Substance-Related Disorders
Conditions
Keywords
drug cues
Brief summary
The purpose of the study is to determine how associations between drugs and the places where they are experienced influence drug seeking, mood and acute drug responses.
Detailed description
Learned associations between drug effects and the people, places, and paraphernalia (cues) linked with drug experiences are a major barrier to the treatment of drug addiction. These links are remarkably persistent and can cause relapse to drug taking even after long periods of abstinence. They are also key features in some of the foremost theories of addiction, yet there is little clinical evidence of how these associations are formed and how they come to profoundly control behavior. The long-term goal of this research is to understand how drug cues become powerfully linked with drug experiences and their influence on mood and behavior. In the proposed project, the investigators will use a de novo conditioning paradigm to examine the influence of drug contexts on drug seeking, mood and acute drug responses. The hypothesis is that drug-paired contexts gain motivational salience, induce approach, and alter acute subjective responses to the drug.This knowledge will lead to novel treatment strategies to counteract the effects of drug cues on mood and behavior, and also to prevent relapse.
Interventions
DRUGPlacebo
CS- for paired, CS0 for unpaired
BEHAVIORALPaired
Drug conditioning is assessed by pairing drug administration with a given context.
DRUGStimulant or sedative
CS+ for paired, CS0 for unpaired
Sponsors
National Institute on Drug Abuse (NIDA)
University of Illinois at Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* past use of stimulants * bmi 19-26 * hormonal birth control for women
Exclusion criteria
* current or recent (Past year) history of major axis I disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Time Spent in Drug-paired Room | Measured through study completion (maximum 5 weeks). | The amount of time spent in the two testing rooms is assessed during a 10min exploration test conducted at the orientation session (pre-test) and again at the testing session (post-test). Between the pre- and post-tests, participants complete 4 drug administration sessions; 2 with 20mg MA, 2 with 0mg MA. The Paired Group always receives 20mg MA in the room they spent the least time in at pre-test, and 0mg MA in the other room. The Unpaired Group receives 20mg MA and 0mg MA once in each room. The research question is whether the Paired Group spends significantly more time in the room paired with 20mg MA in comparison to the Unpaired Group. Thus, the outcome measure is the difference in time spent in the room paired with drug administration (i.e. the room that they spent the least time in at pre-test) between pre- and post-tests (i.e., post-test time spent - pre-test time spent) which is compared between the groups. NOTE: Time spent is NOT obtained during drug administration sessions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subjective Drug Effects | Self-reported drug effects are measured 30min before drug administration and at 30min intervals after drug administration for 4h during each drug administration session. | Self-reported drug effects are measured using standardized questionnaires 30min before capsule administration (baseline) and at 30min intervals after capsule administration for 4h during each drug administration session. The peak change from baseline is calculated for each session and averaged across drug and placebo sessions. A net difference is calculated by subtracting the mean peak change from baseline during placebo sessions from the mean peak change from baseline during drug (20mg MA) sessions. Outcome measure: Subjective stimulation (i.e., feeling alert, aroused, energetic) is measured using the Amphetamine scale of the Addiction Research Center Inventory. Scores range from 0-11 with greater scores indicating greater drug effects. |
Countries
United States
Participant flow
Recruitment details
Participants (N=133) were enrolled in the study between November 2015 and May 2018. All procedures were completed at the Human Addiction Pharmacology Laboratory at the University of Illinois at Chicago.
Pre-assignment details
Participants underwent screening procedures to exclude participants who did not meet the study eligibility criteria.
Participants by arm
| Arm | Count |
|---|---|
| Paired Individuals receive drug (stimulant, or sedative) on two separate occasions and placebo on two separate occasions. Individuals receive drug in only one room.
Paired: Drug conditioning is assessed by pairing drug administration with a given context.
Stimulant or sedative: CS+ for paired, CS0 for unpaired
Placebo: CS- for paired, CS0 for unpaired | 74 |
| Unpaired Individuals receive drug (stimulant, or sedative) on two separate occasions and placebo on two separate occasions. Individuals receive drug in both rooms.
