Effects of Citicoline on Brain Function and Behavior in Marijuana-Dependent Individuals

• Sponsor: Mclean Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00158249
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 21
• Location: 1
• Arms: 2
• Duration (Months): 61
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

1. 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.

1. 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.

Condition or Disease	Intervention/Treatment	Phase
Marijuana Abuse	Drug: citicoline; Drug: placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Cannabis Dependence: Imaging and Medication Development - 1
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: placebo matched capsules	Drug: placebo; matched for physical appearance
Experimental: citicoline 2 gm/day	Drug: citicoline; 2 gm/day, 8 weeks treatment

Outcome Measures

Primary Outcome Measures

1. Marijuana Use [Measured for 8 weeks of treatment]

Secondary Outcome Measures

1. Neurocognitive Function [Before and after 8 weeks of treatment]

   Multiple Source Interference Test (MSIT)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	McLean Hospital, Department of Psychiatry	Belmont	Massachusetts	United States	02478 9106

Sponsors and Collaborators

• Mclean Hospital
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Scott E. Lukas, PhD, Mclean Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Scott Lukas, Director, MIC & BPRL, Mclean Hospital
• ClinicalTrials.gov Identifier: NCT00158249
• Other Study ID Numbers: NIDA-19238-1; R01DA019238; DPMC; R01DA024007
• First Posted: Sep 12, 2005
• Last Update Posted: Oct 22, 2014
• Last Verified: Oct 1, 2014

• Keywords provided by Scott Lukas, Director, MIC & BPRL, Mclean Hospital: citicoline, drug abuse, marijuana
• Additional relevant MeSH terms: Marijuana Abuse; Cytidine Diphosphate Choline

Study Results

Participant Flow

Arm/Group Title	Placebo	Citicoline
Arm/Group Description	matched capsules placebo: matched for physical appearance	2 gm/day citicoline: 2 gm/day, 8 weeks treatment
Period Title: Overall Study
STARTED	11	10
COMPLETED	9	10
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Placebo	Citicoline	Total
Arm/Group Description	matched capsules placebo: matched for physical appearance	2 gm/day citicoline: 2 gm/day, 8 weeks treatment	Total of all reporting groups
Overall Participants	11	10	21
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.4 (7.2)	27.7 (6.9)	29.0 (7.0)
Sex: Female, Male (Count of Participants)
Female	3 27.3%	0 0%	3 14.3%
Male	8 72.7%	10 100%	18 85.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 63.6%	4 40%	11 52.4%
White	3 27.3%	5 50%	8 38.1%
More than one race	1 9.1%	1 10%	2 9.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 18.2%	1 10%	3 14.3%
Not Hispanic or Latino	9 81.8%	9 90%	18 85.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	11 100%	10 100%	21 100%

Outcome Measures

1. Primary Outcome

Title	Marijuana Use
Time Frame	Measured for 8 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Citicoline
Arm/Group Description	matched capsules placebo: matched for physical appearance	2 gm/day citicoline: 2 gm/day, 8 weeks treatment
Measure Participants	9	10
Mean (Standard Error) [Reported uses per day]	2.5 (.71)	3.9 (1.1)

2. Secondary Outcome

Title	Neurocognitive Function
Description	Multiple Source Interference Test (MSIT)
Time Frame	Before and after 8 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Citicoline
Arm/Group Description	matched capsules placebo: matched for physical appearance	2 gm/day citicoline: 2 gm/day, 8 weeks treatment
Measure Participants	9	10
Mean (Standard Error) [Accuracy percent improvement]	32.45 (18.8)	16.08 (7.9)

Adverse Events

Arm/Group Title	Placebo		Citicoline
Arm/Group Description	matched capsules placebo: matched for physical appearance		2 gm/day citicoline: 2 gm/day, 8 weeks treatment
All Cause Mortality
	Placebo		Citicoline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Citicoline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Citicoline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/9 (11.1%)		1/10 (10%)
Gastrointestinal disorders
NAusea/Vomiting	0/9 (0%)	0	1/10 (10%)	1
General disorders
Migraine headache	1/9 (11.1%)	1	0/10 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.