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1

Mitchell, Suzanne H., and William M. Baum. "Maximization should sometimes lead to abstinence." Behavioral and Brain Sciences 19, no. 4 (December 1996): 589–90. http://dx.doi.org/10.1017/s0140525x00043181.

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AbstractHeyman's model, paradoxically, predicts that whereas a maximizing approach to drug choice will prevent escalation of drug use it will never yield complete abstinence. We suggest an alternative model that overcomes this difficulty by focusing on changes in drug tolerance. A small modification allows maximization to predict either abstinence or moderation (e.g., social drinking).
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2

Ainslie, George. "Drugs' rapid payoffs distort evaluation of their instrumental uses." Behavioral and Brain Sciences 34, no. 6 (November 10, 2011): 311–12. http://dx.doi.org/10.1017/s0140525x11000689.

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AbstractScience has needed a dispassionate valuation of psychoactive drugs, but a motivational analysis should be conducted with respect to long-term reward rather than reproductive fitness. Because of hyperbolic overvaluation of short-term rewards, an individual's valuation depends on the time she forms it and the times she will revisit it, sometimes making her best long-term interest lie in total abstinence.
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3

White, Adrian. "Trials of Acupuncture for Drug Dependence: A Recommendation for Hypotheses Based on the Literature." Acupuncture in Medicine 31, no. 3 (September 2013): 297–304. http://dx.doi.org/10.1136/acupmed-2012-010277.

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Objectives After initial promising research into acupuncture for withdrawal from drugs of dependence, two large negative trials were published in 2002 and the use of acupuncture in US rehabilitation facilities fell. However, subsequently it has been maintained, despite a lack of support from systematic reviews. This suggests a mismatch between research and clinical observation, which could be due to the acupuncture technique used, choice of controls or outcome measures. This study aims to explore the mismatch. Methods An exploratory review of all 48 clinical trials on alcohol, cocaine, nicotine or opioid dependence included in current reviews. Results Studies with sham controls (that could be active) were less likely to be positive (33%) than those with non-acupuncture controls (75%). Positive results were more likely when measuring craving (56%) or withdrawal symptoms (58%) than when measuring abstinence (31%) or attrition (31%). Three treatment variables appeared to be associated with positive results: (1) body acupuncture, used in 13 studies, was associated with positive outcomes for craving and withdrawal symptoms but not for abstinence or attrition; (2) electroacupuncture, used in seven studies, was associated with positive results with all four outcomes; and (3) bilateral needling in 20 studies was associated with effects on abstinence, craving and withdrawal symptoms. Conclusions The current evidence suggests that acupuncture may have some effects on drug dependence that have been missed because of choice of outcome in many previous studies, and future studies should use outcomes suggested by clinical experience. Body points and electroacupuncture, used in the original clinical observation, justify further research.
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4

Darriba, H. Becerra. "Concurrent use of alcohol and cocaine: which is the best drug choice?" European Psychiatry 65, S1 (June 2022): S129. http://dx.doi.org/10.1192/j.eurpsy.2022.353.

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Introduction Patients with comorbid cocaine and alcohol dependence have a worse prognosis with lack of adherence to follow-up and treatment, frequent psychosocial problems, and higher rates of relapse [1]. Concurrent use of both substances produces cocaethylene, which is associated with more toxicity than cocaine alone [2]. Objectives To determine the efficacy of disulfiram compared to nalmefene in the treatment of comorbid cocaine and alcohol use. Methods A quasi-experimental open study was designed on 41 outpatients, with a follow-up of at least 1 year at the Mental Health Unit, aged between 18 and 65 years, diagnosed with cocaine and alcohol dependence (ICD-10). A minimum simultaneous weekly consumption of 2 grams of cocaine and 12 SD (Standard Drink) of alcohol during the month before, described by self-records was established. Treatment with oral disulfiram 250mg/day was assigned to 21 patients, and with oral nalmefene 18mg/day to 20 individuals. Observation period was for 6 months. Urinalysis and alcohol breath test were carried out twice a week. Abstinence was defined by obtaining negative results for at least 4 consecutive weeks. Statistical analysis were performed using SPSS v21.0 (significance p<0.05). Results 61.9% of patients treated with disulfiram achieved a minimum of 4 consecutive weeks of abstinence from cocaine and alcohol, compared to 40% in the nalmefene group (χ²=1.188; gl=1; p=0.276). There were no significant differences. Conclusions Disulfiram or nalmefene monotherapy seems clinically ineffective or insufficient in reducing the combined use of cocaine and alcohol. Further research is needed to assess the effect of both drugs simultaneously. Disclosure No significant relationships.
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5

Villeneuve, Jean-Patrick. "Gambling Regulation and Risk." European Journal of Risk Regulation 1, no. 4 (December 2010): 415–18. http://dx.doi.org/10.1017/s1867299x00000878.

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Анотація:
This section discusses the regulation of “lifestyle risks”, a term that can apply to both substances and behaviours. Lifestyle risks take place along the line of “abstinence – consumption – abuse – addiction”. This can concern substances such as food, alcohol or drugs, as well as behaviours such as gambling or sports. The section also addresses the question of the appropriate point of equilibrium between free choice and state intervention (regulation), as well as the question of when risks can be considered to be acceptable or tolerable. In line with the interdisciplinary scope of the journal, the section aims at updating readers on both the regulatory and the scientific developments in the field. It analyses legislative initiatives and judicial decisions and at the same time it provides insight into recent empirical studies on lifestyle risks.
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6

Villeneuve, Jean-Patrick. "Acknowledging and Addressing the Issue of Match Fixing: The Case of Sport Organisations." European Journal of Risk Regulation 6, no. 4 (December 2015): 633–37. http://dx.doi.org/10.1017/s1867299x00005183.

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Анотація:
This section discusses the regulation of “lifestyle risks”, a term that can apply to both substances and behaviours. Lifestyle risks take place along the line of “abstinence – consumption – abuse – addiction”. This can concern substances such as food, alcohol or drugs, as well as behaviours such as gambling or sports. The section also addresses the question of the appropriate point of equilibrium between free choice and state intervention (regulation), as well as the question of when risks can be considered to be acceptable or tolerable. In line with the interdisciplinary scope of the journal, the section aims at updating readers on both the regulatory and the scientific developments in the field. It analyses legislative initiatives and judicial decisions and at the same time it provides insight into recent empirical studies on lifestyle risks.
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7

Loer, Kathrin. "An Ounce for Prevention… Germany’s Public Policy on Health Promotion and Disease Prevention." European Journal of Risk Regulation 7, no. 4 (December 2016): 789–94. http://dx.doi.org/10.1017/s1867299x00010217.

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Анотація:
AbstractThis section discusses the regulation of “lifestyle risks” a term that can apply to both substances and behaviours. Lifestyle risks take place along the line of “abstinence - consumption - abuse - addiction”. This can concern substances such as food, alcohol or drugs, as well as behaviours such as gambling or sports. The section also addresses the question of the appropriate point of equilibrium between free choice and state intervention (regulation), as well as the question of when risks can be considered to be acceptable or tolerable. In line with the interdisciplinary scope of the journal, the section aims at updating readers on both the regulatory and the scientific developments in the field. It analyses legislative initiatives and judicial decisions and at the same time it provides insight into recent empirical studies on lifestyle risks.
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8

Kähkönen, S., and B. Bondarenko. "684 The effects of cardiovascular drugs and central haemodynamics in the late abstinence of alcoholic patients." International Journal of Psychophysiology 30, no. 1-2 (September 1998): 258. http://dx.doi.org/10.1016/s0167-8760(98)90683-3.

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9

Woolverton, W. "A novel choice method for studying drugs as punishers." Pharmacology Biochemistry and Behavior 76, no. 1 (August 2003): 125–31. http://dx.doi.org/10.1016/s0091-3057(03)00219-3.

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10

Reiner, David J., Olivia M. Lofaro, Sarah V. Applebey, Hannah Korah, Marco Venniro, Carlo Cifani, Jennifer M. Bossert, and Yavin Shaham. "Role of Projections between Piriform Cortex and Orbitofrontal Cortex in Relapse to Fentanyl Seeking after Palatable Food Choice-Induced Voluntary Abstinence." Journal of Neuroscience 40, no. 12 (February 12, 2020): 2485–97. http://dx.doi.org/10.1523/jneurosci.2693-19.2020.

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11

Maguire, Denise J. "Mothers on Methadone: Care in the NICU." Neonatal Network 32, no. 6 (2013): 409–15. http://dx.doi.org/10.1891/0730-0832.32.6.409.

