Canada has experienced a public health crisis of high levels of overdose deaths mainly from toxic, synthetic opioids (e.g., fentanyl) drugs for more than a decade. While a wide range of prevention and treatment interventions to reduce overdose risk have been scaled up, drug overdose death levels have overall increased - reflecting similar US-based trends - before abruptly decreasing since 2023. These developments raise the crucial question: What factors have been driving the recent decreases in drug overdose deaths? We considered North America-based studies/data that examined potential supply-related factors. Emerging data suggest that while drug user-oriented prevention and treatment interventions have averted substantial numbers of overdose deaths, recent decreases in death appear to be associated mainly with changes in the global supply dynamics of toxic drugs, possibly related to intensified source control efforts (e.g., on fentanyl precursors) in China. Available data plausibly suggest that these changes may have affected both the composition and/or potency of illicit synthetic opioids available for consumption, and thereby reduced the population-based risks for overdose fatalities from exposure. While requiring further examination, these developments raise important questions about effective health-oriented overdose prevention policy and measures that are independent of unpredictable global drug supply dynamics.

Adolescents with opioid use disorder (OUD) remain vulnerable to fentanyl exposure, opioid‑related harms, and profound treatment gaps, even with recent declines in overdose mortality. Strong evidence demonstrates that buprenorphine is safe and effective for youth, yet adolescents remain the age group least likely to receive medications for OUD (MOUD). This review reassesses buprenorphine access for adolescents through a risk-benefit lens, integrating randomized trials, observational cohorts, international guidelines, and emerging fentanyl‑era data. We synthesized evidence from randomized controlled trials, administrative datasets, qualitative studies, comparative effectiveness research, and narrative reviews through a search of the English-language literature in PubMed for adolescent and young adults; examined U.S., U.K., and WHO policy positions; and evaluated structural, regulatory, and developmental barriers that limit adolescent access to MOUD. Particular attention was given to transmucosal and extended‑release buprenorphine and its potential relevance to adolescent adherence and retention. Across two decades of research, buprenorphine consistently improves retention, reduces opioid use, decreases high‑risk behaviors, and is well tolerated. Longer treatment durations reliably outperform short tapers. Real‑world data show that only 5 to 10% of adolescents with OUD receive MOUD, despite the highest overdose risk of any age group. Comparative effectiveness studies demonstrate lower overdose risk with buprenorphine than methadone, and fentanyl‑era feasibility studies confirm successful induction even among youth using illicit fentanyl exclusively. All major medical organizations, including American Society of Addiction Medicine, the American Academy of Pediatrics, the American Academy of Child & Adolescent Psychiatry, the Society for Adolescent Health and Medicine, the British Columbia Centre on Substance Use, and the WHO, endorse buprenorphine for adolescents with OUD. Persistent undertreatment reflects structural barriers, clinician hesitancy, regulatory misconceptions, and the absence of an FDA indication, not lack of efficacy. Expanding access to both transmucosal and extended‑release formulations is critical to reducing preventable overdose deaths. The evidence supports a shift toward developmentally tailored, medication‑based recovery models that prioritize early initiation, sustained treatment, and removal of structural barriers. With illicitly manufactured synthetic opioids now dominating the drug supply, withholding buprenorphine from adolescents is not evidence‑based; it reflects longstanding epistemic exclusion that has limited youth access to treatments known to save lives.

Opioid addiction is characterized by escalating drug use, driven in part by negative reinforcement from withdrawal, but the neural processes linking withdrawal to increased drug-taking remain poorly understood. Here, we use multisite local field potential recordings and interpretable machine learning to identify large-scale brain networks engaged by repeated opioid exposure and withdrawal. After discovering that repeated fentanyl exposure induces a progressively ramping network of widespread high beta and low gamma oscillations, we then identified a distinct brain network that selectively encodes the emergence and severity of opioid withdrawal. This network, termed EN-Withdrawal , is characterized by regional gamma oscillations and widely synchronized delta/theta oscillations. Its activity patterns predict the emergence of spontaneous and naloxone-precipitated withdrawal across multiple independent cohorts, generalizing across mice, sex, opioids, and dosing regimens, while persisting over multiple days of withdrawal. Using a novel, data-driven severity index, we find that network activity scales with individual behavioral severity without simply reflecting ongoing somatic behaviors or general aversion, suggesting that EN-Withdrawal underlies a withdrawal-induced internal state. Strikingly, network activity predicts the escalation of fentanyl self-administration on a mouse-by-mouse basis in experienced, but not drug-naïve, animals. These findings reveal a neurophysiological substrate of the negative reinforcement cycle of addiction that shapes individual vulnerability.

Minimally invasive cardiac surgery (MICS) causes significant intercostal pain managed traditionally with opioids, risking nausea, hypoventilation and delayed recovery. Therefore, it is of interest to compare ultrasound-guided serratus anterior plane block (SAPB, n=60) versus fentanyl-based analgesia (n=60) in 120 adults undergoing right mini-thoracotomy MICS. SAPB significantly reduced 24-hour opioid requirements (12mg [IQR 8-18] versus 22mg [IQR 15-30] morphine equivalents; p<0.001) and lowered pain scores at rest/coughing (6/12h, all p<0.01). SAPB attenuated stress response (6h cortisol 18.4±6.2 versus 24.9±7.1 ug/dL, p<0.001; IL-6 68 versus 102 pg/mL, p=0.002) and reduced postoperative nausea/vomiting (PONV) (18% versus 35%) without block complications. Thus, we show SAPB as an effective opioid-sparing analgesic technique that enhances recovery and comfort in MICS patients.

The optimal method of intrathecal fentanyl administration with hyperbaric bupivacaine remains uncertain, as premixed and sequential techniques may influence block characteristics differently. In this prospective observational comparative study, 42 ASA I-II adults (21 per group) received fentanyl 0.5 ml with hyperbaric bupivacaine 2.5 ml either premixed or sequentially. Sequential administration produced faster sensory onset at T10 (5.00±1.37 vs 6.48±1.32 min) and motor onset (6.10±1.37 vs 8.00±1.30 min) with longer sensory and motor regression times. Time to first rescue analgesia was also longer (205.33±12.08 vs 175.38±14.41 min), suggesting earlier onset and prolonged block with the sequential technique.

Propofol requires adjuncts for balanced anaesthesia due to cardiovascular depression and lack of analgesia. Dexmedetomidine offers superior sympatholysis versus opioids like fentanyl but risks delayed recovery. Therefore, it is of interest to compare propofol-fentanyl (PF, n=40) versus propofol-dexmedetomidine (PD, n=40) in 80 ASA I-II adults for elective supra-umbilical surgery. Propofol-dexmedetomidine (PD) better attenuated hemodynamic responses (HR/MAP within 10% baseline) versus 20-25% rises in PF, despite modest recovery delays. PD advances knowledge by optimizing intraoperative stability for supra-umbilical surgery at low early recovery cost.