naloxone injection / Generic mfg. - LARVOL DELTA

Combining the alpha-2 adrenergic agonist clonidine with naloxone rescues fentanyl-induced physiologic dysfunction and increases survival. (PubMed, bioRxiv) - "Unlike morphine, high dose fentanyl rapidly produces airway obstruction, muscle rigidity, and cardiovascular failure...We also show that administration of intramuscular naloxone immediately after intravenous infusion of fentanyl did not improve survival...Also, supplementing naloxone with drugs targeting the adrenergic system improves survival primarily by reopening the upper airway, implicating airway obstruction as a significant component of fentanyl-induced respiratory depression. Therefore, reversal of vocal cord closure appears to be the necessary precursor to the restoration of not only respiration, but also vascular autoregulation, a significant determinant of survival from fentanyl overdose."

Journal • Addiction (Opioid and Alcohol) • Cardiovascular • CNS Disorders • Depression • Psychiatry • Respiratory Diseases

Mapping neuronal ensembles associated with intoxication and withdrawal fromfentanyl exposure using a dual-labeling strategy in TRAP2::Ai14 mice (Neuroscience 2025) - "To address this, we used a dual TRAP2::c-Fos labeling approach in mice to compare neuronal activation patterns across fentanyl-induced intoxication and withdrawal.Male and female TRAP2::Ai14 mice (8 weeks old, n=5/group) were implanted with osmotic minipumps delivering fentanyl (0.4 mg/kg/day) or saline as a control...On day 13, withdrawal was induced via naloxone injection (5 mg/kg) and brains were collected 90 min later to examine endogenous Fos protein expression compared with the intoxication activity labeled by tdTomato...Our study shows the utility of dual mapping for dissecting dynamic neural engagement across phases of addiction. Despite minimal intoxication-withdrawal overlap, the elevated withdrawal-associated activity in NAc and PVH highlights these regions as key nodes in opioid withdrawal processing. Ongoing iDISCO+ clearing and light-sheet imaging will validate and extend these findings across distributed networks with greater spatial resolution and..."

Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry • Substance Abuse • FOS

The Dorsal Forearm as a Novel Target for Intramuscular Injections: Clinical Pharmacokinetic Results With Naloxone. (PubMed, Clin Transl Sci) - "The objectives of this study were to administer naloxone via IM injection into the dorsal forearm, characterize the pharmacokinetic (PK) profile of this injection site, and compare it to that of a standard IM injection...The subjects noted minimal discomfort with the forearm injection, and there were no adverse neurovascular events. This represents the first study wherein a drug has been administered in the EDC of the dorsal forearm as an IM target muscle."

Journal • PK/PD data

A RARITY: CONGENITAL BRONCHIAL ATRESIA IN AN ADULT (CHEST 2025) - "CASE PRESENTATION: A 29-year-old male, former smoker with a history of cocaine and opioid use disorder, ADHD, and seizures, presented to our hospital with altered mental status and agonal breathing which significantly improved after the administration of 8 mg of IM naloxone. Urine drug screen was positive for fentanyl... This case not only highlights the crucial role of CT scan of the chest in diagnosing Pulmonary Bronchial Atresia but also underscore the multidisciplinary approach and early surgical referral to prevent future complications."

Clinical • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Epilepsy • Infectious Disease • Pneumonia • Psychiatry • Respiratory Diseases • Substance Abuse

Trends and characteristics during 17 years of naloxone distribution and administration through an overdose prevention program in Pittsburgh, Pennsylvania. (PubMed, PLoS One) - "While state legislation created the environment for expansion, reaching previously underserved communities required intentional new programmatic development and outreach. Long-term consistency of <2 doses per ORE, high survival rate, and robust utilization all lend confidence in prioritizing naloxone distribution directly to people who use drugs and their social networks. Trial registration: This investigation was pre-registered https://osf.io/b2f4h."

Journal • Addiction (Opioid and Alcohol)

Hypoxia and Hypercapnia Have Little Impact on Remifentanil-Induced Changes in Respiratory Phase Timing and Neuronal Activity in the preBötzinger Complex in Adult Rabbits (ASA 2025) - "Background: We have previously shown that respiratory depression from intravenous (IV) remifentanil could be partially reversed with naloxone injection into the preBötzinger complex (preBötC) during moderate hypercapnia (PCO2 50 mmHg)(1). Although hypercapnia and hypoxia increase chemodrive to the respiratory rhythm generator and had substantial effects on phase timing and tidal volume in normoxic, normocapnic individuals (1), the effect we observed during remifentanil-induced respiratory depression was very limited. This matched the effect on individual respiratory neuronal discharge. Changes in I parabolic and E decrementing neuron activity were associated with changes in timing and PPA, which fit current models of respiratory control (2)."

Clinical • Preclinical • Addiction (Opioid and Alcohol) • Anesthesia • CNS Disorders • Depression • Psychiatry

Proof of Concept (PoC) Evaluation of Naloxone Unique Intramuscular (IM) Injection (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: STAT Therapeutics Inc

New P1 trial

Use of a Shoulder-Mounted Wearable Sensor Prototype Designed to Detect Opioid-Related Overdose: A Qualitative User Experience Study. (PubMed, J Med Internet Res) - "Participants expressed a preference for solutions that alert first responders over automated biomedical solutions, such as naloxone injection, because of concerns about device error (eg, false positives) leading to precipitated withdrawal. After wearing a shoulder-mounted prototype, this small group of participants found the idea acceptable and provided feedback to improve usability and design. Data suggest that a variety of devices with differing functions, sizes, and capacities will be needed to meet user needs and increase the likelihood of adoption once devices come to market."

Journal • Addiction (Opioid and Alcohol) • Substance Abuse

Lessons Learned from a Grassroots Harm Reduction Effort to Prevent Drug Overdose Deaths. (PubMed, J Prev Interv Community) - "Inequities with access to naloxone and fentanyl test strips (FTS) due to cost and stigma have reinforced the necessity of community-based distribution of lifesaving harm reduction supplies. In Wichita and Sedgwick County, the epicenter of the opioid epidemic in Kansas, Safe Streets Wichita, a grassroots prevention and harm reduction coalition, started Project Wichita Overdose Recovery Kit Expedited Delivery (WORKED), a free volunteer-led intramuscular naloxone and FTS program...These findings help serve as the foundation by which interviewees envision a more holistic and comprehensive approach to harm reduction. Findings will be used to inform the fidelity, efficiency, accessibility, and longevity of community-based naloxone and FTS distribution and the implementation of harm reduction strategies in general across the state of Kansas."

Journal • Addiction (Opioid and Alcohol)

Developing Novel Treatments for Atypical Features of Fentanyl-Related Toxicity (CPDD 2025) - " Five-minute pretreatment with IM naloxone blocked FIVCC (n=3), but IM naloxone given immediately after IV fentanyl did not reverse FIVCC (n=6). The toxic effects of high dose fentanyl, including FIVCC, can be modeled in rodents. Naloxone alone does not reverse FIVCC, the addition of clonidine, which directly modulates VC activity, reverses 1 FIVCC. These results support supplementing naloxone to address the atypical aspects of fentanyl-related toxicity."

CNS Disorders • Depression • Psychiatry

Reduction of opioid withdrawal symptoms and opioid-induced hyperalgesia by subcutaneous sumatriptan reveals central neuromodulation. (PubMed, J Pain) - "We also found that at the time of naloxone injection sumatriptan reached contents of 294±19 and 371±30 pg/mg of tissue in the RVM and locus coeruleus, respectively. PERSPECTIVE: This article reports that sumatriptan reduces symptoms of morphine withdrawal and morphine-induced hyperalgesia. Data suggests that triptans exert their antinociceptive effects through central mechanisms."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Migraine • Pain

Swimming partially relieves chronic pain after thoracotomy via μ-opioid receptors in rats (Euroanaesthesia 2025) - "Swimming exercise suppressed tumor necrosis factor-alpha and interleukin-6 overexpression in intercostal nerves after thoracotomy.Conclusion(s): The results showed that swimming exercise improves mechanical and cold allodynia after thoracotomy, while naloxone injection partially inhibits the analgesic effect of swimming exercise. Swimming exercise can reduce chronic pain after thoracotomy, which may be related to the inhibition of pro-inflammatory cytokine overexpression in intercostal nerves and activation of mu opioid receptor."

