Acute and Short-term Effects of CBD on Cue-induced Craving in Drug-abstinent Heroin-dependent Humans

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Opiate Addiction	Drug: CBD 400 mg; Drug: CBD 800 mg; Drug: Control (placebo)	Phase 2

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).

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	45 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose:	Treatment
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 Start Date :	September 2015
Actual Primary Completion Date :	May 24, 2017
Actual Study Completion Date :	May 24, 2017

Arms and Interventions

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Arm	Intervention/treatment
Placebo Comparator: Control; Subjects will receive a solution that resemble the Cannabidiol solution but do not have have its properties	Drug: Control (placebo); Subjects will receive a harmless, inactive solution to compare and validate the results of the other arms of the study; Other Name: CBD
Experimental: CBD 400mg; Subjects will receive 400mg of cannabidiol	Drug: CBD 400 mg; Subjects in Arm CBD 400 mg will receive 400mg of Cannabidiol in each of the three test sessions; Other Name: CBD
Experimental: CBD 800mg; Subjects will receive 800 mg of cannabidiol	Drug: CBD 800 mg; Subjects in Arm CBD 800 mg will receive 800mg of Cannabidiol in each of the three test sessions; Other Name: CBD

Outcome Measures

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Primary Outcome Measures :

1. Changes in Cue-Induced In-Clinic Craving (from baseline to post-cue (30 minutes), and from test visit 1 through test visit 4 (1 week)) - via the Visual Analog Scale for Craving (VASC) [ Time Frame: VASC: test visits 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 visit III: at arrival and discharge (approx. 2.5 hours from session start on average) ]
   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 in the clinic will be measured. In this way, changes in craving from baseline (pre-cue to post-cue within each test visit), as well as changes in cue-induced craving over the short-term (test visit 1 through test visit 4 a week later) will be monitored and measured.
2. Changes in Out-of-Clinic Craving (from pre-dose to approximately 4-6 hours post-dose; and from test visit 1 to test visit 4 or 1 week) - via the Heroin Craving Questionnaire (HCQ) [ Time Frame: HCQ: once in clinic pre-dose at each test visit, and once at home after each test visit. ]
   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 (1 week later).

Secondary Outcome Measures :

1. Vital Signs [ Time Frame: At drug/placebo admin, baseline for cue 1, 10 min post-cue I, 30 min post cue I, baseline for cue 2, 10 min post cue II, 30 min post cue II or prior to discharge approximately 2.5 hours from session start on average (no cue sessions in test visit III) ]
   Blood pressure (in mmHg), heart rate (in beats/min), temperature (in degrees Fahrenheit), respiratory rate (in breaths/min), and O2 saturation and pain will be monitored throughout the time course of the study and changes from baseline will be studied across the various time points.

Other Outcome Measures:

1. CBD Effects on Cognitive Behavior [ Time Frame: 2 times: once at pre-screening (visit 1) and once at test session 4 (visit 5), within 2 weeks of each other. ]
   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 comprise the Continuous Performance, Digit Span Backwards, and Digit-Symbol Substitution tasks.
2. Visual Analog Scale for Anxiety (VASA) [ Time Frame: Test visit 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 session start on average); Test visit III: on arrival and prior to discharge ]
   Questionnaires will be used to measure subjective responses. Anxiety will be assessed using a visual analog scale for anxiety (VASA).
3. The Positive and Negative Affect Schedule(PANAS) [ Time Frame: Baseline for cue sessions 1 and 2, post-cue sessions I and 2 (30 min from baseline) during test visits I, II and IV. ]
   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.
4. Physiological Response to Stress - Salivary Cortisol Measures [ Time Frame: Test visit I, II and IV: at drug/placebo admin, baseline for cue session 1, 10 min post-cue I, 30 min post cue I, baseline for cue 2, 10 min post cue II, 30 min post cue II ]
   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 physiological stress of craving will be monitored and measured across the multiple time points to observe any changes from baseline.
5. Adverse Effects - SAFTEE [ Time Frame: Test visit I, II, III and IV: at the end of visit prior to discharge. Average time point: approximately 150 minutes into the session. ]
   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.

Eligibility Criteria

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Ages Eligible for Study:	21 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
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 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)

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, New York
Mount Sinai Beth Israel
New York, New York, United States, 10003

Sponsors and Collaborators

Hurd,Yasmin, Ph.D.

GW Research Ltd

Investigators

Principal Investigator:	Yasmin Hurd, PhD	Mount Sinai Health System

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Yasmin Hurd, Professor of Neuroscience, Psychiatry and Pharmacology & Systems Therapeutics, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier:	NCT02539823 History of Changes
Other Study ID Numbers:	MSBI HSM# 087-14
First Posted:	September 3, 2015
Last Update Posted:	February 21, 2018
Last Verified:	February 2018

Additional relevant MeSH terms:

Opioid-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Heroin; Analgesics, Opioid	Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents