Effects of a New Behavioral Intervention on Alcohol Craving and Drinking

Objective: To evaluate alcohol memory retrieval-extinction, a novel behavioral procedure for
reduction of craving and drinking, in problem drinkers.

Study population: We will collect evaluable data from up to 75 participants. Participants are
evaluable if they complete geographical momentary assessment (GMA, described below). All
participants will be adult alcohol drinkers (men: > 14 drinks/week or > 4 drinks/day; women:
> 7 drinks/week or > 3 drinks/day) whose drinking scores as hazardous on the Alcohol Use
Disorders Identification Test. Participants will not be seeking treatment for an alcohol-use
disorder, be physiologically dependent on alcohol, or have other drug use disorders.

Design: A randomized study with three groups. Participants will use smartphones to provide
geotagged reports of alcohol craving and drinking in daily life (GMA reports) before,
between, and after a series of laboratory sessions. During sessions, participants will drink
an alcoholic beverage (individualized to produce a 0.06 g/dL blood alcohol content) or a soft
drink. Participants will then be repeatedly presented with alcohol- or soft-drink-associated
cues without further drinking. These are the memory retrieval and extinction portions,
respectively, of memory retrieval-extinction. Previous studies suggest this procedure can
robustly reduce Pavlovian associations between cues and responses such as craving. The
mechanism seems to involve memory reconsolidation, in which freshly retrieved associations
(e.g., drink cues and consumption - pleasant effects ) become more vulnerable to disruption
by extinction.

Three groups will be tested: (1) alcohol retrieval / alcohol extinction will be compared to
(2) soft-drink retrieval / alcohol extinction and (3) alcohol retrieval / soft-drink
extinction. Before and after retrieval-extinction, participants will be tested for alcohol
craving and cue-induced physiological responses in laboratory sessions. Retrieval-extinction
will be followed by 1 week of follow-up GMA reporting, with telephone contact 30 days
thereafter.

Outcome parameters: The co-primary outcome measures are: self-reported alcohol craving in the
laboratory sessions before and after retrieval-extinction, and GMA reports of alcohol craving
and drinking. Daily-life responses are important because the version of retrieval-extinction
we will be using, with retrieval induced by drinking alcohol itself, rather than alcohol cues
alone, may be especially likely to have effects that generalize from the laboratory to daily
life. Secondary outcome measures are: (1) self-reported alcohol craving and drinking at
30-day follow-up, (2) physiological reactivity during sessions, and (3) urine biomarkers for
alcohol consumption.

- INCLUSION CRITERIA:

- age between 21 and 65 years inclusive;

- Drinking for at least the last 90 days at the following levels:

- For women, more than 3 drinks on any single day per week or more than 7 drinks
per

- week, during at least 10 different weeks;

- For men, more than 4 drinks on any single day per week or more than 14 drinks per
week, during at least 10 different weeks;

- a score greater than or equal to 8 and less than or equal to 15 on the self-report
version of the Alcohol Use Disorders Identification Test (AUDIT), with endorsement of
at least one item other than 1-3, because 1-3 assess only consumption, not concern or
consequences;

- self-report of liking or having neutral feelings about the sight and smell of
alcoholic beverages;

- for women, practicing an effective method of birth control before entry and throughout
the study (or postmenopausal for at least one year, or surgically sterile); negative
urine pregnancy test at each visit. Effective methods of birth control are those
approved by the Food and Drug Administration (FDA) used as described in the FDA Birth
Control Guide These methods are: (1) intrauterine device (IUD) copper; (2) IUD with
progestin; (3) implantable rod; (4) contraceptive shot/injection; (5) oral
contraceptives (combined pill, progestin-only pill, or extended/continuous-use
combined pill); (6) contraceptive patch; (7) vaginal contraceptive ring; (8) diaphragm
with spermicide; (9) sponge with spermicide; (10) cervical cap with spermicide; (11)
male condom; (12) female condom; (13) male partner with a vasectomy. Abstinence from
sexual intercourse is also an effective method of birth control.

EXCLUSION CRITERIA:

- risk of alcohol withdrawal, as determined by any of the following: a score greater
than or equal to 8 on the Clinical Institute Withdrawal Assessment for Alcohol,
Revised (CIWA-Ar) following a negative breath test for alcohol (i.e., BAC of 0.0),
lifetime history of delirium tremens or seizures (related to alcohol or not),
endorsement of a drinking to avoid withdrawal symptom on the SCID or MINI; or
physician s judgment.

- currently trying to quit drinking, or planning to quit or reduce alcohol drinking via
formal treatment or support-group attendance in the next six months;

- for women: pregnancy, breastfeeding, or planning to become pregnant during the
experiment;

- current liver disease or dysfunction, assessed by physical examination and medical
history; and hepatitis C, chronic hepatitis B, or other current liver disease or
dysfunction as assessed by physical examination and medical history or as reflected in
blood levels more than 5 times the upper limit of normal in any of the following:
aspartate transaminase (AST), alanine transaminase (ALT), or gamma-glutamyltransferase
(GGT)

- any other medical illness or condition that in the judgment of the investigators is
incompatible with alcohol consumption;

- current use of prescription or over-the-counter medications or herbal products for
which drinking alcohol is strictly prohibited. When the metabolic half-life of the
medication/product is known, we will require at least 7 half-lives to have elapsed
before any session involving alcohol consumption. If the half-life is not known (as
might be the case for some herbal preparations), we will require at least 7 days to
have elapsed since the last use before any session involving alcohol consumption;

- substance-use disorder for any drug(s) other than alcohol or nicotine in the previous
12 months;

- past or present diagnosis of bipolar disorder or any psychotic disorder; any history
of suicide attempt or current suicidal ideation; present diagnosis of uncontrolled or
untreated mood or anxiety disorder;

- cognitive impairment severe enough to preclude informed consent or valid self-report