Preclinical • Oncology • Pain • IL6 • TERC • TNFA

A comparison of intramuscular (Zimhi) and intranasal naloxone (Narcan) in reversal of fentanyl-induced apnea: a randomized, crossover, open-label trial. (PubMed, Nat Commun) - "Severe opioid-induced respiratory depression (OIRD) can be treated with intranasal (IN) or intramuscular (IM) naloxone. While the trial shows superiority for IM naloxone with products used in the community, we relate our findings to the higher naloxone plasma concentrations after IM naloxone compared to IN naloxone. The study was registered at https://doi.org/10.1186/ISRCTN21068708 ."

Clinical • Journal • CNS Disorders • Depression • Psychiatry

A Randomized, Blinded, Placebo-Controlled Crossover Study of the Pharmacokinetics and Pharmacodynamics of Naloxone, Naltrexone, and Nalmefene in Methadone-Sedated Working Dogs. (PubMed, J Vet Pharmacol Ther) - "Dogs with a sedation score ≥ 10/14 at 20 min after reversal/placebo were administered 0.1 mg kg-1 of naloxone IM and included all dogs that received saline. These reversal agents may be useful for treating sedation in professional working dogs exposed to opioids prior to seeking veterinary care. Pharmacological differences between methadone and higher potency opioids (fentanyl and its derivatives) preclude interpretation of these findings to non-methadone opioids, and further studies are needed."

Journal • PK/PD data • Anesthesia

Naloxone dosing by non-medical first-responders at opioid overdoses: findings from a qualitative interview study. (PubMed, Harm Reduct J) - "Naloxone dosing is complex and often reactive rather than purely scientific. Non-medical responders are competent at saving lives using naloxone, but do not always achieve resuscitation without negative effects. Findings highlight the value of offering optional advanced training and regular refresher training. This should focus on locally used naloxone products and dosing decision-making, plus experiential training that might enable people to anticipate how they would feel in a time-pressured overdose-related situation and so respond more calmly."

Interview • Journal • Addiction (Opioid and Alcohol) • CNS Disorders

Assessment of laparotomy-induced stress response in opium- and morphine-addicted rats by measuring serum glucose and corticosterone levels: an animal experiment. (PubMed, Ann Med Surg (Lond)) - "Addiction was induced by administering increasing doses of morphine or opium in drinking water, as verified by naloxone injections. Laparotomy was performed under ketamine and xylazine anesthesia...Future studies should use larger, more diverse samples and additional biomarkers. This pilot study highlights the need for further research on altered stress responses in opioid-addicted patients undergoing surgery, emphasizing the importance of tailored postoperative care."

Journal • Preclinical • Addiction (Opioid and Alcohol) • Anesthesia • CNS Disorders • Diabetes • Psychiatry

West Virginia Drug Intervention Institute Awarded $74K Grant to Expand Naloxone Access and Opioid Education (WVNews) - "The West Virginia Drug Intervention Institute (WVDII) has been awarded $74,747.31 through the West Virginia First Foundation’s (WVFF) inaugural Opportunity Grant program. The funding will support the continued expansion of Nalox(ONE) West Virginia, an innovative program aimed at reducing opioid misuse through pharmacist-led patient engagement and naloxone distribution."

