Opioid Withdrawal

IBO-CARE is a single-site Phase 1/2a study evaluating the safety, tolerability, feasibility and preliminary outcomes of medically supervised ibogaine with 12 months of recovery support in adults with moderate-to-severe opioid use disorder. Up to 120 candidates will be screened to enrol 60 adults aged 18-65 into three cohorts of 20. Participants meeting the shared opioid-free and negative naloxone-challenge criteria will be randomised 1:1 to Cohort A or Cohort C. Cohort A receives extended-release naltrexone 380 mg intramuscularly and matching oral placebo. Cohort C receives oral ibogaine hydrochloride and matching intramuscular placebo. Cohort B follows a separate, nonrandomised recent-use ibogaine pathway with matching intramuscular placebo and clinically supervised stabilisation. All cohorts attend three monitored oral-treatment admissions at Months 0, 1 and 2. Repeat ibogaine administrations require individual eligibility and safety release. The planned injection schedule comprises twelve calendar-monthly administrations at Months 0-11, with final follow-up at Month 12. All participants receive equivalent preparation, psychological support, continuing addiction care, monthly clinical review and SENTINEL digital recovery support with a Garmin Venu 4. The acute monitoring model includes continuous telemetry during a 72-hour post-dose window, serial 12-lead ECGs, laboratory monitoring, emergency capability and independent safety oversight. Monitoring is extended when clinically required. Wearable information does not replace clinical cardiac monitoring. SENTINEL combines participant reports, wearable trends and scheduled assessments, with high-risk findings reviewed by qualified clinicians. Cohorts A and C use a double-blind, double-dummy comparison. Cohort B is open to the treating team, with masked outcome assessment where feasible. Treatment guesses are collected because the acute effects of ibogaine may reveal allocation. The study estimates preliminary effects and is not designed to establish confirmatory efficacy. The IND application has not yet been filed. The study remains not yet recruiting. ClinicalTrials.gov registration and assignment of an NCT number do not authorise study conduct. Enrolment and investigational treatment will begin only after the IND is in effect, IRB approval is in place, and all applicable DEA, Colorado, investigational-product, clinical-site and digital-system requirements have been satisfied. The registration will be updated when the actual FDA filing details are available.

Neonatal opioid withdrawal syndrome (NOWS) can affect a newborn infant's ability to eat, sleep, and be consoled after exposure to opioids before birth. Standard care at the participating neonatal units uses the Eat, Sleep, Console (ESC) approach, which emphasizes supportive care and involvement of parents and caregivers. VOICE-NAS is a two-centre feasibility study evaluating whether a recorded parent/caregiver voice can be safely and practically added to usual ESC-based care for infants with NOWS. Approximately 15 to 20 infants will be enrolled at HSC Women's Hospital and St. Boniface Hospital in Winnipeg, Manitoba. A parent or caregiver will make a short voice recording in their preferred or native language. The recording may include natural talking, reading, singing, storytelling, or comforting words. The recording will be played for the infant during clinically appropriate feeding and settling periods, usually during the latter part of a feed and/or after feeding while the infant is trying to settle or sleep. Playback will generally last about 20 minutes and will be delivered at a controlled sound level. The main purpose of the study is to determine whether the intervention can be delivered consistently and safely within routine NICU care. The study will measure whether usable voice recordings can be obtained, how often planned playback sessions are successfully delivered, reasons sessions are missed or stopped, caregiver acceptability, staff workflow issues, and any signs of intolerance. Clinical information such as ESC assessments, feeding support, medication treatment for NOWS, and hospital length of stay will also be described. The study is not designed to determine whether recorded voice therapy is effective. Results will be used to help design a future larger clinical trial.

The primary objective of this trial is to measure changes in physiologic signals to quantify the status of the autonomic nervous system during opioid withdrawal and cravings.

