Addiction Relapse Research Articles

Corticotropin releasing factor (CRF) systems: Promoting cocaine pursuit without distress via incentive motivation.

Corticotropin releasing factor (CRF) systems in limbic structures are posited to mediate stress-induced relapse in addiction, traditionally by generating distress states that spur drug consumption as attempts at hedonic self-medication. Yet evidence suggests that activating CRF-expressing neurons in the central amygdala (CeA) or nucleus accumbens (NAc) can magnify incentive motivation in absence of distress, at least for sucrose rewards. However, traditional CRF hypotheses in addiction neuroscience are primarily directed toward drug rewards. The question remains open whether CRF systems can similarly act via incentive motivation mechanisms to promote pursuit of drug rewards, such as cocaine. Here we tested whether optogenetic excitation of CRF-containing neurons in either NAc medial shell, lateral CeA, or dorsolateral BNST of transgenic Crh-Cre+ rats would spur preference and pursuit of a particular laser-paired cocaine reward over an alternative cocaine reward, and whether excitation served as a positively-valenced incentive itself, through laser self-stimulation tests. We report that excitation of CRF-containing neurons in either NAc or CeA recruited mesocorticolimbic circuitry to amplify incentive motivation to pursue the laser-paired cocaine: focusing preference on the laser-paired cocaine reward in a two-choice task, and spurred pursuit as doubled breakpoint in a progressive ratio task. Crucially indicating positive-valence, excitation of CRF neurons in NAc and CeA also was actively sought after by most rats in self-stimulation tasks. Conversely, CRF neuronal activation in BNST was never self-stimulated, but failed to enhance cocaine consumption. Collectively, we find that NAc and CeA CRF-containing neurons can amplify pursuit and consumption of cocaine by positively-valenced incentive mechanisms, without any aversive distress.

The Health and Health Needs of People under Community Supervision

Americans under community supervision experience high rates of chronic disease, mental illness, and substance use disorders but have poor access to high-quality preventive care and treatment. Pervasive barriers to healthcare and health insurance reinforce poor health, as do restrictions to evidence-based addiction treatment. We propose that community supervision agencies transfer management of the health of supervised individuals to an expanded community-based healthcare system and that they abandon practices at odds with the science of addiction medicine (e.g. prohibitions on medications to treat addiction, and revocation of community release for addiction relapse). Further, we argue that correctional systems should prioritize health of those under supervision by standardizing health-related protocols, including basic needs resources in discharge planning, and leveraging the skills of individuals with lived experiences in the correctional system. If implemented, the success of our recommendations would require expansion of community-based primary care, mental health, and addiction treatment centers.

Structural Relationships of Risk-Taking and Difficulty in Emotion Regulation with Tendency to Addiction Relapse in Patients Undergoing Methadone Maintenance Treatment: Mediating Role of Distress Tolerance and Cognitive Flexibility

Structural Relationships of Risk-Taking and Difficulty in Emotion Regulation with Tendency to Addiction Relapse in Patients Undergoing Methadone Maintenance Treatment: Mediating Role of Distress Tolerance and Cognitive Flexibility

The Hypothesis of Subliminal Cue Reactivity in Addiction Revisited: An fMRI Study

Introduction: Exposure to conditioned cues is a common trigger of relapse in addiction. It has been suggested that such cues can activate motivationally relevant neurocircuitry in individuals with substance use disorders even without being consciously perceived. We aimed to see if this could be replicated in a sample with severe amphetamine use disorder and a control group of healthy subjects. Methods: We used fMRI to test the hypothesis that individuals with amphetamine use disorder, but not healthy controls, exhibit a specific neural reactivity to subliminally presented pictures related to amphetamine use. Twenty-four amphetamine users and 25 healthy controls were recruited and left data of sufficient quality to be included in the final analysis. All subjects were exposed to drug-related and neutral pictures of short duration (13.3 ms), followed by a backward visual mask image. The contrast of interest was drug versus neutral subliminal pictures. Results: There were no statistically significant differences in BOLD signal between the drug and neutral cues, neither in the limbic regions of primary interest nor in exploratory whole-brain analyses. The same results were found both in amphetamine users and controls. Discussion/Conclusion: We found no evidence of neural reactivity to subliminally presented drug cues in this sample of subjects with severe amphetamine dependence. These results are discussed in relation to the earlier literature, and the evidence for subliminal drug cue reactivity in substance use disorders is questioned.

