Ketamine is a white, crystalline powder or clear liquid.
Ketalar®, Ketaject®, Ketaset®, Vetalar®; K, Special K,
Vitamin K, Lady K, Jet, Super Acid, Bump, Special LA Coke, KitKat, Cat
Source: Available by prescription only, and
is commercially available as a veterinary anesthetic. It is difficult
to synthesize clandestinely and is usually stolen from veterinarian offices
or diverted from legitimate pharmaceutical sources in liquid form. Ketamine
is currently a schedule III controlled substance in the US.
Drug Class: Dissociative anesthetic, hallucinogen,
Medical and Recreational Uses: Primarily used
in veterinary applications as a tranquilizer. Also used as an anesthetic
induction agent for diagnostic and surgical procedures in humans, prior
to the administration of general anesthetics. Occasionally used as a
short-acting general anesthetic for children and elderly patients. Recreationally
used as a psychedelic and for its dissociative effects.
Potency, Purity and Dose: Ketamine
is available as a racemic mixture with the S-(+)- isomer being more potent
than the R-(-)- isomer. Commercially supplied as the hydrochloride salt
in 0.5 mg/mL and 5 mg/mL ketamine base equivalents. For induction of
5-10 minutes surgical anesthesia, a dose of 1.0-4.5 mg/kg is intravenously
administered; 6.5-13 mg/kg is given intramuscularly for 12-25 minutes
of surgical anesthesia. The liquid from injectable solutions can be gently
heated to evaporate the water, leaving a white powder (ketamine hydrochloride)
which can be snorted or orally ingested. Recreational doses are highly
variable. Common doses are 25-50 mg intramuscularly, 30-75 mg snorting,
and 75-300 mg oral. Snorting a small line (“bump”, 30-50
mg) usually results in a dreamy effect. “K-hole” can be obtained
following a dose of 60-125 mg intramuscularly, or by snorting 100-250
mg. Impurities are rarely seen, although ketamine hydrochloride itself
can be used as a heroin adulterant.
Route of Administration: Injected, snorted,
orally ingested, and rectally administered. Similar to phencyclidine
(PCP), ketamine can be added to tobacco or marijuana cigarettes and smoked.
Pharmacodynamics: Involves analgesia, anesthetic
and sympathomimetic effects that are mediated by different sites of action.
Non-competitive NMDA receptor antagonism is associated with the analgesic
effects; opiate receptors may contribute to analgesia and dysphoric reactions;
and sympathomimetic properties may result from enhanced central and peripheral
monoaminergic transmission. Ketamine blocks dopamine uptake and therefore
elevates synaptic dopamine levels. Inhibition of central and peripheral
cholinergic transmission could contribute to induction of the anesthetic
state and hallucinations. Ketamine is structurally similar to PCP, but
10-50 times less potent in blocking NMDA effects.
Pharmacokinetics: Bioavailability following
an intramuscular dose is 93%, intranasal dose 25-50%, and oral dose 20±7%.
Ketamine is rapidly distributed into brain and other highly perfused
tissues, and is 12% bound in plasma. The plasma half-life is
2.3 ± 0.5 hours. Oral administration produces lower peak concentrations
of ketamine, but increased amounts of the metabolites norketamine and
dehydronorketamine. Ketamine and its metabolites undergo hydroxylation
and conjugation. Norketamine produces effects similar to those of ketamine.
There are no significant differences between the pharmacokinetic properties
of the S-(+) and R-(-)-isomers.
Molecular Interaction / Receptor Chemistry: Cytochrome
P450 3A4 is the principal enzyme responsible for ketamine N-demethylation
to norketamine, with minor contributions from CYP2B6 and CYP2C9 isoforms
. Potential inhibitors of these isoenzymes could decrease the rate of
ketamine elimination if administered concurrently, while
potential inducers could increase the rate of elimination
Blood to Plasma Concentration Ratio: Data
Interpretation of Blood Concentrations: There
is no direct correlation between ketamine concentrations and behavior.
