Pivotal role of orexin signaling in the posterior paraventricular nucleus of the thalamus during the stress-induced reinstatement of oxycodone-seeking behavior.

BACKGROUND: The orexin (OX) system has received increasing interest as a potential target for treating substance use disorder. OX transmission in the posterior paraventricular nucleus of the thalamus (pPVT), an area activated by highly salient stimuli that are both reinforcing and aversive, mediates cue- and stress-induced reinstatement of reward-seeking behavior. Oral administration of suvorexant (SUV), a dual OX receptor (OXR) antagonist (DORA), selectively reduced conditioned reinstatement of oxycodone-seeking behavior and stress-induced reinstatement of alcohol-seeking behavior in dependent rats. AIMS: This study tested whether OXR blockade in the pPVT with SUV reduces oxycodone or sweetened condensed milk (SCM) seeking elicited by conditioned cues or stress. METHODS: Male Wistar rats were trained to self-administer oxycodone (0.15 mg/kg, i.v., 8 h/day) or SCM (0.1 ml, 2:1 dilution [v/v], 30 min/day). After extinction, we tested the ability of intra-pPVT SUV (15 µg/0.5 µl) to prevent reinstatement of oxycodone or SCM seeking elicited by conditioned cues or footshock stress. RESULTS: The rats acquired oxycodone and SCM self-administration, and oxycodone intake correlated with signs of physical opioid withdrawal, confirming dependence. Following extinction, the presentation of conditioned cues or footshock elicited reinstatement of oxycodone- and SCM-seeking behavior. Intra-pPVT SUV blocked stress-induced reinstatement of oxycodone seeking but not conditioned reinstatement of oxycodone or SCM seeking or stress-induced reinstatement of SCM seeking. CONCLUSIONS: The results indicate that OXR signaling in the pPVT is critical for stress-induced reinstatement of oxycodone seeking, further corroborating OXRs as treatment targets for opioid use disorder.

Generational and Gender Patterns of Prescription Opioid Misuse Among Black Adults.

INTRODUCTION: Opioid-related overdose mortality disproportionally affects Black adults in Kentucky, particularly overdoses associated with prescription opioid misuse (POM). Black adults also face other consequences of POM, such as disparate health and legal outcomes. While several factors effect POM, such as generational factors and gender, these risk factors are understudied among Black adults with a history of POM. Current literature primarily focuses on White individuals who use opioids. METHOD: The present study qualitatively examined reasons for POM, prescription opioids misused, how prescription opioids are obtained, and initiation of POM among Black adults using thematic analysis. Participants included a sample (n = 39) of Black adults from a southern state, stratified by gender and age across four cohorts: born (1) 1995-2001, (2) 1980-1994, (3) 1970-1979, and (4) 1955-1969. RESULTS: Results revealed similarities and differences in these themes across age cohorts and gender. CONCLUSIONS: Implications for findings include the importance of culturally responsive interventions that utilize dual diagnosis treatment and idiographic approaches due to heterogeneous experiences with POM among Black adults.

Prescription Opioid Dose Change Prior to Fatal Opioid-Detected Overdose.

BACKGROUND: The opioid overdose crisis continues within the U.S., and the role of prescribed opioids and prescribing patterns in overdose deaths remains an important area of research. This study investigated patterns of prescription opioids dispensed in the 12 months prior to opioid-detected overdose death in Connecticut between May 8th, 2016 and January 2nd, 2018, considering differences by demographic characteristics. METHODS: The sample included decedents who had an opioid dispensed within 30 days preceding death. Using multilevel modeling, we estimated the slope of change in mean morphine equivalent (MME) daily dose over 12 months prior to death, considering linear and quadratic effects of time. We estimated the main effects of age, sex, race, and ethnicity and their interactions with time on MME. A sensitivity analysis examined how excluding decedents who did not receive long-term (≥90 days) opioid therapy affected mean MME slopes. Secondary analysis explored differences by toxicology results. RESULTS: Among 1,580 opioid-detected deaths, 179 decedents had prescribed opioids dispensed within 30 days preceding death. Decedents' mean age was 47.3 years (±11.5), 65.5% were male, 81% White non-Hispanic, 9.5% Black non-Hispanic, and 9.5% Hispanic. In the time-only model, linear (ß=6.25, p<0.01) and quadratic (ß=0.49, p=0.02) effects of time were positive, indicating exponentially increasing dose prior to death. Linear change in MME was significantly attenuated in men compared to women (ß=-4.87, p=0.03); however, men were more likely to have non-prescription opioids in their toxicology results (p=0.02). Sensitivity analysis results supported primary findings. CONCLUSION: Rapid dose increases in dispensed opioids may be associated with opioid-detected overdose deaths, especially among women.

Association between physical activity and depression in adult prescription opioid users: A cross-sectional analysis based on NHANES 2007-2018.

OBJECTIVE: This study was designed to examine the association between physical activity (PA) and depression among adult prescription opioid users. METHOD: Data of adults who recently took prescription opioids were collected from NHANES 2007-2018. Participants were divided into two groups according to whether PA in each domain was ≥600 MET-min/week. According to weekly activity frequency, recreational physical activity (RPA) was divided into inactivity, insufficient activity, weekend warrior (WW), and regular activity. PHQ-9 scores ≥10 were identified as depression. RESULTS: RPA of ≥600 MET-min/week was associated with a 40% (OR: 0.60, 95%CI: 0.38-0.96, P = 0.032) reduction in the risk of depression. Restricted Cubic Spline plots found a nonlinear dose-response relationship between RPA and depression (P = 0.045), and the turning point of depression risk was around 600 MET-min/week. There was no significant difference in the risk of depression between the WW and inactivity groups (OR: 0.65, 95%CI: 0.25-1.72, P = 0.382). The regular activity group had an 45% (OR: 0.55, 95%CI: 0.31-0.99, P = 0.046)lower risk for depression than the inactivity group. CONCLUSION: Only regular RPA is associated with a reduced risk of depression, and RPA showed a nonlinear dose-response relationship. The antidepressant effect of the WW is not significant.

Prescription Opioid Diversion Sources Among African Americans: Implications for Overdose Prevention.

Recent data show that African Americans (AAs) experienced a greater increase in overdose deaths involving prescription opioids relative to other racial/ethnic groups. One possible mechanism through which elevated risk for overdose is conferred to AAs could be due to greater exposure to contaminated counterfeit pills. Unfortunately, prescription opioid diversion is understudied among AAs and less is known regarding which sources AAs use to access pharmaceutical opioids. The objective of this study, therefore, was to identify and describe the most commonly used diversion sources for prescription opioids among AAs. Qualitative interview data are also presented to contextualize the most prevalent sources. This study used data from the Florida Minority Health Study, a mixed-methods project that included online surveys (n = 303) and qualitative in-depth interviews (n = 30) of AAs. Data collection was conducted from August 2021 to February 2022 throughout Southwest Florida. Analyses revealed that the most widely used sources for prescription opioids were dealers (33.0%) and friends/relatives (34.7%). Additionally, interview data indicated that dealers are the access point where larger volume acquisitions are made and high potency formulations are accessed. These findings suggest that AAs may utilize nonhealthcare related sources at higher rates than healthcare related sources to acquire prescription opioids. This is concerning because opioid pills acquired through nonhealthcare related sources are especially susceptible to fentanyl adulteration. These findings invite further study using nationally representative data to determine if AAs disproportionately use nonhealthcare related sources compared to persons from other racial/ethnic groups.

Knowledge, experiences, and perceptions of medications for opioid use disorder among Black Kentuckians.

BACKGROUND: Opioid overdoses have continued to increase at higher rates among Black Americans compared to people from other racial groups. Despite demonstrated effectiveness of MOUD in reducing risk of opioid overdose, Black Americans face decreased access to and uptake of MOUD. The current study aimed to examine the knowledge, perceptions, and experiences with MOUD among a sample of Black adults who use prescription opioids nonmedically in order to inform tailored efforts to improve MOUD uptake. METHODS: Data were derived from a larger study assessing cultural and structural influences on drug use and drug treatment among people who use prescription opioids nonmedically. Semi-structured qualitative interviews were conducted with 34 Black men and women across four generational cohorts: born 1955-1969; 1970-1979; 1980-1994; and 1995-2001. Participant responses were analyzed using thematic analysis. RESULTS: Nearly half of participants (44.1%) reported no knowledge or experience with MOUD. Among participants who had any knowledge about MOUD, four major themes regarding their perceptions emerged: MOUD Helps with Recovery; Not Needed for Level of Drug Use; Side Effects and Withdrawal; Equivalence with Illicit Drug Use. The majority reported negative perceptions of MOUD (52.6%), and the youngest cohort (born 1995-2001) had a higher proportion of negative perceptions (80%) relative to other age cohorts (born 1980-1994: 50%; 1970-1979: 75%; 1955-1969: 16.6%). DISCUSSION: Findings indicate a significant knowledge gap and clear points of intervention for improving MOUD uptake. Interventions to improve communication of health information in ways that are culturally relevant and tailored by age group can be used in conjunction with efforts to improve MOUD access among Black individuals who use opioids nonmedically.

Half of our sample of Black Americans who use opioids nonmedically had no knowledge of medications for opioid use disorder (MOUD).For those who knew about MOUD, most reported negative perceptions, including concerns about side effects of using MOUD and believing MOUD is equivalent to illicit drug use.The youngest age group endorsed the highest rates of negative perceptions relative to older age cohorts, indicating a need for intervention approaches tailored by age group.

Association of Disability Status and Type With Binge Drinking and Prescription Opioid Misuse Among Adults From a 3-State Sample.

BACKGROUND: Research examining at-risk substance use by disability status is limited, with little investigation into differences by disability type. We investigated binge drinking and prescription opioid misuse among adults with and without disabilities, and by type of disability, to inform need for assessment and intervention within these populations. METHODS: Secondary analyses of adults who completed the disability, alcohol, and prescription opioid misuse items in the 2018 Ohio, Florida, or Nebraska Behavioral Risk Factor Surveillance System surveys (n = 28 341), the only states that included prescription opioid misuse in 2018. Self-reported disability status (yes/no) relied on 6 standardized questions assessing difficulties with: vision, hearing, mobility, cognition, self-care, and independent living (dichotomous, nonmutually exclusive, for each disability). Logistic regression models estimated the association of disability status and type with (1) past 30-day binge drinking and (2) past-year prescription opioid misuse. Additional models were restricted to separate subsamples of adults who: (a) currently drink, (b) received a past-year prescription opioid, and (c) did not receive a past-year prescription opioid. RESULTS: One-third reported at least one disability, with mobility (19.5%), cognitive (11.5%), and hearing (10.2%) disability being the most common. Disability status was associated with lower odds of binge drinking (adjusted odds ratio [AOR] = 0.74, 95% confidence interval [CI] 0.68-0.80, P ≤ .01). However, among adults who currently drink, people with disabilities had higher odds of binge drinking (AOR = 1.11, 95% CI 1.01-1.22, P ≤ .05]. Disability was associated with higher odds of past-year prescription opioid misuse (AOR = 2.51, 95% CI 2.17-2.91, P ≤ .01). CONCLUSIONS: Adults with disabilities had higher odds of prescription opioid misuse, and among adults who currently drink, higher odds for binge drinking were observed. The magnitude of the association between disability status and prescription opioid misuse was particularly concerning. Providers should be trained to screen and treat for substance use problems for people with disabilities.

Stimulant use and opioid-related harm in patients on long-term opioids for chronic pain.

BACKGROUND: There is lack of clarity regarding the impact of and optimal clinical response to stimulant use among people prescribed long-term opioid therapy (LTOT) for pain. OBJECTIVE: To determine if a positive urine drug test (UDT) for stimulants was associated with subsequent opioid-related harm or discontinuation of LTOT. DESIGN: Retrospective cohort study. PATIENTS: People living with and without HIV living in a major metropolitan area with public insurance, prescribed LTOT for chronic, non-cancer pain (n=600). MAIN MEASURES: UDT results from January 2012 to June 2019 were evaluated against 1) opioid-related emergency department (ED) visits (oversedation, constipation, infections associated with injecting opioids, and opioid seeking) or death in each 90-day period following a UDT, using logistic regression, and 2) LTOT discontinuation. RESULTS: There were no opioid overdose deaths within 90 days following a stimulant-positive UDT. A stimulant-positive UDT was not statistically significantly associated with opioid-related ED visits within 90 days (adjusted odds ratio [aOR] 1.39; 95% CI=0.88-2.21). Stimulant-positive UDT was independently associated with subsequent discontinuation of LTOT within 90 days (aOR 2.96; 95% CI=2.13 - 4.12). Living with HIV was independently associated with decreased odds of LTOT discontinuation (aOR 0.65; 95% CI 0.43 - 0.99). CONCLUSIONS: Despite no association between a stimulant-positive UDT and subsequent opioid-related harm, there was an association with subsequent LTOT discontinuation, with heterogeneity across clinical groups. Detection of stimulant use should result in a discussion of substance use and risk, rather than reflex LTOT discontinuation.

Association between trajectories of prescription opioid use and risk of opioid use disorder and overdose among US nonmetastatic breast cancer survivors.

PURPOSE: To examine the association between prescription opioid use trajectories and risk of opioid use disorder (OUD) or overdose among nonmetastatic breast cancer survivors by treatment type. METHODS: This retrospective cohort study included female nonmetastatic breast cancer survivors with at least 1 opioid prescription fill in 2010-2019 Surveillance, Epidemiology and End Results linked Medicare data. Opioid mean daily morphine milligram equivalents (MME) calculated within 1.5 years after initiating active breast cancer therapy. Group-based trajectory models identified distinct opioid use trajectory patterns. Risk of time to first OUD/overdose event within 1 year after the trajectory period was calculated for distinct trajectory groups using Cox proportional hazards models. Analyses were stratified by treatment type. RESULTS: Four opioid use trajectories were identified for each treatment group. For 38,030 survivors with systemic endocrine therapy, 3 trajectories were associated with increased OUD/overdose risk compared with early discontinuation: minimal dose (< 5 MME; adjusted hazard ratio [aHR] = 1.73 [95% CI 1.43-2.09]), very low dose (5-25 MME; 2.67 [2.05-3.48]), and moderate dose (51-90 MME; 6.20 [4.69-8.19]). For 9477 survivors with adjuvant chemotherapy, low-dose opioid use was associated with higher OUD/overdose risk (aHR = 7.33 [95% CI 2.52-21.31]) compared with early discontinuation. For 3513 survivors with neoadjuvant chemotherapy, the differences in OUD/OD risks across the 4 trajectories were not significant. CONCLUSIONS: Among Medicare nonmetastatic breast cancer survivors receiving systemic endocrine therapy or adjuvant chemotherapy, compared with early discontinuation, low-dose or moderate-dose opioid use were associated with six- to sevenfold higher OUD/overdose risk. Breast cancer survivors at high-risk of OUD/overdose may benefit from targeted interventions (e.g., pain clinic referral).

The contribution of pain catastrophizing, depression and anxiety symptoms among patients with persistent pain and opioid misuse behaviours.

BACKGROUND: Anxiety, depression and pain catastrophizing are independently associated with risk of opioid misuse in patients with persistent pain but their relationship to current opioid misuse, when considered together, is poorly understood. This study will assess the relative contribution of these modifiable, and distinct psychological constructs to current opioid misuse in patients with persistent pain. METHODS: One hundred and twenty-seven patients referred to a specialized opioid management clinic for prescription opioid misuse within a tertiary pain service were recruited for this study. The Pain Catastrophizing Scale, Depression, Anxiety and Stress Scales and the Current Opioid Misuse Measure were administered pre-treatment. Pain severity and morphine equivalent dose based on independent registry data were also recorded. RESULTS: Higher levels of pain catastrophizing, depression, and anxiety were significantly associated with higher current opioid misuse (r = .475, 0.599, and 0.516 respectively, p < .01). Pain severity was significantly associated with pain catastrophizing (r = .301, p < .01). Catastrophizing, depression, and anxiety explained an additional 11.56% of the variance (R2 change = 0.34, p < .01) over and above age, gender, pain severity and morphine equivalent dose. Depression was the only significant variable at Step 2 (ß = 0.62, p < .01). CONCLUSION: Findings show that in a sample of people with persistent pain referred for treatment for opioid misuse, depression contributes over and above that of anxiety and pain catastrophizing. Theoretical and clinical practice implications are presented.

Measuring the importance of different barriers to opioid agonist treatment using best-worst scaling in an Australian setting.

OBJECTIVE: Opioid agonist treatment (OAT) is an effective treatment for opioid use disorder (OUD), however several client barriers to OAT are reported. Client importance of these barriers using economic preference elicitation measures have not been identified. This paper determines the most important OAT barriers using best-worst scaling (BWS) and compares the results of BWS to Likert scale. METHODS: Cross-sectional self-completed survey with 191 opioid dependent clients who attended Australian needle and syringe sites. Participants were presented 15 Likert scale barriers and 15 BWS barrier scenarios. The BWS data was presented using count analysis, multinomial logit and mixed logit models. The ranking of barrier items was completed using three BWS methods and one Likert scale method, with share preference results (BWS) or mean scores (Likert) used to rank the 15 barriers. RESULTS: The most important client barriers were 'enjoy using opioids', 'lack of support services' and 'hard to access'. The four ranking methods produced different barrier rankings for the most important barriers, but similar results for the least important barriers. CONCLUSION: Policies around OAT as a harm reduction approach, increased support services and increased availability of OAT services would be beneficial in improving OAT uptake. Comparing BWS and Likert methods produced different highest ranked barriers, indicating the method used to identify preferences has significant implications on the type of intervention prioritised.

Identifying Prescription-Opioid-Related Risks Using Prescription Drug Monitoring Programs' Algorithms and Clinical Screening Tools.

BACKGROUND: Pharmacists adopt various approaches to identifying prescription-opioid-related risks and harms, including prescription drug monitoring programs (PDMPs) and clinical screening tools. This study aims to compare 'at-risk' patients according to the published Australian PDMP algorithms with the validated Routine Opioid Outcome Monitoring (ROOM) clinical screening tool. METHODS: Data were used from an implementation study amongst people who had been prescribed regular opioids. We examined the results from ROOM and the patients' dispensing history over the previous 90 days. A chi-squared test was used to examine the association between risk according to (i) a PDMP alert and a clinical risk per ROOM; (ii) a PDMP alert and positive screening for opioid use disorder; and (iii) a PDMP 'high-dose' alert (average of >100 mg OME/day in the past 90 days) and any ROOM-validated risk. RESULTS: No significant associations were found between being 'at-risk' according to any of the PDMP alerts and clinical risk as identified via the ROOM tool (x2 = 0.094, p = 0.759). There was only minimal overlap between those identified as 'at-risk' via PDMP alerts and those meeting the clinical risk indicators; most patients who were 'at-risk' of clinical opioid-related risk factors were not identified as 'at-risk' based on PDMP alerts. CONCLUSIONS: PDMP alerts were not predictive of clinical risk (as per the ROOM tool), as many people with well-established clinical risks would not receive a PDMP alert. Pharmacists should be aware that PDMPs are limited to identifying medication-related risks which are derived using algorithms; therefore, augmenting PDMP information with clinical screening tools can help create a more detailed narrative of patients' opioid-related risks.

Investigating the co-occurrence of marijuana use and prescription opioid misuse with multiple suicide attempts among adolescents with a history of suicidal ideation.

This study investigated the co-occurrent association of marijuana use and prescription opioid misuse with multiple suicide attempts among adolescents with a history of suicidal ideation. Data came from the 2019 Youth Risk Behavior Survey. The sample was comprised of adolescents ages 14-18 who reported suicidal ideation during the past year (n = 2,562). Multinomial logistic regression was used to examine the co-occurring association of marijuana use and prescription opioid misuse with multiple suicide attempts. Of the 2,562 adolescents who experienced suicidal ideation, 19.2 % also attempted suicide multiple times during the past year and 19.0 % reported ever using marijuana and misusing prescription opioids, 8.8 % misused prescription opioids only, and 33.3 % used marijuana only. In the multivariate model, for adolescents who used marijuana and misused prescription opioid, the risk of attempting suicide once was 1.77 times higher (RRR = 1.77, 95 % CI = 1.22-2.59) and the risk of multiple suicide attempts was 3.23 times higher (RRR = 3.23, 95 % CI = 1.95-5.33) when compared to adolescents who had never used marijuana nor misused prescription opioid. The risk of multiple suicide attempts was greater for bisexual and racial/ethnic minority adolescents and adolescents who felt sad or hopeless. Interventions that prevent prescription opioid misuse among adolescents may be effective in mitigating suicide attempts.

Mental health and substance use disorder comorbidities among Medicaid beneficiaries: Associations with opioid use disorder and prescription opioid misuse.

Background: Medicaid presently insures about one-fourth of the US population and disproportionately insures about 38 % of non-elderly adults with an opioid use disorder (OUD). Owing to Medicaid's prominent role insuring persons with an OUD and that Medicaid coverage includes pharmaceutical benefits, there has been considerable interest in studying potential prescription opioid misuse among Medicaid beneficiaries and identifying subpopulations at higher risk for misuse and possible progression to an OUD. Methods: The study goals were to explore the associations among prescription opioid misuse, OUD, and co-occurring mental health and other substance use disorders (SUD). We analyzed Illinois Medicaid 2018 claims data for 1102479 adult beneficiaries 18 to 64 years of age. Using algorithms based on previous studies, we first determined either the presence or absence of nine SUDS (including OUD), nine mental health disorders and likely prescription opioid misuse. Then, we subdivided the beneficiary sample into five groups: those who were prescribed opioids and evidenced either no, possible, or probable misuse; those evidencing an OUD; and those evidencing no opioid use or misuse. Results: Bivariate analyses, upset plots, and multinomial logistic regressions were used to compare the five subgroups on the prevalence of co-occurring SUDS and mental health disorders. Those with an OUD or with probable prescription opioid misuse had the highest prevalence of most co-occurring conditions with beneficiaries with an OUD the most likely to evidence co-occurring SUDS, particularly tobacco use disorder, whereas those with probable misuse had elevated prevalence rates of co-occurring mental health disorders comparable to those with an OUD. Conclusion: The medical complexity of persons with an OUD or misusing prescription opioids are considered in light of recent attempts to expand buprenorphine provision as a medication for OUD among Medicaid beneficiaries. Additionally, we consider the possibility of gender, co-occurring mental health disorders, and tobacco use disorder as important risk factors for progressing to prescription opioid misuse and an OUD.

"You get stuck in it": Young people's accounts of attempting to quit non-medical tramadol use.

Aim: Non-medical use of tramadol and other prescription opioid use has become a great concern in many countries, including Sweden. This study examines key components in young people's accounts of attempting to quit drugs, focusing on non-medical use of tramadol. Methods: Repeated qualitative interviews were conducted with 12 individuals aged 19-24 years with experiences of problems related to non-medical tramadol use. The analysis used the concepts of autonomy, competence, and relatedness from self-determination theory. Results: Three themes emerged from the young people's accounts: (1) quitting initiated by parents and professionals; (2) being willing, but unable; and (3) between ambivalence and determination. These themes demonstrate conflicting emotions towards drug use along with a significant external pressure to quit, but also difficulties in quitting due to experiences of dependence, withdrawal symptoms, and mental health issues. For most participants, however, an increasing autonomous will and ability to abstain from drugs gradually developed, with the support from trusted relationships with professionals, family, and friends playing a crucial role. Conclusion: The process of trying to quit non-medical tramadol use can be challenging and involve a complex interaction between willingness and capability, where external influence can be either facilitating or hindering. This study highlights the importance of taking into account young people's own perspectives in treatment efforts, where trust is a key component.

Daily treatment with the dual orexin receptor antagonist DORA-12 during oxycodone abstinence decreases oxycodone conditioned reinstatement.

