MONDO:0012292

The study aimed to stop the transmission of Hepatitis C virus (HCV) among networks of persons who inject drugs. The researchers identified HCV RNA-positive specimens from 459 persons in Wisconsin, USA, during 2016-2017. They conducted next-generation sequencing of HCV and analyzed it for phylogenetic linkage. The analysis showed that 126 persons were linked across 42 clusters. The study found that phylogenetic clustering was higher in rural communities and associated with female sex and younger age among rural residents. The data suggests that HCV transmission could be reduced by expanding molecular-based surveillance strategies to rural communities affected by the opioid crisis.


HP:0100735


MONDO:0002025

The paper reviews the factors that influence opioid overdose prevention in justice-involved populations. The study identified five categories: acceptability, accessibility, effectiveness, feasibility, and participant overdose risk. It was found that the acceptability of naloxone, a drug used to counteract opioid overdose, is associated with injection drug use, overdose history, and perceived risk. Accessibility of naloxone is influenced by the interface between corrections and community. Evaluations of overdose prevention interventions are few but show increases in knowledge or reductions in opioid overdose. Overdose is highest immediately following release from prison or jail, often preceded by service-system interactions, and associated with drug-use severity, injection use, and mental health disorders.


EFO:0010702

The study aims to determine if a local change team (LCT) intervention can improve the linkage to medication for opioid use disorder (MOUD) and implementation outcomes. The study also investigates if the outcomes are further enhanced by the use of peer support specialists (PSS). The study will recruit individuals on probation with opioid use disorder (OUD) and will use the exploration, preparation, implementation, sustainability (EPIS) framework to guide system-change. The study will also randomize adults on probation to receive PSS vs. treatment as usual, with assessments at various intervals. The outcomes include participant engagement in MOUD, probation revocation, illicit opioid use, and overdoses.


RXCUI:1494766

The EXIT-CJS study is a randomized controlled trial that aims to compare the effectiveness and retention of extended-release buprenorphine (XR-B) and extended-release naltrexone (XR-NTX) in treating opioid use disorder (OUD) among adults involved in the criminal justice system. The study hypothesizes that XR-B will be noninferior to XR-NTX in terms of retention in medication treatment, self-reported opioid use, opioid-positive urine samples, opioid overdose events, and criminal justice system recidivism.


EFO:0010702

The study aimed to identify strategies to increase the use of medications for opioid use disorder (MOUD) among veterans involved in the legal system, who have a high risk of overdose mortality. The study involved interviews with 18 veterans with a history of opioid use or opioid use disorder (OUD) and legal involvement. The veterans suggested strategies such as providing transportation or telehealth services, increasing access to MOUD during incarceration, reducing physician turnover, improving physician and veteran education about MOUD, and providing social support opportunities. The study suggests that the Veterans Health Administration (VHA) should consider incorporating these strategies into care and evaluate their impact on patients' experience, initiation of and retention on medications, and overdose rates.


NCIT:C50862

The study investigates the prevalence and correlates of witnessing and responding to drug overdoses among people who use drugs (PWUDs) in rural Northern New England. The study found that 84% of PWUDs had witnessed an overdose, which was associated with probable post-traumatic stress disorder (PTSD) symptoms. Despite Good Samaritan Laws (GSLs), some PWUDs faced legal consequences after calling 911 for an overdose. Access to naloxone, a drug used to reverse the effects of an overdose, varied, but 43% of PWUDs had used it to reverse an overdose. The study suggests that providing PWUDs with effective overdose response tools and protective policies could reduce overdose mortality.


PUBCHEM.COMPOUND:5284596


EFO:0010702

The study explores the experiences of people with opioid use disorder (OUD) during the COVID-19 pandemic. The research was conducted through qualitative interviews with 25 individuals in Chicago, most of whom had received methadone treatment during the pandemic. The findings reveal that despite limited knowledge of COVID-19, individuals are keeping safe, the pandemic has increased treatment motivation for some, and the availability of social support has been reduced. The study also highlights the difficulties individuals had in maintaining or obtaining financial support. The results can be used to inform future public health responses, particularly in ensuring that people with OUD receive appropriate health crisis-related information and that funds are properly allocated to address the mental health impacts of social isolation.


MONDO:0021681

The study analyzed online personal advertisements (ads) to understand their potential role in sexual health and risk behaviors. Data was collected from ClassifiedAds.com in the US from August 2019 to February 2020. The study found that most ads were posted by men (72.4%) and were from the southern US (34.7%) and urban areas (89.6%). Few ads contained images (21.9%) or words associated with substance use (1%), while 26% mentioned substance use or STI/HIV concern. The study concluded that personal ads provide insight into Internet-mediated sex encounters and sexual health risks among those who seek sex online.


EFO:0010702

medication positively associated with use

The study found that women who use drugs (WWUD) in rural communities have low rates of contraceptive use and high rates of unintended pregnancy. The study also found that WWUD who had received substance use disorder (SUD) treatment in the past 30 days had increased odds of contraceptive use. There was also a positive association between contraceptive use and recent medications for opioid use disorder and prior 6-month primary care utilization, although these did not meet the threshold for statistical significance.


MONDO:0100096

The study investigates the impact of COVID-19 on individuals with substance use disorders (SUD), particularly opioid use disorder (OUD), who are involved in the criminal justice system. The research was conducted in Illinois, Indiana, and Kentucky, and data was collected from justice system personnel and community-level SUD/OUD providers. The findings indicate that despite rapid adaptations made by systems during the pandemic, more work is needed to better support individuals with OUD who are involved in the justice system. The study also highlights the use of telehealth and telejustice during the pandemic.


RXCUI:1494766

The study investigates the use of extended-release buprenorphine (XR-BUP), a medication for opioid use disorder (MOUD), in correctional settings. The study included 54 individuals who received XR-BUP while incarcerated. The results showed no evidence of tampering with the injection site, indicating no attempts to remove, hoard, or divert the medication. 61% of the participants reported at least one adverse effect after injections, with an average of 2.8 side effects. 61% of those released on XR-BUP continued MOUD after release, with 30% continuing with XR-BUP. The study concludes that XR-BUP is feasible and acceptable in correctional settings and addresses administrative concerns of diversion.


PUBCHEM.COMPOUND:644073

The study explores the reasons for non-adherence to buprenorphine, a medication used to reduce opioid craving and illicit opioid use, and the acceptability of using video directly observed therapy (VDOT) to enhance adherence. The reasons for non-adherence include social and structural factors, the desire to use illicit drugs, and forgetfulness. While VDOT was seen as potentially improving patient accountability and trust from providers, there were concerns about it placing an undue burden on patients and eroding patient-provider trust.


PUBCHEM.COMPOUND:644073


PUBCHEM.COMPOUND:644073

The paper presents the protocol for a pilot randomized controlled trial (RCT) called the Trial of Adherence Application for Buprenorphine treatment (TAAB) study. The study aims to evaluate the effects of video directly observed therapy (DOT) delivered via a smartphone app on office-based buprenorphine treatment outcomes for opioid use disorder (OUD) patients. The primary outcome is the percentage of weekly urines that are negative for opioids over the 12-weeks. The secondary outcome is engagement in treatment at week 12. The study hypothesizes that video DOT delivered through mHealth technology platform can improve patients' buprenorphine adherence by providing additional structure and accountability.


MESH:C009924

Unilateral transcranial photobiomodulation (t-PBM)

The study presents a novel treatment for Opioid use disorders (OUDs) using unilateral transcranial photobiomodulation (t-PBM) to the hemisphere with a more positive valence by Dual Brain Psychology (DBP). The treatment was tested on 22 patients with significant opioid cravings and a history of recent or current OUD. The results showed a significant decrease in opioid cravings, depression, and anxiety after the active treatment compared to the sham treatment. The treatment was found to be safe with only one patient reporting abdominal bloating.


MESH:C009924


NCBIGene:172864

The study aims to evaluate the effectiveness of a digital tool, Realize Analyze Engage (RAE), in supporting recovery from Substance Use Disorder (SUD). The tool focuses on real-time detection of high-risk events such as stress and drug craving, and provides supportive interventions. The study will be conducted in two phases: an observational trial to assess the accuracy of the tool and a randomized controlled trial to evaluate its impact on patient outcomes. The RAE tool could potentially help manage stress and craving outside of clinical settings and provide clinicians with valuable insights for personalized recovery support.


NCBIGene:172864


HP:0012236

The paper reviews the use of wearable biosensors in the treatment of Alcohol Use Disorders (AUD). These devices monitor physiological indicators of intoxication, such as changes in gait and sweat, to understand addiction and inform treatment. The biosensors provide continuous readings in a passive manner, compared to traditional methods like breathalyzer or blood draw. The two primary means of measuring intoxication with biosensors are through gait changes, measured via smart sensors placed on the wrist, in the shoe, and mobile device sensors in smart phones, and sweat, measured by transdermal biosensors that detect the presence of alcohol in the bloodstream. These devices have been used to monitor sobriety among offenders with AUD, track consumption throughout clinical trials for behavioral treatment modalities, and guide behavioral interventions for relapse prevention.


MESH:C571901

The study investigates the effects of RAP-103, a multi-chemokine receptor antagonist (CRA), on opioid-induced adverse effects in male rats. The results show that RAP-103 reduces the severity of withdrawal responses from chronic morphine exposure, reduces heroin acquisition and reinforcing efficacy, and normalizes deficits in oxygen saturation and respiratory rate caused by morphine exposure. Additionally, RAP-103 normalizes morphine-induced deficits in chemokine receptors CCR2 and CCR5 in the nucleus accumbens (NAC).


MESH:C571901


UniProtKB:C5MKJ0

The paper discusses the role of T-type calcium channels, specifically the CaV3.2 isoform, in pain processing. These channels are expressed in nonpeptidergic and peptidergic nociceptive neurons and their expression or activity increases in the spinal dorsal horn and dorsal root ganglia neurons in different inflammatory and neuropathic pain models. The paper suggests that targeting proteins that regulate the trafficking or transcription of CaV3.2, or those that modify the channels via post-translational modifications, could be a new approach to developing drugs for pain control.


UniProtKB:C5MKJ0


UniProtKB:A0A0J9X628

Proteins that regulate the trafficking or transcription of CaV3.2


PUBCHEM.COMPOUND:12346245

The study synthesized a group of 2,5-disubstituted 1,3,4-oxadiazole molecules and evaluated their selective T-type calcium channel inhibitions. The compound 5-Chloro-N-(5-phenyl-1,3,4-oxadiazol-2-yl)thiophene-2-carboxamide (11) was found to selectively inhibit T-type Ca2+ channel over Na+ and K+ channels in mouse dorsal root ganglion neurons and human embryonic kidney (HEK)-293 cells. It also suppressed seizure-induced death in a mouse model. This suggests that compound 11 could be a potential therapeutic for chronic neuropathic and inflammatory pains.


PUBCHEM.COMPOUND:3453348


PUBCHEM.COMPOUND:3453348

Chronic neuropathic and inflammatory pains


MESH:C571901

The study investigates the effect of the multi-chemokine receptor antagonist RAP-103 on pain behaviors in acute and chronic pain models. In the acute model, RAP-103 had no effect on its own, but when combined with morphine, it reduced the effective dose of morphine. In a chronic model of diabetic peripheral neuropathy (DPN), RAP-103 reversed established hypersensitivity. The treatment also resulted in significant reductions in the expression of cytokines IL-1β, TNFα, and chemokine CCL3 in the sciatic nerve of diabetic rats.


PUBCHEM.COMPOUND:135418940

The study demonstrates a new method to generate hyaline cartilage from mesenchymal stem cells (MSCs) with a low risk of ossification. This was achieved by culturing MSCs in a hyaluronic acid hydrogel with transforming growth factor-β (TGFβ) for 14 days, followed by 7 days in TGFβ-free medium, supplemented with Wnt/β-catenin inhibitor XAV939 from day 10-21. This resulted in a significant reduction in hypertrophy phenotype. The stability of the hyaline phenotype was tested through intramuscular implantation in nude mice. After 4 weeks, the optimized group showed no signs of mineralization and maintained cartilaginous histology. The study found that TGFβ treatment time affected p38 expression, while exposure to XAV939 significantly inhibited P-Smad 1/5 level, which together resulted in decreased level of Runx2.


