CHDR has developed and validated an accurate intravenous ethanol infusion procedure to study the effects of ethanol interaction, the EthanolClamp.


  • CHDR's ethanol clamping procedure is validated in both Caucasian and Japanese subpopulations, in men and women, in elderly and obese subjects, and in patients.
  • Using ethanol-clamping, pseudo-steady state conditions can be maintained for hours.
  • Ethanol concentration set-points can be adjusted according to breath ethanol concentrations (BrEC).
  • Ethanol clamping is suitable for interaction studies with CNS-active drugs.
  • The EthanolClamp can easily be incorporated in clinical trials.


CHDR has developed and validated an accurate intravenous ethanol infusion procedure, the EthanolClamp. Real-time individual adjustments in infusion rates are made using breath ethanol samples (BrEC) as a guideline to achieve a pseudo-steady state ethanol level. The BrEC guided method will instantly adapt when a drug modifies ethanol kinetics. Ethanol clamping is able to induce significant pharmacodynamic effects on a wide range of CNS-domains

Interaction studies with CNS-active compounds

Guidelines from the FDA and EMA recommend that Investigational Medicinal Products (IMPs) being developed for the treatment of insomnia, such as hypnotics or sedatives, are tested in combination with alcohol (ethanol) for possible interactions. This can be difficult because of ethanol's variable kinetic and dynamic properties. CHDR’s EthanolClamp largely eliminates this variability, and has allowed the best possible interpretation of drug-ethanol interactions for a wide range of different drug classes. A recent example of its usefulness is a study we performed with a first in class treatment for insomnia, in which we incorporated our EthanolClamp. The data clearly showed additive effects of ethanol on some attention and sedation tasks, but excluded less predictable and hence more problematic supra additive effects.

Driving under influence

EMA guidelines suggest that drugs with sleep-enabling properties are tested for their effect on driving and operating machinery. The EthanolClamp can be used as a suitable positive control. The infusion rate can be set to reach regional driving limits e.g. most of the EU 0.05% (0.5 g/L) or many US states 0.08%. The EthanolClamp has been used together with the NeuroCart and driving simulators for this purpose.

Positive control in essential tremor patients

Essential tremor (ET) is a highly prevalent neurological condition, for which no specific treatments have been developed. About half of all ET patients report tremor reduction after drinking alcohol. CHDR’s EthanolClamp was used as a positive control, early during the development of two novel anti-tremor treatments. In both cases, stable levels of ethanol caused a highly significant suppression of tremors in only a small number of ET patients. This provided a meaningful effect level for clinically significant effects of the two new novel drugs – which both unfortunately had much less effect than ethanol. Our EthanolClamp can also provide a functionally relevant benchmark to determine the clinical relevance of drug-induced CNS-depression.

Contact CHDR