Psychedelic effects of ketamine in healthy volunteers : Relationship to steady-state plasma concentrations

• Published in: Anesthesiology (Philadelphia) Vol. 88; no. 1; pp. 82 - 88
• Main Authors: BOWDLE, T. A, RADANT, A. D, COWLEY, D. S, KHARASCH, E. D, STRASSMAN, R. J, ROY-BYRNE, P. P
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott 1998
• Subjects: Adult; Anesthetics, Dissociative - adverse effects; Biological and medical sciences; Cross-Over Studies; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Hallucinations - chemically induced; Humans; Ketamine - adverse effects; Ketamine - blood; Male; Medical sciences; Pharmacology. Drug treatments; Single-Blind Method; Toxicity: nervous system and muscle; Human; Ketamine; Intravenous administration; General anesthetic; Activity concentration relation; Toxicity; Hallucinogen; General anesthesia; Psychedelic experience
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/00000542-199801000-00015

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. 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. 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. 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.