Psychedelic effects of ketamine in healthy volunteers: relationship to steady-state plasma concentrations
by
Krystal JH, Karper LP, Seibyl JP,
Freeman GK, Delaney R, Bremner JD, Heninger GR,
Bowers MB Jr, Charney DS.
Department of Psychiatry,
Yale University School of Medicine,
New Haven, Conn.
Anesthesiology. 1998 Jan;88(1):82-8.

ABSTRACT

BACKGROUND: Ketamine has been associated with a unique spectrum of subjective "psychedelic" effects in patients emerging from anesthesia. This study quantified these effects of ketamine and related them to steady-state plasma concentrations. METHODS: Ketamine or saline was administered in a single-blinded crossover protocol to 10 psychiatrically healthy volunteers using computer-assisted continuous infusion. A stepwise series of target plasma concentrations, 0, 50, 100, 150, and 200 ng/ml were maintained for 30 min each. After 20 min at each step, the volunteers completed a visual analog (VAS) rating of 13 symptom scales. Peripheral venous plasma ketamine concentrations were determined after 28 min at each step. One hour after discontinuation of the infusion, a psychological inventory, the hallucinogen rating scale, was completed. RESULTS: The relation of mean ketamine plasma concentrations to the target concentrations was highly linear, with a correlation coefficient of R = 0.997 (P = 0.0027). Ketamine produced dose-related psychedelic effects. The relation between steady-state ketamine plasma concentration and VAS scores was highly linear for all VAS items, with linear regression coefficients ranging from R = 0.93 to 0.99 (P < 0.024 to P < 0.0005). Hallucinogen rating scale scores were similar to those found in a previous study with psychedelic doses of N,N-dimethyltryptamine, an illicit LSD-25-like drug. CONCLUSIONS: Subanesthetic doses of ketamine produce psychedelic effects in healthy volunteers. The relation between steady-state venous plasma ketamine concentrations and effects is highly linear between 50 and 200 ng/ml.

Ketamine
Beyond the K-hole
Ketamine: structure
Ketamine and cognition
Anaesthesia and anaesthetics
Ketamine as an antidepressant
Ketamine and opiate withdrawal
Ketamine and the nucleus accumbens
Ketamine: medical and non-medical use
The role of ketamine in pain management
Ketamine and the glutaminergic hypothesis of schizophrenia
Low-dose ketamine as a fast-onset, long-acting antidepressant