Marijuana Abuse
Conditions
Keywords
citicoline, drug abuse, marijuana
Brief summary
The Three Aims of this study are (only studies for Aim 1 were completed) 1. Measure the impact of citicoline on marihuana use patterns in subjects' individualized natural settings and responses to marihuana challenge using functional brain MRI scans. Hypothesis - 2 g/day citicoline will produce greater reductions in marihuana use and craving in heavy marihuana users than placebo citicoline over a 8-week treatment period as measured in their natural environments. The same participants will experience greater improved brain activation patterns and an improvement in cognitive functioning compared to placebo controlled subjects. 2. Measure the effects of citicoline on marihuana absorption and metabolism and determine if these changes parallel changes in subjective and physiological responses in a laboratory setting. Hypothesis - Chronic (8 weeks) treatment with 2 g/day citicoline will produce increases in subjective and physiological effects of both acute marihuana smoking and placebo marihuana smoking compared to chronic placebo citicoline. Citicoline will have no effect on marihuana pharmacokinetics. 3. Measure the effects of citicoline on marijuana-induced cue-induced craving and brain electrical activity (EEG). Hypothesis - Chronic (8 weeks) treatment with 2 g/day citicoline will reduce objective measures of marijuana cue-reactivity, and subjective reports of craving in response to marihuana cues will also be attenuated compared to chronic placebo citicoline treatment.
Detailed description
Marijuana dependence is an important public health problem in the United States, yet still no effective therapies are available. It is unclear how marijuana affects brain function after acute or chronic use. Knowing about the changes in brain function during marijuana dependence would aid in the understanding of the neurobiological basis of marijuana abuse and serve as a foundation for the development of new treatment medications for this disorder. New and improved brain imaging techniques, such as functional MRI (fMRI) and magnetic resonance spectroscopy (MRS), allow the viewing of these subtle, yet important, changes in brain function. Citicoline is used to treat victims of head trauma and neurodegenerative disorders. It has been found to be effective in reducing cocaine use and craving, and it has no known side effects. It has also been shown to reduce marijuana use. This is likely due to citicoline's ability to reduce insomnia and craving, act as a mild antidepressant, and improve cognitive function. How citicoline reduces drug use may be related to effects on cerebral blood flow and/or brain phospholipid metabolism in the reward areas of the brain. This study will determine whether citicoline alters marijuana use patterns, reduces craving, and affects brain phospholipids and metabolism in marijuana-dependent people. The outcome of the study could offer important insights into the pathophysiology and course of marijuana dependence. Furthermore, this study's outcome could potentially relate to other drug dependence disorders.
Interventions
DRUGplacebo
matched for physical appearance
DRUGciticoline
2 gm/day, 8 weeks treatment
Sponsors
National Institute on Drug Abuse (NIDA)
Mclean Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Meets DSM-IV criteria for current marijuana dependence * Women with a negative pregnancy test prior to study entry * Heavy smoker, defined as smoking more than 10 joints per week
Exclusion criteria
* Abnormal electrocardiogram (ECG) * Medical disorder that requires prescription medication * Psychiatric disorder that requires prescription medication * Abnormal liver function tests * Taking herbal preparations * Taking any over-the-counter medications on a chronic basis * Pregnancy or breast feeding * Neurological, infectious, or neoplastic disease * Currently seeking treatment for marijuana abuse * Meets criteria for alcohol, cocaine, or opioid dependence
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Marijuana Use | Measured for 8 weeks of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neurocognitive Function | Before and after 8 weeks of treatment | Multiple Source Interference Test (MSIT) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo matched capsules
placebo: matched for physical appearance | 11 |
| Citicoline 2 gm/day
citicoline: 2 gm/day, 8 weeks treatment | 10 |
| Total | 21 |
Baseline characteristics
| Characteristic | Total | Placebo | Citicoline |
|---|---|---|---|
| Age, Continuous | 29.0 years STANDARD_DEVIATION 7 | 30.4 years STANDARD_DEVIATION 7.2 | 27.7 years STANDARD_DEVIATION 6.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 9 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| 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 | 11 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 1 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 | 8 Participants | 3 Participants | 5 Participants |
| Region of Enrollment United States | 21 participants | 11 participants | 10 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 0 Participants |
| Sex: Female, Male Male | 18 Participants | 8 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 9 | 1 / 10 |
| serious Total, serious adverse events | 0 / 9 | 0 / 10 |
Outcome results
Primary
Marijuana Use
Time frame: Measured for 8 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Marijuana Use | 2.5 Reported uses per day | Standard Error 0.71 |
| Citicoline | Marijuana Use | 3.9 Reported uses per day | Standard Error 1.1 |
Secondary
Neurocognitive Function
Multiple Source Interference Test (MSIT)
Time frame: Before and after 8 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Neurocognitive Function | 32.45 Accuracy percent improvement | Standard Error 18.8 |
| Citicoline | Neurocognitive Function | 16.08 Accuracy percent improvement | Standard Error 7.9 |