Psychedelic Effects of Ketamine in Healthy Volunteers: Relationship to Steady-state Plasma Concentrations

This single-blinded, placebo-controlled, within-subjects, crossover study (n=10) quantified the subjective “psychedelic” effects of subanesthetic ketamine (9, 18, 26, 35 mg/70kg), administered in a stepwise manner that gradually increased plasma concentration. Ketamine produced dose-related psychedelic effects on the Hallucinogen rating scale, with similar scores to DMT, and this effect exhibited a highly linear relationship to plasma concentration.

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.”

Authors: Andrew T. Bowdle, Allen D. Radant, Deborah S. Cowley, Evan D. Kharasch, Rick J. Strassman & Peter P. Roy-Byrne