Spravato (esketamine) has a relatively short half-life, meaning most of the drug clears your body within one to two days. The active compound reaches peak levels in your blood about 20 to 40 minutes after you use the nasal spray, and its elimination half-life is roughly 7 to 12 hours. That means half the drug is gone in that window, and it takes about four to five half-lives for a substance to be effectively eliminated, putting full clearance at roughly two to three days for most people.
How Spravato Moves Through Your Body
After you spray esketamine into your nose, it absorbs quickly through the nasal lining and enters your bloodstream. Blood levels peak within about 20 to 40 minutes, which lines up with when most people feel the strongest effects. From there, your liver breaks the drug down using specific enzymes, primarily CYP2B6 and CYP3A4, with smaller contributions from CYP2C19 and CYP2C9.
The liver converts esketamine into a metabolite called noresketamine, which is pharmacologically active but weaker than the parent drug. Noresketamine has a longer half-life than esketamine itself, so while the primary compound clears relatively fast, its breakdown products linger a bit longer. The body eventually processes these metabolites further, attaching them to other molecules that make them water-soluble and easier to flush out.
The vast majority of esketamine and its metabolites leave through urine. Based on studies of ketamine (the parent compound of which esketamine is one half), about 91% of the administered dose can be recovered in urine over five days. Only about 2% leaves the body as the unchanged original drug. The rest exits as various metabolites, with roughly 80% appearing as conjugated (water-soluble) forms of hydroxylated breakdown products.
How Long the Effects Actually Last
The subjective effects of Spravato are much shorter than the time the drug stays detectable in your body. Dissociative symptoms, the feeling of being detached or “floaty,” typically peak around 40 minutes after a dose and resolve within about 90 minutes. Blood pressure elevations follow a similar pattern, generally peaking around the 40-minute mark and declining from there.
This is why the FDA requires a minimum two-hour observation period at the healthcare facility after every treatment session. During that time, your blood pressure, breathing, and mental state are monitored. Most people feel largely back to normal by the end of that window, though subtle effects on alertness and coordination can persist longer than you might realize.
The official guidance from the manufacturer is clear: do not drive, operate machinery, or do anything requiring full alertness until the next day after a restful sleep. Even if you feel fine leaving the clinic, your reaction time and judgment may still be slightly impaired for hours afterward. You’ll need someone to drive you home after each session.
Factors That Affect Clearance Time
Several variables can shift how quickly your body eliminates esketamine. Because the drug relies heavily on liver enzymes for metabolism, anything affecting liver function will change the timeline. People with moderate to severe liver impairment process the drug more slowly, meaning it stays in the system longer and effects may be more pronounced or prolonged.
Other medications matter too. Drugs that inhibit CYP3A4 or CYP2B6, the two main enzymes responsible for breaking down esketamine, can slow its clearance. Conversely, medications that ramp up the activity of those enzymes (known as inducers) could speed elimination. Your prescriber should already be accounting for these interactions, but it’s worth knowing that your other medications can shift how long Spravato lingers.
Age, body composition, and genetics also play roles. The CYP enzymes involved in esketamine metabolism vary in activity from person to person based on genetic differences. Someone who is a “slow metabolizer” for CYP2B6, for example, will clear the drug more gradually than someone with typical enzyme activity. Older adults and people with higher body fat percentages may also experience slightly longer clearance times.
Drug Testing Considerations
Standard workplace drug panels (the typical 5- or 10-panel tests) do not screen for ketamine or esketamine. However, specialized drug tests can detect ketamine and its metabolites in urine for several days after use. If you’re subject to an extended panel that includes ketamine, traces could potentially show up for roughly three to five days, depending on the sensitivity of the test and your individual metabolism.
In blood, esketamine is generally undetectable within one to two days. Hair testing, which is less common, can theoretically detect ketamine-related compounds for much longer periods, up to 90 days, though this type of testing is rarely used outside forensic or research settings. If drug testing is a concern, having documentation of your Spravato prescription on file can help clarify any positive result.