Clinical trial NCT02539823: Acute and Short-term Effects of CBD on Cue-induced Craving in Drug-abstinent Heroin-dependent Humans
Official title: To Characterize the Acute and Short-term Effects of Cannabidiol (CBD) Administration on Cue-induced Craving in Drug-abstinent Heroin-dependent Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Opiate Addiction
Lead sponsor: Hurd,Yasmin, Ph.D.
Sponsor class: INDIV
Collaborators: name: Jazz Pharmaceuticals
First posted: 2015-09-03
Enrollment: 45
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: There has been an epidemic rise in heroin abuse and overdose in recent years. 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. Preliminary pilot study showed CBD decreased craving. It is the goal of the current study to more fully 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 Diagnostic and Statistical Manual of Mental Disorders (DSM-V) Structured Clinical Interview for DSM (SCID-V) 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-V 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-V (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 (30 Minutes), and From Test Day 1 Through Test Day 4 (1 Week)) - Via the Visual Analog Scale for Craving (VASC)
timeFrame: VASC: test day I, II and IV - at arrival, baseline for cue 1 and 2, post-cue 1 and 2, before discharge (approximately 2.5 hours from session start on average); test day III: at arrival and discharge (approx. 2.5 hours from session start on average)
measure: Changes in Out-of-Clinic Craving (From Pre-dose to Approximately 4-6 Hours Post-dose; and From Test Day 1 to Test Day 4 or 1 Week) - Via the Heroin Craving Questionnaire (HCQ)
timeFrame: HCQ: once in clinic pre-dose at each test day, and once at home after each test day.
Secondary outcomes:
measure: Vital Signs
timeFrame: Pre-placebo/drug, -60 min pre-cue, -40 min pre-cue, -20 min pre-cue, cue (time 0), 15 min post-cue, 35 min post-cue, 50 min post-cue, 65 min post-cue, 85 min post-cue
Other outcomes:
measure: CBD Effects on Cognitive Behavior
timeFrame: 2 times: once at pre-screening and once at test day 4, within 2 weeks of each other.
measure: Visual Analog Scale for Anxiety (VASA)
timeFrame: Test day I, II and IV: on arrival, baseline for cue sessions 1 and 2, post-cue sessions I and 2 (30 min from baseline), prior to discharge (approximately 2.5 hours from test day start on average); Test day III: on arrival and prior to discharge.
measure: The Positive and Negative Affect Schedule(PANAS)
timeFrame: Baseline for cue sessions 1 and 2, post-cue sessions I and 2 (30 min from baseline) during test days I, II and IV.
measure: Physiological Response to Stress - Salivary Cortisol Measures
timeFrame: Test day I: 15 min and 35 min post drug and neutral cue
measure: Adverse Effects - SAFTEE
timeFrame: Test day I, II, III and IV: at the end of day prior to discharge. Average time point: approximately 150 minutes into the test day.
measure: CBD Effects on Cognitive Behavior
timeFrame: 2 times: once at pre-screening and once at test day 4, within 2 weeks of each other.
Locations:
city: New York
country: United States
facility: Mount Sinai Beth Israel
state: New York
Study officials:
affiliation: Mount Sinai Health System
name: Yasmin Hurd, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hurd YL, Spriggs S, Alishayev J, Winkel G, Gurgov K, Kudrich C, Oprescu AM, Salsitz E. Cannabidiol for the Reduction of Cue-Induced Craving and Anxiety in Drug-Abstinent Individuals With Heroin Use Disorder: A Double-Blind Randomized Placebo-Controlled Trial. Am J Psychiatry. 2019 Nov 1;176(11):911-922. doi: 10.1176/appi.ajp.2019.18101191. Epub 2019 May 21.