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Анотація:
When women addicted to opioids seek prenatal care, the treatment of choice is methadone.1,2 Methadone mediates the addiction by reducing fluctuations in maternal serum opioid levels and protecting the fetus from repeated withdrawal episodes.3 Methadone maintenance is associated with increased maternal weight gain, decreased illegal drug use, and improved compliance with prenatal care.4 Although the risks are less when compared with street drugs, the risk to the fetus is physical dependence. Despite the magnitude of this national problem, there is a dearth of literature to guide NICU nurses on how to best support mothers of infants with neonatal abstinence syndrome (NAS) in the care of their infants. The purposes of this article are to review what is known about women in methadone treatment who have a history of opioid addiction and apply that evidence to guide neonatal nurses to support mothers of infants with NAS in the NICU.
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12

Podlesnik, Christopher A., Corina Jimenez-Gomez, and James H. Woods. "A CHOICE PROCEDURE TO ASSESS THE AVERSIVE EFFECTS OF DRUGS IN RODENTS." Journal of the Experimental Analysis of Behavior 93, no. 2 (March 2010): 203–23. http://dx.doi.org/10.1901/jeab.2010.93-203.

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13

Goldnadel Monteiro, Maristela, та Jandira Masur. "Monitoring alcoholism treatment: The appropriateness of choice between γGT or MCV evaluation after a short time of abstinence". Alcohol 3, № 4 (липень 1986): 223–26. http://dx.doi.org/10.1016/0741-8329(86)90029-7.

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14

Lassi, Dângela Layne Silva, André Malbergier, André Brooking Negrão, Lígia Florio, João P. De Aquino, and João Maurício Castaldelli-Maia. "Pharmacological Treatments for Cocaine Craving: What Is the Way Forward? A Systematic Review." Brain Sciences 12, no. 11 (November 14, 2022): 1546. http://dx.doi.org/10.3390/brainsci12111546.

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Background: cocaine craving is a core feature of cocaine use disorder and remains a critical challenge for abstinence and relapse prevention. This review summarizes the anti-craving efficacy of pharmacotherapies tested for cocaine use disorder, in the context of randomized-controlled clinical trials. Objectives: we assessed the databases of the U.S. National Library of Medicine, Google Scholar, and PsycINFO, without date restrictions up to August 2022, to identify relevant studies. Study eligibility criteria, participants, and interventions: we included double-blinded randomized-controlled trials investigating pharmacotherapies for cocaine craving and/or cocaine use disorder whose outcomes included cocaine craving. Study appraisal and synthesis methods: Two authors screened studies’ titles and abstracts for inclusion, and both read all the included studies. We systematically gathered information on the following aspects of each study: title; author(s); year of publication; sample size; mean age; sample characteristics; study set-ting; whether participants were treatment-seeking; study design; craving measures; study interventions; drop-out rates; and other relevant outcomes. Results: Overall, we appraised 130 clinical trials, including 8137 participants. We further considered the drugs from the studies that scored equal to or greater than six points in the quality assessment. There was a correlation between craving and cocaine use outcomes (self-reports, timeline follow-back or urinary benzoylecgonine) in the vast majority of studies. In the short-term treatment, acute phenylalanine-tyrosine depletion, clonidine, fenfluramine, meta-chlorophenylpiperazine (m-CPP) and mecamylamine presented promising effects. In the long term, amphetamine, biperiden, carbamazepine, lisdexamfetamine, lorcaserin, methamphetamine, mirtazapine, pioglitazone, progesterone, guanfacine, levodopa, nefazodone presented promising anti-craving effects. Unfortunately, the highly tested medications were not successful in most of the trials, as follows: propranolol in the short term; amantadine, aripiprazole, bromocriptine, citicoline, ketamine, modafinil, olanzapine, topiramate in the long term. The remaining 52 medications had no positive anti-craving outcomes. Limitations: Our review was limited by high heterogeneity of craving assessments across the studies and by a great range of pharmacotherapies. Further, the majority of the studies considered abstinence and retention in treatment as the main outcomes, whereas craving was a secondary outcome and some of the studies evaluated patients with cocaine use disorder with comorbidities such as opioid or alcohol use disorder, schizophrenia, bipolar disorder or attention deficit hyperactivity. Lastly, most of the studies also included non-pharmacological treatments, such as counseling or psychotherapy Conclusions: There is a direct association between craving and cocaine use, underscoring craving as an important treatment target for promoting abstinence among persons with cocaine use disorder. Clonidine, fenfluramine and m-CPP showed to be promising medications for cocaine craving in the short-term treatment, and amphetamine, biperiden, carbamazepine, lisdexamfetamine, lorcaserin, methamphetamine, mirtazapine, pioglitazone, progesterone, guanfacine, levodopa, nefazodone in the long-term treatment.
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15

Lin, Naili, and John I. Hubbard. "The increased ethanol preference in rats induced by choice, darkness, or drugs is reduced by ritanserin." Brain Research Bulletin 33, no. 6 (January 1994): 633–38. http://dx.doi.org/10.1016/0361-9230(94)90226-7.

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16

Divakaruni, Mahabir, Orrett, Adidam, Venkata, Adidam, and Divakaruni. "Compliance and Treatment Outcomes of Various Regimens for Trichomoniasis in Trinidad and Tobago." Medical Sciences 7, no. 10 (September 20, 2019): 97. http://dx.doi.org/10.3390/medsci7100097.

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Trichomoniasis is the most common non-viral sexually transmitted disease (STD) globally and yet is not a reportable disease. Trichomonas vaginalis is an important source of reproductive morbidity and may increase risk of acquisition and transmission of human immunodeficiency viruses (HIV). The World Health Organization (WHO) and the Control Disease Center (CDC) recommend various regimens of nitroimidazole s for treatment. The common nitroimidazoles used for trichomoniasis are metronidazole and tinidazole, which vary in their cost, efficacy, and side effect profile. It is relevant to study these factors for better management of the patients. This study aimed to compare and study the efficacy, compliance of various treatment regimens, their outcomes, and side-effects for trichomoniasis, among STI clinic attendees in Trinidad. A clinical trial study was designed, and after obtaining the informed consent, a routine clinical examination was conducted and the swabs for trichomoniasis tests were collected for diagnosis from the 692 participants. Out of 692 participants, 82 patients with positive diagnosis of Trichomonas infection were treated according to the patient’s choice, using different drug regimens. Compliance to treatment, side effects, and outcome were evaluated. The prevalence of trichomoniasis in the population attending our STI clinic is 11.9% and prevalence of HIV is 9%. Of the total 82 participants for the treatment, 80% were females; nearly 90% of the patients belonged to age group 15–45 years, and over 60% were below 30 years. Among those diagnosed for Trichomonas vaginalis, 14.6% had coexistent HIV infection. The compliance with respect to single dose treatment was significantly better than the long-duration oral regimen and has a significant relation with side effects of the treatment. The outcome is generally better and comparable and shows no significant difference between different treatment regimens used in the study. Metronidazole and tinidazole are commonly used drugs in various regimens. Compliance is better with those treated with tinidazole and metronidazole single dose than with other groups. Outcome is comparable between these regimens, especially when combined with other important factors like abstinence and treatment of the partners. The treatment regimens mainly differed in the compliance side effects profile and duration of therapy, which suggests that to improve the compliance of the drugs with fewer side effects, short course regimen would be a preferred choice.
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17

Shannon, Harlan E., and Patrick L. Love. "Effects of antiepileptic drugs on attention as assessed by a five-choice serial reaction time task in rats." Epilepsy & Behavior 7, no. 4 (December 2005): 620–28. http://dx.doi.org/10.1016/j.yebeh.2005.08.017.

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18

Burashnikova, I. S., R. F. Khaeva, and D. G. Semenikhin. "Results of the analysis of pharmacotherapy quality in narcology patients." Glavvrač (Chief Medical Officer), no. 6 (June 14, 2022): 70–72. http://dx.doi.org/10.33920/med-03-2206-11.

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The issue of safe and effective use of drugs is relevant for all countries. Errors in pharmacotherapy can be observed at all four stages of drug use, including the prescription of drugs (39% of errors; the wrong choice of drug/s, prescribing without taking into account contraindications, without evaluating the effectiveness and tolerability of drugs, etc.), transferring information about the prescription (12%) (unclear, illegible entries, short-hand notes in prescription sheets, etc.), dosing or dilution errors (11%), and errors at the use stage (reception, administration, 38%), i.e. untimely administration of drugs, the wrong route of administration, lack of control over the effectiveness of treatment, underestimation of the importance of informing the patient about side effects and the rules for taking medications. Errors in prescribing psychotropic drugs are dangerous for the development of serious side effects; meanwhile, those errors are preventable, and therefore their detection, analysis and prevention of recurrences is relevant. The purpose of the study: to analyze the main errors of pharmacotherapy in narcology patients for the period April 2021-April 2022.
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19

Charrier, D., and M. H. Thiébot. "Effects of psychotropic drugs on rat responding in an operant paradigm involving choice between delayed reinforcers." Pharmacology Biochemistry and Behavior 54, no. 1 (May 1996): 149–57. http://dx.doi.org/10.1016/0091-3057(95)02114-0.

