The question of whether esketamine is a psychedelic frequently arises due to its mind-altering effects. While both esketamine and classic psychedelics can induce altered states of consciousness, their fundamental mechanisms and the nature of the experiences they produce are distinct. Understanding these differences is important for clarifying esketamine’s classification and its specific role in medical treatment.
What is Esketamine?
Esketamine, marketed as Spravato, is a specific form of the anesthetic drug ketamine. Chemically, it is the S(+) enantiomer of ketamine. It is used in treating specific mental health conditions and is administered as a nasal spray.
What Defines a Psychedelic?
Classic psychedelic substances are hallucinogenic drugs that trigger non-ordinary mental states. These compounds, often called serotonergic hallucinogens, include psilocybin (found in “magic mushrooms”), LSD, DMT, and mescaline. They produce profound alterations in perception, cognition, emotion, and self-awareness.
The primary mechanism involves activating serotonin 5-HT2A receptors in the brain. This modulates brain circuits involved in sensory perception and cognition, leading to effects such as vivid visual or auditory hallucinations, altered sensory perception, and deep introspective or mystical experiences.
Esketamine: A Dissociative, Not a Classic Psychedelic
Esketamine is classified as a dissociative anesthetic. The key difference from classic psychedelics lies in their primary pharmacological targets within the brain. Classic psychedelics mainly activate serotonin 5-HT2A receptors, while esketamine primarily acts as an N-methyl-D-aspartate (NMDA) receptor antagonist.
Esketamine’s action as an NMDA receptor antagonist modulates the glutamate system, the brain’s main excitatory neurotransmitter. This mechanism can lead to a surge in glutamate by blocking inhibitory neurons, potentially improving mood and cognition. While both can alter consciousness, esketamine’s effects are often dissociative, inward-facing, and dreamlike, sometimes including an “out-of-body” experience. In contrast, classic psychedelics typically induce expansive perceptions, vivid hallucinations, and mystical or visionary states.
Esketamine’s Role in Mental Health Treatment
Esketamine’s rapid-acting antidepressant properties give it a unique position in mental health treatment. Unlike many traditional antidepressants that take weeks to show effects, esketamine can provide noticeable relief from depressive symptoms within hours. This rapid action is an advantage for individuals with severe and persistent depression.
The U.S. Food and Drug Administration (FDA) approved esketamine nasal spray in 2019 for adults with treatment-resistant depression, and its approval was expanded to include major depressive disorder with acute suicidal ideation or behavior. Due to its potential for sedation, dissociation, and misuse, esketamine is administered only in certified healthcare settings under medical supervision. Patients are monitored for at least two hours after administration to ensure safety and manage any temporary side effects like dizziness, nausea, or a temporary increase in blood pressure.