What is Spravato and How Does It Work?
Spravato is the brand name for esketamine, a prescription nasal spray approved by the FDA for adults with treatment-resistant depression (TRD) and for depressive symptoms in adults with major depressive disorder (MDD) with suicidal thoughts or actions [1.4.6, 1.4.7]. It is the S-enantiomer of ketamine, a substance known both as a medical anesthetic and a recreational drug [1.4.7]. Unlike traditional antidepressants that can take weeks to work, Spravato can offer rapid relief, sometimes within hours or days [1.5.4, 1.8.4].
Its mechanism of action is different from most oral antidepressants [1.7.3]. Spravato works by targeting the N-methyl-D-aspartate (NMDA) receptor in the brain, influencing the neurotransmitter glutamate [1.4.5, 1.7.3]. This action helps to restore synaptic connections between brain cells, which can be damaged by long-term depression [1.7.3].
The Sensation: Dissociation, Not a Recreational High
The most discussed question is, 'Does Spravato get you high?' While some of the sensations it causes can be described as a 'high,' it's more accurately termed 'dissociation' in a clinical context [1.2.3, 1.3.3]. The most common side effects reported by patients are dissociative or perceptual changes [1.2.5]. These can include:
- Feeling disconnected from yourself, your thoughts, feelings, and surroundings (dissociation, depersonalization, derealization) [1.2.2, 1.3.3]
- Distortions of time and space [1.2.5]
- Feeling dizzy, lightheaded, or having a spinning sensation (vertigo) [1.3.1, 1.7.2]
- Feeling sleepy or sedated [1.3.1]
- A sensation of feeling 'drunk' or 'spacey' [1.2.1, 1.2.4]
- In some cases, feeling very happy or excited (euphoria) [1.2.2, 1.3.4]
One patient described the dissociative feeling as being akin to viewing an avatar in virtual reality; everything is where it should be, but you don't fully identify with its movements or body [1.2.3]. These effects are transient, typically peaking around 40 minutes after administration and resolving within two hours [1.5.5, 1.6.5]. While these experiences can feel intense or even pleasurable, they are side effects of a potent medication, not the intended therapeutic outcome [1.2.3]. The goal of Spravato is the rapid relief of depressive symptoms, with response rates in some studies showing around 70% of participants achieving a 50% reduction in symptoms after four weeks [1.8.2].
The Spravato® REMS Program: Ensuring Safety and Preventing Misuse
Because of its psychoactive effects and potential for abuse, Spravato is a Schedule III controlled substance [1.5.5]. The FDA requires it to be dispensed under a strict Risk Evaluation and Mitigation Strategy (REMS) program to ensure its benefits outweigh its risks [1.4.1, 1.4.3]. This program is central to why the experience with Spravato is not a recreational 'high.'
Key requirements of the REMS program include:
- Administration in a Certified Setting: Patients must self-administer the nasal spray under the direct observation of a healthcare provider in a certified medical office or clinic [1.4.2, 1.4.3]. Spravato is never dispensed for at-home use [1.4.2].
- Post-Administration Monitoring: After taking the dose, patients must be monitored by a healthcare provider for at least two hours [1.6.3]. This monitoring checks for sedation, dissociation, and changes in blood pressure, which often temporarily increases after dosing [1.6.2, 1.6.5].
- Driving and Activity Restrictions: Patients are instructed not to drive or operate heavy machinery until the next day, following a restful sleep [1.4.6]. They must arrange for transportation home from their appointment [1.6.5].
This controlled environment minimizes the risk of misuse and ensures patient safety during the period of intense side effects [1.5.1]. The strict regulations governing esketamine's use contribute to its significantly lower abuse rates compared to illicitly used ketamine [1.5.1].
Spravato vs. Recreational Ketamine: A Comparison
While Spravato is derived from ketamine, there are critical differences in their composition, administration, and purpose.
| Feature | Spravato (Esketamine) | Recreational Ketamine |
|---|---|---|
| Composition | Contains only the S-enantiomer of ketamine, which is more potent at the NMDA receptor [1.5.4]. | A racemic mixture containing both S-ketamine and R-ketamine [1.5.4]. Often cut with other substances. |
| Legal Status & Use | FDA-approved prescription medication for treatment-resistant depression [1.5.6]. | Illicit substance, often used in club settings for its hallucinogenic effects [1.2.7]. Schedule III controlled substance. |
| Administration | Nasal spray, self-administered under direct medical supervision in a certified clinic [1.4.2, 1.6.5]. | Insufflated (snorted), injected, or taken orally without medical supervision. Dosage is uncontrolled and unknown. |
| Environment | Quiet, monitored, clinical setting focused on therapy and safety [1.4.6, 1.6.1]. | Uncontrolled environments, often social or party settings. |
| Monitoring | Mandatory 2-hour monitoring for blood pressure, sedation, and dissociation by a healthcare professional [1.6.2]. | No medical monitoring, increasing risks of accidents, injury, or adverse health events. |
| Goal of Use | To rapidly alleviate symptoms of severe depression as part of a long-term treatment plan [1.4.5]. | To induce a psychoactive 'high,' dissociation ('K-hole'), and hallucinations for recreational purposes [1.2.7]. |
Conclusion
So, does Spravato get you high? The answer is nuanced. It induces powerful, temporary psychoactive effects, including dissociation and sometimes euphoria, which some might equate to a high [1.2.1, 1.2.2]. However, these are known side effects within a strictly controlled medical treatment. The purpose is not recreation but rapid relief from debilitating depression [1.4.5]. The entire framework of the Spravato REMS program—from the supervised administration to the two-hour monitoring period—is designed to manage these effects safely and prevent the potential for abuse [1.4.3, 1.6.3]. Therefore, while the sensations are real, they are a managed clinical event, distinct from the uncontrolled and dangerous pursuit of a recreational high associated with illicit ketamine.