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20

McMillen, Brian A. "The increased ethanol preference in rats induced by choice, darkness, or drugs is reduced by ritanserin." Alcohol 12, no. 2 (March 1995): 175–76. http://dx.doi.org/10.1016/0741-8329(95)90021-7.

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21

Druzin, Michael Y., Natalia P. Kurzina, Evgenya P. Malinina, and Andrej P. Kozlov. "The effects of local application of D2 selective dopaminergic drugs into the medial prefrontal cortex of rats in a delayed spatial choice task." Behavioural Brain Research 109, no. 1 (April 2000): 99–111. http://dx.doi.org/10.1016/s0166-4328(99)00166-7.

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22

Loganathan, Kavinash, and Eric Tatt Wei Ho. "Neurocognitive interventions based on network neuroscience may break the cycle of drug addiction relapse." Neuroscience Research Notes 3, no. 2 (May 30, 2020): 15–22. http://dx.doi.org/10.31117/neuroscirn.v3i2.48.

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In Malaysia, abstinence-centric programs failed to reduce drug use and stem the spread of HIV. The Malaysian government shifted its focus to implement harm reduction strategies with methadone maintenance therapy (MMT), in particular proving to be effective in improving the overall health and well-being of people who inject drugs (PWIDs). Despite this success, MMT retention rates remain low, as methadone is only able to stall drug consumption, but not stop it completely. Neuroimaging research revealed that PWIDs enrolled in MMT still display addictive behavior, including drug cue sensitivity, craving, and withdrawal, despite treatment adherence. Brain activity amongst treated PWIDs continues to bear similarities to untreated individuals, as they struggle with cognitive impairments and poor self-control. Findings from the emerging field of network neuroscience could provide fresh insight into the mechanics of addiction, especially the impact of substance abuse on brain-wide cognitive networks. Concurrently, the development of non-intrusive cognitive interventions, such as neurofeedback and transcranial magnetic stimulation, shows promise to reprogram a person's patterns of brain activity, including those regulated by large-scale networks, to a state resembling normalcy. We highlight the importance of relapse in the life-long rehabilitation of substance abuse. The lack of treatment options to handle relapse after successful harm-reduction policies is due to the absence of a conceptual framework to reason about interventions. We review recent research in the new field of network neuroscience, which suggests that altered brain activity due to drug addiction underlies the propensity for relapse and that this dysfunction is not addressed in drug rehabilitation programs. We hypothesize that non-invasive, non-pharmacological cognitive interventions based on network neuroscience to correct brain activity dysfunction associated with addiction are potential therapies to treat drug addiction relapse. In complement with medicine-substitution-based therapies, we hope this approach will finally break the cycle of addiction.
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23

Zhang, Tianyao, Xiaoyan He, Lijuan Wu, Xianrong Feng, Yu Yang, and Lu Deng. "Electro-Acupuncture Combined Methadone for Withdrawal Symptoms of Opioid Addiction: A Protocol for Systematic Review and Meta-Analysis." Acupuncture & Electro-Therapeutics Research 46, no. 4 (August 24, 2021): 419–32. http://dx.doi.org/10.3727/036012921x16237619666094.

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Background<br/> Opioid addiction is a chronic brain disorder characterized by a series of withdrawal symptoms in behavioral, psychological, and neurobiological manifestations. Withdrawal symptoms are the main cause of relapse after periods of abstinence; thus, the treatment is focused on abstinence symptoms. Due to most of all types of opioid agonist drugs carry a potential for addiction and exacerbation of withdrawal symptoms, nondrug methods have great potentials in clinical applications. Electro-acupuncture (EA), as a novel nonpharmacological approach, combined with methadone has a long-term positive efficacy on treating addiction. Therefore, we designed a protocol to evaluate the adjuvant effect of EA for treating withdrawal symptoms of opioid addiction.<br/> Method<br/> To review reports of relevant clinical trials, we will search English language databases (EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials) and Chinese databases (Chinese Biomedical Literatures, China National Knowledge Infrastructure, Wanfang, and VIP). We will collect documents from the earliest possible date up to May 2020. We will also search online trial registries such as ClinicalTrials. gov (ClinicalTrials.gov/), the European Medicine Agency (www.ema.europa.eu/ema/), and WHO International Clinical Trials Registry Platform (www.who.int/ictrp). We will select randomized controlled trials (RCT) for withdrawal from opioid addiction involving EA-methadone and methadone alone treatment. We will use psychological assessment scales to evaluate treatment major outcomes which include numerous components such as OWS, VAS, HAMD, HAMA; then urinalysis and methadone dosage also will be measure as the additional outcomes. Finally, RevMan5 software will be used for literature quality evaluation and data analysis.<br/> Result:<br/> To evaluate the efficacy of EA in combination therapy by observing the outcomes of corresponding scale, urinalysis and decreasing methadone.<br/> Conclusion:<br/> This protocol will be used to evaluate the efficacy and safety of EA in combination with methadone in treatment of opioid addiction withdrawal symptoms.<br/> Abbreviations: Opioid dependence, OWS=Opiate Withdrawal Scale, VAS=Craving Visual Analog Scale, PWSS=Post-withdrawal symptoms Scale, HAMD=Hamilton Depression Scale, HAMA=Hamilton Anxiety Scale, RCTs=Randomized Controlled Trials, EA=Electrical Acupuncture, PRISMA=Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
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24

Nunes, Eric J., Patrick A. Randall, Samantha Podurgiel, Mercè Correa, and John D. Salamone. "Nucleus accumbens neurotransmission and effort-related choice behavior in food motivation: Effects of drugs acting on dopamine, adenosine, and muscarinic acetylcholine receptors." Neuroscience & Biobehavioral Reviews 37, no. 9 (November 2013): 2015–25. http://dx.doi.org/10.1016/j.neubiorev.2013.04.002.

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25

Koehl, Jennifer L., David E. Zimmerman, and Patrick J. Bridgeman. "Medications for management of opioid use disorder." American Journal of Health-System Pharmacy 76, no. 15 (July 18, 2019): 1097–103. http://dx.doi.org/10.1093/ajhp/zxz105.

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Abstract Purpose The use of buprenorphine, methadone, and long-acting naltrexone for treatment of opioid use disorder (OUD) is discussed, including a review of current literature detailing treatment approaches and action steps to optimize treatment in acute care and office-based settings. Summary The U.S. epidemic of opioid-related deaths has been driven by misuse of prescription opioids and, increasingly, illicit drugs such as heroin, fentanyl, and fentanyl analogs, necessitating a refocusing of treatment efforts on expanding access to life-saving, evidence-based OUD pharmacotherapy. Inpatient treatment of opioid withdrawal includes acute symptom control through a combination of nonopioid medications and long-term pharmacotherapy to lessen opioid craving and facilitate stabilization and recovery. Methadone and buprenorphine reduce opioid craving, increase treatment retention, reduce illicit opioid use, and increase overall survival. Buprenorphine has logistical advantages over methadone, such as greater flexibility of treatment setting and less risk of adverse effects. Studies have shown the efficacy of long-acting injectable naltrexone to be comparable to that of buprenorphine if patients are detoxified prior to initiation of therapy; however, patients with active OUD are often not able to complete the week-long period of opioid abstinence needed prior to initiation of naltrexone injections. Although buprenorphine is preferred by many patients and can be prescribed in office-based settings, there remains a paucity of physicians certified to prescribe it. Conclusion Buprenorphine has become the medication of choice for many patients with OUD, but its use is limited by the low number of physicians certified to prescribe the agent. Other agents studied for treatment of OUD include methadone and naltrexone.
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Rodolico, Alessandro, Carmen Concerto, Alessia Ciancio, Spyridon Siafis, Laura Fusar-Poli, Carla Romano, Elisa Scavo, et al. "Validation of the Glasgow Antipsychotic Side-Effect Scale (GASS) in an Italian Sample of Patients with Stable Schizophrenia and Bipolar Spectrum Disorders." Brain Sciences 12, no. 7 (July 7, 2022): 891. http://dx.doi.org/10.3390/brainsci12070891.