The investigators propose a rigorous, Phase II, three-group, placebo-controlled double-blind randomized controlled trial (RCT) to evaluate the efficacy of buspirone for both withdrawal and craving among individuals with opioid use disorder (OUD) undergoing a standardized stepwise taper. During this 10 to 12-day residential study, participants with OUD will be enrolled, stabilized on a short-acting opioid, undergo an opioid stepwise taper, and complete a post-taper observation period where participants will have the opportunity to initiate long-term buprenorphine or extended-release naltrexone.

The purpose of the study is to find out how a stimulation device worn on the ear works. This device is thought to stimulate nerves in the area around the ear to change the signals in the brain. The device has been shown to reduce pain and to reduce the symptoms of withdrawal. The investigator will also investigate changes in the way each participant perceive sensations of pressure and heat. The participant will be asked to reduce the amount of pain medication that they take. Then, the participant will spend several days and nights in the Clinical Research Center at UTMB (University of Texas Medical Branch) in Galveston. During that time, the participant will be monitored for withdrawal symptoms and will receive either active (e.g., "real") brain stimulation or sham (e.g., "fake") brain stimulation for two days (four hours each day). At two times over the course of the study (before and after ear stimulation treatment), the participant will complete questionnaires about their pain score and how they are feeling, sensory testing, and will undergo magnetic resonance imaging (MRI) of their brain. The investigator will collect the following information from the participant's medical record: age, gender, medication history, medical diagnoses, recent vital signs, past doctor visits or hospital stays, and results of urine drug tests. Participation in this study will last approximately four days, and the participant will stay in the Clinical Research Center.

This study is evaluating the Sparrow Link, a wearable device that delivers gentle electrical signals to nerves in the outer ear (a technique known as transcutaneous auricular neurostimulation, or tAN). The goal is to assess whether the device is feasible to use, acceptable to patients, and may help reduce opioid withdrawal symptoms in hospitalized adults being treated for opioid use disorder (OUD). Participants will be randomly assigned to receive either the active device or a sham (inactive) version. Neither participants nor their clinical teams will know which version is used. All participants will continue receiving standard hospital care for opioid withdrawal. Researchers will collect information on how long participants use the device, whether they stop using it early, and changes in withdrawal severity. The study will also examine pain, craving, mood, anxiety, heart rate variability, and opioid use during hospitalization.

Unregulated opioids remain a leading driver of preventable mortality and potential years of life lost in Canada. Emergency departments (EDs)-open 24/7 and frequently accessed by people who use drugs-offer critical opportunities to reverse toxicity, mitigate harm, and initiate treatment. Yet, high quality evidence to guide ED care for patients with opioid poisoning and concomitant opioid dependence or opioid use disorder is limited. The investigators aim to establish a pan Canadian registry of patients presenting to EDs with opioid poisoning to generate timely, practice informing evidence. The investigators will create the Canadian Emergency Department Research Network (CEDRN) Opioid Registry across participating EDs nationwide. Using automated screening of electronic health records (EHRs), the investigators will identify consecutive patients of all ages with suspected or confirmed opioid poisoning at their index ED visit. The project's objectives are to establish a pan-Canadian registry of Emergency Department patients presenting with opioid poisoning, harmonize data collection across participating sites, describe variations in patient characteristics, clinical practice and outcomes, and derive a clinical decision rule to predict the risk of dying within 60 days. The expected outcomes include advancing healthcare delivery, improving patient and provider experiences, and enhancing population health and health system sustainability for individuals with opioid poisoning. This research is crucial for addressing the opioid crisis in Canada and has the potential to significantly impact patient care and outcomes.

This study will sequentially evaluate three novel and scalable interventions for at-risk individuals on long term opioid therapy for chronic pain: (1) low-dose transdermal buprenorphine initiation without a period of opioid withdrawal; (2) a brief Cognitive Behavioral Intervention for pain (CBI); and (3) "accelerated" rTMS over the left dorsolateral prefrontal cortex, by examining standardized repeated measures of clinical outcomes at baseline, during treatment, and at 4-, 12-, 24- and 52-week follow-up.

Evaluate individual differences in the expression of opioid withdrawal symptoms in persons with opioid use disorder (OUD) while completing a clinically-indicated medication taper.