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Cannabis and benzodiazepines as determinants of methadone trough plasma concentration variability in maintenance treatment: a transnational study

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

To assess tobacco, alcohol, cannabis and benzodiazepine use in methadone maintenance treatment (MMT) as potential sources of variability in methadone pharmacokinetics.

Methods

Trough plasma (R)- and (S)-methadone concentrations were measured on 77 Australian and 74 Swiss MMT patients with no additional medications other than benzodiazepines. Simple and multiple regression analyses were performed for the primary metric, plasma methadone concentration/dose.

Results

Cannabis and methadone dose were significantly associated with lower 24-h plasma (R)- and (S)-methadone concentrations/dose. The models containing these variables explained 14–16% and 17–25% of the variation in (R)- and (S)-methadone concentration/dose, respectively. Analysis of 61 patients using only CYP3A4 metabolised benzodiazepines showed this class to be associated with higher (R)-concentration/dose, which is consistent with a potential competitive inhibition of CYP3A4.

Conclusion

Cannabis use and higher methadone doses in MMT could in part be a response to—or a cause of—more rapid methadone clearance. The effects of cannabis and benzodiazepines should be controlled for in future studies on methadone pharmacokinetics in MMT.

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Acknowledgements

Dr Andrew Somogyi's contribution to this study was supported by National Health and Medical Research Council of Australia (Project Grants no. 207710, 349537). The work in Switzerland was supported by the Swiss National Research Foundation (project 3200-065427.01) and Swiss Federal Office of Public Health (project 02.001382).

Conflicts of interest

None

Author information

Authors and Affiliations

  1. The Byrne Surgery, Redfern, NSW, Australia

    Richard Hallinan & Andrew Byrne

  2. Unité de Biochimie et Psychopharmacologie Clinique, Centre des Neurosciences Psychiatriques, Département de Psychiatrie-CHUV, Hôpital de Cery, Université de Lausanne, Prilly, Switzerland

    Séverine Crettol & Chin B. Eap

  3. School of Medicine, University of Western Sydney, Sydney, NSW, Australia

    Kingsley Agho

  4. Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, NSW, Australia

    John Attia

  5. Centre St-Martin, Département de Psychiatrie-CHUV, Université de Lausanne, Lausanne-Dorigny, Switzerland

    Jacques Besson

  6. Division d’Abus de Substances, Hôpitaux Universitaire de Genève, Geneva, Switzerland

    Marina Croquette-Krokar

  7. Universitäre Psychiatrische Dienste Bern, Integrierter Drogendienst, Bern, Switzerland

    Robert Hämmig

  8. Fondation Phénix, Chêne-Bourg, Switzerland

    Jean-Jacques Déglon

  9. Division of Clinical Pharmacology and Toxicology, St Vincents Hospital, Darlinghurst, NSW, Australia

    John Ray

  10. Discipline of Pharmacology, School of Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia

    Andrew A. Somogyi

  11. Ecole de Pharmacie Genève-Lausanne, Université de Genève, Université de Lausanne, Geneva, Switzerland

    Chin B. Eap

  12. Hôpital de Cery, 1008, Prilly, Switzerland

    Chin B. Eap

Authors
  1. Richard Hallinan
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  2. Séverine Crettol
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  6. Marina Croquette-Krokar
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  7. Robert Hämmig
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  8. Jean-Jacques Déglon
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  9. Andrew Byrne
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  10. John Ray
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  11. Andrew A. Somogyi
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  12. Chin B. Eap
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Corresponding author

Correspondence to Chin B. Eap.

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Supplementary Table

Univariate regression analysis for (R)-methadone/dose and (S)-methadone/dose, showing only significant variables (coefficient, standard error, 95% confidence intervals, R2 and statistical significance). (DOC 20 kb)

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Hallinan, R., Crettol, S., Agho, K. et al. Cannabis and benzodiazepines as determinants of methadone trough plasma concentration variability in maintenance treatment: a transnational study. Eur J Clin Pharmacol 65, 1113–1120 (2009). https://doi.org/10.1007/s00228-009-0706-8

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  • DOI: https://doi.org/10.1007/s00228-009-0706-8

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