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Antipsychotics are a class of psychotropic drugs that improve psychotic symptoms and reduce relapse risk. However, they may cause side effects (SE) that impact patients’ quality of life and psychosocial functioning. Therefore, there is a need for practical tools to identify them and possibly intervene. The objective of the present study was to translate into Italian the Glasgow Antipsychotic Side Effect Scale (GASS), which is suggested as the questionnaire of choice to collect SE reported by patients treated with antipsychotics. We administered the GASS and the Udvalg for Kliniske Undersøgelser (UKU) SE scale—which is considered the gold standard—to 100 stable patients with schizophrenia and bipolar spectrum disorders. We measured the structural validity, internal consistency, concurrent criterion validity, construct validity, and clinical feasibility. GASS was characterized by modest structural validity and good internal consistency. The binary correlations concerning the presence of specific symptoms investigated with the GASS and the UKU were strong or relatively strong for only half of them. The GASS total scale score was inversely related to patients’ quality of life and psychosocial functioning. The GASS is useful to briefly assess the burden of antipsychotic SE (~5 min) but is not optimal in identifying them.
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Redish, A. David, Steve Jensen, and Adam Johnson. "A unified framework for addiction: Vulnerabilities in the decision process." Behavioral and Brain Sciences 31, no. 4 (July 29, 2008): 415–37. http://dx.doi.org/10.1017/s0140525x0800472x.

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AbstractThe understanding of decision-making systems has come together in recent years to form a unified theory of decision-making in the mammalian brain as arising from multiple, interacting systems (a planning system, a habit system, and a situation-recognition system). This unified decision-making system has multiple potential access points through which it can be driven to make maladaptive choices, particularly choices that entail seeking of certain drugs or behaviors. We identify 10 key vulnerabilities in the system: (1) moving away from homeostasis, (2) changing allostatic set points, (3) euphorigenic “reward-like” signals, (4) overvaluation in the planning system, (5) incorrect search of situation-action-outcome relationships, (6) misclassification of situations, (7) overvaluation in the habit system, (8) a mismatch in the balance of the two decision systems, (9) over-fast discounting processes, and (10) changed learning rates. These vulnerabilities provide a taxonomy of potential problems with decision-making systems. Although each vulnerability can drive an agent to return to the addictive choice, each vulnerability also implies a characteristic symptomology. Different drugs, different behaviors, and different individuals are likely to access different vulnerabilities. This has implications for an individual's susceptibility to addiction and the transition to addiction, for the potential for relapse, and for the potential for treatment.
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Versnel, Huib, Jennifer E. Mossop, Thomas D. Mrsic-Flogel, Bashir Ahmed, and David R. Moore. "Optical Imaging of Intrinsic Signals in Ferret Auditory Cortex: Responses to Narrowband Sound Stimuli." Journal of Neurophysiology 88, no. 3 (September 1, 2002): 1545–58. http://dx.doi.org/10.1152/jn.2002.88.3.1545.

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This paper describes optical imaging of the auditory cortex in the anesthetized ferret, particularly addressing optimization of narrowband stimuli. The types of sound stimuli used were tone-pip trains and sinusoidal frequency and amplitude modulated (SFM and SAM) tones. By employing short illumination wavelengths (546 nm), we have successfully characterized the tonotopic arrangement, in agreement with the well-established electrophysiological tonotopic maps of the ferret auditory primary field (AI). The magnitude of the optical signal increased with sound level, was maximal for a modulation frequency (MF) of 2–4 Hz, and was larger for tone-pip trains and SFM sounds than for SAM sounds. Accordingly, an optimal narrowband stimulus was defined. Thus optical imaging can be used successfully to obtain frequency maps in auditory cortex by an appropriate choice of stimulus parameters. In addition, background noise consisting of 0.1-Hz oscillations could be reduced by introduction of blood pressure enhancing drugs. The optical maps were largely independent of 1) the type of narrowband stimulus, 2) the sound level, and 3) the MF. This stability of the optical maps was not predicted from the electrophysiological literature.
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Desdicioğlu, Raziye, Dilek Oztas, Fatma Tamara Köroğlu, Salih Mollahaliloğlu, Mehmet Uğurlu, and Ayşe Filiz Yavuz. "Comparison of Acupuncture and NSAID Efficacy in Patients with Chronic Pelvic Pain Using Pain Disability Index and Visual Analogue Scale." Acupuncture & Electro-Therapeutics Research 46, no. 4 (August 24, 2021): 395–404. http://dx.doi.org/10.3727/036012921x16237619666102.

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Chronic pelvic pain (CPP) is continuous, noncyclical, and present for more than six months. Nonsteroidal anti-inflammatory drugs (NSAID) are widely used. Complementary medicine is considered when pain treatment is insufficient. There are studies available investigating the effect of acupuncture. In this study, we aimed to compare the effectiveness of acupuncture with NSAIDs. Patients admitted to Ankara Atatürk Research Hospital in a one-year period and diagnosed with CPP were included. Patients with organic pathology were excluded. Acupuncture was applied to 38 patients and 30 patients received NSAIDs according to their choice. Visual Analog Scale (VAS) and Pain Disability Index (PDI) were applied. Pre-treatment PDI in the acupuncture group was 47.15±11.84 and it was 24.95±14.16 after treatment. Pre-treatment VAS score in the acupuncture group was 6.89±1.57 and it was 3.78±1.91 after treatment. Pre-treatment PDI in the NSAID group was 25.7 and it was 15.5 after treatment. VAS in the NSAID group pre-treatment was 4.40±2.44 and it was 2.63±2.20 after treatment. Both of the groups had significant decreases in their scores. The pre-treatment scores in the acupuncture group were higher than the NSAID group. This finding may indicate that patients in the acupuncture group were NSAID resistant. Hence, acupuncture could be a choice for NSAID resistant patients.
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Lanzetta, Paolo. "Anti-VEGF therapies for age-related macular degeneration: a powerful tactical gear or a blunt weapon? The choice is ours." Graefe's Archive for Clinical and Experimental Ophthalmology 259, no. 12 (October 20, 2021): 3561–67. http://dx.doi.org/10.1007/s00417-021-05451-2.

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Abstract Purpose Blindness and vision loss are still frequent disabilities associated with a relevant impact on health care and quality of life, and a high economic burden. Supranational programs established by the World Health Organization (WHO), International Agency for the Prevention of Blindness (IAPB), and World Health Assembly (WHA) aim at reducing avoidable visual impairment. Age-related macular degeneration (AMD), diabetic retinopathy (DR), and other retinal diseases are well known causes of visual disability. Since more than a decade, intravitreal agents are available for the treatment of these diseases. The aim of this study is to review whether pharmacotherapy with anti-vascular endothelial growth factor (VEGF) drugs has led to a decrease in the prevalence of blindness with emphasis on AMD and different countries. A brief analysis of other factors correlated to changes in the rate of blindness is also presented. Methods PubMed and Scopus web platforms were used to identify relevant studies on epidemiology of blindness and vision impairment, the influence of intravitreal therapies, and the existence of different vision care models. Additional data and material was searched in web internet accessed by the web browser Firefox. Results Age-standardized prevalence of blindness secondary to AMD has started to decline as testified by a number of studies in different countries. This is due to the adoption of anti-VEGF therapy and its adequate management. The frequency of treatment and regimens applied are indirect signs of successful treatment. Local rules and regulations may represent an obstacle. Conclusions This review shows that by implementing existing health care systems and dispensing adequate therapies in the field of retinal diseases, the prevalence of blindness due to these conditions can decline.
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Tran, Huu Ngoc Tran, J. Joshua Thomas, and Nurul Hashimah Ahamed Hassain Malim. "DeepNC: a framework for drug-target interaction prediction with graph neural networks." PeerJ 10 (May 11, 2022): e13163. http://dx.doi.org/10.7717/peerj.13163.

