Abstract
The psychomimetic effects that occur after acute administration of ketamine can constitute a model of psychosis and antipsychotic drug action. However, the optimal dose/concentration has not been established and there is a large variety in outcome measures. In this study, 36 healthy volunteers (21 males and 15 females) received infusions of S(+)-ketamine or placebo to achieve pseudo-steady state concentrations of 180 and 360 ng/mL during two hours. The target of 360 ng/mL induced increasingly more intensive effects than expected, and the targets were subsequently reduced to 120 and 240 ng/mL, which were considered tolerable. There was a clear, concentration-dependent psychomimetic effect as shown on all subscales of the positive and negative syndrome scale (e.g. positive subscale +43.7%, 95%CI 34.4-53.7%, p < 0.0001 for 120 ng/mL and +70.5%, 95%CI 59.0-82.8%, p < 0.0001 for 240 ng/mL) and different visual analogue scales. The startle reflex was inhibited (prepulse inhibition) by both main target concentrations to a similar extent, suggesting a maximum effect. Ketamine was found to constitute a robust model for induction of psychomimetic symptoms and the optimal concentration range for a drug interaction study would be between 100 and 200 ng/mL.
Original language | English |
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Pages (from-to) | 401-13 |
Number of pages | 13 |
Journal | Journal of Psychopharmacology |
Volume | 29 |
Issue number | 4 |
DOIs | |
Publication status | Published - Apr-2015 |
Externally published | Yes |
Keywords
- Adolescent
- Adult
- Cross-Over Studies
- Dose-Response Relationship, Drug
- Double-Blind Method
- Excitatory Amino Acid Antagonists
- Female
- Humans
- Ketamine
- Male
- Psychiatric Status Rating Scales
- Psychoses, Substance-Induced
- Reflex, Startle
- Young Adult
- Journal Article
- Randomized Controlled Trial