Pharmacodynamic and pharmacokinetic effects of the intravenous CB1 receptor agonist Org 26828 in healthy male volunteers

J Psychopharmacol. 2010 Nov;24(11):1689-96. doi: 10.1177/0269881109106913. Epub 2009 Nov 25.

Abstract

An ideal drug for outpatient treatments under conscious sedation would have both sedative and analgesic properties. CB1/CB2 agonists are expected to have sedative, amnestic, analgesic and anti-emetic properties. The main objective of this first study in humans was to assess the sedative properties of intravenous Org 26828. In addition, pharmacokinetics, amnestic properties, postural stability, and behavioural and cardiovascular effects were studied. Midazolam intravenous 0.1 mg/kg and placebo were used as controls. The pharmacokinetic parameters (Cmax and AUC0-inf) of the main metabolite Org 26761 were proportional to dose. No effects were observed after doses up to 0.3 μg/kg of Org 26828. Dose-related effects were observed at higher doses. Although subjects reported subjective sedation after administration of Org 26828 at 3 and 6 μg/kg, the observed sedation was considerably less than after midazolam. Doses higher than the maximum tolerated dose of 1 μg/kg of Org 26828 caused unpleasant central nervous system effects (anxiety, paranoia, hallucinations). Therefore, Org 26828 is not suitable for providing sedation for outpatient surgical procedures.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Ambulatory Surgical Procedures
  • Conscious Sedation*
  • Dose-Response Relationship, Drug
  • Dronabinol / adverse effects
  • Dronabinol / analogs & derivatives*
  • Dronabinol / blood
  • Dronabinol / pharmacokinetics
  • Dronabinol / pharmacology
  • Humans
  • Hypnotics and Sedatives / adverse effects
  • Hypnotics and Sedatives / pharmacokinetics*
  • Hypnotics and Sedatives / pharmacology*
  • Infusions, Intravenous
  • Injections, Intravenous
  • Male
  • Midazolam / pharmacokinetics*
  • Midazolam / pharmacology*
  • Receptor, Cannabinoid, CB1 / agonists*
  • Receptor, Cannabinoid, CB1 / drug effects*
  • Young Adult

Substances

  • Hypnotics and Sedatives
  • Org 26828
  • Receptor, Cannabinoid, CB1
  • Dronabinol
  • Midazolam