| Eligibility |
- ELIGIBILITY CRITERIA:
Participants will be healthy 21-60 year-old male and female heavy drinkers. An equal number
of participants with OPRM 118 AA genotype and those with 1 or 2 copies of the G allele (AG
or GG) will be enrolled. Inclusion and exclusion criteria will be evaluated following
screening conducted under the NIAAA screening protocol as described below
INCLUSION:
- Male and female participants between 21-60 years of age.
- Male participants must have consumed an average of greater than 14 standard drinks per
week, and females must have consumed an average of greater than 7 standard drinks per
week during the past 3 months [assessment: 90-day timeline followback (TLFB)completed
at screening visit].
- In addition, participants must have on average at least 1 binge drinking day per week
during the last 90 days, defined as a day in which 4 or more standard drinks were
consumed for females and 5 or more standard drinks were consumed for males. Average
number of binge drinking days will be calculated based on total number of binge
drinking days from the TLFB (e.g., for 90 days worth of data, participants with a
total of 13 or more binge drinking days will be eligible).
- Participants must be willing and able to refrain from using alcohol one day prior to
each study, and non-prescription medication for 3 days prior to each visit
[assessment: medical history].
- Inclusion criteria for women:
- Use of adequate method of birth control during the study, if female is sexually
active and is not surgically sterilized. Adequate methods of contraception
include: use of oral contraceptives; use of barrier method of contraceptive; use
of an approved IUD or other long-acting reversible contraceptive (LARC); have a
male sexual partner who is surgically sterilized; or have exclusively female
sexual partner(s) [assessment: medical history].
EXCLUSION:
- Current or prior history of major medical illness, including CNS, cardiovascular,
respiratory, gastrointestinal, hepatic, renal, endocrine, or reproductive disorders
[assessment: clinically significant findings on medical history and physical exam,
ECG, laboratory tests].
- Participation in any other pharmacological intervention study within 4 months prior to
the start of this study [assessment: medical history].
- Positive hepatitis A, B Antigen, or C, or HIV test [assessment: laboratory test].
- An aspartate transaminase (AST) / alanine transaminase (ALT) ratio 3 times greater
than the normal limit [assessment: laboratory test].
- Diagnosis of Axis-I anxiety disorders or major depressive disorders in the past 12
months [assessment: SCID interview].
- Lifetime diagnosis of Axis-I bipolar disorders or psychotic disorders [assessment:
SCID interview].
- Suicidal ideation in the past 6 months or suicidal behavior in the past 12 months
[assessment: Columbia Suicide Severity Rating Scale].
- Current diagnosis of substance use disorder (SUD), other than alcohol use disorder,
mild cannabis use disorder (less than 4 criteria), or current SUD in remission.
Current smoking or nicotine dependence is not exclusionary [assessment: SCID-IV/SCID-5
interview, FTND].
- Positive result on urine drug screen or breathalyzer test during screening. Positive
urine drug screen or breathalyzer reading during more than 1 study visit will result
in participant withdrawal from the study [assessment: laboratory tests and
breathalyzer test performed at screening or update visit under 14-AA-0181 most
proximal to enrollment].
- Currently (i.e., at the time of screening) seeking treatment for alcohol problems or
have undergone inpatient or outpatient detoxification or treatment for alcohol
problems in the past 6 months. [assessment: medical history and physical exam].
- Lactose intolerance or rare hereditary problems of galactose intolerance, Lapp lactase
deficiency, or glucose-galactose malabsorption [assessment: medical history and
physical exam].
- Alcohol use:
- Current or prior history of alcohol-induced flushing reaction, including rapid
reddening of the face, rapid heart rate and breathing, and nausea after 1 or 2
drinks [assessment: medical history and physical exam, alcohol flushing
questionnaire].
- History of delirium tremens, hallucinations or seizures related to alcohol
withdrawal [assessment: medical history, CIWA-Ar, SCID interview].
- Medication exclusion criteria:
- Any regular or prescribed use of opioid analgesics in the past 3 months.
- Use of prescription or OTC medications known to interact with alcohol within 2
weeks of the study. These include, but may not be limited to: isosorbide,
nitroglycerine, benzodiazepines, warfarin, anti-depressants such as
amitriptyline, clomipramine and nefazodone, anti-diabetes medications such as
glyburide, metformin and tolbutamide, H2-antagonists for heartburn such as
cimetidine and ranitidine, muscle relaxants, anti-epileptics including phenytoin
and phenobarbital codeine, opioid analgesics including darvocet, percocet and
hydrocodone, cough-and-cold preparations which contain anti-histamines, pain
medicines and anti-inflammatories such as aspirin, ibuprofen, acetaminophen,
celecoxib and naproxen.
- Use of medications known to inhibit or induce enzymes that metabolize alcohol for
4 weeks prior to the study. These include chlorzoxazone, isoniazid, metronidazole
and disulfiram.
- Use of drugs known to affect hemodynamic response. These include
antihypertensives, insulin and thyroid medications. [assessment: medical history
and physical exam].
- Exclusion criteria for MRI:
- Presence of ferromagnetic objects in the body that are contraindicated for MRI of
the head (including but not limited to pacemakers or other implanted electrical
devices, brain stimulators, some types of dental implants, aneurysm clips,
metallic prostheses, permanent eyeliner, implanted delivery pump, or shrapnel
fragments).
- Fear of enclosed spaces.
- Inability to lie comfortable on back for up to 2 hours in the MRI scanner
[assessment: NIAAA MRI Safety Screening Questionnaire].
- Exclusion criteria for women:
- Pregnant [assessment: urine beta-hCG test at screening]. Women must also test
negative on urine beta-hCG test at the start of every study visit.
- Breast-feeding [assessment: medical history and physical exam].
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