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The exploration of drug-target interactions (DTI) is an essential stage in the drug development pipeline. Thanks to the assistance of computational models, notably in the deep learning approach, scientists have been able to shorten the time spent on this stage. Widely practiced deep learning algorithms such as convolutional neural networks and recurrent neural networks are commonly employed in DTI prediction projects. However, they can hardly utilize the natural graph structure of molecular inputs. For that reason, a graph neural network (GNN) is an applicable choice for learning the chemical and structural characteristics of molecules when it represents molecular compounds as graphs and learns the compound features from those graphs. In an effort to construct an advanced deep learning-based model for DTI prediction, we propose Deep Neural Computation (DeepNC), which is a framework utilizing three GNN algorithms: Generalized Aggregation Networks (GENConv), Graph Convolutional Networks (GCNConv), and Hypergraph Convolution-Hypergraph Attention (HypergraphConv). In short, our framework learns the features of drugs and targets by the layers of GNN and 1-D convolution network, respectively. Then, representations of the drugs and targets are fed into fully-connected layers to predict the binding affinity values. The models of DeepNC were evaluated on two benchmarked datasets (Davis, Kiba) and one independently proposed dataset (Allergy) to confirm that they are suitable for predicting the binding affinity of drugs and targets. Moreover, compared to the results of baseline methods that worked on the same problem, DeepNC proves to improve the performance in terms of mean square error and concordance index.
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Padała, Olga, Anna Taracha, Adrianna Krupa, Małgorzata Drwal, Katarzyna Głaszcz, and Ryszard Maciejewski. "Opinion of students of Medical University of Lublin on emergency contraception." Polish Journal of Public Health 126, no. 1 (March 1, 2016): 41–45. http://dx.doi.org/10.1515/pjph-2016-0009.

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Abstract Introduction. Many women at the reproductive age face the dilemma of choosing the best contraceptive method. Apart from the natural birth control methods, there is a large selection of barrier, hormonal or invasive procedures. Birth control also includes emergency contraception, which can be used in a short period of time after an unprotected sex. In 2015, Ella One (uliprystal acetate) has been approved as an over-the-counter drug in Poland. Aim. The purpose of this study was to check the knowledge and survey opinions of students of various faculties of Medical University of Lublin concerning the topic of emergency contraception. Material and methods. An anonymous online questionnaire was used in the study. It included single and multiple-choice questions. The results were analyzed using Microsoft Excel 2011. Results. 256 students, aged 19-27 took part in the study. 81.3% of the respondents declared themselves as Christians. 47% of interviewees said that using emergency contraception is ethical. In the group of Christians, 37.5% claimed that emergency contraceptives should not definitely be sold as an OTC drug while among the non-religious individuals, only 6% shared that view. 60.6% of students decided that EC is not a form of abortion, On the other hand, 29.9% opted for it being an abortion. In the group of female participants, 14.9% said that they had used emergency contraception at least once in their lives. As it comes to evaluation of students’ knowledge about the topic, only 15.23% knew the way of uliprystal acetate worked and even less (11.32%) were able to explain the way levonorgestrel works. Discussion. According to the Catholic Church, the only acceptable forms of family planning include sexual abstinence during fertile days or calendar-based contraceptive methods. Postcoital contraception is treated as a sin punished with excommunication. Therefore, adhering by the rules imposed by the Roman Catholic Church has huge impact on the choices that believers make, also when it comes to birth control. This statement has been confirmed by many studies conducted in Poland, where 90% of population consider themselves Catholics. Conclusions. Emergency contraception remains a controversial topic in Poland. Students of Medical University of Lublin seem to have insufficient knowledge about the effects of available drugs. There is a need to educate future healthcare providers, so they could provide reliable advice and recommendations to their patients.
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Neo, Shermyn, Sheng Yong Aidan Wong, Hwee Lan Ng, Wei Li, Kay Yaw Tay, Wing Lok Au, and Louis Chew Seng Tan. "Evolution of Initial Pharmacologic Treatment of Newly Diagnosed Parkinson’s Disease Patients over a Decade in Singapore." Parkinson's Disease 2020 (March 30, 2020): 1–7. http://dx.doi.org/10.1155/2020/6293124.

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Objective. The aim of this study is to compare Parkinson’s disease (PD) treatment practices by movement disorder (MD) specialists across a decade, and to determine the factors that influence drug choice for the motor symptoms of PD in newly diagnosed drug-naïve patients. Methods. This prospective temporal analysis included patients seen at the National Neuroscience Institute in Singapore and diagnosed with PD by MD specialists in the years 2007 and 2017. Primary outcomes were use of specific PD drugs and changes in drug-prescribing patterns. Descriptive analyses and multivariable logistic regression models determined the extent to which patient characteristics were associated with type of PD treatment. Results. Of 230 patients with PD (mean (SD) age, 66.7 (10.3) years), 131 (57.0%) were male. From 2007 to 2017, the use of ergot dopamine agonists and anticholinergics decreased from 19.3% to 2.0% (P<0.001) and from 12.0% to 2.7% (P=0.004), respectively. The use of monoamine oxidase B inhibitors (MAOBI) increased from 13.3% to 25.2% (P=0.033). The use of levodopa (LD)-sparing strategies decreased nonsignificantly from 33.7% to 24.5% (P=0.133). Overall, 196 (85.2%) patients were initiated on symptomatic monotherapy, with LD being the most commonly prescribed. MAOBI was the most common drug used in combination therapy. Age ≤70 (adjusted OR, 11.9; 95% CI, 4.5–31.5) and Hoehn and Yahr (HY) stage <2 (adjusted OR, 3.4; 95% CI, 1.5–7.7) were independent factors for LD-sparing strategies. Non-LD prescriptions (13 of 92; 14.1%) were more likely to be discontinued compared to LD ones (6 of 149; 4.0%) (P=0.005). Conclusions. Drug-prescribing patterns in PD have changed significantly through the last decade, influenced by emerging evidence and reports of adverse drug effects. Choosing drugs based on the patient’s age and disease severity remain sound guiding principles across the years. It is important that international and national guidelines for pharmacotherapy in PD be updated consistently throughout different socioeconomic settings to optimize care.
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William, James, Peter John, Muhammad Waseem Mumtaz, Ayoub Rashid Ch, Ahmad Adnan, Hamid Mukhtar, Shahzad Sharif, Syed Ali Raza та Muhammad Tayyab Akhtar. "Antioxidant activity, α-glucosidase inhibition and phytochemical profiling of Hyophorbe lagenicaulis leaf extracts". PeerJ 7 (20 червня 2019): e7022. http://dx.doi.org/10.7717/peerj.7022.

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Background Diabetes mellitus type II (DMT-2) is a widely spread metabolic disorder both in developed and developing countries. The role of oxidative stress is well established in DMT-2 pathogenesis. The synthetic drugs for DMT-2 are associated with serious side complications. Antioxidant and α-glucosidase inhibitory actions of phytochemicals from various plant species are considered as an alternative to synthetic drugs for DMT-2 management. The present study aimed to evaluate the antioxidant activity, α-glucosidase inhibitory potential and phytochemical profiling of Hyophorbe lagenicaulis. Methods The total phenolic and flavonoid contents, in vitro antioxidant activity (α, α-diphenyl-β-picrylhydrazyl (DPPH) free radical scavenging and phosphomolybdenum method) and α-glucosidase inhibition of ultrasonicated hydroethanolic H. lagenicaulis leaf extracts were determined spectrophotometrically. The results of DPPH assay and α-glucosidase inhibition were reported in terms of IC50 value. The phytochemical profiling was accomplished by UHPLC-Q-TOF/MS/MS technique. Results and Discussion Findings leaped 60% ethanolic extract as rich fraction regarding total phenolic and flavonoid contents. The 60% ethanolic fraction was a promising source of natural antioxidants and α-glucosidase inhibitory agents as indicated by anti-radical and enzyme inibitory activities. Kaempferol, rutin, hesperetin 5-O-glucoside, kaempferol-coumaroyl-glucoside, luteolin 3-glucoside, Isorhamnetin-3-O-rutinoside, trimethoxyflavone derivatives and citric acid were identified by UHPLC-Q-TOF-MS/MS. These compounds were believed to be responsible for the strong antioxidant and enzyme inhibitory activity of plant extracts. The extensive metabolite profiling of H. lagenicaulis was carried out the first time as never reported previously. The H. lagenicaulis might be an appropriate choice to manage diabetes mellitus in an alternate way. The findings may be further exploited extensively for toxicity evaluation to proceed with functional food development having antidiabetic attributes.
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Jan, Saber, Frances J. Northington, Charlamaine M. Parkinson, and Carl E. Stafstrom. "EEG Monitoring Technique Influences the Management of Hypoxic-Ischemic Seizures in Neonates Undergoing Therapeutic Hypothermia." Developmental Neuroscience 39, no. 1-4 (2017): 82–88. http://dx.doi.org/10.1159/000454855.

