The purpose of this study is to determine the safest dose of d-methadone that can be given, without causing severe side effects in most patients with chronic pain. Patients are being asked to participate in the Phase I portion of this study.

Inclusion Criteria:

Phase I and Phase II portions of the study:

• 18 years of age or older
• Chronic pain with average 24 hour intensity rated at least 3 on a verbal numerical scale from 0-10 during the 24 hours prior to study entry.
• Give informed consent to participate in this study.
• Karnofsky Performance Score (KPS) >= to 80
• Negative urine pregnancy test, verified by the study nurse, at study entry (for women of child-bearing potential). Patients must also use a medically approved contraceptive method during the study period.

Phase I only:

• Responsible companion living with patient during study.

Phase II only:

• Group 1 -- Patients must be taking chronic opioid therapy (long acting morphine, long acting oxycodone, transdermal fentanyl) at a stable dose for a minimum of four days. The dose of as needed short acting opioid does not need to be stable.
• Group 2 -- Patients must not be receiving opioids and must have cancer related neuropathic pain secondary to post-chemotherapy peripheral neuropathy, post-radiation and/or post surgical plexopathy, radiculopathy or neuropathy, or post- herpetic neuralgia.

Exclusion Criteria:

Phase I and Phase II:

• Known hypersensitivity to methadone

• Patient taking methadone or with a history of methadone treatment within one month of study enrollment.

• Patient that requires changes in the dose of one of the following medications within 2 weeks of study enrollment:

  • Abacavir,
  • Benzodiazepines,
  • Carbamazepine,
  • Efavirenz,
  • Fluconazole,
  • Fluvoxamine,
  • FOS amprenavir,
  • Fosphenytoin,
  • Naltrexone,
  • Nelfinavir,
  • Nevirapine,
  • Phenytoin,
  • Rifampin,
  • Rifapentine,
  • Risperidone,
  • Ritonavir,
  • St. John's Wort,
  • Zidovudine

• Hepatic function tests (SGOT, alkaline phosphatase, bilirubin) greater than 2 times the upper limit of normal or creatinine greater than 1.4 within 30 days of study entry.

• Neurologic or psychiatric disease sufficient, in the investigator's opinion, to compromise data collection.

• Women who are pregnant or nursing.

• Women of childbearing potential who do not agree to use a medically recognized method of contraception during the study period.