Imaging Cannabinoid CB1 Receptors in Alcohol Dependence

NCT00816439 | Completed

• 2 other identifiers: 09004009-M-0040
• Study Type: observational
• Target: 101
• Locations: 1 country
• Sites: 1

Brief Summary

The cannabinoid type 1 (CB1) receptor is a protein found in the brain that is involved with the effects of marijuana; it may also play a role in the effects of alcohol dependence and withdrawal. Earlier animal studies have shown that although long-term alcohol use decreases the number of CB1 receptors in the brain, the number returns to normal after alcohol use stops. This study will use positron emission tomography (PET) and magnetic resonance imaging (MRI) scans to trace a radioactive chemical called \[11C\]MePPEP, which can locate and measure the number of CB1 receptors in the brain. Researchers will study the CB1 receptors in the brains of people with alcohol dependence, and compare the results to the CB1 receptors in the brains of people without alcohol dependence. The results of this study will be used to further research into appropriate treatment procedures for alcohol dependence. This study will include 30 men with alcohol dependence and 50 men without alcohol dependence. All of the men must be between 18 and 65 years of age. Participants in both groups must not have any medical conditions that will prevent them from undergoing PET or MRI scans. For the PET scan, participants will be injected with a small amount of \[11C\]MePPEP and will then be brought to the PET scanner. The scan will take between 3 and 4 hours, but participants will be allowed to take breaks over the course of the scan. The MRI scan will not require any injections and will take approximately 1 hour to complete. Participants without alcohol dependence will make three visits to the National Institutes of Health Clinical Center. Blood and urine samples will be taken during one visit, and participants will arrange to have an MRI scan on one visit and a PET scan on the other visit, in whichever order they prefer. Participants with alcohol dependence will undergo two PET scans: the first will be performed between 3 and 7 days after the participant last consumed alcohol, and the second will be performed approximately 2 to 4 weeks after the first scan (with no alcohol consumption permitted in the interval). Participants will alcohol dependence will also undergo an MRI scan and will provide blood and urine samples.

Conditions

Alcoholism

Keywords

Positron Emission Tomography; Brain Imaging; Alcoholism

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ALCOHOL DEPENDENT SUBJECTS:
• All subjects must be male, 18-65 years of age and be able to give written informed consent.
• All subjects must be healthy based on history and physical examination.
• 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.
• 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:
• All subjects must be male, 18-65 years of age and be able to give written informed consent.
• This comparison group must be healthy based on history and physical examination.
• About half of the healthy subjects will currently smoke cigarettes and about half will not.
• About half of the healthy subjects will be carriers of the C allele of the rs2023239 SNP and half will not.
• CANNABIS USERS:
• All subjects must be male, 18-65 years of age and be able to give written informed consent.
• All subjects must be healthy based on history and physical examination.
• 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.
• A positive urine cannabinoid test within 90 days of admission.

You may not qualify if:

• ALCOHOL DEPENDENT PATIENTS:
• Any serious medical condition as judged by the investigator in consultation with the attending physician in the NIAAA program.
• 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.
• \. Positive test for HIV.
• \. 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.
• \. Head trauma resulting in a period of unconsciousness lasting longer than 1 hour.
• \. History of fetal alcohol syndrome or other neurodevelopmental disorder.
• \. History of seizures, other than in childhood and related to fever.
• \. Recent exposure to radiation (i.e., PET from other research) which when combined with this study would be above the allowable limits.
• \. Positive urine drug screen.
• \. Inability to lie flat on camera bed for about 2.5 h
• HEALTHY SUBJECTS:
• Any current Axis I diagnosis; and any lifetime diagnosis of drug abuse or dependence.
• Clinically significant laboratory abnormalities.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Basavarajappa BS, Hungund BL. Role of the endocannabinoid system in the development of tolerance to alcohol. Alcohol Alcohol. 2005 Jan-Feb;40(1):15-24. doi: 10.1093/alcalc/agh111. Epub 2004 Nov 18.

  PMID: 15550443 BACKGROUND

• Brown AK, George DT, Fujita M, Liow JS, Ichise M, Hibbeln J, Ghose S, Sangare J, Hommer D, Innis RB. PET [11C]DASB imaging of serotonin transporters in patients with alcoholism. Alcohol Clin Exp Res. 2007 Jan;31(1):28-32. doi: 10.1111/j.1530-0277.2006.00261.x.

  PMID: 17207098 BACKGROUND

• Cippitelli A, Bilbao A, Hansson AC, del Arco I, Sommer W, Heilig M, Massi M, Bermudez-Silva FJ, Navarro M, Ciccocioppo R, de Fonseca FR; European TARGALC Consortium. Cannabinoid CB1 receptor antagonism reduces conditioned reinstatement of ethanol-seeking behavior in rats. Eur J Neurosci. 2005 Apr;21(8):2243-51. doi: 10.1111/j.1460-9568.2005.04056.x.

  PMID: 15869521 BACKGROUND

• Hirvonen J, Zanotti-Fregonara P, Gorelick DA, Lyoo CH, Rallis-Frutos D, Morse C, Zoghbi SS, Pike VW, Volkow ND, Huestis MA, Innis RB. Decreased Cannabinoid CB1 Receptors in Male Tobacco Smokers Examined With Positron Emission Tomography. Biol Psychiatry. 2018 Nov 15;84(10):715-721. doi: 10.1016/j.biopsych.2018.07.009. Epub 2018 Jul 21.

  PMID: 30121138 DERIVED

MeSH Terms

Conditions

Alcoholism

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Robert B Innis, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH

Study Record Dates

• First Submitted: December 31, 2008
• First Posted: January 1, 2009
• Study Start: December 29, 2008
• Study Completion: August 28, 2014
• Last Updated: July 5, 2018

Record last verified: 2014-08-28

Locations

US (1)