Objective: N-methyl-D-aspartate antagonists were shown to be effective in suppressing the symptoms of opiate withdrawal. Intravenous anesthetic, ketamine, is the most potent N-methyl-D-aspartate antagonist available in clinical practice. The present study was designed to evaluate the effects of subanesthetic ketamine infusion, as little human data are available on ketamine in precipitated opiate withdrawal.
Materials And Methods: A total of 58 opiate-dependent patients were enrolled in a randomized, placebo-controlled, double-blind study. Patients underwent rapid opiate antagonist induction under general anesthesia. Prior to opiate antagonist induction patients were given either placebo (normal saline) or subanesthetic ketamine infusion of 0.5 mg/kg/h. Further evaluations were divided into three phases: anesthetic, early postanesthetic (48 hours), and remote at 4 months after procedure. Cardiovascular, respiratory, renal, and gastrointestinal responses to opiate antagonist induction were monitored during anesthesia phase. Changes in plasma cortisol concentrations were measured as stress-response markers. Evaluations during early postanesthetic phase were based on Subjective and Objective Opiate Withdrawal Scales. Remote effects were assessed according to questionnaire based on Addiction Severity Index.
Results: Altogether, 50 patients were included in the final analysis. Ketamine group presented better control of withdrawal symptoms, which lasted beyond ketamine infusion itself. Significant differences between Ketamine and Control groups were noted in anesthetic and early postanesthetic phases. There were no differences in effects on outcome after 4 months.
Conclusion: In this study, subanesthetic ketamine infusion was an effective adjuvant in the correction of acute precipitated opiate withdrawal although it had no long-term effects on treatment of opiate dependence.
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Bioorg Chem
January 2025
School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China. Electronic address:
An alternative approach for the management of acute and chronic pains involves prolonging the half-life of endogenous opiates, such as enkephalins that are released in response to nociceptive stimuli. This can be achieved through the inhibition of enzymatic pathways responsible for the hydrolysis of these peptides, particularly targeting Aminopeptidase N (APN) and Neutral Endopeptidase (NEP). In this study, we designed and synthesized a series of dual enkephalinase inhibitors (DENKIs) targeting both APN and NEP as novel analgesic treatments.
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January 2025
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, United States.
Reversing opioid overdoses in rats using a drug that does not enter the brain prevents the sudden and severe withdrawal symptoms associated with therapeutics that target the central nervous system.
View Article and Find Full Text PDFJAMA Netw Open
January 2025
San Francisco Department of Public Health, San Francisco, California.
Importance: The rise of high-potency opioids such as fentanyl makes buprenorphine initiation challenging due to the risks of precipitated withdrawal, prompting the exploration of strategies, such as low-dose initiation (LDI) of buprenorphine. However, no comparative studies on LDI outcomes exist.
Objective: To evaluate outpatient outcomes associated with 2 LDI protocols of buprenorphine among individuals with opioid use disorder (OUD) using fentanyl.
Nat Commun
January 2025
Department of Pharmaceutical Sciences, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, CA, US.
The opioid crisis, driven by synthetic opioids like fentanyl, demands innovative solutions. The opioid antidote naloxone has a short action ( ~ 1 hour), requiring repeated doses. To address this, we present a new and simple naloxone prodrug delivery system repurposing a hydrophilic derivative of acoramidis, a potent transthyretin ligand.
View Article and Find Full Text PDFPrehosp Emerg Care
January 2025
Medical College of Wisconsin, Department of Emergency Medicine.
Objectives: Medication for opioid use disorder (MOUD) reduces morbidity and mortality for patients with opioid use disorder (OUD). Recent administrative and legislative changes have made MOUD possible in the prehospital setting. We use an implementation science framework to outline the Reach of a fire department EMS-based Mobile Integrated Health (MIH) prehospital MOUD program.
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