Acetylcholine, Tobacco Smoking, Genes and Nicotinic Receptors


Schizophrenia | Smoking

Trial Phase

Trial Purpose and Description

Trial Purpose

The purpose of the study is to measure the sensitivity of NCFHEB binding to changes in endogenous acetylcholine levels in healthy smoking and nonsmoking subjects, and in schizophrenic smoking and nonsmoking subjects. We hypothesize that physostigmine-induced elevated ACh levels will lead to a reduction in the availability of nicotinic receptors for the binding of the radioligand. We hypothesize there will be greater increase in ACh level (or greater reduction in radio tracer binding) in smoking as compared to nonsmoking subjects. We hypothesize there will be greater increase in ACh level (or greater reduction in radio tracer binding) in smoking as compared to nonsmoking subjects with schizophrenia, but the extent of this change will be different than in controls.

Participation Guidelines

18 Years - 60 Years

Eligibility Criteria

Inclusion Criteria:

- who are able to read and write

- who are able to give voluntary written informed consent

- have no current uncontrolled medical condition such as neurological, cardiovascular,
endocrine, renal, liver, or thyroid pathology

- have no history of a neurological or psychiatric disorder (DSMIV Axis 1 and 2) other
than schizophrenia in schizophrenia subgroup

- have not regularly used any prescription, herbal or illegal psychotropic medications
(e.g. antidepressants, antipsychotics, anxiolytics, ecstasy) in the past 6 months

- Subjects with schizophrenia have not used any herbal or illegal substances in the
past 6 months (medication inclusion listed below in Aim 5)

- drink less than <21 drinks/week for women and less than <35 drinks per week for men

- have not used marijuana in the past 30 days and have not met criteria for dependence
in the past 2 years

- If female, not pregnant or breast feeding

- If female of childbearing age, must use an acceptable method of birth control, as
determined by the principal investigator

- do not suffer from claustrophobia or any MR contradictions

- willing to donate blood for genetic studies

- willing to be followed up monthly after study participation via phone or email

Exclusion Criteria:

- Presence of acute or unstable medical or neurological illness. Subjects will be
excluded from the study if they present with any history of serious medical or
neurological illness or if they show signs of a major medical or neurological illness
on examination or lab testing including history of seizures, head injury, brain
tumor, heart, liver or kidney disease, eating disorder, diabetes.

- Presence of an Axis I diagnosis other than nicotine dependence and schizophrenia (for
schizophrenia subgroup) in the past 2 years

- Regular use of any psychotropic drugs including anxiolytics and antidepressants and
other over-the-counter medications and herbal products within the last year, and none
within the last month for healthy controls.

- Regular use of antidepressants or psychotropic over-the-counter medications and
herbal products within the last year

- For subjects with Schizophrenia, use of SSRI's (Paxil, Prozac Zoloft, Lexapro and
Celexa) and use of tricyclic anti-depressants, except for a minimal dose used to
treat anything other than depression, per the Investigator's discretion.

- Pregnancy/Breast feeding

- Subjects with a pacemaker or other ferromagnetic material in body.

- Subjects with a sitting pulse rate >100 bpm will be excluded

- Subjects with hypertension defined as sitting systolic blood pressure of >160 mmHg
and/or sitting diastolic blood pressure of >100 mmHg will be excluded. Those
individuals with hypertension that is well controlled by medication (e.g., within the
above mentioned range) are not excluded

- Specifically, we will exclude subjects who have any active clinically significant
deviation from the normal range in their electrocardiogram (EKG). However, subjects
who have abnormalities in their EKG but the condition has been present for a while
and the study cardiologist has evaluated and feels comfortable with the condition,
would not be excluded on the basis of their cardiac condition. Examples of conditions
that may meet these criteria (e.g., condition has been present for a while) include
but are not limited to T-wave abnormalities, atrial fibrillation, prolonged PR
interval, and right bundle branch block.

- Subjects with an allergy to salicylates

- Subjects with history of prior radiation exposure for research purposes within the
past year such that participation in this study would place them over FDA limits for
annual radiation exposure. This guideline is an effective dose of 5 rem received per

- Subjects with current, past or anticipated exposure to radiation in the work place

- Blood donation within eight weeks of the start of the study.

National Institute on Drug Abuse
Last Updated:
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