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

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.

Time frame: 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)

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).

Time frame: HCQ: once in clinic pre-dose at each test day, and once at home after each test day.

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.

Time frame: 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

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.

Time frame: 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.

Continuous Performance Test is a computerized assessment of attention. The outcome measures include correct responses (hits), missed responses (misses), incorrect responses (false hits), correct misses, and reaction time of both hits and misses. Mean correct response times (hits) are reported below. Shorter response times indicate better participant outcomes.

Time frame: 2 times: once at pre-screening and once at test day 4, within 2 weeks of each other.

Digit Span Backwards (DSB) is a memory task consisting of a span of digits recalled in reverse order. Participants are read a series of digits (e.g., 4,7,1) and must immediately repeat them back in reverse order (e.g., 1,7,4). Mean correct response times (hits) are reported below in milliseconds. Shorter response times indicate better participant outcomes. Digit Symbol Substitution Task (DSST) is a neuropsychological test consisting of digit-symbol pairs.The goal is to complete as many correct patterns as possible in 3 mins. Mean response times reported below in ms, with shorter times indicating better outcomes.

Time frame: 2 times: once at pre-screening and once at test day 4, within 2 weeks of each other.

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. Note, cue sessions occur consecutively in the same test day. Thus, the physiological stress of craving will be monitored and measured across the multiple time points to observe any changes from baseline. Results reported below are mean percent change from baseline following exposure to neutral and heroin-associated cues in Session 1 in subjects with CBD or placebo administration.

Time frame: Test day I: 15 min and 35 min post drug and neutral cue

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. Note, cue sessions occur consecutively in the same test day. Positive affect scores range from 10 - 50. Higher scores represent higher levels of positive affect. Negative affect scores range from 10 - 50. Higher scores represent high levels of negative affect.

Time frame: Baseline for cue sessions 1 and 2, post-cue sessions I and 2 (30 min from baseline) during test days I, II and IV.

Questionnaires will be used to measure subjective responses. Anxiety will be assessed using a visual analog scale for anxiety (VASA). VASA scale ranges from 0 for Not Anxious at All to 10 for Extremely Anxious. Note, cue sessions occur consecutively in the same test day.

Time frame: 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.