Effects of Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 on the Reinstatement of Cocaine-Mediated Conditioned Place Preference in Mice.

A high percentage of relapse to compulsive cocaine-taking and cocaine-seeking behaviors following abstinence constitutes a major obstacle to the clinical treatment of cocaine addiction. Thus, there is a substantial need to develop effective pharmacotherapies for the prevention of cocaine relapse. The reinstatement paradigm is known as the most commonly used animal model to study relapse in abstinent human addicts. The primary aim of this study is to investigate the potential effects of systemic administration of glucagon-like peptide-1 receptor agonist (GLP-1RA) exendin-4 (Ex4) on the cocaine- and stress-triggered reinstatement of cocaine-induced conditioned place preference (CPP) in male C57BL/6J mice. The biased CPP paradigm was induced by alternating administration of saline and cocaine (20 mg/kg), followed by extinction training and then reinstatement by either a cocaine prime (10 mg/kg) or exposure to swimming on the reinstatement test day. To examine the effects of Ex4 on the reinstatement, Ex4 was systemically administered 1 h after the daily extinction session. Additionally, we also explored the associated molecular basis of the behavioral effects of Ex4. The expression of nuclear factor κβ (NF-κβ) in the nucleus accumbens (NAc) was detected using Western blotting. As a result, all animals that were treated with cocaine during the conditioning period successfully acquired CPP, and their CPP response was extinguished after 8 extinction sessions. Furthermore, the animals that were exposed to cocaine or swimming on the reinstatement day showed a significant reinstatement of CPP. Interestingly, systemic pretreatment with Ex4 was sufficient to attenuate cocaine- and stress-primed reinstatement of cocaine-induced CPP. Additionally, the expression of NF-κβ, which was upregulated by cocaine, was normalized by Ex4 in the cocaine-experienced mice. Altogether, our study reveals the novel effect of Ex4 on the reinstatement of cocaine-induced CPP and suggests that GLP-1R agonists appear to be highly promising drugs in the treatment of cocaine use disorder.

Substance use disorders during the COVID-19 pandemic: looking for new innovative approaches.

Background and aim:The destructive impact of the still ongoing COVID-19 pandemic on those struggling with substance use disorders (SUD) stems from the daunting challenges which SUD patients experience in terms of coping with their condition and receiving care in a timely fashion.Methods:Patients struggling with addiction are at particularly high risk, due to the underlying vulnerabilities in their conditions and the stigmatization they often suffer. New Psychoactive Substances stand out as a critical area of concern. The authors have conducted a broad-ranging search to assess the impact of SUDs, along with their related mental, physical, and behavioral symptoms, against the backdrop of the COVID-19, taking into account how drug trafficking and consumption trends have evolved as the emergency draws out, and the cyberspace comes to play an ever-bigger role.Results:Given that roughly 1.5%-5% of the global burden of disease can be ascribed to alcohol abuse and substance addiction, the role of pandemic-related potential contributing factors in the exacerbation and relapse of SUDs and behavioral addiction cannot be discounted and needs targeted measures tailored to the special needs of SUD patients. Escalating environmental stressors stemming from abnormal circumstances can undermine recovery efforts and threaten the very survival of countless SUD patients, increasing the likelihood of relapsing for those in recovery.Conclusions:Policymakers and legislators have not yet put in place targeted measures and adjustments in the health care delivery mechanisms in order to countervail the pandemic impact on SUD sufferers, and the ever-evolving patterns of use and trafficking. (www.actabiomedica.it)

Oxytocin Attenuates the Stress-Induced Reinstatement of Alcohol-Seeking in Male Rats: Role of the Central Amygdala.

