naloxone injection / Generic mfg. - LARVOL DELTA

Acupuncture inhibits the tolerance of analgesics of morphine (Neuroscience 2026) - "For the intracerebral injection of naloxone, picrotoxin, and 2-hydroxysaclofen, the guide cannula was implanted into the rostromedial tegmental nucleus (RMTg), and for the injection of SCH23390 and sulpiride, the guide cannula was implanted into the nucleus accumbens (NAc). When microinjected into the RMTg, naloxone and picrotoxin, but not the 2-hydroxysaclofen, blocked the SI5 acupuncture’s effect, and in the NAc injection, sulpiride, but not the SCH23390, blocked SI5. These findings suggest that SI5 acupuncture can be used to prevent the tolerance of opioid analgesic and that this SI5’s effect is mediated through the µ-opioid receptor and the GABAA receptor in the RMTg and through the dopamine D2 receptor in the NAc."

Addiction (Opioid and Alcohol) • CNS Disorders • BDNF • DRD2 • FOS

Molecular Characterization of the Parabrachial Nucleus after Opioid Exposure and Withdrawal (Neuroscience 2026) - "Mice then either had their tissue collected with morphine still on board (Dep:Mor), underwent either naloxone injection to precipitate withdrawal (ND:Nal or Dep:Nal) or saline injection as a control (ND:Sal), or underwent spontaneous withdrawal (Dep:Spont). RRHO analysis revealed concordant and discordant gene expression between males and females in the Dep:Nal vs Dep:Spont comparison, whereas the Dep:Spont vs Dep:Mor showed discordant gene expression. These findings contribute to a better understanding of how opioid exposure and withdrawal affect the PBN."

Addiction (Opioid and Alcohol) • CNS Disorders • Substance Abuse

Effects of thymoquinone on acute corneal and orofacial pains in rats: central involvement of opioid, cannabinoid, muscarinic cholinergic, and serotonin receptors. (PubMed, Vet Res Forum) - "Intracerebro-ventricular injections of naloxone (an antagonist of opioid receptors), (N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (an antagonist of CB1 receptors), atropine (an antagonist of muscarinic cholinergic receptors), and ondansetron (an antagonist of 5-hydroxytryptamine 3 receptors) at a similar dose of 10.00 µg kg-1 inhibited corneal and orofacial pains suppression caused by 40.00 mg kg-1 TQ. It is concluded that TQ caused analgesia in the acute corneal and orofacial pains. Central opioid, cholinergic muscarinic, CB1, and 5-hydroxytryptamine 3 receptors might be involved in the anti-nociceptive effects of TQ."

Journal • Preclinical • Pain

Preliminary evaluation of tissue hypoxia in a mouse model of fentanyl overdose by [18F]FMISO PET (SNMMI 2026) - "For the FNT group, fentanyl (0.7 mg/kg BW, 400 uL i.p.) was administrated at 30 min after the initiation of PET imaging, followed by naloxone injection (2 mg/kg BW, 100 uL i.p.) 15 minutes later. This study is the first to apply non-invasive dynamic [18F]FMISO PET imaging to understand tissue oxygen status in a toxicology model and provides a novel dynamic PET evidence of organ-specific hypoxic responses to fentanyl overdose. Based on our results, it is suggested that fentanyl overdose induces significant radiotracer retention, indicative of hypoxia, in the liver. Further studies are necessary to understand whether this hypoxia is solely due to respiratory depression responding to fentanyl overdose or is also caused by increased oxidative metabolic activity associated with drug metabolism."

Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Respiratory Diseases

Preliminary evaluation of tissue hypoxia in a mouse model of fentanyl overdose by [18F]FMISO PET (SNMMI 2026) - "For the FNT group, fentanyl (0.7 mg/kg BW, 400 uL i.p.) was administrated at 30 min after the initiation of PET imaging, followed by naloxone injection (2 mg/kg BW, 100 uL i.p.) 15 minutes later. This study is the first to apply non-invasive dynamic [18F]FMISO PET imaging to understand tissue oxygen status in a toxicology model and provides a novel dynamic PET evidence of organ-specific hypoxic responses to fentanyl overdose. Based on our results, it is suggested that fentanyl overdose induces significant radiotracer retention, indicative of hypoxia, in the liver. Further studies are necessary to understand whether this hypoxia is solely due to respiratory depression responding to fentanyl overdose or is also caused by increased oxidative metabolic activity associated with drug metabolism."

Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Respiratory Diseases

Prehospital outcomes associated with an initial strategy of intranasal vs. intramuscular naloxone administration by EMS clinicians: a nationwide cohort study. (PubMed, Prehosp Emerg Care) - "In this large cohort, initial IM naloxone administration was associated with more favorable physiologic and operational outcomes compared with an initial IN strategy. Importantly, IM administration was not associated with increased EMS treatment for agitation or nausea/vomiting, which suggests no observed increase in precipitated withdrawal in the prehospital setting."

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

The atypical antidepressant tianeptine causes opioid-receptor-dependent beta oscillations in the rat hippocampus. (PubMed, Neuropharmacology) - "Injection of the opioid buprenorphine (0.03 mg/kg) had similar effects, but ketamine (10 mg/kg), another atypical antidepressant, caused a distinct pattern of LFP changes characterised by a naloxone-insensitive increase in slow-gamma activity...Injection of tianeptine also caused a reduction in the amplitude of the inhibitory 'tail' of the fEPSP, consistent with a blockade of feedforward inhibition. These results indicate that tianeptine, like several other atypical antidepressant drugs, enhances hippocampal beta/gamma-frequency LFP activity. This action is dependent on opioid-receptor activation and may depend on the disinhibition of principal neurons, a possibility that we are exploring."

Journal • Preclinical • Addiction (Opioid and Alcohol) • Anesthesia • CA3

Opioid Modulation of Differential Gene Expression and Neuronal Differentiation in the Ventricular-subventricular Zone of Adult Male Zebra Finches. (PubMed, Ann Neurosci) - "To explore gene expression changes underlying the increase in cell proliferation in the V-SVZ of these birds after blocking opioid receptors (ORs) with systemic injections of naloxone...Given the established role of miR-124 in promoting neuronal differentiation, its upregulation suggests that OR blockade may enhance neuronal differentiation via microRNA (miRNA)-mediated pathways. This finding provides the first evidence linking opioid modulation to miRNA-driven neurogenic processes in an adult avian brain."

Journal • Pain • MIR124-3

Microinjection of morphine into the nucleus accumbens and CA1 modulates pain-related behaviors in an animal model of inflammatory pain in male rats. (PubMed, Behav Pharmacol) - "In addition, naloxone injection, administered before the effective dose of morphine, reduced its analgesic effects in both the NAc and CA1. These findings showed that opioidergic neurons exert antinociceptive effects through modulation of the μ-opioid receptor in the NAc and CA1 regions of the brain."

Journal • Preclinical • Pain

Medications for Opioid Use Disorder, Opioid Withdrawal, and Opioid Overdose: A Review. (PubMed, JAMA) - "Methadone, buprenorphine, and naltrexone are medications approved by the US Food and Drug Administration (FDA) to reduce unregulated opioid use...Medications for opioid withdrawal include opioid agonists (eg, methadone and buprenorphine), α2-receptor agonists (eg, lofexidine and clonidine), and medications to treat pain (ibuprofen) and nausea (ondansetron)...Opioid overdose can be treated or can be reversed with naloxone, an opioid antagonist that is FDA approved and should be administered at the lowest dose needed to restore a normal respiratory rate (eg, naloxone 0.4 mg intramuscularly or 2-4 mg intranasally)...Opioid withdrawal symptoms may be treated with opioid agonists, α2-receptor agonists, and medications for pain and nausea. All individuals with OUD should have access to opioid antagonists, such as naloxone, to treat opioid overdose."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Insomnia • Mood Disorders • Pain • Psychiatry • Sleep Disorder • Substance Abuse

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