Oral ketamine as a positive control in human abuse potential studies

The selection of a relevant and appropriate positive control is of key importance in the design of a clinical abuse potential study. Ketamine is a N-methyl-d-aspartate receptor antagonist used clinically as an anaesthetic, yet also abused for its euphoric and perceptual properties. The current study sought to identify 2 doses of oral ketamine that are safe and produce subjective effects that would make them suitable for use as positive controls in abuse potential studies. A single-center, partially double-blind, placebo-controlled, ascending dose (65, 100 and 150 mg) study was carried out in 11 healthy recreational polydrug users who first passed a pharmacologic qualification session to ensure they could distinguish and like the effects of a psychoactive drug (20mg d-amphetamine) compared to placebo. Subjective data were collected through questionnaires (e.g., Addiction Research Center Inventory [ARCI] scales) and visual analog scales (VAS). Generally, oral ketamine was well tolerated and could be used safely at 65 mg and 100mg. Peak responses to ketamine were significantly different (p<0.05) from placebo on measures of positive (e.g., drug liking VAS), perceptual (e.g., VAS of floating, detached, hallucinating) and sedative (e.g., ARCI phenobarbital-chlorpromazine-alcohol group scale) effects. Effects were generally not dose-dependent, though significant differences for some subjective effects measures were observed between 65 mg and 100mg ketamine. The current study indicates that oral ketamine doses of 65 mg and 100mg are useful positive controls for future abuse potential studies of compounds with a similar mechanism of action, or with possible perception-altering and euphoric effects.