Psychedelic effects of ketamine in healthy volunteers: relationship to steady-state plasma concentrations.
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.
Bowdle
T A
TA
Department of Psychiatry, Harborview Medical Center, University of Washington, Seattle 98195, USA. bowdle@u.washington.edu
Radant
A D
AD
Cowley
D S
DS
Kharasch
E D
ED
Strassman
R J
RJ
Roy-Byrne
P P
PP
D000328:Adult; D000778:Anesthetics, Dissociative / Q000009:adverse effects*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D006212:Hallucinations / Q000139:chemically induced*; D006801:Humans; D007649:Ketamine / Q000009:adverse effects* / Q000097:blood; D008297:Male; D016037:Single-Blind Method
D000778:Anesthetics, Dissociative; D007649:Ketamine