Factors such as stress and anxiety often contribute to alcohol-dependent behavior and can trigger a relapse of alcohol addiction and use. Therefore, it is important to investigate potential pharmacological interventions that may alleviate the influence of stress on addiction-related behaviors. Previous studies have demonstrated that the neuropeptide oxytocin has promising anxiolytic potential in mammals and may offer a pharmacological target to diminish the emotional impact on reinstatement of alcohol-seeking. The purpose of the present study was to investigate the effect of oxytocin on stress-induced alcohol relapse and identify a neural structure mediating this effect through the use of an ethanol self-administration and yohimbine-induced reinstatement paradigm. While yohimbine administration resulted in the reinstatement of ethanol-seeking behavior, the concurrent administration of yohimbine and oxytocin attenuated this effect, suggesting that oxytocin may disrupt stress-induced ethanol-seeking behavior. The central amygdala (CeA) is a structure that drives emotional responses and robustly expresses oxytocin receptors. Intra-CeA oxytocin similarly attenuated the yohimbine-induced reinstatement of ethanol-seeking behavior. These results demonstrate that oxytocin has the potential to attenuate stress-induced relapse into ethanol-seeking behavior, and that this mechanism occurs specifically within the central amygdala.

909. Treating Hepatitis C Virus (HCV) in Young Adult Active Drug Users Is Possible

Abstract Background Successful treatment of HCV in persons who inject drugs (PWIDS), has been reported for patients who were older or who had used drugs more than 6 months prior. The young, < 35 year of age (yoa), active user has not been well studied or reported. We performed a pilot treatment study in a young cohort of PWIDS to evaluate cure rates of HCV in this population. Methods Young, active PWIDS using < 6months earlier, < 35 yoa were identified. Treatment for HCV with glecaprevir/pibrentasvir (G/P) and concurrent treatment for opiate use disorder with XR Naletrexone (XR-NTX) was provided. Two patients chose methadone. Patients were followed up to 12 months after enrollment. Patients were evaluated for adherence, side effects, alanine aminotransferase (ALT) levels, urine drug screens (UDS) and opioid craving scores using a visual analog scale (VAS) while on XR-NTX to assess management of their addiction. Rates of treatment completion, SVR 4 & 12 were determined. Results 30 patients were recruited: 18 were women. Average age was 28 with a range of 23-35. Recent injection drug use was common with 22 (73%) having injected within the 30 days and all having injected within 3 months of recruitment. The average ALT on enrollment was 106. Genotypes were 1 (15), 3a (11), and unknown (4). Of the 30 patients, 15 failed to come for the required 2 visits prior to starting G/P. Lost to follow up occurred due to relapse of addiction (9), overdose death (1), lost communication and suspected relapse (4). 15 began and completed G/P. 15 were cured of their HCV infection. 17 patients receive one or more doses of XR-NTX. On average patients were on XR-NTX for 4.8 months. Sobriety was measured for patients on XR-NTX using Opiate Craving Scores using the Visual Analogue Scale (VAS) and UDS (Figure 1) demonstrating excellent control of craving and significant declines positive UDS. Toxicities were uncommon with no treatment limiting adverse events. Adverse effects of XR-NTX included mild injection site irritation. No ALT abnormalities were noted. Conclusion Young active PWIDS can successfully be cured of HCV. Their addiction can be concurrently managed with XR-NXT. Our findings suggest it is safe to treatment active users with active HCV with XR-NXT improving elimination goals. Disclosures Ronald G. Nahass, MD, Abbvie (Grant/Research Support, Speaker’s Bureau)Alkermes (Grant/Research Support)Gilead (Grant/Research Support, Speaker’s Bureau)Merck (Grant/Research Support, Speaker’s Bureau) Kathleen H. Seneca, MSN, Abbvie (Research Grant or Support)Alkermes (Research Grant or Support)Gilead (Speaker’s Bureau) Ruth A. Homer, MSW, Abbvie (Grant/Research Support)Alkermes (Grant/Research Support)

Assessing Warning Signs of Relapse in Drug Addicts: Translation and Validation of AWARE Questionnaire

Aim: To translate and validate Advance Warning of Relapse (AWARE) Questionnaire in to Urdu language for assessing relapse among drug addicts of Pakistan. Methods: The research comprises of translation of AWARE, temporal validation of translated scale, and its construct validation. Two items (22, 28) were modified keeping structural and functional equivalence. Sample for validation was obtained from rehabilitation centers of Islamabad and Rawalpindi, with age ranging from 18-60 years (M=29.3; SD=8.2). Temporal validity was determined by test-retest reliability. Exploratory factor analysis (EFA) was used to determine the valid factor structure, whose model fitness was assessed using Confirmatory factor analysis (CFA). Reliability was used to assess the internal consistency. Results: It was found that translated scale possess significant temporal validity (α= .81). EFA demonstrate a unifactorial structure (λ > .30) explaining variance of about 34.3%; such that four items (8, 14, 20, 26) were removed based on poor factor loadings. Indices of model fit through CFA confirm factor structure. Reliability of scale was also significant (α= .90). Conclusion: Findings suggested the reliable and valid nature of AWARE-Urdu to assess warning signs of relapse in drug addicts. Keywords: Warning signs, relapse, drug addicts, Urdu translation, validation, AWARE

Drug Repurposing Patent Applications April–June 2021

Drug Repurposing Patent Applications April–June 2021

Opioids cause dissociated states of consciousness in C57BL/6J mice.

The electroencephalogram (EEG) provides an objective, neural correlate of consciousness. Opioid receptors modulate mammalian neuronal excitability, and this fact was used to characterize how opioids administered to mice alter EEG power and states of consciousness. The present study tested the hypothesis that antinociceptive doses of fentanyl, morphine, or buprenorphine differentially alter the EEG and states of sleep and wakefulness in adult, male C57BL/6J mice. Mice were anesthetized and implanted with telemeters that enabled wireless recordings of cortical EEG and electromyogram (EMG). After surgical recovery, EEG and EMG were used to objectively score states of consciousness as wakefulness, rapid eye movement (REM) sleep, or non-REM (NREM) sleep. Measures of EEG power (dB) were quantified as δ (0.5-4 Hz), θ (4-8 Hz), α (8-13 Hz), σ (12-15 Hz), β (13-30 Hz), and γ (30-60 Hz). Compared with saline (control), fentanyl and morphine decreased NREM sleep, morphine eliminated REM sleep, and buprenorphine eliminated NREM sleep and REM sleep. Opioids significantly and differentially disrupted the temporal organization of sleep/wake states, altered specific EEG frequency bands, and caused dissociated states of consciousness. The results are discussed relative to the fact that opioids, pain, and sleep modulate interacting states of consciousness.NEW & NOTEWORTHY This study discovered that antinociceptive doses of fentanyl, morphine, and buprenorphine significantly and differentially disrupt EEG-defined states of consciousness in C57BL/6J mice. These data are noteworthy because: 1) buprenorphine is commonly used in medication-assisted therapy for opioid addiction, and 2) there is evidence that disordered sleep can promote addiction relapse. The results contribute to community phenotyping efforts by making publicly available all descriptive and inferential statistics from this study (Supplemental Tables S1-S8).

Psychological and mental health impacts of COVID-19 pandemic on healthcare workers in China: A review.

The coronavirus disease-19 (COVID-19) pandemic has put healthcare workers in an unprecedented situation, increasing their psychological and mental health distress. Much research has focused on the issues surrounding anxiety, depression, and stress among healthcare workers. The consequences of mental health problems on healthcare workers’ physical health, health-compromising behaviours, suicide ideation, family relationships, and job satisfaction during the COVID-19 pandemic are not well studied. Enhanced psychological stress has known effects on an individual’s physical health. In healthcare workers with pre-existing comorbidities, psychological stressors may exacerbate their current health problems. Healthcare professionals are known to have a high risk of substance use, hence they may be at risk of development of substance use addiction or vulnerable to addiction relapse. Frontline COVID-19 healthcare workers are being pushed above and beyond their limits, possibly resulting in suicidal tendencies. Furthermore, the burden of high workload and burnout may also have serious manifestations in relationships with family and an intention to quit their jobs. Future studies should explore the above-mentioned deleterious consequences to provide insight into the development of mental healthcare strategies to combat the psychological impact of COVID-19 on healthcare workers during the COVID-19 emergency. It is imperative to employ strategies to care for and policies to protect the psychological well-being of healthcare workers.

4R Tau Modulates Cocaine-Associated Memory through Adult Dorsal Hippocampal Neurogenesis.

The development, persistence and relapse of drug addiction require drug memory that generally develops with drug administration-paired contextual stimuli. Adult hippocampal neurogenesis (AHN) contributes to cocaine memory formation; however, the underlying mechanism remains unclear. Male mice hippocampal expression of Tau was significantly decreased during the cocaine-associated memory formation. Genetic overexpression of four microtubule-binding repeats Tau (4R Tau) in the mice hippocampus disrupted cocaine memory by suppressing AHN. Furthermore, 4R Tau directly interacted with phosphoinositide 3-kinase (PI3K)-p85 and impaired its nuclear translocation and PI3K-AKT signaling, processes required for hippocampal neuron proliferation. Collectively, 4R Tau modulates cocaine memory formation by disrupting AHN, suggesting a novel mechanism underlying cocaine memory formation and provide a new strategy for the treatment of cocaine addiction.SIGNIFICANCE STATEMENT Drug memory that generally develops with drug-paired contextual stimuli and drug administration is critical for the development, persistence and relapse of drug addiction. Previous studies have suggested that adult hippocampal neurogenesis (AHN) plays a role in cocaine memory formation. Here, we showed that Tau was significantly downregulated in the hippocampus in the cocaine memory formation. Tau knock-out (KO) promoted AHN in the hippocampal dentate gyrus (DG), resulting in the enhanced memory formation evoked by cocaine-cue stimuli. In contrast, genetically overexpressed 4R Tau in the hippocampus disrupted cocaine-cue memory by suppressing AHN. In addition, 4R Tau interacted directly with phosphoinositide 3-kinase (PI3K)-p85 and hindered its nuclear translocation, eventually repressing PI3K-AKT signaling, which is essential for hippocampal neuronal proliferation.

Attention bias modification in drug addiction: Enhancing control of subsequent habits

A relapse in addiction is often precipitated by heightened attention bias to drug-related cues, underpinned by a subcortically mediated transition to habitual/automatized responding and reduced prefrontal control. Modification of such automatized attention bias is a fundamental, albeit elusive, target for relapse reduction. Here, on a trial-by-trial basis, we used electroencephalography and eye tracking with a task that assessed, in this order, drug cue reactivity, its instructed self-regulation via reappraisal, and the immediate aftereffects on spontaneous (i.e., not instructed and automatized) attention bias. The results show that cognitive reappraisal, a facet of prefrontal control, decreased spontaneous attention bias to drug-related cues in cocaine-addicted individuals, more so in those with less frequent recent use. The results point to the mechanisms underlying the disruption of automatized maladaptive drug-related attention bias in cocaine addiction. These results pave the way for future studies to examine the role of such habit disruption in reducing compulsive drug seeking outside the controlled laboratory environment, with the ultimate goal of developing a readily deployable cognitive-behavioral and personalized intervention for drug addiction.

Neurocognitive Empowerment for Addiction Treatment (NEAT): study protocol for a randomized controlled trial

BackgroundNeurocognitive deficits (NCDs) and associated meta-cognition difficulties associated with chronic substance use often delay the learning and change process necessary for addiction recovery and relapse prevention. However, very few cognitive remediation programs have been developed to target NCDs and meta-cognition for substance users. The study described herein aims to investigate the efficacy of a multi-component neurocognitive rehabilitation and awareness program termed “Neurocognitive Empowerment for Addiction Treatment” (NEAT). NEAT is a fully manualized, cartoon-based intervention involving psychoeducation, cognitive practice, and compensatory strategies relevant across 10 major cognitive domains, including aspects of attention, memory, executive functions, and decision-making.Method/designIn a single-blind randomized controlled trial (RCT), 80 female opioid and/or methamphetamine users will be recruited from an addiction recovery program providing an alternative to incarceration for women with substance use-related offenses. Eight groups of 9–12 participants will be randomized into NEAT or treatment-as-usual (TAU). NEAT involves 14 90-min sessions, delivered twice weekly. The primary outcome is change in self-reported drug craving from before to after intervention using Obsessive Compulsive Drug Use Scale. Secondary and exploratory outcomes include additional psychological, neurocognitive, and structural and functional neuroimaging measures. Clinical measures will be performed at five time points (pre- and post-intervention, 3-, 6-, and 12-month follow-up); neuroimaging measures will be completed at pre- and post-intervention.DiscussionThe present RCT is the first study to examine the efficacy of an adjunctive neurocognitive rehabilitation and awareness program for addiction. Results from this study will provide initial information concerning potential clinical efficacy of the treatment, as well as delineate neural mechanisms potentially targeted by this novel intervention.Trial registrationClinicalTrials.govNCT03922646. Registered on 22 April 2019

Effectiveness and Utility of Mobile Device Assessment of Subjective Craving during Residential Opioid Dependence Treatment

Background: Craving is a dynamic state that is both theoretically and empirically linked to relapse in addiction. Static measures cannot adequately capture the dynamic nature of craving, and research has shown that these measures are limited in their capacity to link craving to treatment outcomes. Methods: The current study reports on assessments of craving collected 4x-day across 12 days from 73 patients in residential treatment for opioid dependence. Analyses investigated whether the within-person assessments yielded expected across- and within-day variability, whether levels of craving changed across and within days, and, finally, whether individual differences in craving variability predicted post-residential treatment relapse. Results: Preliminary analyses found acceptable levels of data entry compliance and reliability. Consistent with expectations, craving varied both between (46%) and within persons, with most within-person variance (over 40%) existing within days. Other patterns that emerged indicated that, on average, craving declined across the 12-days of assessment, and was generally strongest at mid-day. Analyses also found that patients’ person-level craving variability predicted post-treatment relapse, above and beyond their mean levels of craving. Conclusion: Analyses support the reliability, sensitivity, and potential utility of the 4x-day, 12-day assessment protocol for measuring craving during residential treatment.

Analysis of Demographic Characteristics and Psychological Factors of Opioid Addicts in Zhengzhou Area

Objective: To explore the demographic characteristics and psychological factors of patients with opioid addiction. Methods: A random number method was used to select 200 opioid-addicted patients admitted to the 7th People’s Hospital of Zhengzhou from January 2019 to February 2020. Demographic characteristics and psychosocial factors were analyzed. Result: The proportion of opioid addicts aged 21 ~ 30 was the highest; the proportion of men was significantly higher; the proportion of people who is between jobs/unemployed is the highest; the proportion of junior middle school was the highest, and the proportion of unmarried was relatively high; the proportion of opioid addicts with ignorance/curiosity for the cause of first addiction was the highest; the use of suction is snorting, accounting for the highest proportion. According to the analysis of relevant social and psychological factors, the proportion of single parent family group is the highest, the proportion of parent tension is the highest, and the proportion of bad life coping style is relatively high. At the same time, dependent psychology occupies the highest proportion in psychological factors of relapse patients. Conclusion: By analyzing the demographic characteristics of opioid addicts and the psychosocial factors of their addiction, we can strengthen prevention and management for specific groups to reduce the new addition and relapse of opioid addicts.

عوامل الانتکاسة من وجهة نظر القائمین على علاج الإدمان Relapse factors from the point of view of the Addictive therapists

يهدف البحث إلى التعرف على أسباب الانتکاسة للإدمان لدى المدمن المتعافى من وجهة نظر القائمين على علاج الإدمان ؛ و التعرف على ترتيب أسباب الانتکاسة للإدمان لدى المدمن المتعافى من وجهة نظر القائمين على علاج الإدمان ، و التعرف على مدى اختلاف أسباب الانتکاسة للإدمان لدى المدمن المتعافى بناء على عدد سنوت الخبرة و نوع العمل (طبيب – إخصائى نفسى – تمريض – إخصائى اجتماعى – موجه ) الذى يقوم به القائمين على علاج الإدمان .، وقد تم تطبيق الاستبيان على عينة عددها ( 48) شخصا من القائمين على علاج الإدمان (طبيب – إخصائى نفسى – تمريض – إخصائى اجتماعى – موجه ) . وقد أظهرت النتائج أن السبب الأول للعودة للإدمان من وجهة نظر القائمين على علاج الإدمان هى العوامل التى تتعلق بالعلاج بنسبة 28.7%. ثم يأتى فى المرتبة الثانية العوامل الشخصية بنسبة 26.8% ، ثم جاءت العوامل الأسرية فى المرتبة الثالثة بنسبة 13.4% ، أما العوامل التى تتعلق بالأصدقاء فقد احتلت المرتبة الرابعة بنسبة 12.6% ، وجاءت العوامل الاجتماعية فى المرتبة الخامسة بنسبة 6.7% ، ثم العوامل التى تتعلق بالبيئة المحيطة فى المرتبة السادسة بنسبة 5.9% ، ثم العوامل الاقتصادية فى المرتبة السابعة بنسبة 3.1% ، ثم العوامل التى تتعلق بوسائل الإعلام والانترنت فى المرتبة الثامنة بنسبة 2.0% ، ثم العوامل الجنسية فى المرتبة التاسعة والأخيرة بنسبة 0.8 % . للانتکاسة للإدمان فى حدود عينة البحث . The research aims to identify the causes of addiction relapse in the recovering addict from the point of view of the Addictive therapists . And to identify the order of the causes of addiction relapse of the recovering addict from the point of view of those in charge of treating addiction, and to identify the extent of the different causes of addiction relapse of the recovering addict based on the number of years of experience and the type of work (Psychatres - psychologist - nursing - social worker - mentor) The questionnaire was applied to a sample of (48) persons who of the Addictive therapists The results showed that the first cause of re-addiction from the point of view of addiction treatment agents is the treatment-related factors, by 28.7%. Personal factors came in second place with a rate of 26.8%, then family factors came in third place with a rate of 13.4%, and factors related to friends ranked fourth with a rate of 12.6%, and social factors came in fifth place with a rate of 6.7%, then factors related to the environment The surrounding ranked sixth with 5.9%, then economic factors ranked seventh by 3.1%, then factors related to media and the Internet ranked eighth with 2.0%, then sexual factors ranked ninth and last by 0.8%. Relapse of addiction within the limits of the research sample.

