Enhancing Cue Exposure Treatment for Smoking Reduction With Isradipine

The proposed proof-of-concept study will utilize a prospective, experimental research design.
The investigators will recruit adult daily smokers who will be randomly assigned to either:
(1) Cue Exposure Treatment with Isradipine (CET+ISR )or (2) CET with placebo (CET+PBO). Two
90-minute CET sessions will be conducted to expose participants to interoceptive and
situational cues for tobacco use and craving. In the first session, participants will receive
a dose of ISR or PBO and begin the CET session after waiting 75 minutes. CET has three
components: exposure to slides depicting smoking cues (visual exposure), exposure to emotions
and imagined situations that most reliably triggered an urge to smoke (emotional/imaginal),
and exposure to a participant's own cigarettes (in vivo). The second session will be
conducted 24 h after the first in a medication-free state. Clinicians will record craving
throughout the CET sessions. Participants will return one week after the second CET session
to complete several questionnaires related to smoking and mood, provide a carbon monoxide
sample to verify abstinence, and report craving to smoking related cues.

Inclusion Criteria:

- Male and female patients ages 18-65 capable of providing informed consent

- Willing and able to provide informed consent, attend all study visits and comply with
the protocol

- Daily smoker for at least one year

- Currently smoke an average of at least 10 cigarettes per day

- Report a motivation to quit smoking in the next month of at least 7 on a 10-point
scale

Exclusion Criteria:

- Current diagnosis of a psychotic, eating, developmental or bipolar disorder

- Significant suicide risk as determined by structured interview

- Exclusion criteria related to isradipine administration:

- Potential participants will be excluded if they report any history of the
following:

1. known allergy or sensitivity to isradipine,

2. hypertension,

3. congestive heart failure,

4. any type of liver disease,

5. current pregnancy, or

6. women of childbearing potential who are not using medically accepted forms
of contraception (e.g., IUD, oral contraceptives, barrier devices, condoms
and foam, or implanted progesterone rods stabilized for at least 3 months).

- Potential participants will also be excluded if they are currently taking:

1. Rifampin, or

2. Tagamet. Rifampin has been shown to decrease availability of calcium channel
blockers and concurrent administration of Tagamet and isradipine has been
shown to increase hypotensive effects and inhibit hepatic metabolism of
isradipine.

- Psychoactive substance use assessed with urinalysis

- A history of significant medical condition and/or be deemed as currently unhealthy by
the Dr. Young

- Limited mental competency and the inability to give informed, voluntary, written
consent to participate

- Current use of any pharmacotherapy or psychotherapy for smoking cessation not provided
by the researchers during the quit attempt

- Concurrent psychotherapy initiated within three months of screening, or ongoing
psychotherapy of any duration directed specifically toward treatment of anxiety or
mood disorder other than general supportive therapy initiated at least 3 months prior
to the study

- Use of other tobacco products, including e-cigarettes

- Insufficient command of the English language