Methadone-Nicotine Interactions in Methadone Maintenance Treatment Patients

Abstract

Smoking is highly prevalent (85%-98%) in methadone maintenance treatment (MMT) patients. Methadone has been shown to increase cigarette smoking in a dose-dependent manner, whereas smoking/nicotine has been shown to increase methadone self-administration and reinforcing properties. The objective of this study was to evaluate methadone-nicotine interactions in MMT patients during trough and peak methadone effect conditions. Subjective effects of nicotine (administered by cigarette smoking, 4 mg of nicotine gum and placebo gum) and methadone and their combination were assessed in 40 regularly smoking, stabilized MMT patients using a randomized, placebo-controlled, within-subject study design. Subjects responded to a battery of subjective assessments before and after nicotine administration both before methadone administration (cycles 1 and 2) and 3 hours after methadone administration (cycles 3 and 4). There was a main effect of methadone on the decrease of opioid withdrawal scores (P < 0.001), and cigarette smoking enhanced this effect (day x methadone interaction, P = 0.031). Both nicotine and methadone had main effects on the decrease of nicotine withdrawal scores (P < 0.001 and P = 0.001, respectively); this was associated with the cigarette day (day x nicotine interaction, P = 0.003, and day x methadone interaction, P = 0.004). Nicotine plasma levels were highest on the cigarette smoking day (P < 0.001). Methadone and nicotine shared main effects on the increase of ratings of euphoria and drug liking and on the decrease of restlessness, irritability, and depression. The overall results may help to explain high smoking rates in the MMT population and may account for reports of increased positive effects of methadone when the drugs are taken together.

Methadone’s effect on nAChRs—a link between methadone use and smoking?

“…In addition to higher nicotine craving, smokers on methadone maintenance suffer from more severe withdrawal symptoms after smoking cessation than do smokers not receiving methadone [12,16]. On the other hand, opioid withdrawal symptoms that are reduced by methadone administration are even further attenuated by smoking [10]. This may be the reason why methadone-maintained patients smoke a greater number of cigarettes during a period of two to four hours after methadone administration than during any other period of the day [8].…”

“…Approximately 77-95% of all methadone maintenance treatment patients are smokers [8][9][10][11]. Methadone administration increases tobacco smoking in a dose-dependent manner [12] and vice versa; heavy smokers use higher doses of methadone [13].…”

OPRM1 genetic polymorphisms are associated with the plasma nicotine metabolite cotinine concentration in methadone maintenance patients: a cross sectional study

“…These results support the finding that cigarette smoking may enhance the effect of methadone on the decrease in the opioid withdrawal symptom scores. 52 This may in part explain a high cigarette smoking rate in patients undergoing MMT.…”

Predictors of Tobacco Use Among New York State Addiction Treatment Patients

“…That the highest smoking prevalence is found among people in methadone maintenance treatment, however, may reflect synergistic interactions between nicotine and methadone. 66 Limitations include the use of administrative data sets, which are developed for management and reporting purposes rather than for research. The outcome measure of tobacco use changed in 2009 from tobacco use in the past week to frequency of use in the past month.…”