Drugs and Human Performance Fact Sheets
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Index

Technical Report Documentation Page

Introduction

Cannabis/Marijuana

Carisoprodol (and Meprobamate)

Cocaine

Dextromethorphan

Diazepam

Diphenhydramine

Gamma-Hydroxybutyrate (GHB, GBL, and 1,4-BD)

Ketamine

Lysergic acid diethylamide (LSD)

Methadone

Methamphetamine (and Amphetamine)

Methylenedioxymethamphetamine (MDMA, Ecstasy)

Morphine (and Heroin)

Phencyclidine (PCP)

Toluene

Zolpidem (and Zaleplon, Zopiclone)

Biographical Sketches of Lead Authors and Main Contributors

 


Ketamine

Ketamine is a white, crystalline powder or clear liquid.

Synonyms: (+/-)-2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone; Ketalar®, Ketaject®, Ketaset®, Vetalar®; K, Special K, Vitamin K, Lady K, Jet, Super Acid, Bump, Special LA Coke, KitKat, Cat Valium.

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, psychotomimetic.

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 not available.

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 stimuli.

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 residual effects.

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 Psychiat 1998;43(11):811-6.

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 Analg 1998;86(6):1250-6.

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.