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

Hallinan, Richard; Crettol, Séverine; Agho, Kingsley; Attia, John; Besson, Jacques; Croquette-Krokar, Marina; Hämmig, Robert; Déglon, Jean‐Jacques; Byrne, Andrew; Ray, John E.; Somogyi, Andrew A.; Eap, Chin B.

doi:10.1007/s00228-009-0706-8

Cited by 14 publications

(7 citation statements)

References 43 publications

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“…Decreases in the rate of cannabis‐positive UDS were also observed during this transition, but it is unknown if this decline in cannabis use was related to diminished withdrawal symptoms, as clinical data regarding this phenomenon is limited. One group found that cannabis use was positively associated with lower plasma methadone concentrations, and while cannabis use could have caused metabolic changes that resulted in this finding, it is also possible that “cannabis use may be a compensatory response to opioid withdrawal symptoms in some individuals with more rapid methadone clearance.” In a study on the efficacy of non‐opioid drugs for opiate withdrawal, cannabis was reported by patients to be less effective in reduction of symptoms than benzodiazepines, but more effective than cocaine, alcohol, and nicotine . There was a positive correlation between rates of cannabis and benzodiazepine use (based on monthly UDS results) in our sample.…”

Section: Discussionmentioning

confidence: 53%

Impact of Cannabis Use during Stabilization on Methadone Maintenance Treatment

et al. 2013

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Background and Objectives Illicit drug use, particularly of cannabis, is common among opiate-dependent individuals, and has the potential to impact treatment in a negative manner. Methods To examine this, patterns of cannabis use prior to and during methadone maintenance treatment (MMT) were examined to assess possible cannabis-related effects on MMT, particularly during methadone stabilization. Retrospective chart analysis was used to examine outpatient records of patients undergoing MMT (n=91), focusing specifically on past and present cannabis use and its association with opiate abstinence, methadone dose stabilization, and treatment compliance. Results Objective rates of cannabis use were high during methadone induction, dropping significantly following dose stabilization. History of cannabis use correlated with cannabis use during MMT, but did not negatively impact the methadone induction process. Pilot data also suggested that objective ratings of opiate withdrawal decrease in MMT patients using cannabis during stabilization. Conclusions and Scientific Significance The present findings may point to novel interventions to be employed during treatment for opiate dependence that specifically target cannabinoid-opioid system interactions.

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Section: Discussionmentioning

confidence: 53%

Impact of Cannabis Use during Stabilization on Methadone Maintenance Treatment

et al. 2013

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“…For patients with substance use disorders and dependence syndromes, the available medications with proven efficacy are candidates for TDM [163,396,477,496,689]. Their drug concentrations are highly variable between individuals [163].…”

Section: Recommendationmentioning

confidence: 99%

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

Bergemann²,

et al. 2017

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Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs.

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“…Methadone plasma concentration is not affected by nicotine, although it does impact subjective measures of opiate withdrawal(Elkader, Brands et al 2009). Cytochrome P450 metabolized benzodiazepines (excluding oxazepam and lorazepam), and specifically CYP3A4 metabolized benzodiazepines are associated with higher trough plasma R- and, to a greater extent, S-methadone/dose(Hallinan, Crettol et al 2009). Women who are adherent to their MMTP should be supported to breastfeed(The Academy of Breastfeeding Medicine Protocol Committee and Jansson 2009) due to very low levels in milk(Jansson, Choo et al 2008; Bogen, Perel et al 2011) and increasing evidence that breastfeeding is associated with improved neonatal outcomes(Ballard 2002; Arlettaz, Kashiwagi et al 2005; Abdel-Latif, Pinner et al 2006); however, the effect of breastfeeding on maternal methadone plasma concentrations has not been studied.…”

Section: Discussionmentioning

confidence: 99%

Pharmacologic evidence to support clinical decision making for peripartum methadone treatment

et al. 2012

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Rationale Limited pharmacological data are available to guide methadone treatment during pregnancy and postpartum. Objectives Study goals were to: 1) Characterize changes in methadone dose across childbearing, 2) Determine enantiomer-specific methadone withdrawal kinetics from steady-state during late pregnancy, 3) Assess enantiomer-specific changes in methadone level/dose (L/D) ratios across childbearing, and 4) Explore relationships between CYP2B6, CYP2C19 and CYP3A4 single nucleotide polymorphisms and maternal dose, plasma concentration and L/D. Methods Methadone dose changes and timed plasma samples were obtained for women on methadone (n=25) followed prospectively from third trimester of pregnancy to three months postpartum. Results Participants were primarily white, Medicaid insured and multiparous. All women increased their dose from first to end of second trimester (mean peak increase=23 mg/day); 71% of women increased from second trimester to delivery (mean peak increase=19 mg/day). Half took a higher dose 3 months postpartum than at delivery despite significantly larger clearance during late pregnancy. Third trimester enantiomer-specific methadone half-lives (range R-methadone 14.7-24.9 hours; S-methadone 8.02-18.9 hours) were about half of those reported in non-pregnant populations. In 3 women with weekly 24-hour methadone levels after delivery, L/D increased within 1-2 weeks after delivery. Women with the CYP2B6 Q172 variant GT genotype have consistently higher L/D values for S-methadone across both pregnancy and postpartum. Conclusions Most women require increases in methadone dose across pregnancy. Given the shorter half-life and larger clearances during pregnancy, many pregnant women may benefit from split methadone dosing. L/D increases quickly after delivery and doses should be lowered rapidly after delivery.

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

Abstract: 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.

Cited by 14 publications

References 43 publications

Impact of Cannabis Use during Stabilization on Methadone Maintenance Treatment

Impact of Cannabis Use during Stabilization on Methadone Maintenance Treatment

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

Pharmacologic evidence to support clinical decision making for peripartum methadone treatment

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