The purpose of this study is threefold: 1) to develop a device and procedure to permit humans to smoke a marihuana cigarette while receiving a MRI. 2) to measure the effects of smoked marihuana on brain activity and to match these up with changes in mood state and levels of intoxication. 3) to test whether short term treatment with citicoline will reduce marihuana use and alter the effects of smoked marihuana. We hypothesize that changes in regional blood flow in areas associated with reinforcement will be altered immediately after smoking marihuana. Citicoline will reduce marihuana intake in this open label outpatient trial, but will not alter the acute effects of smoked marihuana.

Condition	Intervention	Phase
Marijuana Abuse	Drug: Marijuana Abuse	Phase II

Further Study Details: 

Primary Outcomes: Marihuana use measured at weeks 1-4

Cannabis dependence is an important public health problem in the United States, but no effective therapies are available. It is unclear how cannabis affects brain function, after acute or chronic use. Knowledge of the changes in brain function during cannabis dependence will aid in our understanding of the neurobiological bases of cannabis abuse and serve as a foundation for developing new medications to treat this disorder. New and improved brain imaging techniques such as fMRI and MRS allow us to view these subtle, yet important changes in brain function.

Citicoline is used to treat victims of head trauma and neurodegenerative disorders. We have found that citicoline is effective in reducing cocaine use and craving and it is without any side effects. We discovered that marihuana use also was reduced in the citicoline group. We surmised that citicoline might be effective in reducing cannabis use by reducing insomnia and craving, acting as a mild antidepressant and improving cognitive function. The mechanism of how citicoline reduces drug use may be related to its effects on cerebral blood flow and/or brain phospholipid metabolism in the reward areas of the brain.

We will determine whether citicoline alters cannabis use patterns, reduces craving and affects brain phospholipids and metabolism in cannabis-dependent persons. The outcome of the proposed project could offer important insights into the pathophysiology and course of cannabis dependence (and potentially on other drug dependence disorders).

The aims are:

Acute Effects of Cannabis

1. Does marihuana alter regional cerebral blood flow, brain phospholipids and metabolism?

2. Is regional cerebral blood flow and brain metabolism altered during chronic cannabis use?

   Medication Development Studies

3. Does citicoline alter the acute intoxicating effects of cannabis?
4. Does citicoline treatment reverse the cannabis-induced changes in brain function?

Ages Eligible for Study:  21 Years   -   40 Years,  Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

• The process of employing a general newspaper advertisement followed by a careful telephone interview will ensure that cannabis-naive are excluded from the study. This is because subjects are not aware of the drug use history criteria that we employ. Should they fail, they are not told the reason, only that there was not a "match". A detailed health and drug history as well as family history of alcoholism status will be obtained prior to selection. No subject with neurological, infectious, or neoplastic disease or a chronic medical or psychiatric disorder will be accepted for this study. All women must have a negative pregnancy test before participating in any study and will continue to receive tests during their participation in the longer studies.

We will be recruiting heavy smokers for these studies. Light smokers will not meet criteria for cannabis abuse or dependence and will generally smoke < 4 joints per week. Heavy smokers will meet DSM-IV criteria for cannabis abuse and dependence and typically smoke >10 joints per week. However, they must not be currently seeking treatment for their cannabis abuse or meet criteria for alcohol, cocaine or opiate dependence.

Exclusion Criteria:

• Any EKG abnormalities
• Any medical disorder that requires prescription medication
• Any psychiatric disorder that requires prescription medication
• Any abnormal liver function tests
• Taking any herbal preparations
• Taking any OTC mediations on a chronic basis
• Pregnancy or breast feeding

Please refer to this study by ClinicalTrials.gov identifier  NCT00158249

Massachusetts
      McLean Hospital, Dept. of Psychiatry, Belmont,  Massachusetts,  02478 9106,  United States; Recruiting

Study chairs or principal investigators

Scott E Lukas, Ph.D.,  Principal Investigator,  Mclean Hospital   

Study ID Numbers:  NIDA-19238-1; R01-19238-1
Last Updated:  September 10, 2005
Record first received:  September 8, 2005
ClinicalTrials.gov Identifier:  NCT00158249
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-09-13