The purpose of this study is to assess the cognitive effects associated with administration of intranasal esketamine 84 mg.

This is a randomized (participants assigned to 1 of 2 treatment sequences by chance), double-blind (identity of study drugs will not be known to participant or members of study staff), placebo-controlled (a substance without active drug identical in appearance to esketamine), 2-period crossover study (participants assigned to each treatment sequence will receive 1 dose of esketamine and 1 dose of placebo administered intranasally [through the nose]) conducted in healthy adult participants at a single center. Participants will complete 3 study phases: A screening phase of up to 3 weeks; a 2-week double-blind treatment phase, which includes 2 treatment periods (Periods 1 and 2) separated by a washout interval of at least 7 days; and, a 1-week posttreatment (follow up) phase, if applicable. The duration of the study for each participant will be approximately 6 weeks. Blood and urine samples will be collected during the study for laboratory assessments. Participants will be monitored for safety from the time of signing the informed consent form up until 1 week after the last dose of study drug (or end of treatment).

Inclusion Criteria:

• Body mass index (BMI) (weight [kg]/height[m2]) between 18 and 30 kg/m2 (inclusive), and body weight not less than 45 kg
• Blood pressure (after the subject is supine for 5 minutes) between 90 and 140 mmHg systolic, inclusive, and no higher than 90 mmHg diastolic at Screening and predose on Day 1 of Period 1
• A 12-lead ECG consistent with normal cardiac conduction and function at Screening and predose on Day 1 of Period 1
• Comfortable with self-administration of intranasal medication and able to follow instructions provided
• Non-smoker for at least 6 months before first study drug administration

Exclusion Criteria:

• Subject has clinically significant liver or renal insufficiency; cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances. A significant primary sleep disorder is exclusionary
• Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening or on Day 1 of Period 1, as deemed appropriate by the investigator
• Clinically significant abnormal physical examination, vital signs, or 12-lead ECG at screening or on Day 1 of Period 1, as deemed appropriate by the investigator
• Anatomical or medical conditions that may impede delivery or absorption of study medication (e.g., undergone facial reconstruction, rhinoplasty, significant structural or functional abnormalities of the nose or upper airway; obstructions or mucosal lesions of the nostrils or nasal passages; undergone sinus surgery in the previous 2 years; or signs and symptoms of rhinitis predose on Day 1 of Period 1)
• Has an abnormal or deviated nasal septum with any 1 or more of the following symptoms: blockage of 1 or both nostrils, nasal congestion (especially 1-sided), frequent nosebleeds, frequent sinus infections, and at times has facial pain, headaches, and postnasal drip