Stimulant or sedative: CS+ for paired, CS0 for unpaired
Placebo: CS- for paired, CS0 for unpaired | 35 |
| Total | 109 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Scheduling difficulties | 15 | 9 |
Baseline characteristics
| Characteristic | Paired | Unpaired | Total |
|---|---|---|---|
| Age, Continuous | 24.7 years STANDARD_DEVIATION 5 | 25.0 years STANDARD_DEVIATION 4.6 | 24.8 years STANDARD_DEVIATION 4.8 |
| Race/Ethnicity, Customized Race American Indian | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Asian | 7 Participants | 5 Participants | 12 Participants |
| Race/Ethnicity, Customized Race Black or African American | 6 Participants | 7 Participants | 13 Participants |
| Race/Ethnicity, Customized Race More than 1 | 11 Participants | 3 Participants | 14 Participants |
| Race/Ethnicity, Customized Race Unknown | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 47 Participants | 20 Participants | 67 Participants |
| Region of Enrollment United States | 74 participants | 35 participants | 109 participants |
| Sex: Female, Male Female | 24 Participants | 14 Participants | 38 Participants |
| Sex: Female, Male Male | 50 Participants | 21 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 109 | 0 / 109 |
| other Total, other adverse events | 0 / 109 | 0 / 109 |
| serious Total, serious adverse events | 11 / 109 | 2 / 109 |
Outcome results
Primary
Change in Time Spent in Drug-paired Room
The amount of time spent in the two testing rooms is assessed during a 10min exploration test conducted at the orientation session (pre-test) and again at the testing session (post-test). Between the pre- and post-tests, participants complete 4 drug administration sessions; 2 with 20mg MA, 2 with 0mg MA. The Paired Group always receives 20mg MA in the room they spent the least time in at pre-test, and 0mg MA in the other room. The Unpaired Group receives 20mg MA and 0mg MA once in each room. The research question is whether the Paired Group spends significantly more time in the room paired with 20mg MA in comparison to the Unpaired Group. Thus, the outcome measure is the difference in time spent in the room paired with drug administration (i.e. the room that they spent the least time in at pre-test) between pre- and post-tests (i.e., post-test time spent - pre-test time spent) which is compared between the groups. NOTE: Time spent is NOT obtained during drug administration sessions.
Time frame: Measured through study completion (maximum 5 weeks).
Population: Video recordings of the exploration tests (used to calculate time spent) were unavailable (corrupted) for at least one test (pre- or post-) for 3 Paired participants and 2 Unpaired participants. Thus, the participant numbers for this analysis are reduced in comparison to the total number of participants who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paired | Change in Time Spent in Drug-paired Room | 24.5 seconds | Standard Deviation 115.5 |
| Unpaired | Change in Time Spent in Drug-paired Room | 6.2 seconds | Standard Deviation 122.4 |
Secondary
Subjective Drug Effects
Self-reported drug effects are measured using standardized questionnaires 30min before capsule administration (baseline) and at 30min intervals after capsule administration for 4h during each drug administration session. The peak change from baseline is calculated for each session and averaged across drug and placebo sessions. A net difference is calculated by subtracting the mean peak change from baseline during placebo sessions from the mean peak change from baseline during drug (20mg MA) sessions. Outcome measure: Subjective stimulation (i.e., feeling alert, aroused, energetic) is measured using the Amphetamine scale of the Addiction Research Center Inventory. Scores range from 0-11 with greater scores indicating greater drug effects.
Time frame: Self-reported drug effects are measured 30min before drug administration and at 30min intervals after drug administration for 4h during each drug administration session.
Population: Data was analyzed only for participants who had complete data for the primary outcome (time spent).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paired | Subjective Drug Effects | 3.4 units on a scale | Standard Deviation 2.5 |
| Unpaired | Subjective Drug Effects | 4.1 units on a scale | Standard Deviation 2.5 |