Medications for opioid use disorder (MOUD) have reduced fentanyl-related mortality by approximately 20% over the past five years. However, MOUD-associated dental caries has become an important clinical concern that may negatively affect treatment adherence, patient quality of life, and long-term treatment outcomes as the number of patients receiving MOUD continues to rise. Two key questions remain unresolved: (1) Why are buprenorphine (BUP) and methadone (MTD) associated with dental complications, whereas naltrexone (NLX) carries a substantially lower risk? (2) Why do transmucosal BUP formulations, including sublingual and buccal products, appear to pose a greater risk of dental injury than other MOUD products? To address these questions, this review evaluates MOUD-associated dental problems from two perspectives: formulation-related factors and drug-related factors, with an emphasis on the role of drug administration routes. From the formulation perspective, acid excipients used in transmucosal formulations can directly alter the oral microenvironment by reducing local pH and saliva buffering capacity, leading to increased enamel demineralization. These acid excipients may also indirectly affect oral health by supporting cariogenic bacterial growth, altering bacterial metabolism, and facilitating biofilm formation. From the drug perspective, opioid receptor agonists or partial agonists may impair salivary secretion and alter oral fluid composition, whereas BUP may persist in oral fluid at high levels and accumulate in salivary glands following transmucosal dosing. Overall, MOUD-associated dental injury should be understood as a multifactorial process involving baseline oral-health vulnerability, the unique transmucosal delivery route, drug-related factors, and formulation-related factors. Importantly, comprehensive oral health care will improve patients' life quality, leading to better adherence, suggesting that understanding and preventing this adverse effect may improve adherence and long-term clinical outcomes. Among available MOUDs, transmucosal BUP provides a clinically relevant model for addressing current mechanistic gaps and developing preventive, formulation-based, and administration route-informed interventions.

In recent years, numerous countries have recorded a steady increase in opioid use. Although prescribing practices vary considerably among them, fentanyl is among the most frequently prescribed strong opioids in several European countries and in Spain. In this study, we analyzed the evolution of outpatient fentanyl dispensing in Galicia, Spain, between January 2019 and December 2025, using the Anatomical Therapeutic Chemical Classification/Defined Daily Dose (ATC/DDD) system. We paid particular attention to differences between provinces and explored temporal trends broken down by route of administration (buccal, nasal, sublingual and transdermal). Dispensing data were obtained from the General Sub-directorate of Pharmacy of the Galician Health Service (SERGAS) from the monthly billing database of official prescriptions dispensed in Galician pharmacies and were expressed as defined daily dose per 1000 inhabitants per day (DID). Dispensing rates between provinces were compared using the non-parametric Kruskal-Wallis test, considering a p-value less than 0.05 as statistically significant. We observed an increase in fentanyl use between 2019 and 2021, followed by a systematic decrease during the 2022-2025 period. Significant differences (p < 0.001) were found in the defined daily dose per 1000 inhabitants per day (DID) among the four Galician provinces, and demographic and socioeconomic factors partially explain the observed disparities. Regarding pharmaceutical presentations, transdermal patches were the most frequently used form during the study period. While some limitations should be noted, the results suggest that the observed decrease in fentanyl dispensing in Galicia could be associated with the implementation of the Ministry of Health's 2021 optimization plan, with a sustained reduction in its dispensing from 2022 onwards. However, it is necessary to maintain pharmacovigilance at the provincial level.

In this review, our intention was to shed some light on the history of sublingual and buccal delivery over the past 75 years. By searching the query sublingual and buccal, we noticed four steady growth periods in the number of publications between 1950 and 2025. The early phase of sublingual and buccal drug delivery (1950-1982) saw limited attempts to explore this delivery route. The exploratory growth phase (1983-1993) was marked by the use of nitroglycerin to treat angina, calcium channel blockers to treat hypertension, ACE inhibitors to treat heart conditions, the use of opioids in pain management therapy, and peptide and hormonal therapy. The diversification and discovery phase (1994-2009) was marked by the introduction of small molecules for the treatment of opioid use disorder and analgesia, the use of animal models to enhance the pharmacokinetic understanding of the sublingual and buccal route, the use of penetration enhancers, peptide and hormonal therapy, and few marked FDA drug approvals in this area. The innovation and integration phase (2010-2025) was marked by the use of nanoparticles, multilayered mucoadhesive systems, pediatric formulations (fast-dissolving films and tablets), immunotherapy and vaccine delivery, and a broad spectrum of therapeutic agents, such as steroids, antifungals, cannabinoids, antidepressants, antipsychotics, and narcotics (e.g., buprenorphine and apomorphine), novel formulations of fentanyl and diazepam for pain and seizure control, and the introduction of buccal vitamin D3 sprays. Understanding the history of sublingual and buccal delivery demonstrates a growing area of research focused on enhancing mucosal drug delivery for achieving local and systemic therapeutic benefits.

