Buprenorphine is a semi-synthetic opioid derived from thebaine, a naturally occurring alkaloid of the opium poppy, Papaver somniferum. The pharmacology of buprenorphine is unique in that it is a partial agonist at the opioid mu receptor. Buprenorphine undergoes extensive first-pass metabolism and therefore has very low oral bioavailability; however, its bioavailability sublingually is extensive enough to make this a feasible route of administration for the treatment of opioid dependence. The mean time to maximum plasma concentration following sublingual administration is variable, ranging from 40 minutes to 3.5 hours. Buprenorphine has a large volume of distribution and is highly protein bound (96%). It is extensively metabolised by N-dealkylation to norbuprenorphine primarily through cytochrome P450 (CYP) 3A4. The terminal elimination half-life of buprenorphine is long and there is considerable variation in reported values (mean values ranging from 3 to 44 hours). Most of a dose of buprenorphine is eliminated in the faeces, with approximately 10-30% excreted in urine. Naloxone has been added to a sublingual formulation of buprenorphine to reduce the abuse liability of the product. The presence of naloxone does not appear to influence the pharmacokinetics of buprenorphine. Buprenorphine crosses the placenta during pregnancy and also crosses into breast milk. Buprenorphine dosage does not need to be significantly adjusted in patients with renal impairment; however, since CYP3A activity may be decreased in patients with severe chronic liver disease, it is possible that the metabolism of buprenorphine will be altered in these patients. Although there is limited evidence in the literature to date, drugs that are known to inhibit or induce CYP3A4 have the potential to diminish or enhance buprenorphine N-dealkylation. It appears that the interaction between buprenorphine and benzodiazepines is more likely to be a pharmacodynamic (additive or synergistic) than a pharmacokinetic interaction. The relationship between buprenorphine plasma concentration and response in the treatment of opioid dependence has not been well studied. The pharmacokinetic and pharmacodynamic properties of buprenorphine allow it to be a feasible option for substitution therapy in the treatment of opioid dependence.

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.

Many patients enrolled in methadone maintenance treatment experience significant interdose opioid withdrawal. Mood states have been related to patient satisfaction with treatment and may influence how methadone patients experience opioid withdrawal. The objective of this study was to investigate the influence of major depressive disorder on response to methadone in patients on methadone maintenance treatment. Seventeen methadone patients (7 depressed and 10 not depressed) had pharmacokinetic and pharmacodynamic assessments (opioid withdrawal, drug effects, and mood) over one 24-hour dosing interval. Subjects were also divided based on their satisfaction with methadone treatment: 12 holders and 5 nonholders. Depressed subjects experienced more dysphoric opioid effects as measured by the Addiction Research Centre Inventory (area under the effect versus time curve, 14 +/- 32 vs -31 +/- 47, P < 0.04) and had higher scores on the Subjective Opioid Withdrawal Scale (area under the effect versus time curve, 33 +/- 97 vs -74 +/- 67, P < 0.02) over the dosage interval. Hamilton Depression scores significantly correlated with trough subjective opioid withdrawal scale scores (r = 0.7, P < 0.004). Nonholders had significantly higher exposure to unbound (S)-methadone compared with holders, specifically: trough concentration (6.1 +/- 2.7 ng/mL vs 2.7 +/- 1.7 ng/mL, P < 0.01), average steady-state concentration (7.6 +/- 4.0 ng/mL vs 4.1 +/- 2.5 ng/mL, P < 0.05), maximum concentration (14.6 +/- 7.1 ng/mL vs 7.5 +/- 4.2 ng/mL, P < 0.04), and area under the curve (183 +/- 95 h*ng/mL vs 99 +/- 61 h*ng/mL, P < 0.05). Study findings suggest that (S)-methadone may relate to patients' dissatisfaction with methadone treatment. Depressed methadone patients may be more sensitive to negative opioid effects and opioid withdrawal.

The annual "Roll Up the Rim to Win" contest at Tim Hortons restaurants provides customers the opportunity to win prizes. This study investigated win ratios, prize types and patterns of coffee consumption.