Clinical Textbook of Addictive Disorders 3rd ed - R. Frances, S. Miller, A. Mack (Guilford, 2005) WW

170 III. SUBSTANCES OF ABUSE2002). The liquid form is easily evaporated into a powder, the form in which itis most often sold. Ketamine can be administered in a variety of ways. At clubs,most people snort lines of the powder. Ketamine may also be dabbed on thetongue or mixed with a liquid and imbibed.Physiological EffectsKetamine has been studied extensively in humans. It is a noncompetitive N-methyl-D-aspartate (NMDA) antagonist (Curran & Monaghan, 2001). Recreationalusers of ketamine report feeling anesthetized and sedated in a dosedependentmanner (Krystal et al., 1994). Ketamine can influence all modes ofsensory function (Garfield et al., 1994; Óye, Paulsen, & Maurset, 1992). Attypical dosages, ketamine distorts sensory stimuli, producing illusions (Garfieldet al., 1994). In higher than typical dosages, hallucinations and paranoid delusionscan occur (Malhotra et al., 1996).Ketamine substantially disrupts both attention and learning. In humanresearch subjects, ketamine affects the ability to modify behavior, to learn newtasks, and to remember (Curran & Monaghan, 2001; Krystal et al., 1994). Therecreational dosage of ketamine is approximately 0.4 mg/kg, and the anestheticdosage is almost double that. The median lethal dose (LD 50) is nearly 30 timesthe anesthetic dosage, which makes overdose from ketamine very rare.One dose of ketamine creates a “trip” that lasts about 1 hour (Delgarno &Shewan, 1996). Larger doses last longer and have a more intense effect(Malhotra et al., 1996). The user feels physical tingling, followed by a feelingof removal from the outside sensory world. Tolerance develops rapidly toketamine, and dependence, though rare, is well known. Flashbacks have beenreported, and their incidence may be higher than with many other hallucinogens(Siegel, 1984). Ketamine works in a dose-dependent fashion. Mild dosesinvolve an autistic stare and a paucity of thinking. Higher doses result in the K-hole phenomenon, which is characterized by social withdrawal, autistic behavior,and an inability to maintain a cognitive set. Such individuals may bedescribed as zombie-like (Gay Men’s Health Crisis, 1997).Mechanism of ActionKetamine is chemically similar to PCP but has important differences (Jansen,1990). Ketamine binds to the NMDA receptor complex on the same site asPCP, located inside the calcium channel. It works by inhibiting several ofthe excitatory amino acid neurotransmitters (Cotman & Monaghan, 1987;Hampton et al., 1982). Ketamine works globally, affecting numerous neurotransmittersystems, but its action, as an NMDA antagonist, is likely the causeof its schizotypal and dissociative symptoms. NMDA blockade causes anincrease in dopamine release in the midbrain and prefrontal cortex as well