Cytochrome P450-2D6 activity in people with codeine use disorder

Area of Science:

• Pharmacogenetics
• Addiction Medicine
• Clinical Pharmacology

Background:

• Compound-analgesics containing codeine (CACC) are a common source for individuals seeking opioid replacement therapy (ORT) for codeine use disorder (CUD).
• Previous research indicated no correlation between pre-treatment CACC dosage and ORT buprenorphine doses.
• CYP2D6 enzyme activity was hypothesized to explain this observed disconnection.

Purpose of the Study:

• To investigate the role of CYP2D6 activity in individuals with CUD.
• To compare CYP2D6 activity scores between patients with CUD and the general population.
• To examine the relationship between CYP2D6 activity, CACC use, and buprenorphine dosage in ORT.

Main Methods:

• A cohort of 106 participants with CUD was compared to a population sample of 5408 Australian patients.
• CYP2D6 activity scores were calculated for all participants.
• The association between pre-treatment CACC dose, CYP2D6 activity, and buprenorphine dose was analyzed.

Main Results:

• Participants with CUD exhibited significantly higher mean CYP2D6 activity scores compared to the general population (1.65 vs. 1.39, p < 0.001).
• Pre-treatment CACC dose weakly predicted sublingual buprenorphine doses, with a stronger association observed in ultrarapid CYP2D6 metabolizers.
• Normal and ultrarapid CYP2D6 metabolizers were more likely to have a CUD diagnosis.

Conclusions:

• CYP2D6 activity significantly influences codeine use disorder.
• Individuals with poor or intermediate CYP2D6 metabolizer status may be protected against developing CUD.
• CYP2D6 genotype should be considered in understanding CUD and tailoring ORT.