The research study is being conducted to better understand the effects of ketosis on brain functioning and the acute effects of alcohol. Participants will be asked to undergo ~4 weeks of ketogenic diet intervention. The study involves three lab visits: Lab 1 before starting the diet, Lab 2 after about 2 weeks after starting the diet, and Lab 3 after being on the diet for 4 weeks. All of the labs will include an alcohol tolerance test, and blood draws. Lab 1 and Lab 3 will also include an Magnetic resonance imaging scan. Due to scheduling, study procedures at 2 and 4 weeks may occur +/- 3 days. Magnetic resonance imaging (MRI) of the brain will measure levels of nicotinamide adenine dinucleotide (NAD) (a coenzyme that is important for energy metabolism), lactate (a metabolite produced during energy metabolism), and neurotransmitters glutamate and GABA. Alcohol tolerance will be tested using a dose of alcohol (approximately 4-5 alcohol beverages) to will elevate breath alcohol levels to approximately 0.08% to measure the acute effects of alcohol. Blood samples will be collected to measure varying metabolites.

Consent and Screening Session (approximately 4 hours).

The following will occur at this visit. The visit may be completed on more than one day at the CSA following signed consent:

• Participants will be asked to show a legal photo ID and then undergo a breathalyzer test to ensure that they are able to make a well-reasoned decision about whether or not to participate in the study. The breath alcohol level must be 0.000% to sign the consent form.
• Participants will be asked to provide demographic information, including current address to be registered as a patient at the University of Pennsylvania.
• A clinician will perform a medical history and physical examination. Trained study staff will draw a total of approximately 3 tablespoons (44 mL) of blood for standard laboratory tests and genetic analysis.
• A urine sample is required for routine urinalysis, drug screen, ketone levels, and a pregnancy test for woman who are able to become pregnant.
• Study personnel will measure vital signs (blood pressure and pulse), weight, and height.
• Study personnel will complete a brief psychiatric interview record alcohol and cigarette use over the past 90 days.
• Participants must complete a screening evaluation form in advance of the MRI exam for the presence of medical implants or other foreign bodies that could pose an injury when undergoing MRI.

Staff will call participants within 5 business days of completing the screening visit to confirm whether study eligibility and schedule the rest of the study visits.

Dietary Intervention (4 weeks each)

Participants will be asked to adhere to a 4-weeks ketogenic diet. Depending on scheduling availability, in may include an additional 3 days. All meals will be provided by a commercial meal service (Factor75) and will be delivered to participants residence weekly. Participants are asked to just eat the food provided for the 4-weeks of the study. Compliance to the dietary intervention will be assessed daily with a urine ketone levels test that will be performed each morning. A picture of the test will be sent by text or email daily. Blood ketone levels will be checked on the days of the lab visits. Each week a staff member will call participants to check on their health and wellbeing, make sure they are receiving study meals and record the amounts of each meal consumed during the week. Staff will also ask questions about mood and record alcohol use for each week.

Study lab visits lab 1 and 3 (week 4; approximately 8 hours. each) Staff will call the night before to reminder participants not to eat or drink anything except water after midnight the day before and on the day of the study visit. The study will provide breakfast and lunch. Staff will review the current list medications and vitamins provided at the screening visit, and will inquire about any changes.

Lyft ride service will be used to bring participants to Stellar Chance Laboratories (440 Curie Blvd.).

On the day of the study lab visits, the following will occur:

• A light meal will be provided, participants must have a breath alcohol level of 0.000% to continue, finger stick for blood glucose level, and vital signs. Participants will be asked about recent use of drugs, alcohol, and nicotine. Staff will collect a urine sample to conduct a drug screen, urine ketone level, and a pregnancy test (for woman able to become pregnant).
• A brain 7-Tesla MRI scan (~1.5 hour) will be performed. An MRI is a type of scan that uses radio waves to take detailed pictures of the body. Participants will be asked to lie on an MRI table where the technologist will place a receiver on the head. A blanket can be provided for comfort and earplugs since the MRI makes noises while it is scanning. Participants will still be able to hear some sound to ensure communication with the technologist and can follow any direction given throughout the MRI scan. The technologist will slowly slide participants into the MRI magnet where radio waves will be transmitted into the head.

