The purpose of this study is to evaluate the pharmacokinetics of intranasally administered esketamine in healthy Han Chinese, Korean, Japanese, and Caucasian participants and to evaluate the effects of rifampin on the pharmacokinetics of intranasally administered esketamine in healthy Caucasian participants.

Inclusion Criteria:

• For Cohort 1: healthy Han Chinese participants 20 to 55 years of age, inclusive, who have resided outside of China for no more than 10 years and have parents and maternal and paternal grandparents who are of Han Chinese ethnicity For Cohort 2: healthy Korean participants 20 to 55 years of age, inclusive, who have resided outside of Korea for no more than 10 years and have parents and maternal and paternal grandparents who are of Korean ethnicity For Cohort 3: healthy Japanese participants 20 to 55 years of age, inclusive, who have resided outside of Japan for no more than 10 years and have parents and maternal and paternal grandparents who are of Japanese ethnicity For Cohort 4: healthy Caucasian participants 20 to 55 years of age, inclusive Participants must be within +/-7 years and +/-20 percent (%) of the combined mean age and mean body weight at Screening, respectively, of Cohort 1, Cohort 2, and Cohort 3
• Body mass index (BMI; weight [kilogram]/height^2 [m]^2) between 18 and 30 kilogram per meter square (kg/m^2), inclusive, and a body weight not less than 47 kilogram (kg)
• If a woman, must have a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test at Screening
• If a woman, must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 1 month after receiving the last dose of study drug
• Creatinine clearance more than equal to (>=)80 milliliters per minute (mL/min) based on Cockroft-Gault equation

Exclusion Criteria:

• Current significant psychiatric disorder including but not limited to psychotic, bipolar, major depressive, or anxiety disorder
• Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at Screening or Day -1 of Period 1 as deemed appropriate by the investigator
• Clinically significant abnormal physical examination, vital signs, or 12 lead electrocardiogram (ECG) at Screening or Day -1 of Period 1 as deemed appropriate by the investigator
• History of drug or alcohol abuse disorder within the past 1 year, or a reason to believe a participant has such a history
• Regular use of intranasal tobacco powder within the past 1 year, or a reason to believe a participant has such a history