BACKGROUND This study assessed the effects of buccal acupuncture on perioperative analgesia and serum inflammatory factors in patients undergoing laparoscopic gynecological surgery. MATERIAL AND METHODS Eighty patients who underwent elective laparoscopic gynecological surgery were selected and randomly allocated to the control and buccal acupuncture groups, with 40 patients in each group. Hemodynamic indices and dosages of propofol, remifentanil, sufentanil, and vasoactive drugs used during the surgery were recorded. We collected the Ramsay sedation score (RSS) and visual analog scale (VAS) scores of the patients at T4. Magnetic-sensitive immunoassay kits were used to measure plasma IL-6, SAA, CRP, and PCT concentrations in the venous blood at T0, T3, and T5. RESULTS The average dosage of sufentanil in the control group was significantly higher than that in the buccal acupuncture group (P<0.05). There were no statistically significant differences in the dosages of remifentanil and propofol or in the usage rates of urapidil, phenylephrine, atropine, and metoprolol between the 2 groups (all P>0.05). Furthermore, there were no statistically significant differences in SBP, DBP, HR, and MAP at T0-T5 (all P>0.05). There were no statistically significant differences in IL-6, SAA, CRP, or PCT levels at T0, T3, or T5 (all P>0.05). At T4, the RSS and VAS pain scores were similar (all P>0.05). CONCLUSIONS Buccal acupuncture therapy for laparoscopic gynecological surgery can reduce the dosage of sufentanil and does not aggravate fluctuations in hemodynamic indices, inflammatory responses, or the incidence of adverse reactions. This has practical clinical significance in reducing the burden on patients.

The opioid overdose epidemic remains a critical public health crisis. In recent years, synthetic opioids like fentanyl and nitazenes, have driven a sharp rise in deaths. Naloxone, an opioid receptor antagonist, has been established as a key intervention for reversing opioid overdoses and saving lives. However, there remains a critical need to optimize naloxone dosing strategies. This article examines the challenges of both under-dosing and over-antagonism in naloxone administration, emphasizing the importance of a tailored approach to overdose management. A 'just the right dose' approach is essential for minimizing the risks of over-antagonism while still reversing opioid overdose. This involves starting with a modest naloxone dose and carefully titrating it based on the patient's response, considering factors such as opioid type, overdose severity, and opioid tolerance. A tailored approach to naloxone dosing may present challenges for non-medically trained responders but it can ensure that as many people as possible receive the right dose of naloxone when they need it. Training programs should also emphasize the importance of first aid and supportive care, including airway management and alerting emergency services, as well as careful monitoring of the patient's response.

The opioid crisis has claimed approximately one million lives in the United States since 1999, underscoring a significant public health concern. This surge in opioid use disorder (OUD) fatalities necessitates improved therapeutic options. Current OUD therapies often require daily clinical visits, leading to poor patient compliance and high costs to the health systems. Levo-alpha-acetylmethadol (LAAM) is a long-lasting OUD drug, and the thrice-weekly oral LAAM solution can offer better patient compliance compared to the traditional daily methadone therapies. However, LAAM is FDA-approved but withdrawn from the market. As part of the NIH HEAL Initiative, we aim to reintroduce LAAM back to the market to improve OUD therapeutic options by developing a novel Janus LAAM-loaded fibrous buccal film (LFBF) formulation made of a drug-containing electrospun fibrous layer and a backing layer. The buccal administration of LFBF exhibited superior transmucosal delivery of LAAM to systemic circulation with a nearly 4-fold higher drug bioavailability than the conventional oral LAAM solution in rabbits. Furthermore, upon buccal administration in an opioid-dependent rat model, the LFBF significantly decreased fentanyl choice in the fentanyl-dependent rats, while the conventional oral LAAM solution did not at the same dose. Both the buccal film and oral solution of LAAM reduced somatic withdrawal signs in the experimental animals. These findings highlight the buccal delivery of LAAM using electrospun fibers as a promising strategy with improved drug bioavailability. Furthermore, it sheds light on future clinical applications aiming for enhanced treatment outcomes in the battle against the current opioid crisis.

Pain is one of the most burdensome symptoms in people with cancer, and opioid analgesics are considered the mainstay of cancer pain management. For this review, the authors evaluated the efficacy and toxicities of opioid analgesics compared with placebo, other opioids, nonopioid analgesics, and nonpharmacologic treatments for background cancer pain (continuous and relatively constant pain present at rest), and breakthrough cancer pain (transient exacerbation of pain despite stable and adequately controlled background pain). They found a paucity of placebo-controlled trials for background cancer pain, although tapentadol or codeine may be more efficacious than placebo (moderate-certainty to low-certainty evidence). Nonsteroidal anti-inflammatory drugs including aspirin, piroxicam, diclofenac, ketorolac, and the antidepressant medicine imipramine, may be at least as efficacious as opioids for moderate-to-severe background cancer pain. For breakthrough cancer pain, oral transmucosal, buccal, sublingual, or intranasal fentanyl preparations were identified as more efficacious than placebo but were more commonly associated with toxicities, including constipation and nausea. Despite being recommended worldwide for the treatment of cancer pain, morphine was generally not superior to other opioids, nor did it have a more favorable toxicity profile. The interpretation of study results, however, was complicated by the heterogeneity in the study populations evaluated. Given the limited quality and quantity of research, there is a need to reappraise the clinical utility of opioids in people with cancer pain, particularly those who are not at the end of life, and to further explore the effects of opioids on immune system function and quality of life in these individuals.