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Electroencephalogram (EEG) monitoring techniques for neonatal hypoxia-ischemia (HI) are evolving over time, and the specific type of EEG utilized could influence seizure diagnosis and management. We examined whether the type of EEG performed affected seizure treatment decisions (e.g., the choice and number of antiseizure drugs [ASDs]) in therapeutic hypothermia-treated neonates with HI from 2007 to 2015 in the Johns Hopkins Hospital Neonatal Intensive Care Unit. During this period, 3 different EEG monitoring protocols were utilized: Period 1 (2007-2009), single, brief conventional EEG (1 h duration) at a variable time during therapeutic hypothermia treatment, i.e., ordered when a seizure was suspected; Period 2 (2009-2013), single, brief conventional EEG followed by amplitude-integrated EEG for the duration of therapeutic hypothermia treatment and another brief conventional EEG after rewarming; and Period 3 (2014-2015), continuous video-EEG (cEEG) for the duration of therapeutic hypothermia treatment (72 h) plus for an additional 12 h during and after rewarming. One hundred and sixty-two newborns were included in this retrospective cohort study. As a function of the type and duration of EEG monitoring, we assessed the risk (likelihood) of receiving no ASD, at least 1 ASD, or ≥2 ASDs. We found that the risk of a neonate being prescribed an ASD was 46% less during Period 3 (cEEG) than during Period 1 (brief conventional EEG only) (95% CI 6-69%, p = 0.03). After adjusting for initial EEG and MRI results, compared with Period 1, there was a 38% lower risk of receiving an ASD during Period 2 (95% CI: 9-58%, p = 0.02) and a 67% lower risk during Period 3 (95% CI: 23-86%, p = 0.01). The risk ratio of receiving ≥2 ASDs was not significantly different across the 3 periods. In conclusion, in addition to the higher sensitivity and specificity of continuous video-EEG monitoring, fewer infants are prescribed an ASD when undergoing continuous forms of EEG monitoring (aEEG or cEEG) than those receiving conventional EEG. We recommend that use of continuous video-EEG be considered whenever possible, both to treat seizures more specifically and to avoid overtreatment.
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Connick, Peter, Floriana De Angelis, Richard A. Parker, Domenico Plantone, Anisha Doshi, Nevin John, Jonathan Stutters, et al. "Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART): a multiarm phase IIb randomised, double-blind, placebo-controlled clinical trial comparing the efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis." BMJ Open 8, no. 8 (August 2018): e021944. http://dx.doi.org/10.1136/bmjopen-2018-021944.

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IntroductionThe major unmet need in multiple sclerosis (MS) is for neuroprotective therapies that can slow (or ideally stop) the rate of disease progression. The UK MS Society Clinical Trials Network (CTN) was initiated in 2007 with the purpose of developing a national, efficient, multiarm trial of repurposed drugs. Key underpinning work was commissioned by the CTN to inform the design, outcome selection and drug choice including animal models and a systematic review. This identified seven leading oral agents for repurposing as neuroprotective therapies in secondary progressive MS (SPMS). The purpose of the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART) will be to evaluate the neuroprotective efficacy of three of these drugs, selected with distinct mechanistic actions and previous evidence of likely efficacy, against a common placebo arm. The interventions chosen were: amiloride (acid-sensing ion channel antagonist); fluoxetine (selective serotonin reuptake inhibitor) and riluzole (glutamate antagonist).Methods and analysisPatients with progressing SPMS will be randomised 1:1:1:1 to amiloride, fluoxetine, riluzole or matched placebo and followed for 96 weeks. The primary outcome will be the percentage brain volume change (PBVC) between baseline and 96 weeks, derived from structural MR brain imaging data using the Structural Image Evaluation, using Normalisation, of Atrophy method. With a sample size of 90 per arm, this will give 90% power to detect a 40% reduction in PBVC in any active arm compared with placebo and 80% power to detect a 35% reduction (analysing by analysis of covariance and with adjustment for multiple comparisons of three 1.67% two-sided tests), giving a 5% overall two-sided significance level. MS-SMART is not powered to detect differences between the three active treatment arms. Allowing for a 20% dropout rate, 110 patients per arm will be randomised. The study will take place at Neuroscience centres in England and Scotland.Ethics and disseminationMS-SMART was approved by the Scotland A Research Ethics Committee on 13 January 2013 (REC reference: 13/SS/0007). Results of the study will be submitted for publication in a peer-reviewed journal.Trial registration numbersNCT01910259; 2012-005394-31;ISRCTN28440672.
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Shapira, Barak, Paola Rosca, Ronny Berkovitz, Igor Gorjaltsan, and Yehuda Neumark. "The switch from one substance-of-abuse to another: illicit drug substitution behaviors in a sample of high-risk drug users." PeerJ 8 (July 17, 2020): e9461. http://dx.doi.org/10.7717/peerj.9461.

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Background Substitution can be defined as the consciously motivated choice to use one drug, either licit or illicit, instead of another, due to perceptions of cost, availability, safety, legality, substance characteristics, and substance attributions. Substitution represents a potential risk to drug users, mainly when substitutes are of higher potency and toxicity. This study offers a basic conceptualization of illicit substitution behavior and describes substitution patterns among users of two highly prevalent drugs of abuse—heroin and cannabis. Methods Here, 592 high-risk drug users undergoing pharmacological and psycho-social treatment were interviewed. Patients were asked questions about current drug use, lifetime substitution, and substitution patterns. Descriptive statistics, chi-square tests of independence, and multinomial logistic regressions were used to identify and test correlates of substitution patterns for heroin and cannabis. Results Of the 592 drug users interviewed, 448 subjects (75.7%) reported having substituted their preferred drug for another illicit substance. Interviews yielded a total of 275 substitution events reported by users of cannabis, and 351 substitution events reported by users of heroin. The most frequently reported substitution substances for responders who preferred heroin were illicit non-prescribed “street” methadone (35.9%), followed by oral and transdermal prescription opioids (17.7%). For responders who preferred cannabis, substitution for synthetic cannabinoid receptor agonists (33.5%) followed by alcohol (16.0%) were the most commonly reported. Age at onset–of–use (p < 0.005), population group (p = 0.008), and attending treatment for the first time (p = 0.026) were significantly associated with reported lifetime substitution. Past-year use of stimulants, heroin, hallucinogens, methylenedioxymethamphetamine (MDMA), and novel psychoactive substances were—at the 95% confidence level—also significantly associated with reported lifetime substitution. In multivariate analysis, the odds for methadone substitution among heroin users were significantly affected by age at onset-of-use, type of treatment center, and education. Odds for substitution for synthetic cannabinoid receptor agonists among cannabis users were significantly affected by age, population group, type of treatment center, and education. Conclusion Self-substitution behavior should be considered by clinicians and policymakers as a common practice among most drugusers. Substitution for street methadone provides evidence for the ongoing diversion of this substance from Opioid Maintenance Treatment Centers, while the prominence of substitution of synthetic cannabinoids among dual-diagnosis patients should be regarded as an ongoing risk to patients that needs to be addressed by clinicians. Analysis of additional substitution patterns should provide further valuable insights into the behavior of drugusers.
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Lin, Ming-Hwai, Hsiao-Ting Chang, Tzeng-Ji Chen, and Shinn-Jang Hwang. "Why people select the outpatient clinic of medical centers: a nationwide analysis in Taiwan." PeerJ 8 (August 27, 2020): e9829. http://dx.doi.org/10.7717/peerj.9829.

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Introduction In contrast to other countries, Taiwan’s National Health Insurance (NHI) program allows patients to freely select the specialists and tiers of medical care facility without a referral. Some medical centers in Taiwan receive over 10,000 outpatients per day. In the NHI program, the co-payment was increased for high-tier facilities for outpatient visits in 2002, 2005, and 2017. However, the policies only mildly reduced the use of high-tier medical care facilities. The main purpose of this study was to evaluate the factors contributing to the patients’ selection of the outpatient clinic of medical centers without a referral. Methods An online anonymous survey was conducted by using the Google Forms platform utilizing a self-constructed questionnaire from September to October 2018. A nationwide sample in Taiwan was recruited using convenience sampling through social media. Based on a literature review and a focus group, 20 factors that may affect the choice of the outpatient institution were constructed. The associations between items that affect the patients selection of outpatient clinics were assessed using exploratory factor analysis. Principal axis factoring was performed to identify the major factors affecting the decision. Multiple logistic regression was performed to determine which factors satisfactorily explained “visiting the outpatient clinic of the medical center for an illness without a referral.” Results During the survey period, 5,060 people browsed the online survey, and 1,003 responded and completed the online questionnaire. Therefore, the response rate was 19.8%. A total of 987 valid responses was collected. Exploratory factor analysis revealed that three main factors, namely the “physician factor”, “image and reputation factor”, and “facility and medication factor”, affected the selection of outpatient clinics. A series of logistic regressions indicated that patients who reported that hospital facilities, high-quality drugs, and diverse specialties were very important were more likely to select the outpatient clinic of a medical center (OR = 2.218, 95% CI [1.514–3.249]). Patients who reported that physician factors were very important were less likely to select a medical center (OR = 0.717, 95% CI [0.523–0.984]). Patients who were previously satisfied with their experience of the primary clinics or had a regular family doctor were less likely to choose a medical center (OR = 0.509, 95% CI -0.435–0.595] and OR = 0.676, 95% CI [0.471–0.969]). Conclusion In Taiwan, patients with good primary medical experience and regular family physicians had significantly lower rates by selecting the outpatient clinic of a medical center. The results of this study support that the key to establishing graded medical care is to prioritize the strengthening of the primary medical system.
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Xu, Xing, Nanqin Li, Jun Wen, Ping Yang, Xue Lu, Zilin Wang, Teng He, et al. "Specific inhibition of interpeduncular nucleus GABAergic neurons alleviates anxiety-like behaviors in male mice of prolonged abstinence from methamphetamine." Journal of Neuroscience, December 23, 2022, JN—RM—1767–22. http://dx.doi.org/10.1523/jneurosci.1767-22.2022.