PR:000014246


MESH:D014408

The paper discusses the opioid crisis and the need for collaboration among academic, government, and industrial partners to develop effective nonaddictive pain medications, interventions for opioid overdose, and addiction treatments. The National Institutes of Health (NIH) held a 2-day meeting to address these concerns and to chart a collaborative path forward. The meeting was supported by the NIH Helping to End Addiction Long-TermSM (HEAL) Initiative. The symposium aimed to improve understanding of the etiology of acute and chronic pain, discover novel targets and regulatable pain circuits for safe and effective therapeutics, and identify relevant biomarkers for adequate testing in clinical trials.


MESH:D054316

Nociceptor-specific voltage-gated sodium ion channels

The study presents a method to assess the quality of cell-based assays using extracellular recordings from dorsal root ganglion (DRG) sensory neurons cultured on multi-well microelectrode arrays. The researchers applied data transformations to electrophysiological parameters for valid normality assumptions and suitability for use as a sample signal. They used a robust version of the Z'-factor, based on the median and median absolute deviation, to indicate assay quality and assess hit identification of potential pharmacological compounds. The approach demonstrated a large signal dynamic range and reduced sensitivity to data variation compared to the standard Z'-factor used in high throughput screening (HTS). Known antagonists of nociceptor-specific voltage-gated sodium ion channels were identified as true hits in the assay format under both spontaneous and thermally stimulated conditions.


UniProtKB:A9JQD6

The study investigates the role of Nav1.7 and Nav1.8 voltage-gated sodium channels in inflammatory pain. The research shows that the presence of inflammatory mediators, nerve growth factor (NGF) and interleukin-6 (IL-6), increases the firing rates of adult dorsal root ganglion (DRG) neurons. The proteins Nav1.7 and Nav1.8 are found in cultured neurons and contribute to this increased activity. Blocking both Nav1.7 and Nav1.8 significantly impacts thermally evoked firing after treatment with IL-6 and NGF, suggesting their key role in inflammatory pain.


NCBIGene:266809


NCBIGene:58133


NCBIGene:24498


MONDO:0100096

The paper discusses the impact of COVID-19 on individuals with opioid use disorder (OUD), highlighting the similar effects of COVID-19 and opioid exposure such as compromised neuroimmunity, hypoxia, and respiratory depression. The authors propose the use of iPSC-derived brain organoid models as a potential tool to study the physiological connection between COVID-19 and OUD.


MONDO:0100096


EFO:0010702


NCIT:C35918


PUBCHEM.COMPOUND:5288826

The study presents a novel bioengineered microphysiological system that allows for the coculturing of peripheral and dorsal spinal cord nerve cells. This system facilitates the emergence of native nerve tissue macrostructure and concerted synaptic function. The researchers found that different analgesics - morphine, lidocaine, and clonidine - modulate this microphysiological synaptic transmission in predictable ways. This system could be used to screen drug candidates for analgesic potential more efficiently.


PUBCHEM.COMPOUND:3676


PUBCHEM.COMPOUND:2803


NCIT:C143751


UBERON:0005054


CHEBI:132889

enhances production, retention, and biological activity of

The study investigates the use of graphene oxide (GO)-based nanosheets incorporated into methacrylated gelatin (GelMA) scaffolds to enhance osteogenesis in human mesenchymal stem cells (hMSCs). The results showed high viability and metabolic activities in hMSCs encapsulated in the nanocomposites. The incorporation of GO and silica-coated graphene oxide (SiGO) significantly increased mineralization within hMSC-laden constructs. This was due to the enhancement of the production, retention, and biological activity of endogenous bone morphogenetic proteins (BMPs), specifically through the BMP-SMAD1/5 signaling pathway. Inhibition of this pathway with LDN-193189 treatment abolished the osteoinductive effect of the nanosheets. In vivo tests further confirmed the bone formation potential of this technology.


MESH:C000628730


PUBCHEM.COMPOUND:54613581


UniProtKB:H6R1E8

The study investigates the voltage-gated calcium channels in human and rat dorsal root ganglion neurons. The high voltage-activated (HVA) Ca2+ currents in both species share basic biophysical and pharmacological properties. However, there are significant differences in the HVA currents in human neurons compared to rat neurons. These differences include a smaller Ca2+ current density, a greater proportion of nifedipine-sensitive currents, and a subpopulation of human neurons displaying relatively large constitutive current inhibition.


UniProtKB:H6R1E8


UniProtKB:A0A504XA82

High voltage-activated (HVA) Ca2+ currents


PUBCHEM.COMPOUND:4485

High voltage-activated (HVA) Ca2+ currents


CHEBI:35482

The paper discusses the challenges in developing effective, non-addictive analgesics for treating acute and chronic pain. The authors suggest that traditional target-based drug discovery methods, which focus on single targets, often fail due to poor clinical efficacy. They propose the use of stem cell-derived neuronal-based screening approaches for identifying analgesic targets and compounds.


CHEBI:35482


UniProtKB:A0A1A8YVS7

The study investigates the role of eukaryotic initiation factor 5A (eIF5A) in pain perception by sensory neurons derived from human induced pluripotent stem cells (hiPSCs). The researchers found that eIF5A, which undergoes a unique posttranslational hypusine modification, is consistently expressed in different species and culture systems. Inhibition of hypusine biosynthesis prevented hyperalgesic priming by inflammatory mediators, suggesting that hypusine could be a potential target for treating inflammation-associated pain.


UniProtKB:A0A1A8YVS7

undergoes posttranslational modification by


PUBCHEM.COMPOUND:65396

inhibition prevents hyperalgesic priming


PUBCHEM.COMPOUND:65396


UniProtKB:A0A212CHQ1

The study identifies STK25 as a kinase of the type Iα regulatory subunit PRKAR1A in human induced pluripotent stem cell cardiomyocytes (iPSC-CMs). The phosphorylation of PRKAR1A by STK25 inhibits the activity of protein kinase A (PKA) and increases its binding to the catalytic subunit in the presence of cAMP. In mice, the absence of Stk25 reduces Prkar1a phosphorylation, increases Pka activity, and enhances the contractile response to beta-adrenergic stimulation. This suggests that STK25 negatively regulates PKA signaling through the phosphorylation of PRKAR1A.


UniProtKB:A0A7J7JRJ7


UniProtKB:A0A212CHQ1

negatively regulates through PRKAR1A phosphorylation


PUBCHEM.COMPOUND:6610315


RXCUI:216284

The study analyzed the association between prescription opioid use and suicide attempts using medical claims data from Connecticut. The study found that patients prescribed opioid medications for at least 6 months during the past year and at 20-50 MME levels or higher had 4.44 to 7.23 times the risk of attempted suicide compared to those not prescribed opioids. The risk of suicide attempt was significantly higher among patients with psychiatric conditions other than anxiety who were prescribed more frequent and higher opioid doses. However, more frequent and higher doses of prescription opioids were associated with lower risk of suicide attempts among patients with medical conditions necessitating pain management.


PR:000044656

The paper discusses the potential of two ion channels, ryanodine receptors (RyRs) and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, as targets for non-opioid pain medications. RyRs are intracellular calcium channels, and HCN channels belong to the superfamily of voltage-gated K+ channels. Both channels play a role in nociception, the response of the sensory nervous system to a noxious stimulus that commonly leads to pain, and neuropathic pain.


PR:000000676

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels


PR:000044656


PR:000000676


UniProtKB:Q8CGS1

Single-chain variable fragment (scFv) small antibodies

The study generated non-opioid single-chain variable fragment (scFv) small antibodies to block the P2X4R receptor as a method of reducing pain. The scFv antibodies were found to have similar binding activity to monoclonal antibodies but with stronger affinity and increased tissue penetrability due to their smaller size. Two anti-P2X4R scFv clones (95, 12) were tested in male and female mice with trigeminal nerve chronic neuropathic pain. A single dose of P2X4R scFv successfully, completely, and permanently reversed chronic neuropathic pain-like measures in male mice only. Untreated mice retained hypersensitivity and developed anxiety- and depression-like behaviors within 5 weeks. In vitro P2X4R scFv 95 treatment significantly increased the rheobase of larger-diameter trigeminal ganglia neurons from mice compared to controls.


UniProtKB:Q8CGS1

Trigeminal nerve chronic neuropathic pain


UniProtKB:A0A8S3SH31


PUBCHEM.COMPOUND:12225304

The study focuses on the Mas-related G protein-coupled receptor X1 (MRGPRX1), a human sensory neuron-specific receptor that could be a potential target for pain treatment. The researchers synthesized and evaluated a series of thieno[2,3-d]pyrimidine-based molecules as positive allosteric modulators (PAMs) of MRGPRX1 in HEK293 cells transfected with the human MrgprX1 gene. They discovered an orally available compound, 6-(tert-butyl)-5-(3,4-dichlorophenyl)-4-(2-(trifluoromethoxy)phenoxy)thieno[2,3-d]pyrimidine (1t), which can reach the spinal cord, the presumed site of action, after oral administration. This compound reduced behavioral heat hypersensitivity in a neuropathic pain model induced by sciatic nerve chronic constriction injury (CCI) in humanized MRGPRX1 mice, demonstrating the potential of MRGPRX1 PAMs in treating neuropathic pain.


PUBCHEM.COMPOUND:163391881


PUBCHEM.COMPOUND:132556404

The study focuses on the design of peptides to target the NaV1.7 channel, which plays a significant role in pain transmission. The researchers used the ProTx-II peptide toxin from tarantula venom as a basis for designing potent and selective inhibitors of the human NaV1.7 channels. Two peptides, PTx2-3127 and PTx2-3258, were identified as having high potency and selectivity for the NaV1.7 channel. These peptides showed efficacy in rat models of chronic and thermal pain.


PUBCHEM.COMPOUND:132556404


MONDO:0024317

The study aimed to assess the feasibility and initial efficacy of an integrated psychosocial treatment for Veterans with chronic pain and hazardous opioid use. The treatment integrated two interventions: Acceptance and Commitment Therapy for chronic pain and Mindfulness Based Relapse Prevention for opioid misuse. The results indicated a significant effect in favor of the integrated intervention for opioid misuse, pain interference, and pain behavior, supporting the feasibility of providing an integrated treatment for both opioid risk and pain interference.


HP:0032941

The study aims to test the effectiveness of a digital peri-operative cognitive-behavioral intervention (SurgeryPalTM) in preventing the transition from acute to chronic postsurgical pain in adolescents undergoing spinal fusion surgery. The intervention targets baseline psychosocial risk factors such as psychological distress, sleep disturbance, and low pain self-efficacy, which are known to predict higher acute pain and likelihood of developing chronic postsurgical pain. The study will assess acute pain severity and interference, opioid use, chronic pain severity and interference, health-related quality of life (HRQL), parent and adolescent distress, sleep quality, and opioid use/misuse.


HP:0002360


CHEBI:30879

The study examined the misuse of opioids and alcohol in 211 veterans with chronic pain who were prescribed opioids. The results showed that 32% were not misusing either substance, 23% were misusing both, 40% were misusing opioids, and 5% were misusing alcohol. Veterans not misusing either substance were generally less distressed compared to those misusing opioids or both. The study suggests a need for increased focus on polysubstance misuse and the development of integrated treatment.


CHEBI:30879


PUBCHEM.COMPOUND:126961754

The study investigates the effects of intranasal leptin on opioid-induced sleep-disordered breathing in obese mice. The researchers found that morphine, an opioid, significantly increased the frequency of apneas and the severity of hypoventilation and obstructive sleep apnea in obese mice. However, treatment with intranasal leptin decreased the frequency of apneas, improved obstructive sleep apnea, and completely reversed hypoventilation. Additionally, the analgesic effect of morphine was enhanced. In vitro studies showed that the μ-opioid receptor agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin reduced the frequency of excitatory postsynaptic currents in hypoglossal motoneurons, and the application of leptin restored excitatory synaptic neurotransmission.


PR:000009758


PUBCHEM.COMPOUND:5288826


PUBCHEM.COMPOUND:101981638


MONDO:0007147

The paper discusses the relationship between opioid use and obstructive sleep apnea (OSA). Opioids, which are commonly prescribed for pain management, can affect breathing control and impair upper airway function, leading to central apneas, upper airway obstruction, and hypoxemia during sleep. The presence of OSA increases the risk of opioid-induced respiratory depression. However, the question of whether opioids can aggravate OSA remains unanswered. The paper also discusses the effects of opioids on the upper airway and hypoglossal motor activity.


PUBCHEM.COMPOUND:3345

The study investigates the effects of high-dose fentanyl-induced acute muscle rigidity on respiratory mechanics and metabolic rate in sedated rats. The results showed that fentanyl significantly decreased the compliance of the respiratory system and increased oxygen consumption, leading to hypoxemia. Dexmedetomidine, a central α-2 agonist, was found to counteract these effects, increasing respiratory compliance, decreasing metabolic rate, and restoring normoxemia. The researchers suggest that the changes in respiratory mechanics and metabolism caused by opioid-induced muscle rigidity contribute to fentanyl toxicity.


PUBCHEM.COMPOUND:3345


PUBCHEM.COMPOUND:5311068


MONDO:0017146

The study aimed to assess the feasibility and acceptability of acupuncture as a treatment for chronic pain in adults with sickle cell disease (SCD). The pilot study involved six adults with SCD who reported chronic pain for at least three months. The acupuncture treatment was administered twice per week for five weeks. The results showed that all participants had reduced pain intensity and pain interference after the intervention. The study concluded that it was feasible and acceptable to implement acupuncture in adults with SCD.


EFO:0003843

The study investigates pain management practices among American Indians and Alaska Natives in a rural tribal clinic in Southern California. The study found that being male, younger, and having less education were strong predictors for riskier methods for managing pain. The findings will help in developing strategies for reducing and preventing misuse and abuse of prescription medications and other drugs in rural American Indian and Alaska Native communities.


PUBCHEM.COMPOUND:71774987

The study investigates the impact of naloxone access laws (NALs) on fatal and nonfatal opioid overdoses in the United States from 2005 to 2016. The results show that NALs granting direct authority to pharmacists to provide naloxone were associated with significant reductions in fatal overdoses. However, these laws may also increase nonfatal overdoses resulting in emergency department visits. The effect sizes for fatal overdoses grew over time relative to the adoption of the NALs. There was little evidence of an association for indirect authority to dispense and other NALs.


HP:0033360

The study presents findings from a trial conducted in rural communities where juvenile probation/parole officers (JPOs) were trained to deliver contingency management (CM), an evidence-based intervention for substance use, to justice-involved youth. The results showed that JPOs can feasibly incorporate CM into their services and deliver it at similar or even greater capacities than clinically trained therapists. This task-shifting approach could significantly increase access to substance use services for high-risk youth in rural areas where such services are limited or nonexistent.


HP:0030157

The study investigates the risk factors associated with opioid misuse among adolescents who received opioid prescriptions for acute pain treatment in pediatric ambulatory care settings. The study found that 90% of the adolescents reported two or more risks for future opioid misuse, with pain catastrophizing and alcohol use being the most common risk factors. Parental factors such as a history of chronic pain and anxiety were also identified as risk factors. The study also found that 71% of parents reported keeping opioids at home, which is a potential risk factor for future misuse.


HP:0012532


EFO:0005230


CHEBI:22720

The study reviews state laws that mandate or recommend healthcare providers to prescribe naloxone to patients at high risk of opioid overdose. As of September 2019, 17 states had enacted naloxone co-prescribing laws. Over half of these states mandate that providers prescribe naloxone if patient overdose risk criteria are met. Most states define patient overdose risk based on opioid dosages prescribed, concomitant opioid and benzodiazepine prescriptions, and patient history of substance use disorder or mental illness. The study suggests that naloxone prescribing requirements could increase naloxone prescribed, destigmatize naloxone use, and reduce overdose harms.


PUBCHEM.COMPOUND:126961754

The paper reviews the separation of research on treatment for opioid use in pregnant women and preventive interventions for postpartum psychopathology, despite their significant overlap. It suggests that best practice guidelines for pregnant women with opioid use disorder include medication-assisted treatment and comprehensive care, including behavioral and mental health interventions. The paper argues for the integration of research on opioid use in pregnant women and preventive perinatal mental health interventions to better address the opioid epidemic in this population.


HP:0003581

Physical victimization in young adulthood

The study investigates the long-term effects of physical victimization during adolescence on substance use disorders in adulthood. The data was obtained from the Monitoring the Future Study, which included both men and women who were surveyed from age 18 to 30, and again at 35. The study found that adolescents who were threatened with or experienced physical violence had more symptoms of alcohol use at age 35 than those who were not victimized. However, when victimization during young adulthood was accounted for, only victimization during this period was associated with alcohol use symptoms at age 35. The effects of young adult victimization were stronger for women. Victimization was mostly unrelated to cannabis use symptoms at age 35.


MESH:D062789

The study found that cannabis and tobacco use in early adolescence are associated with opioid use in young adulthood. The research was conducted over a 12-year period on a cohort of adolescents from urban elementary schools in Baltimore, MD, United States. The study found significant positive associations between the frequency of cannabis or tobacco use at age 14 and the frequency of opioid use at age 19.


CHEBI:30879

The study examined adolescent factors related to alcohol and marijuana use that are associated with a higher or lower risk for opioid misuse during emerging adulthood. The study found that positive expectancies, peer approval, and older sibling use predicted a higher probability of opioid misuse. However, most adolescent factors were no longer associated with subsequent opioid misuse after adjusting for history of other substance use.


MESH:D064086


NCBITaxon:3482

The study investigates the association between cannabis use from adolescence to young adulthood and opioid misuse in a primarily urban Black cohort. Four cannabis use trajectories were identified: Low/Non-Users, Adolescent Onset Limited, Young Adult Onset, and Adolescent Onset Chronic. The study found that Adolescent Onset Chronic cannabis users had the highest rate of opioid misuse, followed by Adolescent Onset Limited, Young Adult Onset, and Low/Non-Users. The prevalence was significantly higher for Adolescent Onset groups relative to Low/Non-Users even after adjusting for individual, neighborhood, and peer factors.


EFO:0003843

The study examined opioid use in adolescents aged 14-18 years who were prescribed these medications for acute noncancer pain in pediatric outpatient medical settings. It was found that the majority of the youth filled the opioid prescription and the frequency of use varied widely. No gender differences were observed in the percentage of opioid use days, despite females reporting higher pain and mood symptoms. Greater pain experiences and the number of pills prescribed were positively associated with opioid use. Higher depressive symptoms were associated with greater opioid use, while higher daily reports of worried or scared affect were associated with lower opioid use.


NCIT:C150140


NCIT:C117196


PUBCHEM.COMPOUND:5462328

The study examined the co-use of methamphetamine and opioids among people in treatment in Oregon. Initial urinalysis of 102 specimens showed that 61% contained methamphetamine, with non-fentanyl opioids being three times as common in methamphetamine positive specimens. The study found three main factors impacting co-use: stigma regarding methamphetamine use, community-level factors and temporality, and patient rationales for co-use, such as mitigating the harms of heroin or managing its effects. The study emphasizes the importance of considering the expertise of people who co-use opioids and methamphetamine in future program planning.


PUBCHEM.COMPOUND:9887568

The study assessed the impact of the Opioid Reduction Act (SB 273) in West Virginia, which limited the supply of chronic and first-time opioid prescriptions. Data from the state Prescription Drug Monitoring Program (PDMP) was analyzed, including the number of opioid prescriptions, first-time opioid prescriptions, average daily morphine milligram equivalents (MME), and prescription duration. The results showed a significant decrease in overall state opioid prescribing and a small change in average daily MME associated with the date of the legislation's enactment. However, there was no association found with first-time opioid prescriptions or days' supply of opioid medication.


PUBCHEM.COMPOUND:9887568


MONDO:0005618

The study found that among youth aged 11 to 25 years who were prescribed an initial opioid, 0.3% developed an opioid use disorder or experienced an overdose within the following year. Factors associated with increased risk included mood/anxiety disorders, substance use, and prescriptions involving long-acting opioids or long durations. Comorbid substance use disorders were present in 72.8% of youth experiencing an opioid-related complication, including alcohol, cannabis, nicotine, and other substance use disorders.


RXCUI:1013930

The study investigates the relationship between retention in outpatient substance use disorder (SUD) treatment and pharmacotherapy for comorbid attention-deficit/hyperactivity disorder (ADHD). The study found that ADHD was diagnosed in 9.4% of outpatients and was associated with younger age, comorbid cocaine use, and private insurance. Individuals not receiving ADHD pharmacotherapy were younger than those receiving medication. ADHD pharmacotherapy was associated with greater long-term retention in SUD treatment, with those not receiving ADHD medication having a 4.9-fold increased likelihood of attrition within 90 days. The study concludes that ADHD pharmacotherapy is robustly associated with improved short- and longer-term retention in outpatient SUD treatment.


MONDO:0007743


MONDO:0100096

The study examined the use of buprenorphine, a medication used to treat opioid use disorder, among adults with employer-based insurance during the initial phase of the COVID-19 pandemic. The research found that the weekly use of buprenorphine remained relatively stable from January to August 2020. The study did not find any consistent change in the use of buprenorphine based on county-level measures of COVID-19 case rate, fatal drug overdose rate, and racial composition. However, use was consistently higher in counties with the highest fatal drug overdose rates.


NCIT:C115220

The study investigates the effectiveness of the Families Actively Improving Relationships (FAIR) program in treating families involved in the child welfare system with parental substance abuse, specifically opioid and methamphetamine abuse. The FAIR program integrates substance abuse and mental health treatment, parent skills training, and supportive case management. The study found significant reductions in parental opioid and methamphetamine use, mental health symptoms, and parenting risk, and improvements in stability in parents receiving FAIR. However, providing services to families who require travel in excess of 20 miles for sessions has challenging implications for program costs under a Medicaid structure.


NCIT:C115220


PUBCHEM.COMPOUND:126961754

The paper discusses the development of an online version of the Family Check-Up (FCU), a program designed to enhance parenting skills and prevent substance use, specifically targeting families with opioid use histories. The online platform and telehealth model allow for wide-scale dissemination, especially in remote, rural areas where addiction rates are high but services are limited. The FCU Online includes new modules focusing on harm reduction for parents with substance abuse histories, including opioid use.


PUBCHEM.COMPOUND:5284596

The study investigates the community-level factors associated with the distribution of naloxone, a medication that reverses opioid overdoses, under a naloxone standing order (NSO) in Massachusetts. The research found that naloxone dispensing under NSO has increased over time. However, communities with a higher percentage of Hispanic ethnicity and rural communities were less likely to dispense naloxone under NSO. Communities with more individuals treated with buprenorphine and those with more opioid-related overdose deaths dispensed more naloxone under NSO. The findings suggest a need for more equitable access to naloxone.


PUBCHEM.COMPOUND:644073


HP:5200103

The study investigates the presence of autism spectrum disorder (ASD) symptoms in young adults seeking treatment for substance use disorders (SUD). Using the Social Responsiveness Scale-2 (SRS-2), the study found that a significant proportion of these patients exhibited clinically elevated autistic traits. Furthermore, those with elevated SRS-2 scores were more likely to have a stimulant use disorder or an opioid use disorder, as well as alcohol use in the week prior to intake.


MONDO:0005258


PUBCHEM.COMPOUND:5284596

The study conducted a trial to determine the effects of pharmacy-based naloxone co-dispensing with opioids. The trial found that co-dispensing naloxone with opioids did not increase opioid risk behavior. However, it did increase naloxone acquisition and patient knowledge about naloxone administration. There was no significant change in opioid dose and other substance use.


CHEBI:35475

The study examined trends in prescriptions for opioid and non-opioid pain medications in the U.S. from 2014 to 2018. It was found that the percentage of participants receiving a prescription for opioids declined, remained stable for non-steroidal anti-inflammatory drugs, and increased for acetaminophen, antidepressants, and gabapentinoids. The adjusted odds of receiving an opioid prescription decreased, while the adjusted odds of receiving antidepressant, gabapentinoid, and acetaminophen prescriptions increased. Physicians are increasingly turning to CDC-recommended non-opioid medications for pain management, particularly antidepressants and gabapentinoids.


NCIT:C27003

The study investigated the patterns and predictors of daily acute pain in adolescents undergoing treatment for pain. Three trajectories of pain intensity were identified: slow decrease, rapid decrease, and stable or slight increase. Adolescents with stable pain showed the highest levels of anxiety. Better sleep quality was associated with lower pain intensity and interference the following day, even when accounting for opioid use. The study suggests that future research should use intensive longitudinal methodology to guide intervention development and prevent the transition to chronic pain.


EFO:0005272


NCIT:C27003


PUBCHEM.COMPOUND:6321408

The study used a mathematical model to estimate the impact of offering buprenorphine-naloxone treatment at syringe service programs (SSPs) in Massachusetts, USA. The results showed that the intervention scenario, where 30% of SSP clients initiated buprenorphine treatment on-site at least once annually, averted 4797 fatal opioid overdoses and resulted in 129,359 additional treatment initiations compared to the status quo. The intervention scenario was also found to be cost-effective, saving $3612 per person and accumulating more quality-adjusted life-years (QALYs) compared to the status quo.


EFO:0030082

associated with increased risk of misuse

The study found that higher polygenic risk scores (PRS) for lifetime cannabis use, heavy drinking, and alcohol consumption were associated with an increased risk of opioid misuse in an African-American sample. The study also found that higher PRS for heavy drinking and alcohol consumption were associated with a higher likelihood of opioid misuse among males, but not females.


PUBCHEM.COMPOUND:5284596

The study aimed to understand expert views on state-level naloxone access laws (NALs) in the US, which are used to expand naloxone availability as a harm reduction strategy against the opioid epidemic. The study found that the effectiveness of NALs in reducing opioid-related mortality depends on their ability to significantly increase population-level naloxone availability. Experts generally believed that increased naloxone availability does not significantly impact the prevalence of opioid misuse, opioid use disorder (OUD), and non-fatal opioid overdoses. However, implementation barriers include public stigma, naloxone affordability, and reliance on an inequitable healthcare system. Experts suggest that high-value NALs should address these issues and target settings beyond community pharmacies to distribute naloxone.


PUBCHEM.COMPOUND:5284596


PUBCHEM.COMPOUND:126961754

The Helping to End Addiction Long-Term (HEAL) Prevention Cooperative (HPC) is developing 10 different interventions to prevent opioid misuse and opioid use disorder. The aim is to compare the impacts of these interventions on the initiation, escalation, severity, and disorder of opioid misuse and to identify if any interventions are more effective for certain individuals. The paper discusses the strategies and processes used to harmonize HPC data, including a strategy to measure opioid use that spans the spectrum of opioid use experiences. The limitations and opportunities of this approach are also reviewed.


MGI:96212


MONDO:0005473

The study investigates the role of jaw function, psychological factors, and chronic overlapping pain conditions (COPCs) in the development of pain-related disability in patients with chronic Temporomandibular disorders (TMD). Data was collected from 400 participants with chronic TMD and analyzed using structural equation modeling. The results suggest that jaw function is the strongest predictor of pain-related disability, followed by psychological unease and COPCs. The findings support the potential value of targeting physical therapy such as jaw exercise along with psychological interventions as multidisciplinary nonpharmacological therapeutic solutions.


MONDO:0024317

Chronic overlapping pain conditions (COPCs)


HP:0041234


MGI:2684161

The study found that the paraventricular nucleus of the thalamus (PVT) plays a key role in the acquisition and maintenance of opiate-associated memories through its projections to the central nucleus of the amygdala (CeA) and nucleus accumbens (NAc). The activity of the PVT→CeA pathway associates morphine reward with the environment. Transient inhibition of the PVT→NAc pathway during retrieval provides enduring protection against opiate-primed relapse. The study also found that activating the downstream NAc→lateral hypothalamus (LH) pathway can prevent relapse. These findings suggest that the PVT→NAc→LH pathway could be a potential target for treating opioid addiction.


MGI:2684161


MGI:2684161

inhibition during retrieval provides protection against


NCBIGene:40981


HP:0002360

The paper discusses the bi-directional relationship between sleep/alertness disturbance and substance use disorders (SUD). It suggests that sleep/alertness disturbance impacts all phases of the addiction cycle, including initiation, maintenance, and relapse of SUD. The study reviews various substances and concludes that sleep/alertness disturbance is a crucial factor in understanding and treating SUD.


MONDO:0100081

The paper reviews the relationship between sleep deficiency and opioid use, suggesting a bidirectional association between sleep efficiency and opioid abstinence. The authors propose that normalizing sleep deficiency could potentially improve opioid abstinence and vice versa. They also discuss potential mechanisms that could link improvements in sleep to opioid abstinence. The paper suggests that sleep-restorative therapeutic approaches should be examined in clinical trials as a potential solution to the opioid epidemic.


HP:5200292


EFO:0010702

The paper discusses the role of sleep health in opioid use disorder (OUD). It highlights that sleep disturbances are common in individuals with OUD, particularly during opioid withdrawal and maintenance therapies. These disturbances, which include reduced total sleep time, disrupted sleep continuity, and poor sleep quality, are often associated with negative OUD treatment outcomes. The paper also notes that sleep disturbances are bidirectionally linked with factors such as chronic stress, stress reactivity, low positive affect, high negative affect, chronic pain, and drug craving. Despite the potential benefits, there are few studies aimed at improving sleep health in OUD patients. The paper suggests that therapeutic interventions targeting sleep could be a promising avenue to improve OUD treatment.


EFO:0010702


EFO:0010702

The study conducted RNA sequencing on the dorsolateral prefrontal cortex and nucleus accumbens of postmortem brains from subjects with Opioid Use Disorder (OUD) and unaffected comparison subjects. The results revealed significant overlap in transcripts between the two brain regions in OUD, related to synaptic remodeling and neuroinflammation. The identified transcripts were enriched for factors controlling proinflammatory cytokine, chondroitin sulfate, and extracellular matrix signaling. Microglia were implicated as potential drivers for opioid-induced neuroplasticity. Genetic liabilities for risky behavior, attention-deficit/hyperactivity disorder, and depression were suggested in subjects with OUD.


EFO:0010702

The study investigates the correlation of drug-related dreams with opioid use disorder (OUD). The research found that individuals who recalled a drug-related dream in the past week were more likely to report recent sleep disturbances, including poor sleep quality, increased insomnia symptoms, and a higher risk for sleep apnea. Post-dream craving and distress were associated with greater insomnia symptoms, poor sleep hygiene behaviors, and increased anxiety symptoms. Those who had ever experienced a drug-related dream were more likely to report a history of severe withdrawal, overdose, and intravenous opioid use. The study suggests that interventions treating co-occurring OUD, pain, sleep symptoms, and affective symptoms may improve overall well-being in this population.


EFO:0010702

The study found that individuals with opioid use disorder (OUD) reported worsening sleep quality over their lifespan. Persistent sleep disturbances were associated with female sex, a greater number of treatment episodes, and positive screens for chronic pain and insomnia. The study suggests that OUD treatment providers should routinely screen for co-occurring sleep disturbance and chronic pain.


GO:0030237


HP:0000725


HP:0012532


MONDO:0013600


EFO:0010702

The study found that people with opioid use disorder (OUD) have altered molecular rhythms in the dorsolateral prefrontal cortex (DLPFC) and nucleus accumbens (NAc), two key brain areas involved in OUD. In the DLPFC, fewer rhythmic transcripts were identified in subjects with OUD compared to unaffected subjects. In contrast, the NAc had nearly double the number of rhythmic transcripts in subjects with OUD. These rhythmic transcripts were associated with opioid, dopamine, and GABAergic neurotransmission. The study also found that these rhythmic transcripts were enriched for genomic loci associated with sleep-related traits, including sleep duration and insomnia.


GO:0007622


EFO:0010702

The paper discusses the relationship between opioid use disorder (OUD) and sleep deficiency. OUD is a chronic brain disease that affects cognitive function, mood, pain perception, and autonomic activity. Sleep deficiency, which can be caused by various factors such as sleep disorders, circadian disruption, and poor sleep quality, is found in over 75% of OUD patients. The paper suggests that there are bidirectional mechanisms between OUD and sleep deficiency and identifies potential therapeutic targets.


EFO:0005272


UniProtKB:I7GMK5

The study investigates the role of the circadian protein, neuronal PAS domain protein 2 (NPAS2), in the effects of the opioid fentanyl on pain, tolerance, and physical dependence. The research used male and female wild-type and NPAS2-deficient mice. The results showed that female NPAS2-deficient mice exhibited increased analgesic tolerance and more behavioral symptoms of physical dependence to fentanyl. Male NPAS2-deficient mice showed increased fentanyl-induced hypersensitivity compared to wild-type males. This suggests that NPAS2 has sex-specific effects on fentanyl-induced tolerance, hyperalgesia, and dependence.


UniProtKB:I7GMK5


MONDO:0005015

Painful diabetic neuropathy (PDN) is a common complication of chronic diabetes that can lead to significant disability and healthcare costs. Early symptom identification and aggressive glycemic control are crucial in controlling the development of neuropathic complications. However, adequate pain relief remains a challenge. Pharmacotherapy with anticonvulsants (pregabalin, gabapentin) and antidepressants (duloxetine) are common first-line agents. The use of oral opioids is discouraged due to associated morbidity, mortality, and potential for opioid-induced hyperalgesia. Neuromodulation treatment modalities including intrathecal drug delivery, spinal cord stimulation, and dorsal root ganglion stimulation are emerging as potential treatments. Holistic alternative therapies such as yoga and acupuncture may also be beneficial.


PUBCHEM.COMPOUND:5486971


PUBCHEM.COMPOUND:3446


PUBCHEM.COMPOUND:60835


HP:0002064

The study investigates the impact of Sickle cell disease (SCD) on gait in humanized transgenic BERK sickle mice. The researchers found that Purkinje cells, which are associated with movement and neural function, undergo increased apoptosis in sickle mice, potentially leading to compensatory gait changes. Using an automated gait measurement system, MouseWalker, they found that sickle mice showed alterations in stance instability and dynamic gait parameters. These alterations may be due to motor dysfunction from damaged Purkinje cells or from fear and/or anticipation of movement-evoked pain. The study also found correlations between certain gait parameters and both mechanical and deep tissue hyperalgesia.


HP:0100561

The study investigates the management of generator site pain, also known as "pocket pain", in patients undergoing spinal cord stimulation (SCS). The research involved a review of all SCS permanent implants and implantable pulse generator (IPG) placements over a period of 9 years. Out of 785 cases, 43 patients were identified with pocket pain. The study found that females were overrepresented in the pocket pain cohort. The diagnoses included failed back surgery syndrome, complex regional pain syndrome, and chronic neuropathic pain. None of the patients improved with conservative therapy, and all either underwent revision or explant. The study also found that significantly more pocket pain patients had workers' compensation insurance. The study concluded that pocket pain was inadequately managed with conservative treatments and that being female and having SCS filed under workers' compensation increased the risk of pocket pain.


MONDO:0004566


MONDO:0019369


MONDO:0024317


MONDO:0017146

The paper discusses the pain associated with sickle cell disease (SCD), which can be both acute and chronic. Acute pain is caused by vaso-occlusive crises (VOC), while the cause of chronic pain is still unknown. Opioids are the primary treatment for pain, but concerns over their long-term use and the opioid epidemic have led to a need for non-opioid therapies. The FDA has approved three drugs for the treatment of SCD, specifically to reduce VOC and impact the pathobiology of SCD.


MONDO:0017146


UBERON:0003027

The paper discusses the link between chronic low back pain (CLBP) and depression, and proposes a novel approach to treat CLBP using deep brain stimulation (DBS) of the subgenual cingulate cortex (SCC). The SCC is structurally connected to brain regions that mediate emotional processes and are implicated in both CLBP and depression, including the anterior cingulate cortex, medial prefrontal cortex, nucleus accumbens, and amygdala. The authors suggest that CLBP and depression share a common underlying brain network interconnected by the SCC.


HP:0100561

The study presents an automated data visualization tool that generates patient-specific activity maps using intraoperatively collected signals. The tool is based on JavaScript/Python and provides a fast and robust visualization of electromyography (EMG) activity. The tool was tested using a High-resolution (HR)-SCS lead with 8 columns of electrodes spanning the dorsal columns. The tool provides a rapid and robust analysis of stimulation effects on various muscle groups and allows for direct comparison across subjects and/or stimulation settings.