PSYCHEDELIC EFFECTS OF KETAMINE IN HEALTHY-VOLUNTEERS - RELATIONSHIP TO STEADY-STATE PLASMA-CONCENTRATIONS

Background: Ketamine has been associated with a unique spectrum of sub jective ''psychedelic'' effects in patients emerging from anesthesia. This study quantified these effects of ketamine and related them to st eady-state plasma concentrations. Methods: Ketamine or saline was admi nistered in a single-blinded crossover protocol to 10 psychiatrically healthy volunteers using computer-assisted continuous infusion. A step wise 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 aft er 28 min at each step. One hour after discontinuation of the infusion , a psychological inventory, the hallucinogen rating scale, was comple ted. Results: The relation of mean ketamine plasma concentrations to t he target concentrations was highly linear, with a correlation coeffic ient of R = 0.997 (P = 0.0027). Ketamine produced dose-related psyched elic effects. The relation between steady-state ketamine plasma concen tration and VAS scores was highly linear for all VAS items, with linea r 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 fo und in a previous study with psychedelic doses of N,N-dimethyltryptami ne, an illicit LSD-25-like drug. Conclusions: Subanesthetic doses of k etamine produce psychedelic effects in healthy volunteers. The relatio n between steady-state venous plasma ketamine concentrations and effec ts is highly linear between 50 and 200 ng/ml.