Inclusion Criteria:
All Subjects
- Signed informed consent prior to any study-related procedures,
- Subjects understand the nature and the procedures related with the study design of the trial and accept to fulfill all activities related to this trial,
- Subjects 18 to 60 years of age,
- Body mass index between 18 and 35 kg/m2, with a weight above 60 kg.
- No (history of) clinically significant conditions and/or concomitant medications which in the opinion of the investigator could endanger the safety of the subject or impact the validity of the study results,
- Male subjects who wish use condoms for the duration of the study and for a suitable time period after the last drug dose (e.g., 5 half-lives),
- Female subjects who are not pregnant or breast-feeding or who do not wish to become pregnant during the period of the clinical study and for three months later,
- Female subjects of childbearing potential (less than 24 months after the last menstrual cycle) who use adequate contraceptive methods. Adequate contraceptive methods may include any approved method of birth control such as combined estrogen and progestogen containing hormonal contraception, associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intra-uterine devices, condoms, abstinence or vasectomized partner. Contraception should be maintained until study end.
Additional Criteria for AUD Subjects
Treatment seeking subjects with AUD meeting DSM-5 criteria as assessed by SCID by qualified medical staff and:
- Consumed at least 4 binge drinking days (i.e. ≥ 5 standard drinks in a day for men or ≥ 4 standard drinks in a day for women) in the month prior to screening.
- A desire to reduce or stop drinking.
- Stable housing in the 3 months prior to screening with no foreseeable risk to lose this in the 3 months after screening,
- Agree to abstain from new/additional psychotropic medications, except for benzodiazepines as rescue medication prescribed by the PI or a stable dose of psychotropic medications in the 14 days (or 5 half-lives; whichever is longer) prior to enrollment/randomization with the intention to continue this medication during the study.
Exclusion Criteria All Subjects
- The subject has a clinically significant history of a disease or a disorder that could interfere with the interpretation of the results or could increase the risk to the subject all according to the opinion of the PI,
- Subject has a substance use disorder at time of screening (except for alcohol use in AUD subjects and nicotine use disorders),
- Subjects with cannabis or other drug use for at least 5 half-lives prior to screening, including nicotine use (i.e., subjects must abstain from nicotine use for at least five half-lives prior to screening).
- Subjects with symptoms of alcohol withdrawal or intoxication at time of screening (assessed using CIWA-Ar tool). if medically appropriate, intoxicated individuals will be provided transportation home while those experiencing alcohol withdrawal will be referred to an appropriate level of care.
- Subjects with history of seizures or epilepsy,
- Current or past history of Major Depressive Disorder (MDD) (within past 1 years), Bipolar Disorder, Schizophrenia, suicidal ideation (within past 2 years) or suicide attempts in the past 2 years,
- Uncontrolled inter-current illness (i.e., active infection),
- Clinically significant abnormal vital signs (e.g., systolic blood pressure ≥139 mmHg, diastolic blood pressure ≥90 mmHg, heart rate >90 beats per minute) at separate three measures before dosing,
- Clinically significant abnormal ECG parameters, including subjects with QTc greater than 450 msec.
- Clinically significant abnormal liver functions (ALT and AST), higher than three times the upper normal amount, clinically significant abnormal Hb, and/or clinically significant laboratory abnormalities (e.g., abnormal renal function, electrolyte derangements, etc.)
- Subjects who take, or are planning to take, any prescription or non-prescription medications, within at least 14 days (or 5 half-lives; whichever is longer) prior to enrollment/randomization, and for the entire duration of the study including: antipsychotic and mood stabilizing medications (including SSRIs such as Fluoxetine and Paroxetine, SNRIs and trazodone), OCT1 and OCT2 substrates (such as Metformin, Cisplatin, Imatinib, Procainamide, Citalopram, Cimetidine, Quinidine), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs) or lithium, serotonin-acting herbal medicines and supplements, dietary supplements (such as 5-hydroxy-trypthophan or St. John Wort), and enzyme altering agents (such as and/or grapefruit juice and/or rifampin, barbiturates, phenothiazines, cimetidine, etc.) or any other medications that may have significant interaction with the study medication,
- Received an experimental drug or used an experimental medical device within 1 month or within a period <5 times the drug's half-life for small molecules, or 3 months for biologics, whichever is longer, before the study drug is administered for the first time,
- Donated blood within 90 days or plasma within 30 days of study dosing,
- Any subject who may not be able to fulfill the study requirements per the investigator's clinical judgement.
Additional Criteria for Healthy Subjects
• Subject is unable to abstain from ingesting alcohol for 72 hours prior to dosing.