Codeine and clinical impairment in samples in which morphine is not detected

Abstract

Codeine metabolises partly to morphine by the liver enzyme CYP2D6, which is subject to genetic polymorphism. It has been suggested that analgesic effects of codeine are due to the morphine metabolite. Codeine effects other than analgesia have been less investigated in this regard, but it has been suggested that sedation, for example, might be independent of morphine formation. The aim of our study was to investigate the influence of codeine alone, without concomitant presence of morphine, on a clinical test for drunkenness (CTD) performed in relation to suspected drugged driving. Cases with detected codeine but not morphine, nor any other drug above the limit of detection, were selected from the database of suspected drugged drivers at National Institute for Forensic Toxicology, Oslo, Norway. Codeine blood concentration in these samples was compared with the conclusions from the corresponding individual CTD. Of the 43 cases fulfilling the selection criteria, 23 were judged as "not impaired", and 20 as "impaired". Mean blood codeine concentration in the "not impaired" group was 143 ng/ml (95% CI 48-238, median 63 ng/ml). Mean concentration in the "impaired" group was 213 ng/ml (95% CI 146-279, median 159 ng/ml). There was a statistically significant concentration difference between the two groups. Codeine blood concentrations were further grouped as "moderate", "medium high" and "high". When adjusted for age, gender and chronic use, the odds ratios for being judged as impaired were 6 (95% CI 1-32, P=0.04) and 19 (95% CI 2-182, P=0.01) for the "medium high" group and the "high" group, respectively, relative to the "moderate" group. Codeine appeared to have some dose-dependent effect on the central nervous system that may lead to impairment as judged from a CTD, independent of measurable blood morphine concentrations. This supports the view that some codeine effects do not seem to be mediated by morphine.