Methamphetamine Dependence
Conditions
Keywords
methamphetamine withdrawal, mood, retention, sleep
Brief summary
Methamphetamine use is very common in the US and is associated with serious medical and psychiatric problems. There has also been a significant increase in the number of patients entering treatment for methamphetamine dependence, however, no pharmacologic treatment has been identified as effective in treating methamphetamine addiction. Given that withdrawal from methamphetamine is thought to contribute to relapse to methamphetamine use during early treatment, it is important to examine potential pharmacologic agents for alleviating withdrawal. Thus, this study is designed to study methamphetamine withdrawal in humans. To this end, 30 methamphetamine dependent participants (ages 18-65 years) will be entered into a 4-week residential study. Urine samples will be obtained at baseline to ensure recent methamphetamine use. Intake assessments will include cognitive testing, standardized assessment of depression and anxiety, profile of mood states, methamphetamine selective severity assessment, methamphetamine withdrawal assessment, sleep quality and quantity, a pre-attentional measure and attentional measure. Upon admission to the residential facility, all study participants will be started on (20-30mg) long acting amphetamine/d-amphetamine and stabilized over the first 5 days. After stabilization participants will be randomized based on sex, amphetamine withdrawal questionnaire score, and methamphetamine selective severity assessment score to either continued treatment with amphetamine/d-amphetamine or placebo for 2 weeks. All subjects will then be placed on placebo for the last 7 days. The investigators hypothesis is that stopping amphetamine administration in methamphetamine dependent individuals will negatively impact mood, sleep and cognitive function in a time-limited fashion that may differ depending upon the measure and that attentional, but not pre-attentional, measures will be adversely affected in those receiving placebo compared to those maintained on amphetamine.
Interventions
Thirty treatment-seeking methamphetamine dependent volunteers will be admitted to a residential facility and be inducted onto d-amphetamine during week 1 of the study. 15 Participants then will be randomized by severity of methamphetamine dependence, sex, amphetamine withdrawal questionnaire score and history of Attention Deficit Hyperactivity Disorder to receive oral d-amphetamine at a dose of 30 mg twice daily for 2 weeks.
DRUGPlacebo
Thirty treatment-seeking methamphetamine dependent volunteers will be admitted to a residential facility in this 4-week, double-blind, placebo-controlled, clinical trial and be inducted onto d-amphetamine during week 1 of the study. 15 Participants then will be randomized by severity of methamphetamine dependence, sex, amphetamine withdrawal questionnaire score and history of Attention Deficit Hyperactivity Disorder to receive oral placebo tablets twice daily for 2 week.
Sponsors
University of Arkansas
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 21-65 years old * not currently enrolled in a treatment program * history of methamphetamine use with recent use confirmed by a positive urine toxicology screen for amphetamines during the month prior to study entry * self-reported Methamphetamine use on at least 15 of the past 30 days * use of at least one half gram of methamphetamine per week during the month prior to study entry * women of childbearing age must have a negative pregnancy test to enroll in this study
Exclusion criteria
* current diagnosis of alcohol, opiate, or sedative physical dependence * ill health (e.g., major cardiovascular, renal, endocrine, hepatic disorder) * history of schizophrenia, or bipolar type I disorder * present or recent use of over-the-counter or prescription psychoactive drug or drug(s) that would be expected to have major interaction with d-amphetamine * medical contraindication to receiving study medications (e.g., previous adverse reaction to d-amphetamine) * chronic pain condition (due to impact on neurophysiological responses * current suicidality or psychosis * liver function tests (i.e., liver enzymes) greater than three times normal levels * pregnancy or breastfeeding * children 18-20 will be excluded because the P50 potential is not fully developed in children and adolescents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measure of Methamphetamine Withdrawal | at the end of week 4 | Total score on the Methamphetamine Withdrawal Assessment scale (MAWA) based on DSMIV criteria for amphetamine withdrawal. This questionnaire is comprised of 13 items which describe symptoms associated with the cessation of chronic amphetamine use for which participants indicate severity on a 4-point scale. The minimum score indicating no methamphetamine withdrawal symptoms is 0 and the maximum score is 4 indicating that a patient has the most severe withdrawal symptom related to that question. The subscales are the 13 questions and the total score is the sum of all the scores for the 13 items on the scale. The range minium and better outcome is a lower score. The range is from 0-52. The worse outcome is reflected in a higher score. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dextroamphetamine Dextroamphetamine: Thirty-five treatment-seeking methamphetamine dependent volunteers were admitted to a residential facility and inducted onto d-amphetamine during week 1 of the study. 18 Participants were be randomized by severity of methamphetamine dependence, sex, amphetamine withdrawal questionnaire score and history of Attention Deficit Hyperactivity Disorder to receive oral d-amphetamine at a dose of 30 mg twice daily for 2 weeks. | 18 |
| Placebo Placebo: Thirty-four treatment-seeking methamphetamine dependent volunteers will be admitted to a residential facility in this 4-week, double-blind, placebo-controlled, clinical trial and be inducted onto d-amphetamine during week 1 of the study. 17 Participants were randomized by severity of methamphetamine dependence, sex, amphetamine withdrawal questionnaire score and history of Attention Deficit Hyperactivity Disorder to receive oral placebo tablets twice daily for 2 weeks. | 17 |
| Total | 35 |
Baseline characteristics
| Characteristic | Total | Dextroamphetamine | Placebo |
|---|---|---|---|
| Age, Continuous | 35.36 years STANDARD_DEVIATION 8.86 | 41.00 years STANDARD_DEVIATION 9.76 | 33.67 years STANDARD_DEVIATION 6.34 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 35 Participants | 18 Participants | 17 Participants |
| Region of Enrollment United States | 35 participants | 18 participants | 17 participants |
| Sex: Female, Male Female | 18 Participants | 9 Participants | 9 Participants |
| Sex: Female, Male Male | 17 Participants | 9 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 18 | 9 / 17 |
| serious Total, serious adverse events | 0 / 18 | 0 / 17 |
Outcome results
Primary
Measure of Methamphetamine Withdrawal
Total score on the Methamphetamine Withdrawal Assessment scale (MAWA) based on DSMIV criteria for amphetamine withdrawal. This questionnaire is comprised of 13 items which describe symptoms associated with the cessation of chronic amphetamine use for which participants indicate severity on a 4-point scale. The minimum score indicating no methamphetamine withdrawal symptoms is 0 and the maximum score is 4 indicating that a patient has the most severe withdrawal symptom related to that question. The subscales are the 13 questions and the total score is the sum of all the scores for the 13 items on the scale. The range minium and better outcome is a lower score. The range is from 0-52. The worse outcome is reflected in a higher score.
Time frame: at the end of week 4
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dextroamphetamine | Measure of Methamphetamine Withdrawal | 3.7283 units on a scale | Standard Error 3.37 |
| Placebo | Measure of Methamphetamine Withdrawal | 10.056 units on a scale | Standard Error 3.45 |