Participants will be asked to:

• fill out an MRI safety form.
• remove any metal from the body.
• Staff will provide earplugs for the noise from the MRI scanner, and position participants on the imaging table with their head in the scanner, held comfortably in a special head holder.
• Participants will be instructed not to move the head and to lie as still as possible during the scan (~ 90 minutes). There will be several scans, during which staff will obtain a structure image of the brain, NAD (a cofactor involved in energy metabolism), lactate (a byproduct of energy metabolism) and neurotransmitter GABA and glutamate.

After the scan Lyft will be used to travel to 3535 Market St. for the reminder of the laboratory visit.

• A blood sample will be collected, and lunch will be provided
• A dose of alcohol calculated to elevate breath alcohol concentration to approximately 0.08% will be provided. Staff will measure alcohol intoxication prior to and at pre-specified times following alcohol administration using the following measurements: breath alcohol concentration, motor (groove pegboard task) and cognitive (go-no-go task) tests, and questionnaires. Study personnel will ask about side effects that may have occurred throughout the laboratory procedures.
• At the end of the laboratory procedures, participants will be provided a snack and staff will measure blood glucose and ketone levels. Participants will return home by Lyft.

Study lab visit 2 (week 2; approximately 5 hours.) Staff will call the day before to reminder participants not to drink alcohol after 10pm the night before and set up a Lyft ride to 3535 Market St. Participants are asked to eat breakfast at home before coming to the visit. Staff will review the current list medications and vitamins provided at the last study visit, and record any changes.

On the day of the study lab visits, the following will occur:

• Staff will record participants breath alcohol level (must be 0.000% to continue), finger stick for blood glucose level, and vital signs. Staff will ask about recent use of drugs, alcohol, and nicotine. Participants will be asked to provide a urine sample to conduct a drug screen, urine ketone level, and a pregnancy test (for woman able to become pregnant).
• Blood sample will be collected, and lunch will be provided
• A dose of alcohol calculated to elevate breath alcohol concentration to approximately 0.08% will be provided. Staff will measure alcohol intoxication prior to and at pre-specified times following alcohol administration using the following measurements: breath alcohol concentration, motor (groove pegboard task) and cognitive (go-no-go task) tests, and questionnaires. Study personnel will ask about side effects throughout the laboratory procedures.
• At the end of the laboratory procedures, a snack will be provided and staff will measure blood glucose and ketone levels. Participants will return home by Lyft.

Inclusion Criteria:

1. Age 21 years to 50 years old.
2. Willingness to provide signed, informed consent and commit to completing study procedures. Reported on at least one day in the month prior to consent of consuming 2 or more standard alcohol drinks on a single day.

Exclusion Criteria:

1. Unwilling or unable to refrain from use, within 24 hours of the alcohol lab procedures, psychoactive medications or medication that may affect study results.
2. Current DSM-5 diagnosis of any major psychiatric disorder (other than nicotine use disorders, or marijuana use disorders) as identified by clinical examination or structured interview that could interfere with study participation or make it hazardous for the subject.
3. Currently taking medication(s) that could interfere with study participation or make it hazardous for the subject to participate. (e.g. anticholinergics; antipsychotics; lithium; psychotropic drugs not otherwise specified)
4. Positive urine drug screen, positive for all substances but marijuana at screening or study visits (may be repeated once and if the result is negative on repeat, it is not exclusionary).
5. A current, clinically significant physical disease or abnormality on the basis of medical history, or routine laboratory evaluation that can impact brain function, the use of a ketone supplement, administration of ketogenic diet, or the use of alcohol (e.g., epilepsy, diabetes, irritable bowel syndrome, Crohn's disease, liver disease, kidney disease, kidney stones, chronic metabolic acidosis or a cardiomyopathy as determined by history and clinical exam).
6. Currently suffering from or has a history of stroke and/or stroke related spasticity.
7. Head trauma with loss of consciousness for more than 30 minutes or associated with skull fracture, inter-cranial bleeding or abnormal MRI (self-report, medical history).
8. Weight greater than 225lbs (Need to cap amount of alcohol given based on weight to individuals).
9. Females who are pregnant or breast-feeding
10. Contraindication to MRI, including presence of ferromagnetic objects, claustrophobia or fear of enclosed, medical conditions that prevent subjects from lying comfortably flat on his/ her back for up to 2 hrs.