Conditions: Opiate Addiction
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 45
Healthy volunteers: no

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).

Arms:
arm 1: Subjects will receive a solution that resemble the Cannabidiol solution but do not have have its properties arm 2: Subjects will receive 400mg of cannabidiol arm 3: Subjects will receive 800 mg of cannabidiol

Interventions: intervention 1: CBD 400 mg intervention 2: CBD 800 mg intervention 3: Control (placebo)
Intervention descriptions: intervention 1: Subjects in Arm CBD 400 mg will receive 400mg of Cannabidiol in each of the three test sessions intervention 2: Subjects in Arm CBD 800 mg will receive 800mg of Cannabidiol in each of the three test sessions intervention 3: Subjects will receive a harmless, inactive solution to compare and validate the results of the other arms of the study

Protocol document:
Prot_000.pdf: 
 
 
 
 
 
 
 
BI IRB# 087-14 Acute and Short-Term Effects of CBD on Cue-Induced Craving in Drug- 
Abstinent Heroin-Dependent Humans 
 
NCT # 02539823 
 
 
Version: March 12, 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


The purpose of this study is to determine if Cannabidiol (CBD) - one of the natural components of the 
cannabis plant) is effective in reducing heroin craving. Current therapies available for heroin treatment 
such as methadone and buprenorphine, do not block heroin craving. Craving is a distressing symptom 
which is linked to relapse and ultimately the continued cycle of heroin abuse. 
45 healthy male and female subjects between the ages of 21 and 65, who are currently abstinent from 
drug use but who have a recent history (past 3 months) of heroin-dependence will be recruited for the 
study. There will be 3 groups of 15 subjects. One group will receive a placebo (a solution that does 
not contain the experimental drug), 15 participants will receive 400 mg of Cannabidiol (CBD), and 15 
participants will receive 800 mg of CBD. Dispensation of investigational drug will be randomized and 
double-blinded. 
 
Participation in this research study will consist of 5 visits in total over a two week period, and will 
consist of one prescreening session (about 2 hours) and four test sessions. Test sessions 1, 2 and 4 
include Cue sessions and will last 3 hours per visit. Test session 3 (no cue session) will last 90 
minutes. The investigational drug (CBD) or placebo will be administered during test sessions 1, 2, and 
3. There is a 1 week break between test session 3 and 4. There will be no CBD/placebo 
administration during test session 4. 
 
 
The prescreening session will consist of: 
 
ï 
Basic Physical exam 
ï 
Toxicological assessments: urine drug screening including opioid metabolite screening and 
Breathalyzer. Positive findings will result in exclusion. 
ï 
Urine pregnancy test, blood test (complete blood count, liver function tests, electrolytes, urea, 
creatinine, glucose), EKG, vital signs (heart rate, blood pressure, weight and height measurement, 
Body Mass Index calculation), survey of medical history (including tobacco use assessment). MD 
will determine medical eligibility based on physical exam and lab results. 
ï 
Computerized Structured Clinical Interview for DSM-V (SCID-V) for diagnosing drug dependence. 
Participants must be positive for current dependence for heroin (within past 3 months), but must 
not be currently using any drugs (including heroin) besides nicotine. 
ï 
MINI International Neuropsychiatric Interview which is used for the detection of psychiatric 
conditions. Positive findings for current mood disorders, bipolar disorders and psychotic disorders 
will result in exclusion. 
ï 
Clinical assessment for withdrawal symptoms - Clinical Opiate Withdrawal Scale (COWS) 
ï 
PI will review pre-screening findings and determine eligibility for enrollment. 
ï 
Computerized attention performance tasks/test 
 
Test Sessions will consist of: 
 
Sessions 1 and 2: 
 
o Urine drug screening (including opiate metabolite screen), breathalyzer, pregnancy test, 
questionnaires. Positive findings will result in exclusion. 


