Analgesic effects of dihydrocodeine and tramadol
when administered either in the morning or evening

Hummel T, Kraetsch HG, Lotsch J,
Hepper M, Liefhold J, Kobal G
Department of Experimental and
Clinical Pharmacology and Toxicology,
University of Erlangen-Nurnberg,
Chronobiol Int 1995 Feb; 12(1):62-72


The aim of the study was to investigate the analgesic effects of two opioids [dihydrocodeine (DHC) and tramadol] when administered either in the morning or evening. The experimental technique used is based on chemosomatosensory event-related potentials (CSSERPs) in response to painful chemical stimuli that are applied to the nasal mucosa. Eighteen healthy volunteers participated in the experiments. The study followed a controlled, randomized, double-blind, sixfold, cross-over design. Thus, each of the three medications (90 mg DHC, 50 mg tramadol, or placebo) was perorally administered to all subjects on different days at 08:00 or 20:00 h. Measurements were performed before and 60, 120, 240, and 360 min after administration of the medication. In addition to the assessment of CSSERP, subjects rated the intensity of the stimuli. Moreover, unspecific drug effects were monitored by means of acoustical event-related potentials and the subjects' performance in a video game. The results indicated that the painful intensity of the chemical stimuli strongly increased during evening sessions. In addition, both DHC and tramadol exerted stronger analgesic effects when administered in the evening. Thus, an inflexible scheme of prescription might produce either an increase of pain in the morning due to insufficient analgesia or the unnecessary overdosing of analgesics in the evening.
Novelty and pain
The tramadol option
Dihydrocodeine: dosage
Dihydrocodeine: structure
Dihydrocodeine: metabolism