The purpose of this protocol is to measure brain CB1 receptors in the hope to better understand how they work, so that one day we can understand how the CB1 receptors are involved in psychiatric, neurological, and behavioral disorders.

MePPEP ((3R,5R)-5-(3-methoxy-phenyl)-3-((R)-1-phenyl-ethylamino)-1-(4-trifluoromethyl-phenyl)-pyrrolidin-2-one) was developed through a CRADA between Lilly at NIMH and is a ligand that is highly selective for the cannabinoid type 1 (CB1) receptor. This receptor is considered the most common G-coupled protein receptor in the brain (Pacher et al., 2006). The CB1 receptor is the site of action of Delta-9-tetrahydrocannbinol (THC), the active compound in marijuana, and is found primarily on the presynaptic terminals of dopaminergic, glutamatergic, GABAergic neurons (Howlett et al., 2002). The function of the CB1 receptor is not entirely clear; however, it has been implicated in several neurological and psychiatric disorders, and a selective inverse agonist, rimonabant, is currently in use in Europe for the treatment of obesity (Van Gaal et al., 2005). [11C]MePPEP was developed to enhance our understanding of the in vivo characteristics of the CB1 receptor (e.g., receptor density and receptor occupancy with pharmaceuticals).

The purpose of this protocol is to establish an accurate method to measure CB1 receptor levels in brain by performing test/retest brain imaging studies. The results of this overall study are required to apply this PET ligand in various neurological and psychiatric disorders in the future.

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• INCLUSION CRITERIA:

All subjects must be healthy and aged 18-65 years, with history/physical exam, ECG, and laboratory tests within one year of the PET scan. The volunteer must sign an informed consent form.

EXCLUSION CRITERIA:

• Current psychiatric illness, substance abuse including marijuana use, or severe systemic disease based on history and physical exam.
• Laboratory tests with clinically significant abnormalities or positive urine toxicology screen.
• Prior participation in other research protocols in the last year such that radiation exposure would exceed the annual limits.
• Pregnancy and breast feeding.
• Claustrophobia.
• Presence of ferromagnetic metal in the body or heart pacemaker.
• Positive HIV test.
• Employee of the investigative site or an immediate family member of an employee of the investigative site. Immediate family member is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
• Employee of Eli Lilly and Company.