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Anxiety is one of the most common withdrawal symptoms of methamphetamine (METH) abuse, which further drives relapse to drugs. Interpeduncular nucleus (IPN) has been implicated in anxiety-like behaviors and addiction, yet its role in METH abstinence-induced anxiety remains unknown. Here, we found that prolonged abstinence from METH enhanced anxiety-like behaviors in male mice, accompanied by more excited IPN GABAergic neurons, as indicated by the increased c-Fos expression and the enhanced neuronal excitability by electrophysiological recording in the GABAergic neurons. Using the DREADDs method, specific inhibition of IPN GABAergic neurons rescued the aberrant neuronal excitation of IPN GABAergic neurons, and efficiently reduced anxiety-like behaviors, whereas did not induce depression-like behaviors in male mice of prolonged abstinence from METH. These findings reveal that IPN GABAergic neurons should be a promising brain target to alleviate late withdrawal symptoms of METH with few side effects.SIGNIFICANCE STATEMENT:Prolonged abstinence from METH triggers IPN GABAergic neurons, and ultimately increases anxiety in male mice. Suppressing IPN GABAergic neurons rescues METH abstinence-induced aberrant neuronal excitation of IPN GABAergic neurons, and efficiently reduces anxiety in mice.
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"Drugs and society: v.1: Abstinence-drug enforcement administration; v.2: Drug laws-overdose; v.3: Oxycodone-youth culture." Choice Reviews Online 43, no. 07 (March 1, 2006): 43–3761. http://dx.doi.org/10.5860/choice.43-3761.

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Quintana, Gonzalo R. "Commentary: “Hearing, touching, and multisensory integration during mate choice” – Sex, Drugs and Leather Jackets." Frontiers in Neural Circuits 16 (December 8, 2022). http://dx.doi.org/10.3389/fncir.2022.1080276.

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Domi, Ana, Erika Lucente, Davide Cadeddu, and Louise Adermark. "Nicotine but not saline self-administering or yoked control conditions produces sustained neuroadaptations in the accumbens shell." Frontiers in Molecular Neuroscience 16 (January 25, 2023). http://dx.doi.org/10.3389/fnmol.2023.1105388.

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Анотація:
IntroductionUsing yoked animals as the control when monitoring operant drug-self-administration is considered the golden standard. However, instrumental learning per se recruits several neurocircuits that may produce distinct or overlapping neuroadaptations with drugs of abuse. The aim of this project was to assess if contingent responding for nicotine or saline in the presence of a light stimulus as a conditioned reinforcer is associated with sustained neurophysiological adaptations in the nucleus accumbens shell (nAcS), a brain region repeatedly associated with reward related behaviors.MethodsTo this end, nicotine-or saline-administrating rats and yoked-saline stimulus-unpaired training conditions were assessed in operant boxes over four consecutive weeks. After four additional weeks of home cage forced abstinence and subsequent cue reinforced responding under extinction conditions, ex vivo electrophysiology was performed in the nAcS medium spiny neurons (MSNs).ResultsWhole cell recordings conducted in voltage and current-clamp mode showed that excitatory synapses in the nAcS were altered after prolonged forced abstinence from nicotine self-administration. We observed an increase in sEPSC amplitude in animals with a history of contingent nicotine SA potentially indicating higher excitability of accumbal MSNs, which was further supported by current clamp recordings. Interestingly no sustained neuroadaptations were elicited in saline exposed rats from nicotine associated visual cues compared to the yoked controls.ConclusionThe data presented here indicate that nicotine self-administration produces sustained neuroadaptations in the nAcS while operant responding driven by nicotine visual stimuli has no long-term effects on MSNs in nAcS.
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43

Namba, Mark D., Jonna M. Leyrer-Jackson, Erin K. Nagy, M. Foster Olive, and Janet L. Neisewander. "Neuroimmune Mechanisms as Novel Treatment Targets for Substance Use Disorders and Associated Comorbidities." Frontiers in Neuroscience 15 (April 15, 2021). http://dx.doi.org/10.3389/fnins.2021.650785.

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Recent studies examining the neurobiology of substance abuse have revealed a significant role of neuroimmune signaling as a mechanism through which drugs of abuse induce aberrant changes in synaptic plasticity and contribute to substance abuse-related behaviors. Immune signaling within the brain and the periphery critically regulates homeostasis of the nervous system. Perturbations in immune signaling can induce neuroinflammation or immunosuppression, which dysregulate nervous system function including neural processes associated with substance use disorders (SUDs). In this review, we discuss the literature that demonstrates a role of neuroimmune signaling in regulating learning, memory, and synaptic plasticity, emphasizing specific cytokine signaling within the central nervous system. We then highlight recent preclinical studies, within the last 5 years when possible, that have identified immune mechanisms within the brain and the periphery associated with addiction-related behaviors. Findings thus far underscore the need for future investigations into the clinical potential of immunopharmacology as a novel approach toward treating SUDs. Considering the high prevalence rate of comorbidities among those with SUDs, we also discuss neuroimmune mechanisms of common comorbidities associated with SUDs and highlight potentially novel treatment targets for these comorbid conditions. We argue that immunopharmacology represents a novel frontier in the development of new pharmacotherapies that promote long-term abstinence from drug use and minimize the detrimental impact of SUD comorbidities on patient health and treatment outcomes.
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44

Hirschbichler, Stephanie T., John C. Rothwell, and Sanjay G. Manohar. "Dopamine increases risky choice while D2 blockade shortens decision time." Experimental Brain Research, November 9, 2022. http://dx.doi.org/10.1007/s00221-022-06501-9.

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AbstractDopamine is crucially involved in decision-making and overstimulation within dopaminergic pathways can lead to impulsive behaviour, including a desire to take risks and reduced deliberation before acting. These behavioural changes are side effects of treatment with dopaminergic drugs in Parkinson disease, but their likelihood of occurrence is difficult to predict and may be influenced by the individual’s baseline endogenous dopamine state, and indeed correlate with sensation-seeking personality traits. We here collected data on a standard gambling task in healthy volunteers given either placebo, 2.5 mg of the dopamine antagonist haloperidol or 100/25 mg of the dopamine precursor levodopa in a within-subject design. We found an increase in risky choices on levodopa. Choices were, however, made faster on haloperidol with no effect of levodopa on deliberation time. Shortened deliberation times on haloperidol occurred in low sensation-seekers only, suggesting a correlation between sensation-seeking personality trait and baseline dopamine levels. We hypothesise that levodopa increases risk-taking behaviour via overstimulation at both D1 and D2 receptor level, while a single low dose of haloperidol, as previously reported (Frank and O’Reilly 2006), may block D2 receptors pre- and post-synaptically and may paradoxically lead to higher striatal dopamine acting on remaining striatal D1 receptors, causing speedier decision without influencing risk tolerance. These effects could also fit with a recently proposed computational model of the basal ganglia (Moeller and Bogacz 2019; Moeller et al. 2021). Furthermore, our data suggest that the actual dopaminergic drug effect may be dependent on the individual’s baseline dopamine state, which may influence our therapeutic decision as clinicians in the future.
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45

Sazonova, Elena V., Gelina S. Kopeina, Evgeny N. Imyanitov, and Boris Zhivotovsky. "Platinum drugs and taxanes: can we overcome resistance?" Cell Death Discovery 7, no. 1 (June 2021). http://dx.doi.org/10.1038/s41420-021-00554-5.

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AbstractCancer therapy is aimed at the elimination of tumor cells and acts via the cessation of cell proliferation and induction of cell death. Many research publications discussing the mechanisms of anticancer drugs use the terms “cell death” and “apoptosis” interchangeably, given that apoptotic pathways are the most common components of the action of targeted and cytotoxic compounds. However, there is sound evidence suggesting that other mechanisms of drug-induced cell death, such as necroptosis, ferroptosis, autophagy, etc. may significantly contribute to the fate of cancer cells. Molecular cross-talks between apoptotic and nonapoptotic death pathways underlie the successes and the failures of therapeutic interventions. Here we discuss the nuances of the antitumor action of two groups of the widely used anticancer drugs, i.e., platinum salts and taxane derivatives. The available data suggest that intelligent interference with the choice of cell death pathways may open novel opportunities for cancer treatment.
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46

Allichon, Marie-Charlotte, Vanesa Ortiz, Paula Pousinha, Andry Andrianarivelo, Anna Petitbon, Nicolas Heck, Pierre Trifilieff, Jacques Barik, and Peter Vanhoutte. "Cell-Type-Specific Adaptions in Striatal Medium-Sized Spiny Neurons and Their Roles in Behavioral Responses to Drugs of Abuse." Frontiers in Synaptic Neuroscience 13 (December 14, 2021). http://dx.doi.org/10.3389/fnsyn.2021.799274.

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Drug addiction is defined as a compulsive pattern of drug-seeking- and taking- behavior, with recurrent episodes of abstinence and relapse, and a loss of control despite negative consequences. Addictive drugs promote reinforcement by increasing dopamine in the mesocorticolimbic system, which alters excitatory glutamate transmission within the reward circuitry, thereby hijacking reward processing. Within the reward circuitry, the striatum is a key target structure of drugs of abuse since it is at the crossroad of converging glutamate inputs from limbic, thalamic and cortical regions, encoding components of drug-associated stimuli and environment, and dopamine that mediates reward prediction error and incentive values. These signals are integrated by medium-sized spiny neurons (MSN), which receive glutamate and dopamine axons converging onto their dendritic spines. MSN primarily form two mostly distinct populations based on the expression of either DA-D1 (D1R) or DA-D2 (D2R) receptors. While a classical view is that the two MSN populations act in parallel, playing antagonistic functional roles, the picture seems much more complex. Herein, we review recent studies, based on the use of cell-type-specific manipulations, demonstrating that dopamine differentially modulates dendritic spine density and synapse formation, as well as glutamate transmission, at specific inputs projecting onto D1R-MSN and D2R-MSN to shape persistent pathological behavioral in response to drugs of abuse. We also discuss the identification of distinct molecular events underlying the detrimental interplay between dopamine and glutamate signaling in D1R-MSN and D2R-MSN and highlight the relevance of such cell-type-specific molecular studies for the development of innovative strategies with potential therapeutic value for addiction. Because drug addiction is highly prevalent in patients with other psychiatric disorders when compared to the general population, we last discuss the hypothesis that shared cellular and molecular adaptations within common circuits could explain the co-occurrence of addiction and depression. We will therefore conclude this review by examining how the nucleus accumbens (NAc) could constitute a key interface between addiction and depression.
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47

Duttke, Sascha H., Patricia Montilla-Perez, Max W. Chang, Hairi Li, Hao Chen, Lieselot L. G. Carrette, Giordano de Guglielmo, et al. "Glucocorticoid Receptor-Regulated Enhancers Play a Central Role in the Gene Regulatory Networks Underlying Drug Addiction." Frontiers in Neuroscience 16 (May 16, 2022). http://dx.doi.org/10.3389/fnins.2022.858427.

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Substance abuse and addiction represent a significant public health problem that impacts multiple dimensions of society, including healthcare, the economy, and the workforce. In 2021, over 100,000 drug overdose deaths were reported in the US, with an alarming increase in fatalities related to opioids and psychostimulants. Understanding the fundamental gene regulatory mechanisms underlying addiction and related behaviors could facilitate more effective treatments. To explore how repeated drug exposure alters gene regulatory networks in the brain, we combined capped small (cs)RNA-seq, which accurately captures nascent-like initiating transcripts from total RNA, with Hi-C and single nuclei (sn)ATAC-seq. We profiled initiating transcripts in two addiction-related brain regions, the prefrontal cortex (PFC) and the nucleus accumbens (NAc), from rats that were never exposed to drugs or were subjected to prolonged abstinence after oxycodone or cocaine intravenous self-administration (IVSA). Interrogating over 100,000 active transcription start regions (TSRs) revealed that most TSRs had hallmarks of bonafide enhancers and highlighted the KLF/SP1, RFX, and AP1 transcription factors families as central to establishing brain-specific gene regulatory programs. Analysis of rats with addiction-like behaviors versus controls identified addiction-associated repression of transcription at regulatory enhancers recognized by nuclear receptor subfamily 3 group C (NR3C) factors, including glucocorticoid receptors. Cell-type deconvolution analysis using snATAC-seq uncovered a potential role of glial cells in driving the gene regulatory programs associated with addiction-related phenotypes. These findings highlight the power of advanced transcriptomics methods to provide insight into how addiction perturbs gene regulatory programs in the brain.
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48

Alghamdi, Badrah S., та Fahad S. Alshehri. "Melatonin Blocks Morphine-Induced Place Preference: Involvement of GLT-1, NF-κB, BDNF, and CREB in the Nucleus Accumbens". Frontiers in Behavioral Neuroscience 15 (14 жовтня 2021). http://dx.doi.org/10.3389/fnbeh.2021.762297.

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Opioid addiction remains a widespread issue despite continuous attempts by the FDA to help maintain abstinence. Melatonin is a neurohormone considered to be involved only in the neuroendocrine and reproductive systems; however, recent reports have demonstrated its potential to attenuate drug addiction and dependence. Cumulative studies have suggested that melatonin can attenuate the rewarding effects of several drugs of abuse, including opioids. This study aimed to investigate the effect of melatonin (50 mg/kg) on morphine (5 mg/kg) to produce place preference. We also investigated the effect of melatonin and morphine on the expression of GLT-1, BDNF, NF-κB, and CREB within the nucleus accumbens. Male Wistar rats were divided into control, morphine, melatonin, and the morphine + melatonin groups. The study involved a two-phase habituation phase from day 1 to day 3 and an acquisition phase from day 5 to day 14. The conditioned place preference (CPP) score, distance traveled, resting time, ambulatory count, and total activity count were measured for all animals. Rats that received morphine showed a significant increase in CPP score compared to those in the control group. Morphine treatment reduced the mRNA expression of GLT-1, BDNF, and CREB and increased that of NF-κB. However, melatonin treatment administered 30 min before morphine treatment attenuated morphine place preference and reversed GLT-1, BDNF, NF-κB, and CREB expression levels. In conclusion, the study results indicate, for the first time, the new potential targets of melatonin in modulating morphine-induced CPP.
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49

Pomrenze, Matthew B., Franciely Paliarin, and Rajani Maiya. "Friend of the Devil: Negative Social Influences Driving Substance Use Disorders." Frontiers in Behavioral Neuroscience 16 (February 10, 2022). http://dx.doi.org/10.3389/fnbeh.2022.836996.

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Substance use disorders in humans have significant social influences, both positive and negative. While prosocial behaviors promote group cooperation and are naturally rewarding, distressing social encounters, such as aggression exhibited by a conspecific, are aversive and can enhance the sensitivity to rewarding substances, promote the acquisition of drug-taking, and reinstate drug-seeking. On the other hand, withdrawal and prolonged abstinence from drugs of abuse can promote social avoidance and suppress social motivation, accentuating drug cravings and facilitating relapse. Understanding how complex social states and experiences modulate drug-seeking behaviors as well as the underlying circuit dynamics, such as those interacting with mesolimbic reward systems, will greatly facilitate progress on understanding triggers of drug use, drug relapse and the chronicity of substance use disorders. Here we discuss some of the common circuit mechanisms underlying social and addictive behaviors that may underlie their antagonistic functions. We also highlight key neurochemicals involved in social influences over addiction that are frequently identified in comorbid psychiatric conditions. Finally, we integrate these data with recent findings on (±)3,4-methylenedioxymethamphetamine (MDMA) that suggest functional segregation and convergence of social and reward circuits that may be relevant to substance use disorder treatment through the competitive nature of these two types of reward. More studies focused on the relationship between social behavior and addictive behavior we hope will spur the development of treatment strategies aimed at breaking vicious addiction cycles.
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50

Peregud, Danil, Mikhail Stepanichev, and Natalia Gulyaeva. "Drinking Pattern in Intermittent Access Two-Bottle-Choice Paradigm in Male Wistar Rats Is Associated with Exon-Specific BDNF Expression in the Hippocampus During Early Abstinence." Journal of Molecular Neuroscience, June 26, 2020. http://dx.doi.org/10.1007/s12031-020-01645-1.

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