AUTHOR PROOF Approval for publication Signed Date Number of amended pages returned CNS Drugs 2006; 20 (1): 1 REVIEW ARTICLE 1172-7047/06/0001-0001/$39.95/0  2006 Adis Data Information BV. All rights reserved. Ketamine From Medicine to Misuse Kim Wolff 1 and Adam R. Winstock 2 1 National Addiction Centre, Institute of Psychiatry, Kings College, London, England 2 South Western Sydney Area Health Service, Area Drug Health Services, Liverpool, New South Wales, Australia Contents Abstract ..................................................................................... 1 1. Pharmacodynamics ....................................................................... 2 1.1 Mechanisms of Action ................................................................. 4 1.2 Optical Isomers of Ketamine ........................................................... 5 2. Pharmacokinetics ......................................................................... 7 3. Medical Uses ............................................................................. 7 4. Research Uses ............................................................................ 8 5. Recreational Uses ......................................................................... 9 5.1 Ketamine and the Dance Scene ....................................................... 10 5.2 Sought-After Effects of Ketamine ....................................................... 11 5.3 Ketamine and Sexual Assault .......................................................... 12 5.4 Toxicological Testing for Ketamine ...................................................... 12 6. Adverse Effects ........................................................................... 12 6.1 Long-Term Effects ..................................................................... 14 6.2 Tolerance and Dependence ........................................................... 15 7. Conclusions .............................................................................. 15 This review describes the medical, research and recreational uses of ketamine, Abstract an anaesthetic derivative of phencyclidine that has dissociative, analgesic and psychedelic properties. Ketamine has a complex mechanism of action that is further complicated by stereo selectivity. However, antagonism of glutamate NDMA receptors is thought to underlie it analgesic, dissociative and neuroprotec- tive effects. While ketamine use in medical and veterinary settings is well documented and has a good safety record, the increase in its unregulated use outside of such controlled environments is a cause for concern. The impact on higher centres in the brain, particularly altered perception of auditory, visual and painful stimuli, results in a general lack of responsive awareness that puts the recreational user at (often unrecognised) risk of personal harm. The perceptual and mood changes observed in those who have consumed ketamine are highly sensitive to age, dose, route of administration, previous experience and setting. At low doses, stimulant effects predominate and the effect of environmental conditions are significant; with higher doses, psychedelic effects predominate and the effect of the environ- ment diminishes.