Drowsiness, perceptual distortions and intoxication may be dose related
in a concentration range of 50 to 200 ng/mL, and analgesia begins at
plasma concentrations of about 100 ng/mL. During anesthesia, blood ketamine
concentrations of 2000-3000 ng/mL are used, and patients may begin to
awake from a surgical procedure when concentrations have been naturally
reduced to 500-1000 ng/mL.
Interpretation of Urine Test Results: Urinary excretion
of unchanged drug is 4±3%, and ketamine use can be detected in
urine for about 3 days. Concentration ranges for ketamine in urine have
been reported as low as 10 ng/mL and up to 25,000 ng/mL.
Effects: Users have likened the physical effects
of ketamine to those of PCP, and the visual effects to LSD.
Psychological: Decreased awareness of general environment,
sedation, dream-like state, vivid dreams, feelings of invulnerability,
increased distractibility, disorientation, and subjects are generally
uncommunicative. Intense hallucinations, impaired thought processes,
out-of-body experiences, and changes in perception about body, surroundings,
time and sounds. Delirium and hallucinations can be experienced after
awakening from anesthesia.
Physiological: Anesthesia, cataplexy, immobility, tachycardia,
increased blood pressure, nystagmus, hypersalivation, increased urinary
output, profound insensitivity to pain, amnesia, slurred speech, and
lack of coordination.
Side Effect Profile: High incidence of adverse
effects, including anxiety, chest pain, palpitations, agitation, rhabdomyolysis,
flashbacks, delirium, dystonia, psychosis, schizophenic-like symptoms,
dizziness, vomiting, seizures, and paranoia.
Duration of Effects: Onset of effects is within
seconds if smoked, 1-5 minutes if injected, 5-10 minutes if snorted and
15-20 minutes if orally administered. Effects generally last 30-45 minutes
if injected, 45-60 minutes if snorted, and 1-2 hours following oral ingestion.
Ketamine is often readministered due to its relatively short duration
of action. Some subjects may experience dreams 24 hours later. Marked
dissociative effects, schizotypal symptoms and impaired semantic memory
are found in some recreational users days after drug use.
Tolerance, Dependence and Withdrawal Effects: In
long-term exposure, high tolerance, drug craving, and flashbacks are
described. Little evidence of a physiological withdrawal syndrome unless
abrupt discontinuation in chronic users.
Drug Interactions: Midazolam attenuates altered
perception and thought processes. Lorazepam may decrease ketamine-associated
emotional distress but does not decrease cognitive or behavioral effects
of ketamine. Acute administration of diazepam increases the half-life
of ketamine. Lamotrigine significantly decreases ketamine-induced perceptual
abnormalities, but increases the mood elevating effects. Haloperidol
may decrease impairment by ketamine in executive control functions, but
does not affect psychosis, perceptual changes, negative schizophrenic-like
symptoms, or euphoria. Alfentanil is additive to ketamine in decreasing
pain and increasing cognitive impairment. Physostigmine and 4-aminopyridine
can antagonize some pharmacodynamic effects of ketamine.
Performance Effects: Broad spectrum of cognitive
impairments and marked dissociative effects. Increased distractibility
and intensely visual or polysensual hallucinations. Impairment of immediate
and delayed recall, and verbal declarative memory. Memory impairment
is associated with encoding or retrieval processes, and not accounted
for by decreased attention. Impaired language function, failure to form
and use memory traces of task relevant information. Overall decreased
awareness, increased reaction time, distorted perceptions of space, non-responsiveness,
and blurred vision. The S-(+) isomer impairs psychomotor function 3-5
times more than the R-(-) isomer.
Effects on Driving: The drug manufacturer
suggests that patients should be cautioned that driving an automobile
should not be undertaken for 24 hours or more following anesthesia. No
driving studies have been performed.
DEC Category: Phencyclidine.
DEC Profile: Horizontal gaze nystagmus present;
vertical gaze nystagmus present; lack of convergence present; pupil size
normal; reaction to light normal; pulse rate elevated; blood pressure
elevated; body temperature elevated. Other characteristic indicators
may include rigid muscles, cyclic behavior, and lack of response to painful
Panel’s Assessment of Driving Risks: The
use of ketamine is not conceivably compatible with the skills required
for driving due to its moderate to severe psychomotor, cognitive, and
References and Recommended Reading:
Adams VHA. The mechanisms of action of ketamine. Anaesthes Reanim 1998;23(3):60-3.