Associative processes in addiction relapse models: A review of their Pavlovian and instrumental mechanisms, history, and terminology

Animal models of relapse to drug-seeking have borrowed heavily from associative learning approaches. In studies of relapse-like behaviour, animals learn to self-administer drugs then receive a period of extinction during which they learn to inhibit the operant response. Several triggers can produce a recovery of responding which form the basis of a variety of models. These include the passage of time (spontaneous recovery), drug availability (rapid reacquisition), extinction of an alternative response (resurgence), context change (renewal), drug priming, stress, and cues (reinstatement). In most cases, the behavioural processes driving extinction and recovery in operant drug self-administration studies are similar to those in the Pavlovian and behavioural literature, such as context effects. However, reinstatement in addiction studies have several differences with Pavlovian reinstatement, which have emerged over several decades, in experimental procedures, associative mechanisms, and terminology. Interestingly, in cue-induced reinstatement, drug-paired cues that are present during acquisition are omitted during lever extinction. The unextinguished drug-paired cue may limit the model’s translational relevance to cue exposure therapy and renders its underlying associative mechanisms ambiguous. We review major behavioural theories that explain recovery phenomena, with a particular focus on cue-induced reinstatement because it is a widely used model in addiction. We argue that cue-induced reinstatement may be explained by a combination of behavioural processes, including reacquisition of conditioned reinforcement and Pavlovian to Instrumental Transfer. While there are important differences between addiction studies and the behavioural literature in terminology and procedures, it is clear that understanding associative learning processes is essential for studying relapse.

Investigating the CYP2B6 rs3745274 and rs3211371 polymorphisms in Methadone-Responder and Non-Responder Addicts in Iran.

Methadone therapy is a major protocol in opioid addiction cases in many health care systems. Population-based studies have shown that in addicted people, the genetic profile affects their response to methadone therapy. Therefore, this study designed to examine the frequency of two SNPs of the CYP2B6 gene (rs3745274 and rs3211371) in addicted cases in two methadone-responders and methadone non-responders groups. A total of 199 opioid-addicted individuals and 117 unaffected control subjects were genotyped for rs3745274 and rs3211371 polymorphisms of the CYP2B6 gene using the tetra-primer amplification refractory mutation system-polymerase chain reaction. Results of this study revealed the significant association of rs3745274 GG (p < 0.001; OR = 0.027; 95% CI = 0.14-0.49) and GT (p < 0.001; OR = 4.04; 95% CI = 2.26-7.21) genotypes with the risk of addiction in methadone-responders. Also, a significant association between rs3745274 GG (p < 0.001; OR = 0.28; 95% CI = 0.15-0.51) and GT (p < 0.001; OR = 5.1; 95% CI = 2.8-5.28) genotypes and addiction relapse was found in methadone non-responders. Based on our findings, we can conclude that rs3745274 variant of CYP2B6 gene could serve as a potential biomarker, to evaluate the prognosis of addicted people fate under treatment with methadone.