Buprenorphine (BUP) offers a therapeutic approach for opioid use disorder (OUD) due to its unique pharmacodynamic properties, primarily as a partial agonist with high affinity for the mu-opioid receptor (MOR). BUP's partial agonism and ceiling effect on respiratory depression enhance its safety profile. However, BUP can induce precipitated withdrawal when administered after a full agonist, leading to severe withdrawal symptoms. This Perspective builds on prior work that has linked BUP's high-affinity partial agonism to precipitated withdrawal and low-dose induction strategies. We focus on how BUP's capacity to promote MOR externalization, together with its activity at the nociceptin opioid peptide (NOP) receptor, can help explain why it precipitates withdrawal when administered in the presence of full agonists yet relieves withdrawal once spontaneous withdrawal has begun. Understanding these mechanisms is critical for optimizing BUP protocols in OUD treatment and informs the potential development of new biased MOR agonists (i.e., ligands that preferentially activate specific signalling pathways) for addiction therapy.

Buprenorphine (BUP) is widely used in the treatment of neonatal opioid withdrawal syndrome (NOWS). However, the most compounded formulation contains 30% ethanol, despite regulatory and clinical concerns regarding ethanol exposure in pediatric patients. Thus, this research aimed to develop an ethanol-free sublingual (SL) gel formulation of BUP that would be safe, stable, and suitable for NOWS. Multiple polymers were screened as gelling agents, with hydroxypropyl methylcellulose (HPMC) emerging as the ideal base polymer for the formulation due to its optimal pH, rheological characteristics, and stability. The formulated gels were stored at room temperature and refrigerated conditions for 30 days and evaluated for stability using pH, rheology, and liquid chromatography-mass spectrometry. BUP content was between 90-110% of the labeled amount of the dosage form (75 µg/mL) at all time-points, and the pH remained close to physiological values. Release studies demonstrated a drug release of 23-24% for SL gels without surfactants stored at room temperature and refrigerated conditions, respectively. Incorporation of non-ionic surfactants (Tween 20 and Tween 80) significantly increased drug release to 33% and 40%, respectively, reflecting enhanced solubilization and improved mucosal penetration. The ethanol-free formulation demonstrated physicochemical stability and favorable release characteristics suitable for neonatal administration. These findings represent a meaningful advance in the development of safer pediatric formulations for NOWS.

Background The rising prevalence of fentanyl has complicated buprenorphine (BUP) initiation due to increased risks for precipitated withdrawal. Low-dose initiation (LDI), or “micro-dosing”, has been proposed as an alternative to standard-dose initiation (SDI) to improve tolerability and engagement with care. This study aimed to compare inpatient and post-discharge outcomes of LDI versus SDI among patients with opioid use disorder (OUD) undergoing medically managed withdrawal. Methods This retrospective cohort study included adults admitted for medically managed OUD withdrawal during two time periods: SDI (February 2020–April 2021) and LDI (May 2021–August 2022). Sociodemographic, clinical, and treatment data were extracted from electronic medical records. Outcomes included inpatient length of stay (LOS), BUP acceptance and discharge dose, transition to rehabilitation, readmissions within one year, BUP refill rates, and outpatient treatment engagement. Analyses included logistic regression and negative binomial regression with adjustment for baseline urine drug screen results. Results The sample included 184 patients (127 SDI, 57 LDI) with a mean age of 37 years, predominately White N=140 (76.1%) and female. Groups were demographically similar. Inpatient outcomes did not differ in LOS, BUP acceptance, or discharge dose. The LDI group was less likely to transition to rehabilitation (26% vs 48%). LDI was associated with significantly lower odds of readmission within 1 year, while 30-day readmission rates showed a similar directional trend that did not reach statistical significance. Post-discharge BUP refill rates and outpatient attendance rates were similar between groups. Conclusions LDI and SDI produced comparable outcomes across most measures, with LDI associated with fewer readmissions over one year. Both approaches appear to be viable strategies in the fentanyl era.

Anecdotal accounts suggest an increase in problems initiating buprenorphine (BUP) treatment among individuals using illicitly manufactured fentanyl. Limited empirical data illuminate these challenges. To determine the prevalence of clinician-reported problems initiating BUP treatment among patients using fentanyl and describe clinical strategies used to overcome engagement challenges. For this survey study, an online survey was pilot tested and refined with a convenience sample of physicians. The final survey included 96 items and took less than 15 minutes to complete. The survey queried patients' use of fentanyl, BUP induction problems (precipitated or prolonged withdrawal), strategies to overcome induction problems, clinician characteristics, and practice characteristics. Eligible clinicians initiated BUP for at least 10 patients with opioid use disorder in the past year and at least 1 patient in the past 90 days. The survey was live from June 2, 2023, to March 18, 2024. The main outcome of interest was precipitated and/or prolonged opioid withdrawal. Descriptive statistics are reported, and logistic regression was used to identify factors associated with BUP initiation problems. A random sample of physicians and advanced practice clinicians in the US Drug Enforcement Administration (DEA) registrant dataset from October 2022 (n = 3141) were invited to participate; of 2485 eligible for inclusion, 649 (26.1%) completed the prescreen survey. Of 421 (64.9%) eligible to complete the survey, the final sample included 396 (94.1%) clinicians who completed at least 50% of the survey items. Of 390 participants, 284 (72.8%) reported problems when initiating BUP in patients using fentanyl, with 242 of 394 (61.4%) reporting patients' experiencing precipitated withdrawal. A total of 264 or 392 participants (67.3%) reported modifying their standard induction procedures, changing how they counsel patients, or changing both medication and counseling protocols. In multivariable modeling, clinicians were more likely to report problems initiating BUP in patients if they had a DEA waiver to treat more than 100 patients (OR, 1.92; 95% CI, 1.08-3.40), vs those waivered to treat fewer patients; if they reported at least 75% of their patients using fentanyl (OR, 6.31; 95% CI, 2.59-15.35), vs no patients; or if they inducted patients in noninpatient settings (OR, 2.79; 95% CI, 1.39-5.61), vs inpatient settings. In this survey study of clinician-reported problems initiating BUP treatment, clinicians working in high-volume noninpatient settings reported more problems initiating BUP in patients using fentanyl, and many reported changing their clinical practices in response to these problems. Further research is warranted to match alternate BUP induction strategies by clinical settings.

Opioid use disorder (OUD) during pregnancy is a leading contributor to peripartum morbidity and mortality, with overdose deaths rising significantly in recent years. Despite the identification of various factors associated with overdose events, including social, demographic, psychiatric, and neonatal outcomes, the relative contributions of these factors to peripartum overdose history (or lack thereof) remain unclear. Thus, this study aims to characterize factors associated with lifetime opioid-involved overdose events among currently pregnant individuals receiving buprenorphine (BUP) treatment for OUD. Treatment-seeking pregnant individuals with an estimated gestational age of 6 to 30 weeks were enrolled in a large multisite randomized controlled trial evaluating 2 BUP formulations for OUD. Participant baseline demographic, substance use, and mental health data were collected using validated measures, and random forest modeling identified key factors associated with lifetime opioid overdose events. The 140 pregnant participants (Mage = 31.2 years, SD = 4.7; 87.1% White) reported an average of 8.7 years (SD = 5.8) of opioid use, with 92.1% endorsing lifetime prescription opioid use and 82.9% reporting heroin use. The average lifetime number of nonfatal opioid overdose events was 4.8 (SD = 12.1); an overdose was reported by 55% of the sample (n = 77). Random forest analysis (area under the receiver operating characteristic curve = 0.797) incorporating sociodemographic, substance use, and mental health characteristics found that the most important factors associated with lifetime overdose events were, in order, lifetime heroin use, trauma exposure, reliance on partners or parents for financial support, depressive symptoms, and lifetime cocaine use. These findings underscore the critical need to address substance use, co-occurring mental health, and socioeconomic challenges that are associated with previous opioid overdose. Identifying and targeting key modifiable overdose risk factors can inform the development of tailored interventions to improve outcomes for this population.

Real-world longitudinal treatment trajectories following opioid use disorder diagnosis among commercially insured beneficiaries in the United States.

Buprenorphine (BUP), a partial mu-opioid receptor (MOR) agonist, is an effective analgesic and is standard-of-care for treating opioid use disorder (OUD). Transitioning from full MOR agonists to stable BUP dosing can be challenging as some patients experience BUP-precipitated opioid withdrawal (BPOW) due to its ability to displace full MOR agonists. To improve patient tolerability low-dose BUP initiation protocols deliver small, progressively escalating BUP doses, allowing gradual displacement of other opioids and replacement with BUP. We describe a case series using a novel intravenous BUP "micro-infusion" protocol for rapid medication transition with no patients meeting the operational criteria for BPOW. A retrospective case series of patients who received an 8-hour 1200mcg BUP infusion (150mcg/hr) and one (or more) sublingual BUP doses after medical or nonmedical full MOR agonist administration. Variables included demographic characteristics, presence of OUD, opioid medications, BUP continuation/prescription fill rates, and evidence of BPOW based on Clinical Opiate Withdrawal Scale (COWS) scores. Of 23 patients included, 8 presented with current OUD (34.8%) and 15 were treated with full MOR agonists for analgesia (65.2%) before BUP micro-infusion. There were no instances of BPOW. Among the 8 patients with OUD, 5 (62.5%) continued sublingual BUP and filled their prescription for BUP upon discharge. Overall, the 8-hour intravenous 1200mcg BUP micro-infusion protocol was well-tolerated with no clinically apparent cases of BPOW and similar rates of continued sublingual BUP treatment post-discharge among patients with OUD compared with other low-dose BUP initiation protocols.

Methadone (MET) and buprenorphine (BUP)-mu-opioid receptor (MOR) agonists-are efficacious treatments for opioid use disorder (OUD). Using high-sensitivity, long axial field-of-view PET imaging with [ 11 C]carfentanil, we compared MOR availability in 5 MET and 5 BUP patients and 13 healthy controls (HCs) in five brain regions: ventral tegmentum, thalamus, caudate, putamen, and amygdala. MOR availability differed across groups (F 10,34 =5.6, p<0.001) and was lower in BUP patients than HCs across all brain regions (mean reduction=39.1±15.2%; p<0.001), lower in MET patients than HCs in the ventral tegmentum and amygdala (p's<0.05), and lower in BUP than MET patients in four of five regions (p's<0.05). MOR availability was inversely related to serum drug levels, linear for MET (R²=0.83, linear) and logarithmic for BUP (R²=0.96). [ 11 C]carfentanil PET may be useful in guiding personalized OUD treatment based on receptor engagement, which differs significantly between the two opioid agonist treatments. Studies are needed to link MOR availability with specific clinical characteristics (e.g., hedonic capacity, MOR agonist-associated weight gain) and OUD treatment outcomes.

Hospitalization and emergency department (ED) visits are an underutilized opportunity to reach high-risk patients with opioid use disorder (OUD) with buprenorphine (BUP) treatment and reduce the ongoing and widespread treatment gap. Monthly extended-release BUP (XR-BUP) potentially facilitates successful initiation and delivers sustained treatment. XR-BUP provides up to 30 days of medication for opioid use disorder (MOUD) with each administration and could improve retention in care during transition to outpatient addiction treatment. We aim to describe the patient characteristics and clinical outcomes of hospitalized and ED patients with OUD treated with monthly XR-BUP. We conducted a retrospective chart review of a cohort of ED or hospitalized patients who received monthly XR-BUP at an urban, safety-net hospital over a 6-month period from September 2023 through March 2024. There were 61 patient encounters where XR-BUP was administered. Within 30 days of discharge, 40/61 (65.6%) patients who received XR-BUP engaged in outpatient addiction treatment through an in-person or telemedicine provider visit; within 45 days, 29/61 (47.5%) patients received a subsequent XR-BUP. Thirty-eight (62.3%) initiated XR-BUP with low-dose initiation of sublingual buprenorphine with full agonist opioid continuation, 20 (32.8%) started after high-dose sublingual buprenorphine, 2 (3.3%) after low-dose initiation of IV buprenorphine, and 1 (1.6%) received "direct to inject" XR-BUP. In this observational retrospective study, rates of engagement in addiction treatment after discharge among patients with OUD receiving XR-BUP were high. Clinical teams utilized novel strategies to initiate XR-BUP during ED and hospital-based encounters.

Effects of naltrexone on gabapentin reward and buprenorphine combinations in male mice.

From morphine to buprenorphine - Modeling opioid use disorder and its treatment during pregnancy: Effects on maternal care and offspring neurodevelopment in a translational rodent model.

IntroductionInsomnia is a common complaint among patients with opioid use disorder (OUD) maintained on buprenorphine (BUP). However, people with OUD have historically been excluded from insomnia clinical trials, leaving clinicians without evidence-based treatment options for this patient population. Lemborexant, the Food and Drug Administration (FDA)-approved dual orexin receptor antagonist for the treatment of insomnia, was recently shown to be safe and tolerable among a sample of patients with insomnia who were maintained on BUP. We hypothesise that pharmacologically antagonising the orexin system with lemborexant may improve insomnia symptoms in individuals with OUD and also enhance BUP treatment benefits by improving performance in neurofunctional domains identified in the National Institute on Drug Abuse Phenotyping Assessment Battery.Methods and analysisParticipants with insomnia and OUD who have been stabilised on BUP for at least 4 weeks will be randomly assigned to receive either lemborexant (n=50) or placebo (n=50) for 8 weeks. Participants will complete assessments at baseline, during the 8-week intervention, postintervention and at a 2-week follow-up. Primary outcomes are insomnia severity and impulsivity. Secondary measures include objective sleep metrics (total sleep time, sleep efficiency, sleep onset latency and wake after sleep onset) and performance in the neurofunctional domains of negative emotionality and metacognition.Ethics and disseminationThe study was approved by the Virginia Commonwealth University Institutional Review Board in April 2025 (protocol number HM20031777). Data collection began in May 2025 and is expected to be completed by May 2029. The trial is conducted under FDA IND no. 154797 (FGM). The dissemination plan for the trial includes presentations at local and national conferences, submission of primary and secondary outcome manuscripts for publication in peer-reviewed journals and circulation of findings to popular media outlets, as available. Results will also be shared with interested participants and clinical collaborators upon completion of the trial.Trial registration numberNCT06981195.

To target peripheral opioid receptors for postoperative pain relief while minimizing systemic opioid side effects, low doses of buprenorphine hydrochloride (0.8 up to 4.8 mg mL-1) were loaded into prefabricated, hydrophilic, degradable polyethylene glycol-based micropheres (PEG-MS, 50-100 μm) used as a drug delivery platform. By varying the composition of the degradable crosslinker, the degradation rate of PEG-MS, and consequently the drug release duration, could be tuned from 2 days to 2 months. In a pharmacokinetic study in rabbits, the time to the last quantifiable serum concentration (Tlast) of buprenorphine increased with the degradation time of PEG-MS, reaching 1, 2, 4, and 7 days for microspheres degrading over 2, 6, 12, and 50 days, respectively. PEG-MS demonstrated good biocompatibility, as evidenced by only mild and transient local inflammatory responses during their degradation when implanted in various rabbit tissues, including the dermis, muscle, and subconjunctival space. In a rat incisional pain model, the intraplantar injection of buprenorphine-loaded PEG-MS (degrading over 12 days) at doses of 240 μg and 40 μg increased the paw withdrawal threshold at 24 h by 34% (p < 0.0001) and 20% (p = 0.0466), respectively, compared to drug-free microspheres. Serum concentrations of buprenorphine exceeded the therapeutic threshold, indicating that intraplantar administration resulted in systemic, rather than local, effects. In the context of the opioid crisis, the local administration of a degradable drug delivery system that releases a small amount of buprenorphine in an operative wound for a few days after surgery seems relevant. Nevertheless, while the PEG-MS as buprenorphine delivery system was effective, this preliminary study showed that their local administration resulted in the opioid spreading throughout the body. The future of peripheral analgesia lies in developing opioids with physicochemical properties that prevent them from reaching the brain or being active there.

Opioids are widely used in the management of acute postoperative pain after thoracic surgery. Buprenorphine (BUP), though discovered as an analgesic, with robust evidence supporting its efficacy for this purpose, and possessing important safety advantages compared with commonly used full agonist opioids, is currently rarely used for acute pain management. To assess feasibility of implementing buccal BUP as part of a multimodal analgesia strategy, and to conduct an exploratory comparison of pain outcomes between patients receiving buccal BUP in addition to standard postoperative pain management, and patients receiving standard postoperative pain management alone. Retrospective cohort. Veterans Health Administration. In this single-center, retrospective cohort study of patients undergoing minimally invasive lung surgery, we assessed feasibility of buccal BUP administration for perioperative pain management, and conducted an exploratory analysis of pain outcomes in 29 patients, a subset of which received perioperative buccal BUP. Buccal BUP is feasible, safe, and is associated with improved pain outcomes after thoracic surgery. This retrospective review within a relatively homogenous population lacks a randomization process and size to address bias and confounding. Further study is needed to confirm any identified associations. We did not assess long-term outcomes, such as function and persistent opioid use. We are not aware of prior study of the buccal formulation of BUP for acute pain management. In this retrospective cohort study of largely opioid-naive patients undergoing thoracic surgery, buccal BUP was feasible, safe, and was associated with reduced pain postoperatively.

Opioids remain in common use for postoperative pain management after orthopedic surgery. Buprenorphine (BUP) is a partial agonist opioid best known as a lifesaving medication for opioid use disorder. Although extensively studied for acute pain management with at least the efficacy as full agonist opioids (FAO) and a superior safety profile, it is rarely used for this purpose in contemporary practice. To assess feasibility of inpatient administration of buccal BUP, in addition to usual analgesic care, and conduct an exploratory analysis of pain outcomes in an orthopedic surgery population, including a subset who received twice-daily buccal BUP. Retrospective cohort. Veterans Health Administration. A cohort of patients were treated with buccal BUP perioperatively at the discretion of the anesthesiologist. We subsequently undertook a retrospective chart review of 35 recent orthopedic cases at our institution over several months, including the subset who received buccal BUP, aiming to assess the feasibility of its use and make a preliminary assessment of pain outcomes. Our review found that perioperative buccal BUP was feasible within a population of largely opioid-naïve patients undergoing major orthopedic surgery. Pain outcomes were similar between the groups receiving BUP, in addition to usual care, and those not receiving BUP in addition to usual care. This is a retrospective review and lacks a randomization process and size to address bias and confounding. The largely homogenous patient population further limits generalizability. As such, no conclusions, generalizable or otherwise, should be made about any of the observed results. To our knowledge, the buccal formulation of BUP, which received US Food and Drug Administration approval for chronic pain management in 2015, has not been studied for acute pain management. In a population undergoing total joint arthroplasty, buccal BUP was readily accepted by patients and nursing staff, resulted in pain and opioid consumption outcomes similar to the usual care, was compatible with FAO, and resulted in no safety concerns. Given its expected safety advantages over FAO, BUP deserves further consideration and study as an opioid analgesic within a multimodal analgesic regimen.

Abstract Optimizing treatment for people with opioid use disorder (OUD) represents a critical priority to ameliorate the ongoing opioid crisis in the United States (U.S.). While methadone offered in an office environment (MO) is not currently approved by U.S. regulators, its proof of concept has been demonstrated elsewhere. The U.S.-based health economic literature on MO is limited. Among the few analyses considering MO is a 2009 cost-minimization analysis (CMA). Economists have critiqued CMA in favor of cost-effectiveness analysis (CEA). The 2009 CMA (which showed clinic-based methadone - MC- as optimal) offers an opportunity to both compare the CEA versus CMA results and provide a novel cost-effectiveness result for medication-based OUD treatments inclusive of MO. Inputs derived from a cost-only analysis of MO, MC, and office-based buprenorphine (BO) are applied in a CEA comparing MO, MC, and BO for people with OUD from the health care system perspective. Costs are adjusted to 2006 U.S. dollars. BO is less effective and more costly than – and therefore dominated by – MO. The MO vs. MC probabilistic incremental cost-effectiveness ratio is $5,270 per additional patient retained in six-month treatment. Decision uncertainty is minimal versus BO but significant versus MC. Alternative costing assumptions do not alter the basic results. These data suggest MO may be optimal under CEA, in contrast to conclusions from the published CMA. This finding is accompanied by high decision uncertainty given the limited data. More research can inform cost-effectiveness, one consideration among many to help determine if MO should be considered among U.S. treatments for OUD.

Introduction: As opioid-related drug overdoses remain a public health crisis, there is a critical need for innovative approaches to developing safer analgesics with improved safety profiles. BDH-001 is a fixed-dose combination of low-dose buprenorphine (BUP) and cannabidiol (CBD) being developed as a safer analgesic than currently available opioids. The purpose of this study was to examine the analgesic and opioid-sparing effects of BDH-001 and to complete an invivo safety assessment in rats. Methods: Analgesic effect of BDH-001 was assessed using the chronic constriction injury model of chronic neuropathic pain with pain threshold assessed via Von Frey testing. Drug-drug interaction effects on pharmacokinetic (PK) parameters were assessed in a single dose PK study in rodents. The effects on respiratory depression were also assessed and confirmed in two separate rodent studies performing blood gas analysis and measuring O2 saturation. Results: BDH-001 (combination of subanalgesic BUP dose and CBD) resulted in statistically significant increases in pain threshold compared to saline (p < 0.001), CBD alone (p < 0.01), and BUP alone (p < 0.05). The half-life of BUP was significantly shorter in the presence of CBD compared to BUP alone (p = 0.008), with no significant changes in any other BUP pharmacokinetic parameter assessed. CBD was found to attenuate BUP-induced respiratory depression in rats when assessing blood gases (p < 0.05) and O2 saturation (p < 0.05) over several time bins. Conclusions: Data obtained in the present study indicate the addition of CBD to BUP was opioid-sparing and attenuated BUP- but not morphine-induced respiratory depression. There was no evidence these findings were the result of a PK interaction. Results support the hypothesis that BDH-001, a fixed-dose combination of BUP and CBD, may provide effective analgesia with a more favorable safety profile.

Patients with sickle cell disease (SCD) experience painful vaso-occlusive episodes that increase with age; a subset develops chronic pain (CP). CP is usually managed with acute pain management guidelines despite evidence of ineffectiveness. Buprenorphine (BUP), a partial opioid agonist, is a potent analgesic with less euphoric effect and a respiratory "ceiling effect." BUP therefore provides an alternative "harm reduction" approach for CP management in pediatric SCD patients. This single urban center retrospective study assessed the feasibility of inpatient transition to BUP-containing analgesics in adolescents with SCD and CP. Patients aged 12-20years who transitioned from full opioid agonists (FOA) to BUP between December 2020 and September 2022 were included. Acute care utilization, hospital length of stay, and FOA use in both inpatient and outpatient settings were compared pre- and post-BUP induction for up to a year. Fourteen adolescents with SCD underwent inpatient BUP induction and maintenance therapy. Inpatient transition using a micro-induction approach was feasible and well tolerated in this population. There were low rates of adverse events, such as opioid withdrawal signs. Maintenance on BUP products was sustainable over the 1-year post-induction period. Three patients (21%) discontinued BUP during maintenance therapy. There was a significant reduction (p<0.05) in acute care utilization, length of stay, and FOA use (both inpatient and outpatient). Inpatient micro-induction to BUP from FOA in adolescent SCD patients with CP is feasible with minimal signs of opioid withdrawal. This study suggests decreased acute care utilization with BUP.

Background: Opioid Use Disorder (OUD) has claimed the lives of many Americans, with rates of overdose steadily rising over the past decade. Despite having highly effective medications to treat this condition, many providers still hesitate to prescribe them. Psychiatric inpatient facilities have a unique opportunity to engage patients with co-occurring disorders in the treatment of OUD; however, significant barriers exist. This study describes a novel OUD–buprenorphine (BUP) consultation service that provides such care to hospitalized psychiatric patients. Methods: This IRB-approved retrospective study reviewed the medical records of 123 hospitalized psychiatric patients who received consultations from the BUP consultation service. Descriptive and comparative statistics were performed. Results: The sample was predominantly male, with significant unemployment and housing instability. Patients were hospitalized for depressive, bipolar, and schizophrenia spectrum disorders. Over 90% of patients were discharged on buprenorphine, with over 50% being connected to specialized substance use services. No increase in the length of stay was found, and no difference in outcomes was observed based on diagnosis or BUP discharge status. Discussion/Conclusions: This novel service was effective in providing OUD treatment to patients with complex co-occurring psychiatric disorders without significantly increasing their length of stay. Despite acute exacerbations in psychiatric illness, patients were able to engage in discussions regarding BUP. While the study was limited in scope, it underscores the feasibility of integrating OUD treatment in the acute psychiatric inpatient setting.

To evaluate the duration of action and antinociceptive and sedative effects of buprenorphine hydrochloride following SC administration to orange-winged Amazon parrots (Amazona amazonica). 10 adult, healthy Amazon parrots were included. High-concentration buprenorphine formulation (1.8 mg/mL and 0.1, 1, and 2 mg/kg) and saline solution (0.9% NaCl; 0.55 mL/kg) were administered SC to the parrots in a within-subjects, complete, masked crossover study design. Foot withdrawal thermal threshold was determined prior to administration of treatment and 0.5, 1.5, 3, and 6 hours postinjection. Agitation-sedation scores were determined 1 to 2 minutes prior to each thermal challenge. Buprenorphine at 2 mg/kg significantly increased the thermal foot withdrawal threshold, whereas lower doses evaluated did not have a significant effect. Although no significant interaction effect of treatment*time was observed, the graphical data suggest that the effect could increase over time and still be present at the 6-hour time point. No significant effect of buprenorphine on agitation-sedation score or nausea-like behavior was observed. SC administration of buprenorphine at 2 mg/kg has a mild thermal antinociceptive effect in orange-winged Amazon parrots, which graphically appears to have a slow onset and last for the duration of the testing times. In addition, buprenorphine did not cause agitation or sedation, nausea-like behavior, or vomiting. Further studies are needed to fully evaluate the effects of buprenorphine in psittacines. Buprenorphine hydrochloride could be considered for pain management in the orange-winged Amazon parrot and does not cause significant adverse effects following single SC administration.