PET Study of a2a Agonist Effects on the Ventricular CSF Clearance of [11C]Butanol

Inclusion Criteria:

• Able to give informed consent. No vulnerable populations.
• Age 18-to-89 years old
• Mini-Mental Status Examination of ≥ 28
• Confirmed by the screening procedures to still be reasonably healthy and, in the opinion of the investigators, likely to tolerate the imaging procedures. For example, patients with chronic low back pain might not be able to lie still for very long.
• Confirmed by the screening procedures to have normal hemodynamic function. Systolic blood pressure and pulse must be higher than 120 mmHg and 60 beats per minute (bpm) while sitting. At the discretion of the investigators, athletic people who engage in vigorous exercise of one hour or more at least four times per week may be enrolled if their systolic blood pressure and pulse are higher than 100 mmHg and 50 beats per minute while sitting.
• Unremarkable electrocardiograms with PR intervals of less than 200 mSec and QT interval corrected with Frederica's method (QTcF) of less than 440 mSec.
• Willing and able to refrain from abusing any recreational drugs, including marijuana because of its sleep effects, and drink less than one unit of alcoholic beverages per day starting one week prior to the lead-in period, and avoided for the next three weeks while on study (the one week lead-in period, one week on drug period, and one week washout period).
• Willing to refrain from donating blood during the month of study (because of its potential effect of quickening pulse).
• Willing to refrain from participating in any other research study that requires taking medication during the month of study.
• Willing to refrain from being vaccinated during the month of study.
• Have not participated in research with exposure to ionizing radiation that would result in approaching the exposure limits for healthy volunteers described in the Code of Federal Regulations, Title 21 Part 361.1 (21CFR361.1)

Exclusion Criteria:

• History of allergy to clonidine.
• History of multiple hypersensitivity reactions, as indicated by allergies to multiple medications, foods, and seasonal pollens.
• History or physical examination suggestive of a condition, disorder, or disease that could represent a contra-indication to taking an antihypertensive. The relative contraindications to clonidine listed in the package insert under the section on precautions will be exclusionary in this study. They include subjects with coronary artery insufficiency syndromes, histories of myocardial infarction, cardiac conduction abnormalities, cerebrovascular disease, and chronic renal failure.
• Women who are pregnant or breast feeding will not be eligible to participate in the study, as clonidine is classified as a Class C risk to a fetus. (In fact, there is a safety signal in pregnant animal models that justifies exclusion, even if the signal is weak.)
• History, physical examination or clinical laboratory test result suggestive of a condition, disorder, or disease that could affect the adsorption, distribution, metabolism or excretion of clonidine, including an alcohol abuse or dependence disorder.
• Positive urine toxicology screen for drugs other than cannabis.
• Subjects may not be a member of a vulnerable population.
• May not have donated blood in the 30 days prior to the start of the lead-in period.
• May not have participated in research administering drugs in the last 30 days.
• May not have been vaccinated in the 30 days prior to the start of the lead-in period.