Conditions: Magnetic Resonance Imaging Cognition Nicotine Mecamylamine
Keywords: nicotine mecamylamine attention default network fMRI
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 21
Healthy volunteers: yes

Brief summary:
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.

Detailed 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.

Arms:
arm 1: 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. arm 2: 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. arm 3: 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. arm 4: 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. arm 5: 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. arm 6: 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.

Interventions: intervention 1: Placebo intervention 2: Nicotine intervention 3: Mecamylamine
Intervention descriptions: intervention 1: Participants are administered a placebo patch and a placebo capsule intervention 2: Participants are administered a nicotine patch (7 mg/24 hrs) and a placebo capsule intervention 3: Participants are administered a placebo patch and a capsule containing 7.5 mg of mecamylamine

Protocol document: