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The International Journal of... Dec 2023There is a strong link between chronic stress and vulnerability to drug abuse and addiction. Corticotropin releasing factor (CRF) is central to the stress response that...
BACKGROUND
There is a strong link between chronic stress and vulnerability to drug abuse and addiction. Corticotropin releasing factor (CRF) is central to the stress response that contributes to continuation and relapse to heroin abuse. Chronic heroin exposure can exacerbate CRF production, leading to dysregulation of the midbrain CRF-dopamine-glutamate interaction.
METHODS
Here we investigated the role of midbrain CRF1 receptors in heroin self-administration and assessed neuroplasticity in CRF1 receptor expression in key opioid addiction brain regions.
RESULTS
Infusions of antalarmin (a CRF1 receptor antagonist) into the ventral tegmental area (VTA) dose dependently reduced heroin self-administration in rats but had no impact on food reinforcement or locomotor activity in rats. Using RNAscope in situ hybridization, we found that heroin, but not saline, self-administration upregulated CRF1 receptor mRNA in the VTA, particularly on dopamine neurons. AMPA GluR1 and dopamine reuptake transporter mRNA in VTA neurons were not affected by heroin. The western-blot assay showed that CRF1 receptors were upregulated in the VTA and nucleus accumbens. No significant changes in CRF1 protein expression were detected in the prefrontal cortex, insula, dorsal hippocampus, and substantia nigra. In addition, we found that 15 days of environmental enrichment implemented after heroin self-administration does not reverse upregulation of VTA CRF1 receptor mRNA but it downregulates dopamine transporter mRNA.
CONCLUSIONS
Overall, these data suggest that heroin self-administration requires stimulation of VTA CRF1 receptors and upregulates their expression in brain regions involved in reinforcement. Such long-lasting neuroadaptations may contribute to continuation of drug use and relapse due to stress exposure and are not easily reversed by EE exposure.
Topics: Rats; Animals; Corticotropin-Releasing Hormone; Heroin; Dopamine; Ventral Tegmental Area; Self Administration; Recurrence; RNA, Messenger
PubMed: 37864842
DOI: 10.1093/ijnp/pyad060 -
Frontiers in Immunology 2023Opiate abuse increases the risk of HIV transmission and exacerbates HIV neuropathology by increasing inflammation and modulating immune cell function. Exosomal EVs(xEV)...
Opiate abuse increases the risk of HIV transmission and exacerbates HIV neuropathology by increasing inflammation and modulating immune cell function. Exosomal EVs(xEV) contain miRNAs that may be differentially expressed due to HIV infection or opiate abuse. Here we develop a preliminary exosomal-miRNA biomarker profile of HIV-infected PBMCs in the context of opiate use. PBMCs infected with HIV were treated with increasing dosages of morphine for 72 hours, the culture supernatants were collected, and the exosomes isolated using differential centrifugation. Exosomal miRNAs were extracted, expression levels determined via Nanostring multiplexed microRNA arrays, and analyzed with Webgestalt. The effect of the exosomes on neuronal function was determined by measuring calcium. Preliminary findings show that HIV-1 infection altered the miRNA profile of PBMC-derived EVs concurrently with opiate exposure. MicroRNA, hsa-miR-1246 was up-regulated 12-fold in the presence of morphine, relative to uninfected control. PBMCs infected with HIV-1 MN, an X4-tropic HIV-1 strain and exposed to morphine, displayed a trend which suggests potential synergistic effects between HIV-1 infection and morphine exposure promoting an increase in viral replication. Dose-dependent differences were observed in miRNA expression as a result of opiate exposure. The xEVs derived from PBMCs exposed to morphine or HIV modulated neuronal cell function. SH-SY5Y cells, treated with xEVs derived from ART-treated PBMCs, exhibited increased viability while for SH-SY5Ys exposed to xEVs derived from HIV-1 infected PBMCs viability was decreased compared to the untreated control. Exposing SH-SY5Y to xEVs derived from HIV-infected PBMCs resulted in significant decrease in calcium signaling, relative to treatment with xEVs derived from uninfected PBMCs. Overall, HIV-1 and morphine induced differential miRNA expression in PBMC-derived exosomes, potentially identifying mechanisms of action or novel therapeutic targets involved in opiate use disorder, HIV neuropathology, TNF signaling pathway, NF-κB signaling pathway, autophagy, and apoptosis in context of HIV infection.
Topics: Humans; HIV-1; HIV Infections; Opiate Alkaloids; Leukocytes, Mononuclear; Neuroblastoma; MicroRNAs; Extracellular Vesicles; Morphine; HIV Seropositivity; Opioid-Related Disorders
PubMed: 38022533
DOI: 10.3389/fimmu.2023.1259998 -
British Journal of Anaesthesia Mar 2024Despite the purported link between pholcodine and neuromuscular blocking agent allergy, screening for prior pholcodine use offers no practical benefit to patients, and...
Despite the purported link between pholcodine and neuromuscular blocking agent allergy, screening for prior pholcodine use offers no practical benefit to patients, and anaesthetists should continue to use a neuromuscular blocking agent where this is clinically indicated.
Topics: Humans; Drug Hypersensitivity; Anaphylaxis; Codeine; Neuromuscular Blocking Agents; Morpholines
PubMed: 38071149
DOI: 10.1016/j.bja.2023.11.029 -
Health Promotion Practice Sep 2023. National strategies to end the HIV epidemic and eliminate hepatitis c (HCV) through a syndemic approach require improvements in testing for HIV and HCV. Given the...
Improving HIV and HCV Testing in Substance Use Disorder Programs (SUDs) That Provide Medications for Opiate Use Disorder (MOUD): Role of Addressing Barriers and Implementing Universal and Site-Specific Approaches.
. National strategies to end the HIV epidemic and eliminate hepatitis c (HCV) through a syndemic approach require improvements in testing for HIV and HCV. Given the intersection of the opioid crisis with HIV and HCV acquisition, substance use disorder (SUD) treatment centers providing medications for opiate use disorder (MOUD) provide a critical opportunity to expand testing. Rates of testing in MOUD clinics have been suboptimal. . We employed the Nominal Group Technique (NGT), Ishikawa cause and effect diagrams, and individualized Quality Improvement (QI) efforts at two SUD clinics (SUD A and B) in Connecticut (CT) as part of an HRSA-funded grant focused on improving HCV cure in persons with HIV/HCV coinfection. Baseline and longitudinal data were collected on rates of HIV and HCV testing and positivity as well as linkage to treatment. . Between April 1, 2019, and May 31, 2021, for SUD A and B respectively, HIV testing increased from 13% to 90% and 33% to 83%; HCV testing increased from 4% to 90% and 30% to 82%, with few reported cases of HIV/HCV coinfection. HCV testing revealed new and prior diagnoses at both sites, with subsequent referrals for treatment. Qualitative assessments identified best practices which included the institution of formal policies and procedures, streamlining of testing logistics, designation of a site champion, and broadening relevant education to staff and clients. . Strategic assessment of barriers and facilitators to HIV and HCV testing at MOUD clinics can lead to improved testing and referral rates that are key to improving the cascade of care for both diseases.
Topics: Humans; Opiate Alkaloids; Coinfection; Hepatitis C; Substance-Related Disorders; Hepacivirus; HIV Infections
PubMed: 37439759
DOI: 10.1177/15248399231169791 -
WMJ : Official Publication of the State... Feb 2024Opioids prescribed for postoperative pain have exceeded patient need in the United States, playing a significant role in the opioid epidemic. In the preintervention...
BACKGROUND
Opioids prescribed for postoperative pain have exceeded patient need in the United States, playing a significant role in the opioid epidemic. In the preintervention phase of this project (September 2018 - March 2019), a chart review and patient survey revealed that patients were prescribed double the number of opioids they consumed following gynecologic surgery.
OBJECTIVE
To ascertain whether an educational intervention recommending opiate prescriptions based on postoperative opioid use decreases gynecologic surgeons' opiate prescriptions.
METHODS
An educational intervention implemented in January 2021 communicated the discrepancy between patient need and medications prescribed and made prescribing recommendations for common gynecologic procedures. A postintervention (February 2021 - April 2021) retrospective chart review ascertained postoperative opioid prescribing practices. Residents were surveyed about their prescribing practices in June 2021. Descriptive statistics compared each phase.
RESULTS
For laparoscopic hysterectomy, the median morphine milligram equivalent (MME) was 150 (IQR 112.5-166.9) for preintervention and 150 (IQR 112.5-150) postintervention. For vaginal hysterectomy, median MME declined from 150 (IQR 112.5-225) to 112.5 (IQR 112.5-150). For laparoscopic surgery without hysterectomy, the median MME was 75 for both preintervention (IQR 75-120) and postintervention (IQR 60-80). For vaginal surgery without hysterectomy median MME went from 75 (IQR 75-142.5) to 54 (IQR 22.5-112.5). Median MME for hysteroscopy and dilation and curettage was 0 for both phases. When surveyed, residents reported prescribing lower amounts than actual prescribing practices.
CONCLUSIONS
Despite education informing gynecologic surgeons that their opioid prescribing exceeded patient need, prescribing practices did not change. The difference between actual and resident-reported prescribing practices warrants further investigation.
Topics: Humans; Female; Analgesics, Opioid; Retrospective Studies; Practice Patterns, Physicians'; Gynecologic Surgical Procedures; Opiate Alkaloids; Endrin
PubMed: 38436635
DOI: No ID Found -
Huan Jing Ke Xue= Huanjing Kexue May 2024It is a new approach to identify legal or illegal use of morphine through information on municipal wastewater. However, the sources of morphine in wastewater are...
It is a new approach to identify legal or illegal use of morphine through information on municipal wastewater. However, the sources of morphine in wastewater are complex, and distinguishing the contribution of different sources has become a key issue. A total of 262 influent samples from 61 representative wastewater treatment plants in a typical city were collected from October 2022 to March 2023. The concentrations of morphine, codeine, thebaine, papaverine, noscapine, and monoacetylmorphine were analyzed in wastewater and poppy straws. Combined with the proportion of alkaloids in poppy straws, the source analysis of alkaloids in wastewater was analyzed using the ratio method and positive matrix factorization model (PMF). Only five alkaloids were detected in wastewater, and monoacetylmorphine, a metabolite of heroin, was not detected. The concentrations of morphine and codeine were significantly higher than those of noscapine, papaverine, and thebaine. By constructing the ratios of codeine/(morphine + codeine) and noscapine/(noscapine + codeine), the source of poppy straw could be qualitatively distinguished. The PMF results showed that three sources of morphine for medical use, poppy straw, and codeine contributed 44.9%, 43.7%, and 9.4%, respectively. The different sources varied in these months due to the COVID-19 and influenza A outbreaks, in which the use of drugs containing poppy straws and codeine was the main source, whereas the use of morphine analgesics remained relatively stable. Inventory analysis further demonstrated the reliability of the source contributions from the PMF model, and morphine was not abused in this city.
Topics: Morphine; Wastewater; Papaverine; Thebaine; Noscapine; Reproducibility of Results; Codeine; Morphine Derivatives; Alkaloids; Papaver
PubMed: 38629538
DOI: 10.13227/j.hjkx.202306005 -
Fitoterapia Jan 2024The chemical structure of sinoacutine is formed by a phenanthrene nucleus and an ethylamine bridge. Because it has a similar parent structure to morphine, it is...
The chemical structure of sinoacutine is formed by a phenanthrene nucleus and an ethylamine bridge. Because it has a similar parent structure to morphine, it is subdivided into morphinane. At present, all reports have pointed out that the basic skeleton of morphine alkaloids is salutaridine (the isomer of sinoacutine), which is generated by the phenol coupling reaction of (R)-reticuline. This study shows that the biosynthetic precursors of sinoacutine and salutaridine are different. In this paper, the sinoacutine synthetase (SinSyn) gene was cloned from Sinomenium acutum and expressed SinSyn protein. Sinoacutine was produced by SinSyn catalyzed (S)-reticuline, according to the results of enzyme-catalyzed experiments. The optical activity, nuclear magnetic resonance, and mass spectrum of sinoacutine and salutaridine were analyzed. The classification and pharmacological action of isoquinoline alkaloids were discussed. It was suggested that sinoacutine should be separated from morphinane and classified as sinomenine alkaloids.
Topics: Molecular Structure; Morphinans; Alkaloids; Morphine Derivatives
PubMed: 37949304
DOI: 10.1016/j.fitote.2023.105713 -
Contemporary Clinical Trials Dec 2023First study to assess any compensatory increase in use of non-opioid illicit substances and alcohol in opioid dependent patients randomized to treatment with... (Randomized Controlled Trial)
Randomized Controlled Trial
Risk of relapse to non-opioid addictive substances among opioid dependent patients treated with an opioid receptor antagonist or a partial agonist: A randomized clinical trial.
BACKGROUND AND OBJECTIVE
First study to assess any compensatory increase in use of non-opioid illicit substances and alcohol in opioid dependent patients randomized to treatment with extended-release naltrexone (XR-NTX) or buprenorphine-naloxone (BP-NLX) and in longer term treatment with extended-release naltrexone.
METHOD
A multicenter, outpatient, open-label randomized clinical trial where patients received intramuscular extended-release naltrexone hydrochloride, 380 mg/month, or daily sublingual buprenorphine-naloxone 8-24/2-6 mg for 12 weeks, and an option to continue with extended-release naltrexone for an additional 36 week follow-up. The study was conducted at five urban addiction clinics and detoxification units in Norway between November 2012, and July 2016.
RESULTS
Among the 143 patients, 106 men and 37 women, there were no significant differences between those randomized to XR-NTX or BP-NLX in the risk of first relapse to alcohol (HR 1.31; 0.68-2.53), amphetamines (HR 0.88; 0.43-1.80), benzodiazepines (HR 1.24; 0.74-2.09) or cannabis (HR 1.55; 0.83-2.89). Also in the 36-week (12-48 weeks) follow-up period we found no significant differences between patients continuing with XR-NTX compared to those switching to XR-NTX after the randomized period in risk of first relapse to any non-opioid substance. In both study periods, the mean time in the study were longer among those relapsing to non-opioid addictive substances than those who did not. There was no significant association between first relapse to illicit opioids and first relapse to non-opioid addictive substances.
CONCLUSION
There was no increase in the risk of relapse to non-opioid addictive substances neither in short term nor longer-term treatment with extended-release naltrexone. Trial registrationclinicaltrials.gov Identifier: NCT01717963.
Topics: Male; Humans; Female; Narcotic Antagonists; Naltrexone; Buprenorphine, Naloxone Drug Combination; Analgesics, Opioid; Opioid-Related Disorders; Buprenorphine; Chronic Disease; Recurrence; Delayed-Action Preparations; Injections, Intramuscular
PubMed: 37865138
DOI: 10.1016/j.cct.2023.107360 -
Zhonghua Yi Xue Za Zhi Oct 2023From January 2019 to December 2021, the clinical data of 151 patients with post craniotomy cervicogenic headache from Beijing Tiantan Hospital affiliated to Capital...
From January 2019 to December 2021, the clinical data of 151 patients with post craniotomy cervicogenic headache from Beijing Tiantan Hospital affiliated to Capital Medical University were retrospectively collected. The characteristics of cervicogenic headache were summarized, the numerical rating score (NRS) of patients before and after treatment of compound opioids and/or cervical nerve block was compared, and the occurrence of related adverse reactions and complications was counted. The onset of cervicogenic headache in 151 patients was on the (5.5±2.0) d after craniotomy, of which 131 (86.8%) had unilateral pain, pain in 127 (84.1%) could be induced by cervical activity, and 118 (78.1%) had limited neck movement. Of the 124 patients treated with compound capsule of oxycodone and acetaminophen, 85 (68.5%) patients had an NRS of (8.01±0.82) before treatment and 2.0 (1.0, 3.0) after treatment (<0.001). Thirty-nine patients who did not respond to medical therapy received cervical nerve block, and the NRS scores before and after receiving the nerve block were (7.49±1.12) and 2.0 (1.0, 2.5), respectively, with a statistically significant difference (<0.001). Twenty-seven patients who received cervical nerve block without medical treatment, and the NRS before and after treatment was (9.0±0.9) and 1.0 (1.0, 3.0), respectively, with a statistically significant difference (<0.001). Among the 124 patients receiving medication, 14 (11.3%) developed mild dizziness and nausea, which were resolved after stopping the drug, and no other drug-related adverse reactions were found. None of the patients who received nerve blocks saw complications associated with nerve block procedures. Compound capsule of oxycodone and acetaminophen are effective for most of patients with post craniotomy cervicogenic headache. Cervical nerve block is effective and safe for patients with or without drug resistance.
Topics: Humans; Post-Traumatic Headache; Acetaminophen; Oxycodone; Retrospective Studies; Pain; Craniotomy
PubMed: 37752058
DOI: 10.3760/cma.j.cn112137-20230203-00162 -
The American Journal on Addictions Sep 2023Buprenorphine/naloxone (BUP-NX) and methadone are used to treat opioid use disorder (OUD), yet there is insufficient evidence on the impact of doses on interventions'... (Randomized Controlled Trial)
Randomized Controlled Trial
Associations of methadone and buprenorphine-naloxone doses with unregulated opioid use, treatment retention, and adverse events in prescription-type opioid use disorders: Exploratory analyses of the OPTIMA study.
BACKGROUND AND OBJECTIVES
Buprenorphine/naloxone (BUP-NX) and methadone are used to treat opioid use disorder (OUD), yet there is insufficient evidence on the impact of doses on interventions' effectiveness and safety when treating OUD attributable to other opioids than heroin.
METHODS
We explored associations between methadone and BUP-NX doses and treatment outcomes using data from OPTIMA, a 24-week, pragmatic, open-label, multicenter, pan-Canadian, randomized controlled, two-arm parallel trial with participants (N = 272) with OUD who primarily use opioids other than heroin. Participants were randomized to receive flexible take-home BUP-NX (n = 138) or standard supervised methadone treatment (n = 134). We examined associations between highest BUP-NX and methadone doses, and (1) percentage of opioid-positive urine drug screens (UDS); (2) retention in the assigned treatment; and (3) adverse events (AEs).
RESULTS
The mean (SD) highest BUP-NX and methadone dose were 17.31 mg/day (8.59) and 67.70 mg/day (34.70). BUP-NX and methadone doses were not associated with opioid-positive UDS percentages or AEs. Methadone dose was associated with higher retention in treatment (odds ratio [OR]: 1.025; 95% confidence interval [CI]: 1.010; 1.041), while BUP-NX dose was not (OR: 1.055; 95% CI: 0.990; 1.124). Higher methadone doses (70-110 mg/day) offered higher odds of treatment retention.
DISCUSSION AND CONCLUSION
Methadone dose was associated with higher retention, which may be related to its full µ-opioid receptor agonism. Future research should notably ascertain the effect of pace of titration on a wide range of outcomes.
SCIENTIFIC SIGNIFICANCE
Our results extend previous findings of high doses of methadone increasing retention to be applied in our population using opioids other than heroin, including highly potent opioids.
Topics: Humans; Buprenorphine, Naloxone Drug Combination; Methadone; Analgesics, Opioid; Heroin; Opiate Substitution Treatment; Canada; Opioid-Related Disorders; Buprenorphine; Prescriptions; Narcotic Antagonists
PubMed: 37308805
DOI: 10.1111/ajad.13439