o CBD/Placebo administration 
o Test Session 1 will comprise 2 cue sessions (one 3-minute video of heroin-related imagery 
plus one 3 minute video of neutral imagery). 
o Test Session 2 will comprise 2 cue sessions (one 3-minute video of heroin-related imagery 
plus 2 minutes of exposure to heroin related paraphernalia; then one 3 minute video of neutral 
imagery plus 2 minute exposure to neutral paraphernalia) 
o Vital signs measurements (blood pressure, heart rate and oxygen saturation) at specific time 
points 
o Questionnaires at specific time points after cues 
o 6 saliva samples at specific time points after cues 
o SAFETEE to assess for side effects and/or adverse effects 
o Debriefing: relaxation exercise to ensure subject is in stable condition (in terms of craving 
levels) before he/she is discharged 
o Take home questionnaire to assess craving at home. To be returned to coordinator at 
next session. 
 
Session 3: (no cue session) 
 
o Urine drug screening (including opiate metabolite screen), breathalyzer, 
pregnancy test, questionnaires. Positive findings will result in exclusion. 
o Vital signs at specific time points 
o Questionnaires at specific time points 
o CBD/Placebo administration 
o Computer performance tests to assess attention and memory 
o SAFETEE to assess for side effects and/or adverse effects 
o Take home questionnaire to assess craving at home. To be returned to coordinator at 
next session. 
 
Session 4 (no CBD/Placebo administered): 
 
o Urine drug screening (including opiate metabolite screen), breathalyzer, tobacco use 
assessment, pregnancy test, questionnaires. 
o 2 Cue sessions (one 3-minute video of heroin-related imagery and one 3 minute video of 
neutral imagery) 
o vital signs measurements (blood pressure, heart rate and oxygen saturation) at specific time 
points after cues 
o 6 saliva samples at specific time points after cues 
o SAFETEE to assess for side effects and/or adverse effects 
o Debriefing: relaxation exercise to ensure subject is in stable condition (in terms of craving 
levels) before he/she is discharged 

SAP_001.pdf: 
 
 
 
 
 
 
 
 
 
 
 
BI IRB# 087-14 Acute and Short-Term Effects of CBD on Cue-Induced Craving in 
Drug- Abstinent Heroin-Dependent Humans 
 
NCT # 02539823 
 
 
Version: March 12, 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
A linear mixed-model repeated-measures analysis using the SAS procedure MIXED (SAS Institute, Cary, 
N.C.) was employed to assess the changes in cue- induced in-clinic VAS-C, VAS-A, and PANAS scores. 
Changes in the Heroin Craving Questionnaire out-of-clinic craving scale score were assessed using a 
repeated-measures analysis conducted with the MIXED procedure. At the first stage of all analyses, the 
distributional characteristics of all continuous explanatory and outcome variables were assessed using 
skewness and kurtosis indicators. If necessary, transformations were used to normalize a variable. To 
determine the effectiveness of the randomization procedure for assignment to the drug group, one-way 
analyses of variance were conducted on the session 1 baseline values of each of the outcome variables 
as a function of drug group. Nonsignificant drug group baseline differences were taken as indicators of 
effective randomization. Because a crossover design assumes that there are no carryover effects from 
one assessment period to the next, this possibility was tested using procedures in the Number Cruncher 
Statistical System User’s Guide II. Once the analyses indicated that carryover effects were absent, the 
main analyses of the crossover design variables were undertaken. 
 
Difference scores between the precue baseline scores and postcue scores within each session were 
calculated and used as outcomes in the analytic models. The models themselves were developed 
sequentially in which time was entered first (because there were multiple sessions and two events 
within each session for the crossover outcomes; that is, neutral and drug cues). This procedure was 
followed by entering the variable describing the sequence in which the drug and neutral cues were 
given, the drug group variable, and the cue indicator (neutral or drug cue). A single first-order 
interaction term (drug group by cue) was entered last because it was hypothesized that the cues would 
be responded to differentially depending on the drug group to which the research participant was 
assigned. Any significant mean differences for the main effect analyses or interaction terms were 
followed up by Tukey-adjusted post hoc mean comparisons.