Clinical trial NCT01605539: Acute and Short-term Effects of Cannabidiol Admin on Cue-induced Craving in Drug-abstinent Heroin Dependent Humans
Official title: Cannabidiol as Treatment Intervention for Opioid Relapse
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Opiate Addiction
Lead sponsor: Hurd,Yasmin, Ph.D.
Sponsor class: INDIV
First posted: 2012-05-25
Enrollment: 10
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility 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)

Primary outcomes:
measure: Changes in Cue-Induced In-Clinic Craving (From Baseline to Post-cue or Post-neutral - Via the Visual Analog Scale for Craving (VASC)
timeFrame: VASC: test visits I, II and IV - baseline 1, post cue (PC), baseline 2, post neutral cue (PN)
measure: 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)
timeFrame: 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
Secondary outcomes:
measure: Vital Signs - Blood Pressure
timeFrame: Test sessions 1,2,and 4: baseline 1, post cue (PC), baseline 2, post neutral cue (PN)
measure: Visual Analog Scale for Anxiety (VASA)
timeFrame: Test visit I, II and IV: baseline 1, post cue (PC), baseline 2, post neutral cue (PN)
measure: The Positive and Negative Affect Schedule (PANAS) - Positive Affect Schedule (PAS) Data
timeFrame: Test session 1, 2, and 4: baseline 1, post cue (PC), baseline 2, post neutral cue (PN)
measure: The Positive and Negative Affect Schedule (PANAS) - Negative Affect Schedule (NAS) Data
timeFrame: Test session 1, 2, and 4: baseline 1, post cue (PC), baseline 2, post neutral cue (PN)
measure: Vital Signs - Heart Rate
timeFrame: Test sessions 1,2,and 4: baseline 1, post cue (PC), baseline 2, post neutral cue (PN)
measure: Vital Signs - Respiratory Rate
timeFrame: Test sessions 1,2,and 4: baseline 1, post cue (PC), baseline 2, post neutral cue (PN)
measure: Vital Signs - Temperature
timeFrame: Test sessions 1,2,and 4: baseline 1, post cue (PC), baseline 2, post neutral cue (PN)
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Yasmin Hurd, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: