Buprenorphine Research Articles

Trends in injectable buprenorphine prescribing in Canada: A descriptive analysis in five Canadian Provinces

BackgroundInjectable extended-release buprenorphine (BUP-ER) (Sublocade®) is a newer form of opioid agonist therapy (OAT) administered monthly. It was listed on formularies across Canada in February 2020, expanding the options for OAT across the country. This study describes rates of injectable BUP-ER uptake in five provinces to compare access to this novel medication across Canada. MethodsWe conducted a retrospective time-series analysis among individuals who received injectable BUP-ER in British Columbia, Alberta, Saskatchewan, Manitoba, and Ontario from February 1, 2020, to March 31, 2022. The primary outcome was the population-adjusted rate of injectable BUP-ER in each province, with secondary analyses exploring rates by urban/rural location, and the number of prescribers of injectable BUP-ER per 100,000 population. ResultsIn total, 6528 individuals were treated with injectable BUP-ER, with the majority in British Columbia (29.0 %) and Ontario (47.0 %). By March 2022, the rate of BUP-ER use was highest in British Columbia (16.6 per 100,000), and lowest in Ontario (9.1 per 100,000). The rate of BUP-ER use was higher in rural areas (15.5 per 100,000) compared to urban centres (10.6 per 100,000), and British Columbia had the highest rate of prescribers per 100,000 population (5.9) compared to Ontario (2.2), Alberta (2.3), Saskatchewan (3.4) and Manitoba (3.5) by the end of Q1–2022. ConclusionUptake of BUP-ER varied geographically since being approved by Health Canada. More rapid uptake in rural areas is reassuring and suggests that this form of OAT may be supporting treatment access to those with barriers to more traditional treatment formulations.

Buprenorphine for the Treatment of Military-related PTSD With Treatment-resistant Depression and Unexpected Benefit for Chronic Pain: Case Report.

The prevalence of treatment-resistant depression within global and military populations highlights the need for novel treatment approaches beyond monoamine neurotransmitter modulators. Buprenorphine (BUP), a semi-synthetic partial opioid agonist, is approved for the treatment of opioid use disorder and has shown promise in treating both depression and chronic pain. This case report discusses the use of transdermal BUP in treating a 36 year-old man with treatment-resistant depression with prominent anhedonia, military-related posttraumatic stress disorder, and chronic pain because of barosinusitis. Significant reductions in anxious and depressive symptoms, including in anhedonia, were observed with lasting effects. An unexpected finding was the discontinuation of prescribed hydromorphone for pain, suggesting the potential unique benefit of BUP in treating chronic pain and treatment resistant depression comorbidities. These findings implicate the diverse beneficial potential of BUP in psychiatric treatments for military populations.

Abstract MP25: Buprenorphine pharmacotherapy reduces somatic signs of withdrawal in neonates but may not prevent cardiovascular risk in adult offspring with prenatal fentanyl exposure

Long-term effects on the cardiovascular system of offspring exposed to fentanyl in utero are one of the understudied aspects of the opioid crisis. Previously, we have shown that offspring exposed to opioids in utero display exacerbated somatic signs of withdrawal compared to vehicle-exposed offspring. We also showed that prenatal opioid exposure induce long lasting effects increasing blood pressure (BP) in the adult offspring. Buprenorphine (BUP) is one of the most effective FDA-approved standard-of-care therapies used to treat mothers with opioid use disorder and their newborns with neonatal opioid withdrawal syndrome (NOWS). Yet, long-term effects of BUP in the pediatric population is limited. This study aimed to determine the efficacy of BUP in reducing somatic signs of withdrawal in rat neonates and the long-term effects on BP control. Female Sprague-Dawley rat breeders were implanted with a chronic jugular vein catheter and subjected to 2-hr self-administration (SA) sessions of vehicle (VEH, 0.9% NaCl, n=3) or fentanyl (FEN, 2.5 μg/kg/infusion/lever press, n=3). After rats developed dependence, they were paired during proestrus with males for breeding. SA sessions continued until delivery. There were no changes in maternal weight gain and pup weights at birth. At postnatal day 1, a subset of FEN-SA pups was treated with BUP for 5 consecutive days (1 mg/kg, sc). Video recording was performed daily to quantify somatic signs of withdrawal, including body curls, head movements, and spasms. FEN-SA increased withdrawal at postnatal days 1-3. This effect was attenuated in FEN-SA offspring treated with BUP (p<0.05).14-week-old male offspring were implanted with radiotelemetry (n=4 per group). Compared to VEH-SA, FEN-SA offspring showed: 1) increased BP in response to phenylephrine (PE, 40 µg/kg ip), 2) tachycardic response to 1-hour restraint stress followed by impaired BP recovery (p<0.05, respectively), 3) similar acute responses to AngII (30 µg/kg, sc), 4) exacerbated BP and delayed heart rate recovery in response to acute FEN (20 µg/kg, sc, p<0.05), although plasma clearance was similar between groups. BUP treatment in FEN-SA offspring did not influence acute changes in BP or heart rate to different hypertensive stimuli. Taken together our data suggests that an opioid-based therapy effectively reduced somatic signs of withdrawal; however, it does not seem effective in attenuating the acute and chronic BP responses in prenatal fentanyl-exposed offspring.

Pharmacokinetics of Extended-release Buprenorphine and Clinical Efficacy for Postoperative Pain Management in the Domestic Ferret (Mustela putorius furo).

Buprenorphine hydrochloride (Bup-HCl) is a common injectable opioid analgesic. In ferrets, Bup-HCl must be administered every 8 to 12 h to maintain clinical efficacy. Extended-release analgesics offer multiple advantages, including reduced handling and injection frequency, improved compliance, and increased protection from end-of-dose failure. Although efficacy of extended-release buprenorphine formulations has been demonstrated in other species, their use in the domestic ferret has not been investigated. In this study, we evaluated the pharmacokinetics of a compounded polymeric formulation of buprenorphine (Bup-ER) and a pharmaceutical-grade, FDA-indexed liposomal suspension (Bup-XR). Two doses each of Bup-ER (0.12 and 0.2 mg/kg) and Bup-XR (0.2 and 0.6 mg/kg SC) were administered to young adult female ferrets and plasma concentrations were measured between 0 and 96 h (n = 4 animals per timepoint). All doses of both drugs achieved therapeutic plasma levels by 30 min. Furthermore, high-dose Bup-XR maintained therapeutic levels for 72 h, followed by high-dose Bup-ER (less than 48 h), low-dose Bup-XR (24 h), and low-dose Bup-ER (less than 24 h). In this study, we also developed a pain scoring system and utilized this to compare analgesic efficacy between single high-dose Bup-XR (0.6 mg/kg SC) and a standard postoperative course of Bup-HCl (0.02 mg/kg SC every 10 to 12 h for 8 doses) after ovariohysterectomy. Ferrets receiving Bup-XR had significantly lower respiratory rate and posture scores in the first 24 h postoperatively than did those that received Bup-HCl and were less likely to react to palpation of the surgical incision. Of note, ferrets that received high-dose Bup-ER had a significantly higher incidence of injection site reactions than ferrets that received Bup-HCl (P = 0.0137). This study demonstrates that a single dose of Bup-XR (0.6 mg/kg SC) is a safe and effective analgesic in female ferrets, with a duration of action up to 72 h and minimal side effects, offering a refinement to analgesia in this species.

A Randomized Trial Evaluating Acceptance and Commitment Therapy and Smart Phone Care Management Application to Augment Buprenorphine Therapy for Opioid Use and Chronic Pain.

There is high comorbidity of opioid use disorder (OUD) and chronic pain (CP), which is often addressed by prescribing buprenorphine (BUP). While BUP is effective in preventing overdose, it does not address the psychological aspects of OUD and CP comorbidity and treatment retention rates are as low as 50%. The Virtual Opioid use disorder Integrated Chronic Pain Treatment (VOICE) study (NCT05039554) is a novel effectiveness-implementation trial to test a 12-week virtual group Acceptance and Commitment Therapy (ACT) protocol and a care management smartphone application (app; Valera Health) on pain and opioid use in patients with OUD and CP receiving BUP. Using a 2 × 2 factorial design, participants (expected N = 280) are randomized into: ACT, Valera app, ACT + Valera, or Treatment as Usual arm. This study is taking place in the Bronx, NY, a racially/ethnically diverse community that faces numerous socioeconomic stressors and is one of the nation's epicenters of the opioid epidemic. We created a culturally responsive ACT group protocol, and Valera psychoeducational material. Outcome measures include NIH HEAL Common Data Elements and ACT and Valera-specific measures. We are conducting a novel 2 × 2 trial investigating augmenting BUP treatment with ACT and Valera, with the goal that improved mental health and access to care will result in decreased and opioid use and pain interference.

NIR-Remote Selectively Triggered Buprenorphine Hydrochloride Release from Microneedle Patches for the Treatment of Neuropathic Pain.

Neuropathic pain is a prevalent form of intermittent chronic pain, affecting approximately 7-10% of the global population. However, the current clinical administration methods, such as injection and oral administration, are mostly one-time administration, which cannot achieve accurate control of pain degree and drug dose. Herein, we developed near-infrared (NIR) light-responsive microneedle patches (MNPs) to spatiotemporally control the drug dose released to treat neuropathic pain according to the onset state. The mechanism of action utilizes upconversion nanoparticles to convert NIR light into visible and ultraviolet light. This conversion triggers the rapid rotation of the azobenzene molecular motor in the mesoporous material, enabling the on-demand controlled release of a drug dose. Additionally, MNs are used to overcome the barrier of the stratum corneum in a minimally invasive and painless manner, effectively promoting the transdermal penetration of drug molecules. The effectiveness of these patches has been demonstrated through significant results. Upon exposure to NIR light for five consecutive cycles, with each cycle lasting 30 s, the patches achieved a precise release of 318 μg of medication. In a mouse model, maximum pain relief was observed within 1 h of one cycle of NIR light exposure, with the effects lasting up to 6 h. The same level of precise treatment efficacy was maintained for subsequent pain episodes with similar light exposure. The NIR-controlled drugs precision-released MNPs provide a novel paradigm for the treatment of intermittent neuropathic pain.

The effects of buprenorphine and morphine during pregnancy: Impact of exposure length on maternal brain, behavior, and offspring neurodevelopment

The escalating incidence of opioid-related issues among pregnant women in the United States underscores the critical necessity to understand the effects of opioid use and Medication for Opioid Use Disorders (MOUDs) during pregnancy. This research employed a translational rodent model to examine the impact of gestational exposure to buprenorphine (BUP) or morphine on maternal behaviors and offspring well-being. Female rats received BUP or morphine before conception, representing established use, with exposure continuing until postnatal day 2 or discontinued on gestational day 19 to mimic treatment cessation before birth. Maternal behaviors – including care, pup retrieval, and preference – as well as hunting behaviors and brain neurotransmitter levels were assessed. Offspring were evaluated for mortality, weight, length, milk bands, surface righting latency, withdrawal symptoms, and brain neurotransmitter levels. Our results reveal that regardless of exposure length (i.e., continued or discontinued), BUP resulted in reduced maternal care in contrast to morphine-exposed and control dams. Opioid exposure altered brain monoamine levels in the dams and offspring, and was associated with increased neonatal mortality, reduced offspring weight, and elevated withdrawal symptoms compared to controls. These findings underscore BUP's potential disruption of maternal care, contributing to increased pup mortality and altered neurodevelopmental outcomes in the offspring. This study calls for more comprehensive research into prenatal BUP exposure effects on the maternal brain and infant development with the aim to mitigate adverse outcomes in humans exposed to opioids during pregnancy.

Evaluation of the Hepatotoxicity of Buprenorphine in Rat Pups Born to an Exposed Mother During Lactation.

This study aimed to evaluate the hepatotoxicity of buprenorphine in lactating rat pups of buprenorphine-injected mothers. Buprenorphine (BUP), a semisynthetic opioid, is increasingly administrated as a first-line standard maintenance treatment for opioid dependence due to its high safety and efficacy compared to other opioids. Numerous studies have confirmed the safety of BUP maintenance treatment in addicted patients. This study was designed to assess the effects of BUP on the activities of liver enzymes, oxidative parameters, and liver histopathological changes in pups born to a mother exposed to this drug during lactation. BUP at a dose of 0.5 or 0.1 mg/kg was subcutaneously administrated to lactating rats for 28 days. At the end of the experiment, the pups were anesthetized, and blood samples were obtained from their hearts for measuring liver enzymes. Then the livers of the animals were dissected to measure oxidative stress parameters. In addition, the liver samples were fixed for histopathological evaluation. The findings indicated a decrease in the activities of serum liver enzymes (ALT and AST) of the pups born to mothers exposed to 0.5 and 1 mg/kg of BUP during lactation. BUP could not change malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO) levels, nor superoxide dismutase (SOD) activity in the liver tissue of animals. Some vacuolated hepatocytes with dark, eccentric nuclei, necrosis with karyolytic nuclei, mitotic figures, and multiple binucleated cells were seen in the pups which received 1 mg/kg of BUP. In conclusion, BUP may induce liver dysfunction in pups born to mothers exposed to this drug during lactation.

Perceptions around medications for opioid use disorder among a diverse sample of U.S. adults

IntroductionMedications for opioid use disorder (MOUD) including methadone (MMT), buprenorphine (BUP), and naltrexone (NTX) are safe and effective. However, there are significant negative perceptions surrounding MOUD, creating barriers to uptake. While research on MOUD stigma has largely focused on provider and patient experiences, fewer studies have explored MOUD perceptions among the general public. Given that MOUD stigma expressed by social ties surrounding individuals with OUD can influence treatment choices, we assessed MOUD perceptions among U.S. adults to determine how beliefs impacted treatment preference. We further explored how MOUD perceptions may be amplified among racialized groups with histories of experiencing drug-related discrimination. MethodsThe study collected survey data from a diverse sample of U.S. adults (n = 1508) between October 2020 and January 2021. The survey measured knowledge of MOUD and non-medication treatments, relative agreement with common MOUD perceptions, and treatment preferences. Multinomial logistic regression analysis tested associations with treatment preference, stratified by race/ethnicity. ResultsDescriptive results indicated that across groups, many respondents (66.8 %) had knowledge of MOUD, but believed MOUD was a “substitute” for opioids and had some degree of concern about misuse. Multivariable results showed knowledge of non-medication treatments was positively associated with MOUD preference among White (MMT OR = 3.16, 95 % CI = 1.35–7.39; BUP OR = 2.69, CI = 1.11–6.47), Black (MMT OR = 3.91, CI = 1.58–9.69), and Latino/a (MMT OR = 5.12, CI = 1.99–13.2; BUP OR = 3.85, CI = 1.5–9.87; NTX OR = 4.51, CI = 1.44–14.06) respondents. Among White respondents, we identified positive associations between MOUD experience and buprenorphine preference (OR = 4.33, CI = 1.17–16.06); non-medication treatment experience and preference for buprenorphine (OR = 2.86, CI = 1.03–7.94) and naltrexone (OR = 3.17, CI = 1.08–9.28). Concerns around misuse of methadone were negatively associated with methadone preference among White (OR = 0.65, CI = 0.43–0.98) and Latino/a (OR = 0.49, CI = 0.34–0.7), and concerns around misuse of buprenorphine was negatively associated with preference for MOUD among White (MMT OR = 0.62, CI = 0.39–0.99; BUP OR = 0.48, CI = 0.3–0.77; NTX OR = 0.6, CI = 0.36–0.99) and Latino/a (BUP OR = 0.59, CI = 0.39–0.89) respondents. ConclusionsThis analysis offers critical insights into treatment perceptions beyond the patient population, finding that negative beliefs around MOUD are common and negatively associated with preferences for medication-based treatment. These findings highlight implications for public support of evidence-based treatment and lay the groundwork for future interventions addressing public stigma toward MOUD.

Buprenorphine Dosing Through the Pregnancy-to-Postpartum Transition: A Descriptive Analysis [ID 2683589

INTRODUCTION: Supporting continuation of life-saving medications for opioid use disorder (OUD), like buprenorphine (BUP), is imperative through the postpartum period. However, no clinical guidelines exist to inform BUP dosing in this transition. Our study describes BUP dose changes in the first 3 months postpartum and associated patient characteristics in an OUD clinical sample. METHODS: This is a secondary analysis of an IRB-approved retrospective cohort study of pregnant patients with OUD who delivered at an academic medical center, initiated BUP between January 1, 2018, and March 30, 2020, and remained on BUP until at least 3 months postpartum. The primary outcome was change in BUP dose between delivery and 3 months: a categorical variable with three levels (increase, decrease, or no change) abstracted from medical record. Bivariate analysis assessed the relationship between changes in BUP dosage and patient characteristics. RESULTS: In our sample (N=66), about half maintained their BUP dosage through 3 months postpartum (n=36; 55%); the remaining patients decreased (n=22; 33%) or increased their dose (n=8; 12%). 38% of patients incarcerated at delivery increased their dose, whereas 9% of patients not incarcerated increased their dose. 39% of patients who delivered vaginally decreased their dose; 24% of patients who delivered via cesarean section decreased their dose. CONCLUSION: Our study takes a crucial first step in developing the evidence base for the individualization of BUP dosing for postpartum people. Ultimately, we aim to use these data to inform a decision aid to facilitate shared decision-making about BUP dose changes in the pregnancy-to-postpartum transition.

Simplified processing and rapid quantification of buprenorphine, norbuprenorphine, and their conjugated metabolites in human plasma using UPLC-MS/MS: Assessment of buprenorphine exposure during opioid use disorder treatment.

Opioid use disorder (OUD) is a chronic neurobehavioral ailment and is prevalent in pregnancy. OUD is commonly treated with methadone or buprenorphine (BUP). Pregnancy is known to alter the pharmacokinetics of drugs and may lead to changes in drug exposure and response. A simple, specific, and sensitive analytical method for measuring the parent drug and its metabolites is valuable for assessing the impact of pregnancy on drug exposure. A new liquid chromatography-tandem mass spectrometric method that utilized a simple protein precipitation procedure for sample preparation and four deuterated internal standards for quantification was developed and validated for BUP and its major metabolites (norbuprenorphine [NBUP], buprenorphine-glucuronide [BUP-G], and norbuprenorphine-glucuronide [NBUP-G]) in human plasma. The standard curve was linear over the concentration range of 0.05-100 ng/mL for BUP and NBUP, and 0.1-200 ng/mL for BUP-G and NBUP-G. Intra- and inter-day bias and precision were within ±15% of nominal values for all the analytes. Quality controls assessed at four levels showed high recovery consistently for all the analytes with minimal matrix effect. Adequate analyte stability was observed at various laboratory conditions tested. Overall, the developed method is simple, sensitive, accurate and reproducible, and was successfully applied for the quantification of BUP and its metabolites in plasma samples collected from pregnant women in a clinical study assessing BUP exposure during OUD treatment.

Chronic opioid pain treatment converted to buprenorphine: A case series using a 3-step low-dose incremental dosing guideline.

We report a 30-case series from the Pain Management Center at the Massachusetts General Hospital where we have applied a guideline to convert chronic treatment for pain from full agonist opioids (FAO) to buprenorphine (BUP). Of the patients, 24 (80 percent) elected to continue BUP over FAO. Five conversions were stopped for side effects (fatigue) and/or lack of sufficient pain reduction. One patient elected not to participate on the day that the conversion was to begin. There were no major adverse events. We conclude that conversion to BUP should be considered as an alternative to treat patients on chronic opioids for pain.

Performance Evaluation of Multi-Drug Rapid Test for Rapid Detection of Multiple Drugs and Drug Metabolites in Human Blood Samples

Objective: The Multi-Drug Rapid Test Cassette, developed by Hangzhou AllTest Biotech Co., Ltd, is a rapid chromatographic immunoassay designed for the qualitative detection of multiple drugs and drug metabolites in human whole blood, serum, or plasma. It aims to simultaneously detect various abused substances, including Amphetamine (AMP), Barbiturates (BAR), Benzodiazepines (BZO), Buprenorphine (BUP), Cocaine (COC), Cannabis (THC), Methadone (MTD), Methamphetamine (MET), 3,4-Methylenedioxymethamphetamine (MDMA), Morphine (MOP/OPI), Propoxyphene (PPX), Tricyclic antidepressants (TCA), Oxycodone (OXY), 2-Ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), Cotinine (COT), Tramadol (TML), Fentanyl (FYL), 3,4-Methylenedioxy pyrovalerone (MDPV), Synthetic cannabinoids(K2), Phencyclidine(PCP), Ketamine(KET), Lysergic acid diethylamide(LSD), 3,4-Methylenedioxyamphetamine(MDA), Acetaminophen(ACE), Ketamine(CAT), 6-Monoacetylmorphine (6-MAM), Zolpidem (ZOL), AB-PINACA (ABP/K3). Therefore, the present research was done to evaluate the diagnostic performance of this test. Material and Method: In this study, the accuracy, precision, and sensitivity of the drug testing methods were assessed. Approximately 100 specimens of each drug, obtained from previous drug screening tests, were tested. The results were compared to confirmatory analysis using GC/MS, and the accuracy of the testing was determined based on the comparative classification results. The evaluation of precision included measuring the consistency of measurements within a single run, between different runs, and among different operators, using the AllTest multi-drug detection tool across three different hospitals and three different batches. To evaluate the sensitivity of the detection method, various concentrations of drugs were added to a pool of whole blood, serum, or plasma without any drugs. The positive and negative results obtained from the testing were analyzed to assess the method’s ability to detect drugs at different concentrations. Results: In this study, we evaluated the performance of the Multi-Drug Rapid Test Cassette developed by Hangzhou AllTest Biotech Co., Ltd. The results demonstrated excellent performance of the test in terms of accuracy, sensitivity, and precision. Conclusion: The Multi-Drug Rapid Test Cassette developed by Hangzhou AllTest Biotech Co., Ltd exhibited reliable detection of multiple drugs and drug metabolites, providing trustworthy results for drug abuse screening. These findings have significant implications for drug control and monitoring, as well as supporting the broad application of this test in clinical and legal settings.

Sex specific effects of buprenorphine on adult hippocampal neurogenesis and behavioral outcomes during the acute phase after pediatric traumatic brain injury in mice

Traumatic brain injury (TBI) in children often causes cognitive and mental dysfunctions, as well as acute and chronic pain. Adult hippocampal neurogenesis plays a key role in cognition, depression, and pain. Adult hippocampal neurogenesis can be modulated by genetic and environmental factors, such as TBI and opioids. Buprenorphine (BPN), a semisynthetic opioid, is commonly used for pain management in children, however, the effects of BPN on adult hippocampal neurogenesis after pediatric TBI are still unclear. This study investigated the sex-specific effects of BPN on adult hippocampal neurogenesis during acute phase after pediatric TBI. Male and female littermates were randomized on postnatal day 20–21(P20-21) into Sham, TBI+saline and TBI+BPN groups. BPN was administered intraperitoneally to the TBI+BPN mice at 30 min after injury, and then every 6–12 h (h) for 2 days (d). Bromodeoxyuridine (BrdU) was administered intraperitoneally to all groups at 2, 4, 6, and 8-h post-injury. All outcomes were evaluated at 3-d post-BrdU administration. We found that TBI induced significant cognitive impairment, depression, and reduced adult hippocampal neurogenesis in both male and female mice, with more prominent effects in females. BPN significantly improved adult hippocampal neurogenesis and depression in males, but not in females. We further demonstrated that differential expressions of opioid receptors, transcription factors and neuroinflammatory markers at the neurogenic niche might be responsible for the differential effects of BPN in males and females. In conclusion, this study elucidates the effects of BPN on adult hippocampal neurogenesis and behavioral outcomes at the acute phase after pediatric TBI.

Perinatal morphine but not buprenorphine affects gestational and offspring neurobehavioral outcomes in mice

Within the national opioid epidemic, there has been an increase in the number of infants exposed to opioids in utero. Additionally, opioid agonist medications are the standard of care for women with opioid use disorder during pregnancy. Buprenorphine (BUP), a partial µ -opioid receptor agonist, has been successful in improving gestational and neonatal outcomes. However, in utero exposure has been linked to childhood cognitive and behavioral problems. Therefore, we sought to compare offspring cognitive and behavioral outcomes after prenatal exposure to a clinically relevant low dose of BUP compared to morphine (MO), a full µ -opioid receptor agonist and immediate metabolite of heroin. We used a mouse model to assess gestational and offspring outcomes. Mouse dams were injected once daily s.c. with saline (SAL, n = 12), MO (10 mg/kg, n = 15), or BUP (0.1 mg/kg, n = 16) throughout pre-gestation, gestation, and lactation until offspring were weaned on postnatal day (P)21. Offspring social interaction and exploratory behavior were assessed, along with executive function via the touchscreen 5 choice serial reaction time task (5CSRTT). We then quantified P1 brain gene expression in the frontal cortex and amygdala (AMG). Perinatal MO but not BUP exposure decreased gestational weight gain and was associated with dystocia. In adolescent offspring, perinatal MO but not BUP exposure increased social exploration in males and grooming behavior in females. In the 5CSRTT, male MO exposed offspring exhibited increased impulsive action errors compared to male BUP offspring. In the AMG of P1 MO exposed offspring, we observed an increase in gene expression of targets related to activity of microglia. Importantly, both MO and BUP caused acute hyperlocomotion in the dams to a similar degree, indicating that the selected doses are comparable, in accordance with previous dose comparisons on analgesic and reward efficacy. These data suggest that compared to MO, low dose BUP improves gestational outcomes and has less of an effect on the neonatal offspring brain and later adolescent and adult behavior.

Characteristics, treatment patterns and retention with extended-release subcutaneous buprenorphine for opioid use disorder: A population-based cohort study in Ontario, Canada

BackgroundUptake and retention for opioid agonist treatment (OAT) remains low. Novel extended-release formulations may improve OAT accessibility by reducing the frequency of healthcare visits. Our aim was to examine uptake, characteristics, treatment patterns and retention of individuals initiating extended-release subcutaneous buprenorphine (BUP-ER), a monthly injectable OAT. MethodsWe conducted a population-based cohort study among adults aged 18+ initiated on BUP-ER between February 3, 2020 and March 31, 2022 in Ontario, Canada. Using administrative health data, we defined continuous BUP-ER use based on repeat injections within a 56-day period and used Kaplan-Meier curves to estimate time on treatment. Among new BUP-ER recipients, we described individual and prescriber characteristics, healthcare utilization and treatment patterns. Results2366 individuals initiated BUP-ER. The median time to BUP-ER discontinuation was 183 days (interquartile range: 66–428 days) and 52.0% of individuals were co-prescribed buprenorphine/naloxone at least once throughout the period of BUP-ER receipt. Among individuals who initiated on a dose of 300mg BUP-ER and had three or more injections, 18.8% continued to receive only 300mg doses (N=276 of 1470). Furthermore, 28.6% of those whose dose was reduced to 100mg (N=341 of 1194) had a subsequent dose increase to 300mg. ConclusionsOn average, people initiating BUP-ER discontinue within the first 6 months of treatment. While BUP-ER is likely providing an important OAT option, the high occurrence of discontinuation, supplementation with buprenorphine/naloxone, and frequent dose increases suggest inadequacy of current dosing recommendations among a proportion of individuals.

Legislative and regulatory barriers to pharmacies dispensing buprenorphine for OUD.

Buprenorphine (BUP) is increasingly recognized and utilized as a valuable medication for the treatment of opioid use disorder. This article focuses on the problem of regulatory restrictions on access to buprenorphine products without naloxone (mono-product), involving patients in one geographic area, but which may represent a more general access problem in the United States. In response to an audit by the Tennessee Board of Pharmacy, a pharmacy in northeast Tennessee designed a questionnaire to survey patient motivation for traveling long distances to fill their prescriptions for BUP, rather than buprenorphine/naloxone (BNx, combo-product), and to document their satisfaction with treatment with the mono-product. Questionnaires were submitted by 194 patients, living in northeast Tennessee, southwest Virginia, and southeast Kentucky. Significant, intolerable, side effects were reported by all patients in the survey prescribed BNx, but because of legislative and regulatory restrictions in their respective states, they were unable to obtain BUP closer to home. Consequently, they were required to drive significant distances from their homes to fill their prescriptions, a median distance of 52 miles, and in some cases as far as 216 miles round trip. Intolerable reactions included severe headaches, nausea and vomiting, allergies, and severe dysphoria. All patients tolerated BUP and were clinically well maintained on the mono-product. Severe, intolerable reactions/side effects from the naloxone component of BNx are not uncommon, but legislative and regulatory restrictions on the mono-product prohibit providers and pharmacies in some states from prescribing and dispensing BUP. The participants in this qualitative study found it necessary to travel significant distances to obtain their prescribed medication, thereby potentially limiting access to this life-saving therapy.

A-377 The Selection and Implementation of POC Illicit Drug Toxicology Testing in Hamad Medical Corporation - Doha, Qatar

Abstract Background In 2013, Qatar launched the National Mental Health Strategy which is further supported by National Health Strategy 2018–2022 and Qatar National Vision 2030, where the mental health has been identified as a priority area of development. In doing so, the Ministry of Public Health worked closely with the Ministry of Interior in providing the appropriate treatment rehabilitation. With all considerable advantages of point-of-care testing (POCT) in rapid diagnosis, POC toxicological test has been implemented and used in screening of patients for drugs of abuse. In this study, we highlighted the challenges in selection and implementation process of POC toxicological test in Hamad Medical Corporation (HMC). Methods Due to unavailability of all required drug panels, it had to be customized and tested for the verification purpose before starting the evaluation process. Maintaining HMC procurements regulations and Clinical Laboratory Improvement Amendments (CLIA) and College of American Pathologist (CAP) standards for POC toxicology tests, two POC illicit drug toxicology screening tests has been evaluated, comparison study has been performed against the HMC central laboratory. POCT team conducted training session ensuring the appropriate practice in place. The Extendable Laboratory Information System (LIS) functionality has been utilized for seamless data management and reporting for the automated analyzer. Results QUIDEL triage meter pro is an automated drug testing analyzer which detects Amphetamines, Barbiturates, Benzodiazepines, Cannabinoids, Methadone Metabolite, Methamphetamine, Opiates, Tricyclic and Cocaine Metabolites, while the customized manual testing kit FASTEP detects Tramadol (TRA), Methylenedioxymeth-amphetamine (MDMA), Phencyclidine (PCP), Buprenorphine (BUP), Oxycodone (OXY), Fentanyl (FYL), Ethyl Glucuronide (EtG), Cotinine (COT), Pregabalin (PGB) and Gamma Hydroxybutyrate (GHB). Both analytical performances were verified. Rapid bedside testing performed for more than 100 patients in last 8 months during admission, observation, and pre- discharge process. There is An Obvious improvement observed in testing turnaround time compared to the laboratory, easy results interpretation and reporting as well as cost-effective. Conclusion The implementation of POC illicit drug toxicology testing in HMC aligned with core pillars of the Qatar vision 2030 to deliver the right treatment at the right time and place. Its enhancing patient outcomes and overall Satellite health care sector in Qatar.

Sex-Specific Effects of Buprenorphine on Endoplasmic Reticulum Stress, Abnormal Protein Accumulation, and Cell Loss After Pediatric Mild Traumatic Brain Injury in Mice.

Traumatic brain injury (TBI) in children often leads to poor developmental outcomes attributable to progressive cell loss caused by secondary injuries, including endoplasmic reticulum (ER) stress. Buprenorphine (BPN) is commonly used in children for pain management; however, the effects of BPN on ER stress in the pediatric population are still inconclusive. This study investigated the sex-specific effects of BPN on ER stress, abnormal protein accumulation, and cell loss in a mouse impact acceleration model of pediatric TBI. On post-natal day 20-21 (P20-21), male and female littermates were randomized into sham, TBI + saline and TBI + BPN groups. BPN (0.075 mg/kg) was administered to TBI + BPN mice at 30 min after injury and then every 6-12 h for 2 days. The impact of BPN was evaluated at 1, 3, and 7 days post-injury. We found that TBI induced more prominent ER stress pathway activation at 1 and 3 days post-injury in males, compared to females, whereas abnormal protein accumulation and cell loss were more severe in females at 7 days post-injury, compared with males. Although BPN partially ameliorated abnormal protein accumulation and cell loss in both males and females, BPN only decreased ER stress pathway activation in males, not in females. In conclusion, BPN exhibits sex-specific effects on ER stress, abnormal protein accumulation, and cell loss in a time-dependent manner at the acute phase after pediatric TBI, which provides the rationale to assess the potential effects of BPN on long-term outcomes after pediatric TBI in both males and females.

Solubility of buprenorphine hydrochloride in supercritical carbon dioxide: Study on experimental measuring and thermodynamic modeling

Nowadays, supercritical fluids (SCFs) technologies present a processing option for obtaining new products with noteworthy characteristics. Access to reliable solubility data of pharmaceutical compounds in SCFs is considered as the first step for recrystallizing, separating, and producing nano particles via processes based on this type of technique. In this study, high-pressure solubility of buprenorphine hydrochloride, a strong pain reliever, in supercritical carbon dioxide (scCO2) was measured at temperature and pressure conditions of 308–338 K and 120–270 bar, for the first time. The minimum and maximum solubility values, in terms of equilibrium mole fractions, were found to be 0.131 × 10-4 (at 338 K and 120 bar) and 4.752 × 10-4 (at 338 K and 270 bar), respectively. Thereafter, the obtained data were correlated using two different approaches, namely Peng-Robinson (PR) equation of state (EoS) and a set of semi-empirical models. Results from applying statistical criteria indicated that Jouyban and Sodeifian models are suitable choices for predicting solubility data. Furthermore, using the obtained correlation results, the total and vaporization enthalpies of buprenorphine hydrochloride dissolution in scCO2 were estimated to be 65.59 and 85.60 kJ/mole, respectively.