Methadone seems like a very dangerous drug to use outside of a controlled clinical setting. Terrifying that variance of dosage between users (~18x) is greater than theraputic index (12x) - meaning a dose that is ineffectively low for one person can be an overdose for a another.
"Methadone, an opioid analgesic, is used clinically in pain therapy as well as for substitution therapy in opioid addiction. It has a large interindividual variability in response and a narrow therapeutic index. Genetic polymorphisms in genes coding for methadone-metabolizing enzymes, transporter proteins (p-glycoprotein; P-gp), and mu-opioid receptors may explain part of the observed interindividual variation in the pharmacokinetics and pharmacodynamics of methadone. Cytochrome P450 (CYP) 3A4 and 2B6 have been identified as the main CYP isoforms involved in methadone metabolism. Methadone is a P-gp substrate, and, although there are inconsistent reports, ABCB1 genetic polymorphisms also contribute slightly to the interindividual variability of methadone kinetics and influence dose requirements. Genetic polymorphism is the cause of high interindividual variability of methadone blood concentrations for a given dose; for example, in order to obtain methadone plasma concentrations of 250 ng/mL, doses of racemic methadone as low as 55 mg/day or as high as 921 mg/day can be required in a 70-kg patient without any co-medication."
"Methadone, an opioid analgesic, is used clinically in pain therapy as well as for substitution therapy in opioid addiction. It has a large interindividual variability in response and a narrow therapeutic index. Genetic polymorphisms in genes coding for methadone-metabolizing enzymes, transporter proteins (p-glycoprotein; P-gp), and mu-opioid receptors may explain part of the observed interindividual variation in the pharmacokinetics and pharmacodynamics of methadone. Cytochrome P450 (CYP) 3A4 and 2B6 have been identified as the main CYP isoforms involved in methadone metabolism. Methadone is a P-gp substrate, and, although there are inconsistent reports, ABCB1 genetic polymorphisms also contribute slightly to the interindividual variability of methadone kinetics and influence dose requirements. Genetic polymorphism is the cause of high interindividual variability of methadone blood concentrations for a given dose; for example, in order to obtain methadone plasma concentrations of 250 ng/mL, doses of racemic methadone as low as 55 mg/day or as high as 921 mg/day can be required in a 70-kg patient without any co-medication."
Li Y et al; Mol Diagn Ther 12 (2): 109-24 (2008)