The primary purpose of the study is to evaluate the pharmacokinetics (what the body does to the medication) of intranasally (through the nose) administered esketamine in healthy participants.

This is a single-center study with 3 cohorts (groups). Approximately 58 participants will be enrolled in this study. In Cohort 1, approximately 16 participants will be enrolled for up to 78 days and they will receive 4 different single-dose regimens (Treatment A, B, C and D) of intranasal spray of esketamine solution in a crossover manner (participants will be switched from one single-dose regimen to another) and in an open label manner (both the investigator and the participant know the intervention received by the participant). In Cohort 2, approximately 14 participants will be enrolled for up to 35 days and they will receive 1 regimen of intranasal esketamine (Treatment D) in an open label manner. In Cohort 3, approximately 28 participants will be enrolled and they will be randomly assigned to receive either Treatment E (intranasal esketamine spray) or Treatment F (intranasal placebo spray) in a double blind manner (both the investigator and the participant do not know the intervention received by the participant). Safety evaluations will include assessment of adverse events, targeted nasal examinations, laboratory tests, electrocardiogram, physical examination, pulse oximetery, and vital signs.

Inclusion Criteria:

• Blood pressure between 90 and 145 mmHg systolic and no higher than 90 mmHg diastolic
• A 12-lead electrocardiogram consistent with normal cardiac conduction and function
• Agree to protocol-defined method of contraception
• Comfortable with self-administration of intranasal medication

Exclusion Criteria:

• History of or current clinically significant medical illness including cardiac arrhythmias or other cardiac disease; hematologic disease; coagulation disorders; significant pulmonary disease, including bronchospastic respiratory disease; diabetes mellitus; renal or hepatic insufficiency; thyroid disease; neurologic or psychiatric disease, asthma
• Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening or at admission to the study center
• Clinically significant abnormal physical examination, vital signs or 12 lead electrocardiogram at screening or at admission to the study center
• Known allergy to heparin or history of heparin-induced thrombocytopenia