Modulation of rate of onset and intensity of drug effects reduces abuse potential in healthy males

Drug Alcohol Depend. 2001 Nov 1;64(3):285-98. doi: 10.1016/s0376-8716(01)00127-2.

Abstract

Low, medium, and high doses of flunitrazepam were tested in three independent randomized, double-blind, balanced cross-over, placebo-controlled trials to study the influence of rate of onset of effects and dose administered on its acute effects. Three groups of 12 healthy male volunteers received six oral doses of placebo or flunitrazepam in slow and fast onset conditions as follows: six capsules of 0.16 mg (slow) and a single capsule of 0.8 mg (fast) in the low dose trial; six 0.25 mg (slow) and a single 1.25 mg (fast) capsules for medium dose; and six 0.4 mg (slow) and a single 2 mg (fast) capsule for high dose. At each dose level, slow or fast increasing flunitrazepam plasma concentrations lead to similar peak levels, but induced differential subjective and behavioral effects. In addition to objective and subjective sedation, flunitrazepam induced some pleasurable feelings, which were more intense in the fast than in the slow conditions. At the highest dose, unpleasant sedative effects surmounted positive effects, while at the lowest dose pleasurable effects were of low intensity. At the medium dose, the balance between pleasurable and unpleasant feelings resulted in euphorigenic effects, which were evident in the fast condition but were blunted in the slow condition.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Affect / drug effects
  • Affect / physiology
  • Analysis of Variance
  • Anti-Anxiety Agents / administration & dosage*
  • Anti-Anxiety Agents / blood
  • Area Under Curve
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Flunitrazepam / administration & dosage*
  • Flunitrazepam / blood
  • Humans
  • Male
  • Psychomotor Performance / drug effects
  • Psychomotor Performance / physiology
  • Reinforcement, Psychology*
  • Substance-Related Disorders / blood
  • Substance-Related Disorders / prevention & control*
  • Substance-Related Disorders / psychology

Substances

  • Anti-Anxiety Agents
  • Flunitrazepam