Imaging Cannabinoid CB1 Receptors in Alcohol Dependence

- INCLUSION CRITERIA:

ALCOHOL DEPENDENT SUBJECTS:

1. All subjects must be male, 18-65 years of age and be able to give written informed consent.

2. All subjects must be healthy based on history and physical examination.

3. Subjects must fulfill DSM-IV criteria (American Psychiatric Association 1987) for alcohol dependence. In addition, they must have an alcohol consumption of 35 or more standard drinks per week, as measured by timeline follow-back during the 28-day period preceding admission, as well as during the 7-day period immediately preceding it.

4. About half of the patients with alcohol dependence will be carriers of the C allele of the rs2023239 SNP and half will not.

HEALTHY SUBJECTS:

1. All subjects must be male, 18-65 years of age and be able to give written informed consent.

2. This comparison group must be healthy based on history and physical examination.

3. About half of the healthy subjects will currently smoke cigarettes and about half will not.

4. About half of the healthy subjects will be carriers of the C allele of the rs2023239 SNP and half will not.

CANNABIS USERS:

1. All subjects must be male, 18-65 years of age and be able to give written informed consent.

2. All subjects must be healthy based on history and physical examination.

3. Self-reported cannabis use of at least one year with a typical pattern of use of at least 5 days per week for the six months prior to unit admission.

4. A positive urine cannabinoid test within 90 days of admission.

EXCLUSION CRITERIA:

ALCOHOL DEPENDENT PATIENTS:

1. Any serious medical condition as judged by the investigator in consultation with the attending physician in the NIAAA program.

2. Clinically significant coagulopathies or laboratory abnormalities other than those related to alcohol dependence.

Past or present diagnosis of schizophrenia, bipolar illness or any other psychotic disorder; any current disorder that has required psychoactive medication (other than oxazepam) within the preceding 28-day period (42 days for fluoxetine). 3. Oxazepam is a relatively short acting benzodiazepine and is used clinically during alcohol withdrawal. Any present substance abuse other than alcohol.

4. Positive test for HIV.

5. Metallic foreign bodies that would be affected by the MRI scanner magnet, or fear of enclosed spaces likely to make the subject unable to undergo an MRI scan.

6. Head trauma resulting in a period of unconsciousness lasting longer than 1 hour.

7. History of fetal alcohol syndrome or other neurodevelopmental disorder.

8. History of seizures, other than in childhood and related to fever.

9. Recent exposure to radiation (i.e., PET from other research) which when combined with this study would be above the allowable limits.

10. Positive urine drug screen.

11. Inability to lie flat on camera bed for about 2.5 h

HEALTHY SUBJECTS:

1. Any current Axis I diagnosis; and any lifetime diagnosis of drug abuse or dependence.

2. Clinically significant laboratory abnormalities.

3. Recent heavy use of alcohol. That is, subjects must have an alcohol audit score of less than or equal to 9. In addition, subjects must agree not to consume any alcohol in the three days prior to the PET scan.

4. Psychotropic medication use (including benzodiazepines and illicit drugs) during the 28 days (42 day for fluoxetine) prior to the PET scan.

5. Serious medical problems.

6. Positive test for HIV.

7. Metallic foreign bodies that would be affected by the MRI magnet, or fear of enclosed spaces likely to make the subject unable to undergo an MRI scan.

8. Head trauma resulting in a period of unconsciousness lasting longer than 10 minutes.

9. History of fetal alcohol syndrome or other neurodevelopmental disorder.

10. History of seizures, other than in childhood and related to fever.

11. Recent exposure to radiation (i.e., PET from other research) which when combined with this study would be above the allowable limits.

12. Positive urine drug screen.

13. Inability to lie flat on camera bed for about 2.5 h

EXCLUSION CRITERIA: CANNABIS USERS:

1. History or presence of any clinically significant illness, as determined by history, physical examination, and/or laboratory tests.

2. Past or present diagnosis of schizophrenia, bipolar illness or any other psychotic disorder; any current disorder that has required psychoactive medication within the preceding 28-day period (42 days for fluoxetine).

3. Current physical dependence on any substance other than cannabis, nicotine, or caffeine;

4. Positive test for HIV.

5. Metallic foreign bodies that would be affected by the MRI scanner magnet, or fear of enclosed spaces likely to make the subject unable to undergo an MRI scan.

6. Head trauma resulting in a period of unconsciousness lasting longer than 10 minutes.

7. History of fetal alcohol syndrome or other neurodevelopmental disorder.

8. History of seizures, other than in childhood and related to fever.

9. Recent exposure to radiation (i.e., PET from other research) which when combined with this study would be above the allowable limits.

10. Inability to lie flat on camera bed for about 2.5 h.

11. Regular use of alcohol (greater than or equal to 6 standard drinks per day) four or more times per week in the month prior to study entry.

12. Currently interested in or participating in drug abuse treatment, or participated in drug abuse treatment within 60 days preceding study enrollment.