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

Phase 2

Completed

Conditions: Opiate Addiction

Interventions: Drug: CBD 400 mg
Drug: CBD 800 mg
Drug: Control (placebo)

Registration Number: NCT02539823

Lead Sponsor: Hurd,Yasmin, Ph.D.

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 45

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CBD 400mg	CBD 400 mg	Subjects will receive 400mg of cannabidiol
CBD 800mg	CBD 800 mg	Subjects will receive 800 mg of cannabidiol
Control	Control (placebo)	Subjects will receive a solution that resemble the Cannabidiol solution but do not have have its properties

Primary Outcome Measures

Name	Time	Method
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)	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)	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. Note, cue sessions occur consecutively in the same test day. In this way, changes in craving from baseline (pre-cue to post-cue within each test day), as well as changes in cue-induced craving over the short-term (test day 1 through test day 4 a week later) will be monitored and measured. VASC scale ranges from 0 for "Not Craving at All" to 10 for "Extremely Craving."
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)	HCQ: once in clinic pre-dose at each test day, and once at home after each test day.	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 day 1 through test day 4 (1 week later). Each item is scored on a scale ranging from 1 for "Strongly Disagree" to 7 for "Strongly Agree." Sum of all 14 items are scored and added. Mean scores reported below. Total Score Range: 14 (less cravings) - 98 (more cravings).

Secondary Outcome Measures

Name	Time	Method
Vital Signs	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	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. Note, cue sessions occur consecutively in the same test day. Results reported below are responses from baseline following exposure to neutral and heroin-associated cues in Session 1 in subjects with CBD or placebo administration.