Inclusion Criteria:
1. In the opinion of the investigator, participant is capable of understanding and complying with protocol requirements.
2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
3. Is a healthy adult male.
4. Speaks English as their first language.
5. Is aged 18 to 45 years, inclusive, at the time of informed consent and first dose of study drug.
6. Weighs at least 50 kg and has a body mass index (BMI) between 18 and 32 kilogram per metre square (kg/m\^2), inclusive at Screening.
7. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose.
8. Has a normal magnetic resonance imaging (MRI) scan and electroencephalogram (EEG) measurement at Screening.
Exclusion Criteria:
1. Has received any investigational compound or ketamine within 30 days prior to Day 1 of Period 1.
2. Has received TAK-063 in a previous clinical study or as a therapeutic agent.
3. Is an immediate family member, study site employee, or in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress.
4. Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder, or other abnormality (including MRI or EEG), which may impact the ability of the participant to participate or potentially confound the study results.
5. Has a known hypersensitivity to any component of the formulation of TAK-063 or ketamine.
6. Has a contraindication for ketamine.
7. Has a positive result for drugs or alcohol at Screening or Check-in (Day -1 of Period 1).
8. Has a history of drug or alcohol abuse or dependence (as defined by Diagnostic \& Statistical Manual of Mental Disorders, fourth Edition \[DSM-IV\]) within 1 year prior to the screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
9. Has taken any excluded medication, supplements, or food products listed in the Excluded Medications and Dietary Products.
10. Has evidence of current cardiovascular, central nervous system (CNS), hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma hypoxemia, hypertension, seizures, or allergic skin rash. There is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking TAK-063 or ketamine or a similar drug in the same class, or that might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease, seizure disorders, and cardiac arrhythmias.
11. Has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis frequent \[more than once per week\] occurrence of heartburn, or any surgical intervention \[e.g., cholecystectomy\]).
12. Has a history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to Day 1 of Period 1.
13. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV), or a known history of human immunodeficiency virus infection at Screening.
14. Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 28 days prior to Check-in (Day -1 of Period 1) or cotinine test is positive at Screening or Check-in (Day -1 of Period 1).
15. Has poor peripheral arterial/venous access or recent wrist trauma.
16. Has donated or lost 450 mL or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 3 months prior to Day 1 of Period 1.
17. Has a Screening and/or Check-in (Day -1 of Period 1) abnormal (clinically significant) electrocardiogram (ECG). Participant has a supine blood pressure outside the ranges of 90 to 140 mm Hg for systolic and 50 to 90 mm Hg for diastolic, if out of range may be repeated once for eligibility determination at the Screening Visit or Check-in (Day -1 of Period 1).
18. Has a resting heart rate outside the range 50 to 90 beats per minute (bpm), if out of range may be repeated once for eligibility determination at the Screening Visit and/or Check-in (Day -1 of Period 1).
19. Has a QT interval with Fridericia correction method (QTcF) greater than (\>) 430 milliseconds (ms) or PR outside the range 120 to 220 ms, if out of range may be repeated once for eligibility determination within a maximum of 5 minutes, at the Screening Visit and/or Check-in (Day -1 of Period 1).
20. Has abnormal Screening laboratory values that suggest a clinically significant underlying disease or participant with the following lab abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>1.5 upper limit of normal (ULN).
21. Has a history of Axis I/II mental disorders according to DSM-IV Axis I/II such as depression, anxiety disorders, bipolar disorder, attention deficit/hyperactivity disorder (ADHD), autism spectrum disorders, anorexia nervosa, bulimia nervosa, and schizophrenia.
22. Has a history of head injury or trauma.
23. Has any condition that would prevent an MRI from accurately or safely being performed (e.g., claustrophobia, cardiac pacemaker, metallic implants or clips), as verified per study site's standard MRI assessment questionnaire.
24. Has a risk of suicide according to the Investigator's clinical judgment (e.g., per Columbia-Suicide Severity Rating Scale \[C-SSRS\]) or has made a suicide attempt in the previous 6 months prior to Screening.
