Evaluation of Instruments and Procedures Used to Measure Opioid Withdrawal in Opioid Dependent Participants Who are Seeking to Discontinue Methadone Opioid Substitution Treatment (OST)

To be eligible, participants must opioid dependent and enrolled in a methadone maintenance programme but seeking to withdraw from methadone. They must be on stable doses of methadone for at least 30 days prior to Screening. Participants who meet eligibility criteria will undergo a medically supervised OST withdrawal. Their methadone will be replaced with CR morphine twice daily while they are out-patients (Day -7 to Day -3). An equivalent dose to the methadone will be administered as CR morphine an (using a 1:4 ratio). The participant’s response to CR morphine dosing will be monitored for at least 4 hours post dosing and the investigator may adjust the dose to 1:3 to 1:5 ratios depending on participant response. Participants will be admitted to the Clinical Site on Day -2 and their CR morphine will be replaced with immediate release morphine administered orally as 10mg four times a day on Day -2 and Day -1. On Day 1 the morphine will be with-held; Medical treatment will be provided to minimize symptoms during the withdrawal period. The following rating scales will be used in this study: (1)These will be collected to assess psychological and neurological safety and drug effects. - The Columbia Suicide Severity Rating Scale (C-SSRS): from screening (between Day -28 and Day -9) until Day 3, - Psychotomimetic Rating Scale (PRS): from screening (between Day -28 and Day -9) until Day 1, - Mood Visual Analog Scale (Mood VAS): from screening (between Day -28 and Day -9) until the follow-up Visit one week after discharge from the Clinical Site at Day 3, - Addiction Research Center Inventory (ARCI), from screening (between day -28 and Day -9) until Day 3, - Addiction Severity Index (ASI):from screening (between Day -28 and Day -9) until Day -2, - Readiness for Change (RtC):from screening (between Day -28 and Day -9) until Day -2, (2) Opiate Withdrawal scales will be used to evaluate the progression and suppression of Opiate withdrawal compared to the participant’s baseline: - Handelsman-Kanof OOWS/SOWS and COWS instruments will be used to assess opioid withdrawal. These are conducted from inital screening until the follow-up Visit 1 (one week after their discharge from the Clinical Site at Day 3). The resumption of methadone OST may occur when the participant’s withdrawal symptoms have not been controlled with medical intervention and the intensity is to the point where the participant requests OST. Methadone OST may also be initiated at the investigator’s discretion when his clinical evaluation indicates the participant’s withdrawal is increasing and not responding to medical intervention. All doses of morphine will be administered at the Clinical Site and mouth checks will be performed to ensure compliance.