Nicotinic Modulation of the Default Network

University of Maryland Baltimore (UMB)

Status: Completed

Conditions: Nicotine; Mecamylamine; Cognition; Magnetic Resonance Imaging

Treatments: Drug: Nicotine; Drug: Mecamylamine; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01223404

R21DA027894 (U.S. NIH Grant/Contract)

HP-00042696

Details and patient eligibility

About

Many disorders where attentional problems are a hallmark, such as Alzheimer's disease and schizophrenia, display abnormal regulation of the so-called default network of resting brain function that maintains internally directed thought when the mind is free to wander. There is indication that nicotine may improve attention by aiding the deactivation of the default network, and this mechanism may be of therapeutic benefit for the above disease states. The current project aims at providing a proof of concept by demonstrating that nicotinic drugs modulate default network function. The nicotinic agonist nicotine is hypothesized to improve attention by facilitating the down-regulation of default network activity, and the nicotinic antagonist mecamylamine is hypothesized to impair attention by impeding the down-regulation of default network activity during attentional task performance.

Full description

This study only enrolls healthy non-smokers. Participants perform attention tasks while undergoing functional Magnetic Resonance Imaging on three separate days. Across the three days, three difference conditions are tested in a double-blind manner, in randomized order. In all test sessions, participants receive a skin patch and swallow a capsule. In one session, both are a placebo. In another, the patch is a low-dose nicotine patch, and the capsule is a placebo. In another session, the patch is a placebo and the capsule contains a low dose of mecamylamine.

Enrollment: 21 patients

Sex: All

Ages: 21 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Age 21 through 50.
• Did not consume cigarettes, cigarillos, cigars, or other tobacco or nicotine-containing products more than 20 times in lifetime, and did not use any nicotine-containing product at all within the last two years.
• Normal or corrected to normal vision (at least 20/80).

Exclusion criteria

• Presence of metal objects in the body, implanted electronic devices, or any other counter indication for MRI.
• Claustrophobia.
• Major psychiatric disorders including mood, anxiety or psychotic disorders.
• Cardiovascular or cerebrovascular disease, such as history of myocardial infarction, heart failure, angina, stroke, severe arrhythmias, or EKG abnormalities.
• Kidney or liver disease.
• Hypertension (resting systolic BP above 140 or diastolic above 85 mm Hg).
• Hypotension (resting systolic BP below 95 or diastolic below 60).
• Use of any prescription or over-the-counter drug other than supplements and birth control.
• History of or current neurological illnesses, such as stroke, seizures, dementia or organic brain syndrome.
• Learning disability, attention deficit disorder, or any other condition that impedes memory and attention.
• Glaucoma, organic pyloric stenosis, uremia or renal insufficiency.
• Prostatic hypertrophy, bladder neck obstruction or urethral stricture.
• Left-handed or ambidextrous.
• Pregnant as determined by urine test, or breast-feeding.
• History or current diagnosis of drug or alcohol abuse or dependence.
• IQ < 85 as estimated by the WASI vocabulary subtest.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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21 participants in 6 patient groups

Placebo, Nicotine, Mecamylamine

Experimental group

Description:

Participants undergo 3 test sessions: In the first session ("placebo"), a placebo patch and a placebo capsule is administered. In the second session ("nicotine"), a nicotine patch (7 mg/24 hrs) and a placebo capsule is administered. In the third session ("mecamylamine"), a placebo patch and a mecamylamine capsule is administered.

Treatment:

Drug: Placebo

Drug: Mecamylamine

Drug: Nicotine

Nicotine, Placebo, Mecamylamine

Experimental group

Description:

Participants undergo 3 test sessions: In the first session ("nicotine"), a nicotine patch and a placebo capsule is administered. In the second session ("placebo"), a placebo patch (7 mg/24 hrs) and a placebo capsule is administered. In the third session ("mecamylamine"), a placebo patch and a mecamylamine capsule is administered.

Treatment:

Drug: Placebo

Drug: Mecamylamine

Drug: Nicotine

Placebo, Mecamylamine, Nicotine

Experimental group

Description:

Participants undergo 3 test sessions: In the first session ("placebo"), a placebo patch and a placebo capsule is administered. In the second session ("mecamylamine"), a placebo patch (7 mg/24 hrs) and a mecamylamine capsule is administered. In the third session ("nicotine"), a nicotine patch and a placebo capsule is administered.

Treatment:

Drug: Placebo

Drug: Mecamylamine

Drug: Nicotine

Nicotine, Mecamylamine, Placebo

Experimental group

Description:

Participants undergo 3 test sessions: In the first session ("nicotine"), a nicotine patch and a placebo capsule is administered. In the second session ("mecamylamine"), a placebo patch (7 mg/24 hrs) and a mecamylamine capsule is administered. In the third session ("placebo"), a placebo patch and a placebo capsule is administered.

Treatment:

Drug: Placebo

Drug: Mecamylamine

Drug: Nicotine

Mecamylamine, Placebo, Nicotine

Experimental group

Description:

Participants undergo 3 test sessions: In the first session ("mecamylamine"), a placebo patch and a mecamylamine capsule is administered. In the second session ("placebo"), a placebo patch (7 mg/24 hrs) and a placebo capsule is administered. In the third session ("nicotine"), a nicotine patch and a placebo capsule is administered.

Treatment:

Drug: Placebo

Drug: Mecamylamine

Drug: Nicotine

Mecamylamine, Nicotine, Placebo

Experimental group

Description:

Participants undergo 3 test sessions: In the first session ("mecamylamine"), a placebo patch and a mecamylamine capsule is administered. In the second session ("nicotine"), a nicotine patch (7 mg/24 hrs) and a placebo capsule is administered. In the third session ("placebo"), a placebo patch and a placebo capsule is administered.

Treatment:

Drug: Placebo

Drug: Mecamylamine

Drug: Nicotine