Drug interactions in patients undergoing opioid maintenance therapy

Introduction Patients undergoing opioid maintenance therapy (OMT) have a high rate of additional consumption of cannabis and of somatic (especially hepatitis virus infections) and psychiatric comorbidities. Cannabis interferes with Cytochrome P 450 (CYP) isoenzymes and seems to be a potential inhibitor of CYP3A4 and by this may lead to drug-drug interactions. Buprenorphine (BUB), a partial μ-opioid agonist widely used for opioid maintenance therapy (OMT) is mainly metabolized to pharmacologically active norbuprenorphine by CYP3A4. We present OMT patient data of cannabis use on BUP plasma levels with and without psychiatric comedication duloxetine, trazodone. Further an OMT woman before and after successful hepatitis c treatment.

Methods 1. Retrospective analysis of clinical symptoms and of BUP and nor-BUP plasma levels in liver healthy OMT patients substituted with BUP, either with (n+=+15) or without (n+=+17) concomitant use of cannabis. 2. Analysis of BUPs and antidepressant drug plasma levels of a female OMT patient in various stages of hepatitis virus disease and with and without cannabis use.

Results 1. Cannabis users and non-users received similar doses, but users had 2.7-fold higher concentrations of BUP (p+<+0.01) and 1.4-fold for nor-BUP (1.4-fold, p+=+0.07). The metabolite-to-parent drug ratio was 0.98 in non-users and 0.38 in users (p+=+0.02) with no significant effect of gender. 2. During cannabis abstinence a higher plasma level of duloxetine and trazodone could be found.

Conclusion Cannabis use decreases the formation of nor-BUP and elevates BUP and nor-BUB concentrations and lowers blood plasma levels of duloxetine and trazodone most probably by inhibition of CYP3A4. TDM can detect interaction effects by comedication and/or coconsumption of drugs.

Publication History

Article published online:
16 May 2022