Adler CM, Goldberg TE, Malhotra AK, Pickar D, Breier A. Effects of ketamine
on thought disorder, working memory, and semantic memory in healthy volunteers. Biol
Baselt RC. Drug effects on psychomotor performance. Biomedical
Publications, Foster City, CA; pp 199-200;2001.
Bowdle TA, Radan AD, Cowley DS, Kharasch ED, Strassman RJ, Roy-Byrne
PP. Psychedelic effects of ketamine in healthy volunteers: relationship
to steady-state plasma concentrations. Anesthesiology 1998;88(1):82-8.
Clements JA, Nimo WS, Grant IS. Bioavailability, pharmacokinetics and
analgesic activity of ketamine in humans. J Pharm Sci 1982;71(5):539-42.
Curran HV, Morgan CA. Cognitive, dissociative and psychotogenic effects
of ketamine in recreational users on the night of drug use and 3 days
later. Addiction 2000;95(4):575-90.
Dotson JW, Ackerman DL, West LJ. Ketamine abuse. J Drug Issues 1995;25(4):751-7.
Ghoneim MM, Hinrichs JV, Mewaldt SP, Peterson RC. Ketamine: Behavioral
effects in subanesthetic doses. J Clin Psychopharm 1985;5(2):70-7.
Grant IS, Nimmo WS, Clements JA. (1981) Pharmacokinetics and analgesic
effects of i.m. and oral ketamine. Br J Anaesthes 1981;53(8):805-10.
Hartvig P, Valtysson J, Linder K-J, Kristensen J, Karlsten R, Gustafsswon
LL, Persson J, Svensson JO, Oye I, Antoni G, Westergerg G, Langstrom
B. Central nervous system effects of subdissociative doses of (S)-ketamine
are related to plasma and brain concentrations measured with positron
emission tomography in healthy volunteers. Clin Pharmac Ther 1995;58(2):165-73.
Hass DA, Harper DG. Ketamine: A review of its pharmacologic properties
and use in ambulatory anesthesia.
Anesth Prog 1992;39(3):61-8.
Hetem LSB, Danion JM, Diemujnsch P, Brandt C. Effect of a subanesthetic
dose of ketamine on memory and conscious awareness on healthy volunteers. Psychopharm 2000;152(3):283-8.
Idvall J, Ahlgren I, Aronsen KF, Stenberg P. Ketamine infusions: pharmacokinetics
and clinical effects. Br J Anaesth 1979;51:1167-73.
Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD,
Heninger GR, Bowers MB Jr., Charney DS. Subanesthetic effects of noncompetitive
NMDA antagonist, ketamine, in humans. Arch Gen Psychiat 1994;51(3):199-214.
Malhotra AK, Pinals DA, Weingartner H, Sirocco K, Missar CD, Picker
D, Breier A. NMDA receptor function and human cognition: The effects
of ketamine on healthy volunteers. Neuropychopharm 1996;14(5):301-7.
Mozayani A. Ketamine - Effects on Human Performance and Behavior. Forens
Sci Rev 2002;14(1/2):123-31.
Newcomer JW, Farber NB, Jevtovic-Todoroic V, Selke G, Melson AK, Hershey
T, Craft S, Olney JW. Ketamine-induced NMDA receptor hypofunction as
a model of memory impairment and psychosis. Neuropsychopharm 1999;20(2):106-18.
Sethna NF, Liu M, Gracely R, Bennett GJ, Max MB. Analgesic and cognitive
effects of intravenous ketamine-alfentanil combinations versus either
drug alone after intradermal capsaicin in normal subjects. Anesth
Umbricht D, Schmid L, Koller R, Vollenweider FX, Hell D, Javitt DC.
Ketamine-induced deficits in auditory and visual context-dependent processing
in healthy volunteers: Implications for models for cognitive deficits
in schizophrenia. Arch Gen Psychiatry 2000;57(12):1139-47.
Weiner AL, Vierira L, McKay CA Jr., Bayer MJ. Ketamine abusers presenting
to the Emergency Department: A series of cases. J Emerg Med 2000;18(4):447-51.