, Ph.D.
ClinicalTrials.gov Identifier:
NCT01605539
First received: May 2, 2012
Last updated: March 26, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Opiate Addiction
Drug: Cannabidiol
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Cannabidiol as Treatment Intervention for Opioid Relapse

Further study details as provided by Hurd,Yasmin, Ph.D.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 10
Study Start Date: May 2012
Estimated Study Completion Date: February 2015
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Control
Subjects will receive pills that resemble the Cannabidiol capsule but do not have have its properties.
Drug: Placebo
Subjects will receive a harmless, inactive pill to compare and validate the results of the other arms of the study
Experimental: CBD 400
Subjects will receive 400mg of cannabidiol
Drug: Cannabidiol
Subjects in Arm CBD 400 will receive 400mg of Cannabidiol in each of the three test sessions
Experimental: CBD 800
Subjects will receive 800mg of cannabidiol
Drug: Cannabidiol
Subjects in Arm CBD 800 will receive 800mg of Cannabidiol in each of the three test sessions

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).

  Eligibility

Ages Eligible for Study:   21 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01605539

Locations
United States, New York
Mount Sinai Medical Center
New York, New York, United States, 10029
Sponsors and Collaborators
Hurd,Yasmin, Ph.D.
Investigators
Principal Investigator: Yasmin Hurd, Ph.D. Mount Sinai School of Medicine
  More Information

No publications provided

Responsible Party: Yasmin Hurd, Principal Investigator, Hurd,Yasmin, Ph.D.
ClinicalTrials.gov Identifier: NCT01605539     History of Changes
Other Study ID Numbers: R21 DA027781(2)
Study First Received: May 2, 2012
Last Updated: March 26, 2014
Health Authority: United States: Food and Drug Administration

ClinicalTrials.gov processed this record on November 24, 2014