Financing • Addiction (Opioid and Alcohol)

Nalmefene vs Naloxone for the Treatment of Recurrent Respiratory Depression After Opioid Overdose (clinicaltrials.gov) - P3 | N=0 | Withdrawn | Sponsor: University of New Mexico | N=74 ➔ 0 | Trial completion date: Dec 2026 ➔ Dec 2024 | Recruiting ➔ Withdrawn | Trial primary completion date: Oct 2026 ➔ Dec 2024

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • CNS Disorders • Depression • Mood Disorders • Psychiatry

Role of the amygdala opioid system in the effects of stress on the post-learning sleep patterns of male Wistar rats. (PubMed, Iran J Basic Med Sci) - "Under stress, using the learning protocol increases REM, NREM sleep, and BDNF. Naloxone injection in BLA improves memory and learning, reducing stress-induced memory loss."

Journal • Preclinical • CNS Disorders • BDNF

Managing xylazine-involved overdoses in a community harm reduction setting: lessons from Tijuana, Mexico. (PubMed, Harm Reduct J) - "We describe insights about the clinical management of combined xylazine-fentanyl involved overdoses in the field, from a community harm reduction context where xylazine arrived suddenly spurring a large number of overdoses. In response to the long period of post-naloxone sedation inherent to xylazine overdoses, the clinical team learned to center oxygenation-not consciousness-as the key parameter of interest for the titration of naloxone, increase emphasis on field airway management, portable oxygen administration, and scene safety, and employ xylazine testing strips for urine and direct substance analysis to educate the patient population about health risks."

Journal • Addiction (Opioid and Alcohol) • Anesthesia

Pharmacodynamic Evaluation of Intramuscular Nalmefene Autoinjector 1.5 mg Compared to Intranasal Narcan 4 mg (clinicaltrials.gov) - P1 | N=27 | Completed | Sponsor: Purdue Pharma LP

New P1 trial • CNS Disorders • Depression • Mood Disorders • Psychiatry

Differential Effects of Intrahippocampal Administration of Ceftriaxone on Morphine Dependence and Withdrawal Syndrome in Rats. (PubMed, ACS Omega) - "Two hours after the last morphine injection, naloxone hydrochloride (1.5 mg/kg) was administered, and morphine withdrawal syndrome was recorded for 25 min. However, a single dose of ceftriaxone after becoming dependent could not decrease withdrawal syndrome. More prolonged administration of ceftriaxone could alleviate the induced dependence."

Journal • Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry

Intravenous Bolus Injection of Fentanyl Triggers an Immediate Central and Upper Airway Obstructive Apnea via Activating Vagal Sensory Afferents. (PubMed, J Appl Physiol (1985)) - "Cardiorespiratory and electromyography of external and internal intercostal, thyroarytenoid and superior pharyngeal constrictor muscles (EMGEI, EMGII, EMGTA and EMGSPC) responses to IVb injection of fentanyl were recorded in anesthetized and spontaneously breathing rats with or without bilateral peri-vagal capsaicin treatment or intra-vagal microinjection of naloxone. Vagal C-neurons expressed MORs and were activated by fentanyl. We conclude that IVb injection of fentanyl causes a VCF- and vagal afferent OR-mediated immediate central apnea, upper airway obstruction and chest wall rigidity."

Journal • Anesthesia • Cardiovascular • CNS Disorders • Depression • Hypotension • Obstructive Sleep Apnea • Psychiatry

ROAR: Reversal of Opioid-induced Respiratory Depression with Opioid Antagonists (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Leiden University Medical Center | Recruiting ➔ Completed | Trial completion date: May 2024 ➔ Oct 2024 | Trial primary completion date: May 2024 ➔ Aug 2024

Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Depression • Mood Disorders • Psychiatry

The Respiratory Effects of Xylazine-fentanyl Combination in Awake Mice (Neuroscience 2024) - "Furthermore, the respiratory effects of xylazine-fentanyl coadministration were only partially attenuated by subsequent injections of naloxone; respiratory parameters reflected the intrinsic effects of the administered xylazine dose rather than restoring breathing to baseline levels.Together, these results suggest that xylazine administration suppresses breathing through interactions with α-2 adrenergic receptors, and that exposure to xylazine may both exacerbate opioid-induced respiratory depression and prevent its full reversal by naloxone. These effects may contribute to lethal respiratory effects after xylazine-opioid coadministration."

Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Psychiatry