Chronic opioid use disturbs circadian rhythm and sleep, encouraging opioid use and relapse. The orexin (OX) system is recruited by opioids and regulates physiological processes including sleep. Dual OX receptor antagonists (DORAs), developed for insomnia treatment, may relieve withdrawal-associated sleep disturbances. This study investigated whether DORA-12, a recently developed DORA, reduces physiological activity disturbances during oxycodone abstinence and consequently prevents oxycodone-seeking behavior. Male and female Wistar rats were trained to intravenously self-administer oxycodone (0.15 mg/kg, 21 sessions; 8 h/session) in the presence of a contextual/discriminative stimulus (SD). The rats were subsequently housed individually (22 h/day) to monitor activity, food and water intake. They received DORA-12 (0-30 mg/kg, p.o.) after undergoing daily 1-h extinction training (14 days). After extinction, the rats were tested for oxycodone-seeking behavior elicited by the SD. Hypothalamus sections were processed to assess oxycodone- or DORA-12-associated changes to the OX cell number. In males, oxycodone-associated increases in activity during the light-phase, reinstatement, and decreases in the number of OX cells observed in the vehicle-treated group were not observed with DORA-12-treatment. Oxycodone-associated increases in light-phase food and water intake were not observed by day 14 of 3 mg/kg DORA-12-treatment and dark-phase water intake was increased across treatment days. In females, OX cell number was unaffected by oxycodone or DORA-12. Three and 30 mg/kg DORA-12 increased females' day 7 dark-phase activity and decreased reinstatement. Thirty mg/kg DORA-12 reduced oxycodone-associated increases in light-phase food and water intake. The results suggest that DORA-12 improves oxycodone-induced disruptions to physiological activities and reduces relapse.

Adverse childhood experiences and prescription opioid use during pregnancy: an analysis of the North and South Dakota PRAMS, 2019-2020.

OBJECTIVES: This study assesses the association between adverse childhood experiences (ACEs) and prescription opioid use during pregnancy. METHODS: This study uses data on 2,999 individuals from the 2019 and 2020 Pregnancy Risk Assessment Monitoring System (PRAMS) from North Dakota and South Dakota. The relationship between ACEs and prescription opioid use during pregnancy is examined using multiple logistic regression. RESULTS: The prevalence of prescription opioid use increases alongside more ACE exposure. Compared to those with no ACEs, recent mothers with three or more ACEs have a 2.4 greater odds of prescription opioid use during pregnancy (aOR [adjusted odds ratio] = 2.437; 95% CI [confidence interval] = 1.319, 4.503). CONCLUSION: Exposure to three or more ACEs are associated with a higherrisk of prescription opioid use during pregnancy. Additional research is needed better understand the mechanisms that link ACEs and prescription opioid use during pregnancy, as well as how to best support those with ACEs exposure in a trauma-informed manner to reduce the risk of substance use.

ADX106772, an mGlu2 receptor positive allosteric modulator, selectively attenuates oxycodone taking and seeking.

Opioid abuse and overdose have risen to epidemic proportions in the United States. Oxycodone is the most abused prescription opioid. Treatments for opioid use disorder (OUD) seek to reduce vulnerability to relapse by reducing sources of reinforcement to seek drug (i.e., acute drug effects or drug withdrawal/craving). Accumulating evidence that glutamate release elicits drug-seeking behaviors has generated interest in pharmacotherapies targeting the glutamate system. Agonists and positive allosteric modulators of the metabotropic glutamate 2 (mGlu2) receptor decrease glutamate activity, reducing drug taking and seeking. The present study tested whether the mGlu2 receptor positive allosteric modulator ADX106772 reduces oxycodone self-administration and the conditioned reinstatement of oxycodone seeking without affecting behaviors directed toward a highly palatable nondrug reinforcer (sweetened condensed milk). Male Wistar rats were trained to self-administer oxycodone (0.15 mg/kg/infusion, i.v., 12 h/day) or sweetened condensed milk (SCM; diluted 2:1 v/v in H2O, orally, 30 min/day) for 13 days in the presence of a contextual/discriminative stimulus (SD), and the ability of ADX106772 (0, 0.3, 1, 3 and-10 mg/kg, s. c.) to decrease self-administration was tested. The rats then underwent extinction training, during which oxycodone, SCM, and the SD were withheld. After extinction, the ability of ADX106772 to prevent SD-induced conditioned reinstatement of oxycodone and SCM seeking was tested. ADX106772 reduced oxycodone self-administration and conditioned reinstatement without affecting SCM self-administration or conditioned reinstatement. ADX106772 reduced oxycodone taking and seeking and did not affect the motivation for the palatable conventional reinforcer, SCM, suggesting that activating mGlu2 receptors with a positive allosteric modulator is a potential approach for prescription OUD treatment.