Ketamine (also known as ket, K, special K, kitty, and others) is a classical dissociative substance of the arylcyclohexylamine class. It is one of the most well-known and widely-used dissociatives, a diverse group that includes phencyclidine (PCP), methoxetamine (MXE), dextromethorphan (DXM), and nitrous oxide. It principally acts as an NMDA receptor antagonist.
Ketamine was developed in 1963 by Parke-Davis Laboratories as a replacement for the surgical anesthetic phencyclidine (PCP). It became available by prescription in 1969 under the name Ketalar. Today, ketamine is widely used in human and veterinary medicine, primarily for general anesthesia for surgical procedures.
Recreational use is popularly associated with dance parties, electronic dance music, and the club and rave scenes.
Subjective effects include motor control loss, internal hallucinations, conceptual thinking, euphoria, and, most prominently, dissociation. Dissociation is characterized by perceptual distortions and feelings of detachment from the environment and one’s self. Ketamine’s effects are similar to dissociatives like PCP and DXM; however, ketamine has a shorter duration and more rapid onset. The effects of ketamine are highly dose-dependent. At lower doses, users report disinhibition and relaxation effects similar to those of alcohol. Higher doses exceeding a certain threshold (colloquially known as a “k-hole”) are capable of inducing a trance-like state that is sometimes described as out-of-body or near-death experiences.
Ketamine has moderate to high abuse potential and the health effects of long-term or heavy use are not well-known. There is some evidence that suggests abuse is associated with neurotoxicity and cognitive deficits have been observed in chronic users. Additionally, abuse is linked to bladder and urinary tract dysfunction. It is highly advised to use harm reduction practices if using this substance.
Ketamine, or (RS)-2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone, is a member of the arylcyclohexylamine chemical class. Arylcyclohexylamines are named for their chemical structures which include a cyclohexane ring bound to an aromatic ring along with an amine group. Ketamine is comprised of a phenyl ring with a chlorine substituent at R2 bonded to a cyclohexane ring substituted with an -Oxo group (cyclohexanone). An amino methyl chain (-N-CH3) is bound to the same location (R1) of the cyclohexanone ring.
Ketamine is a chiral molecule and is typically produced as a racemate. Enantiopure versions such as esketamine (S-ketamine) and arketamine (R-ketamine) are sometimes used.
Ketamine acts as a non-competitive antagonist of the NMDA receptor, an ionotropic glutamate receptor. NMDA receptors allow for electrical signals to pass between neurons in the brain and spinal column; for the signals to pass, the receptor must be open. Dissociatives close the NMDA receptors by blocking them. This disconnection of neurons leads to loss of feeling, difficulty moving, and eventually the notorious state known as the “K-hole”.
At high, fully anesthetic level doses, ketamine has also been found to bind to μ-opioid receptors type 2 in cultured human neuroblastoma cells without agonist activity and to sigma receptors in rats. Also, interacts with muscarinic receptors, descending monoaminergic pain pathways and voltage-gated calcium channels. At subanesthetic and fully anesthetic doses, has been found to block serotonin depletion in the brain by inhibiting 5-HT receptors rather than through monoamine oxidase inhibition.