The objective of this proof-of-concept pilot study is to evaluate Donepezil HCL (Aricept) for side effects and effects on smoking behavior and performance on neurocognitive tasks in a population of dependent smokers.

Nicotine dependence is a major public health problem and currently available treatments are ineffective for the majority of smokers. Thus, there is a need to develop and test novel medications to assist smokers to quit smoking. This pilot feasibility study examined: (1) tolerability and medication adherence, and (2) the effects of donepezil versus placebo on smoking behavior and cognitive performance in non-treatment seeking smokers. We predicted that 4 weeks of donepezil would improve working memory at the highest task difficulty level and sustained attention. Because participants in this study were not trying to quit, change in smoking behavior was a secondary outcome.

Inclusion Criteria:

• 30 smokers ages 18-50 who have smoked at least 10 cigarettes per day for the past 6 months, will be eligible to participate. They must be able to provide informed consent.

Exclusion Criteria:

• Smoking Behavior:

  1. Current enrollment or plans to enroll in a smoking cessation program, or use other smoking cessation medications in the next 2 months.
  2. Provide a CO reading less than 10 ppm at medical screening.
  3. Participants who roll their own cigarettes.
  4. Regular use of chewing tobacco or snus.

• Alcohol/Drugs 1) History of substance abuse and/or currently receiving treatment for substance abuse (e.g. alcohol, opioids, cocaine, marijuana, or stimulants). 2) Current alcohol consumption that exceeds 25 standard drinks/week. 3) Providing a breath alcohol concentration (BrAC) reading of greater than or equal to 0.01 at medical screen, baseline, or testing sessions.

• Medical:

  1. Women who are pregnant, planning a pregnancy, or lactating; all female subjects shall undergo a urine pregnancy test prior to enrollment and must agree in writing to use an approved method of contraception.
  2. Lifetime history or current diagnosis of psychosis, bipolar disorder, anxiety disorder, or schizophrenia, as identified by the MINI. Individuals with a past history of depression are eligible as long as their major depression episode was more than 6 months ago.
  3. Serious or unstable disease within the past 6 months i.e. heart disease, liver/kidney failure)
  4. Other medical conditions such as peptic ulcer disease; beign prostatic hypertrophy or bladder outflow problems; asthma or chronic obstructive pulmonary disease.
  5. BP reading of 170/100 at medical screening session.

• Medication:

  1) Current use, recent discontinuation within last 14 days or planned use of the following medications:

• Any form of smoking cessation medication, i.e. Zyban, Wellbutrin, Wellbutrin SR, Chantix, nicotine replacement therapy

• Psychotropic medications (anti-psychotics, anti-depressants, anti-anxiety or anti-panic medications, mood stabilizers and stimulants)

• Current treatment with other acetylcholinesterase inhibitors (ACIs) like donepezil HCL (Aricept), tacrine, rivgastigmine and galantamine

• Anti-seizure meds, and other meds that affect the cholinergic system such as mecamylamine, atropine, succinylcholine, ketocaonazole, quinidine, bethanechol, iprapropium, bromide, dicyclomine, benztropine, carisprodol, zantac, and procardia.

  2) Patients shallbe instructed to refrain from using any study prohibited drugs (note participants are allowed to take prescription medicines not in the exclusion list)throughout their participation in the study.

• Other

  1. Inability to complete the baseline study procedures within thee hours and/or correctly, as determined by the PI.
  2. Non-English speakers.

All participants receiving at least one dose of Donepezil or Placebo are included in the analysis population.

Adverse event data were collected over a 28-day period.

The safety population described within this section includes all subjects who received at least one dose of Donepezil or Placebo.

Systematic Assessment: Side effect severity was rated on a 4-point scale (0 = not present, 1 = mild, 2 = moderate, 3 = severe) using a 38-item self-report measure based on common side effects of Donepezil (e.g., nausea) at all in-person visits (n=9).

Double Blind