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Ketamine and esketamine are increasingly prescribed in the treatment of resistant mood disorders and persons at risk of suicide. Ketamine is a drug of misuse with increasing non-therapeutic use in the general population. Herein, our aim was to determine whether ketamine and/or esketamine are disproportionately associated with reports of substance and/or alcohol misuse. Replicating a similar analysis recently conducted using the Food and Drug Administration Adverse Event Reporting System (FAERS) database, we identified cases of "alcohol problem, alcoholism, alcohol abuse, substance dependence, substance use disorder (SUD), substance abuse, drug dependence, drug use disorder and drug abuse" in association with ketamine and esketamine reported to the World Health Organization Pharmacovigilance Database (WHO VigiBase). We searched the database from inception to January 2024. The reporting odds ratio (ROR) of each of the aforementioned parameters was calculated; acetaminophen was used as the control. The numerator of the equation represents the number of cases (n) and the denominator represents the total cases of psychiatric disorders (N). Significance was obtained when the lower limit of the 95 % confidence (CI) > 1.0. The RORs for ketamine was increased for most parameters (i.e., alcohol abuse (3.24), substance dependence (12.48), substance use disorder (170.44), substance abuse (2.94), drug dependence (2.88), drug use disorder (11.54) and drug abuse (2.85), respectively). With respect to esketamine, the RORs were observed to be different from ketamine insofar as we observed a reduction in the RORs for three parameters (i.e., substance abuse (0.41), drug dependence (0.083) and drug abuse (0.052), respectively). The IC025 values were significant for ketamine in cases of alcohol abuse (0.35), substance dependence (0.50), substance use disorder (2.77), substance abuse (0.83), drug dependence (0.97), drug use disorder (1.95) and drug abuse (0.94). Additionally, oxycontin showed significant IC025 values for substance use disorder (0.0014), substance abuse (0.042), and drug dependence (0.17). Esketamine was not associated with an increased ROR for any parameter of alcohol and/or substance use disorder. Mixed results were observed with ketamine with some RORs increased and others decreased. Estimating RORs using a pharmacovigilance database does not establish causation in the case of elevated RORs and cannot be assumed to be a therapeutic effect when lower RORs were observed. • Esketamine was not associated with an increased ROR for alcohol and/or substance use disorder (SUD) • Mixed results were observed with ketamine, where some RORs were increased while others decreased • Causation cannot be established in the case of elevated RORs derived from a pharmacovigilance database • A therapeutic effect cannot be assumed when lower RORs were observed. [ABSTRACT FROM AUTHOR]

Ketamine and esketamine have been proven to be effective in treating adults with treatment resistant depression (TRD). Preliminary evidence indicates that, when combined with behavioral and psychological interventions, both agents may offer benefits for individuals with substance use disorder (SUD) and alcohol use disorder (AUD). Notwithstanding, concerns have been raised as to whether either or both agents are associated with abuse and/or gateway activity. Herein, we evaluate disproportionate reporting expressed as reporting odds ratios (ROR) for esketamine and ketamine. The outcomes of interest include alcohol problem, alcoholism, alcohol abuse, substance dependence, SUD, substance abuse, drug dependence, drug use disorder and drug abuse as codified by the Medical Dictionary for Regulatory Activities (MedDRA) within the FAERS. The IC025 values were significant for ketamine in cases of alcohol abuse (0.28), substance dependence (1.88), substance use disorder (0.996), substance abuse (0.61), drug dependence (0.56), drug use disorder (1.17) and drug abuse (1.22). Additionally, oxycontin showed significant IC025 values for substance dependence (0.067), substance use disorder (0.094), substance abuse (0.035), and drug dependence (0.27). We observed significant increases in the reporting odds ratios (RORs) for ketamine with respect to various outcomes: alcohol abuse (ROR 2.84, 95 % CI 1.53–5.28; p = 0.0010), substance dependence (ROR 18.72, 95 % CI 8.49–41.30; p ≤ 0.0001), SUD (ROR 11.40, 95 % CI 4.24–30.65; p ≤ 0.0001), substance abuse (ROR 2.29, 95 % CI 1.73–3.04; p ≤ 0.0001), drug dependence (ROR 1.99, 95 % CI 1.64–2.42; p ≤ 0.0001), drug use disorder (ROR 4.50, 2.94–6.88; p ≤ 0.0001) and drug abuse (ROR 3.72, 3.36–4.12; p ≤ 0.0001). For esketamine, we observed that the ROR was significantly reduced for substance abuse (ROR 0.37, 95 % CI 0.22–0.63; p = 0.0003), drug dependence (ROR 0.13, 95 % CI 0.076–0.23; p ≤ 0.0001) and drug abuse (ROR 0.048, 95 % CI 0.030–0.078; p ≤ 0.0001). To our knowledge, this is the first report of spontaneous adverse events related to these outcomes of interest in the FAERS. Mixed RORs were observed across aspects of SUD and AUD for both ketamine and esketamine. Due to limitations in the FAERS, establishing causal links between new onset alcohol and substance misuse with either agent remains inconclusive. Possible beneficial effects on measures of SUD and AUD were observed. It is currently unclear, but possible, whether both agents have differential ameliorative effects across dimensions of SUD and AUD, which is a focus of ongoing research. • Mixed RORs were observed across aspects of SUD and AUD for ketamine & esketamine • Due to limitations of FAERS, causal links between new onset alcohol and substance misuse with either agent is inconclusive • Possible beneficial effects on measures of SUD and AUD were observed • It is unclear if both agents have differential ameliorative effects across dimensions of SUD & AUD [ABSTRACT FROM AUTHOR]

The onset of the disease as a morphine addiction is associated with the appearance in the patient's body of antibodies directed against opiate receptors (ORs). Once anti-opiate receptor antibodies (anti-OR antibodies) appear in the blood they will tend to bind to ORs. Such binding will cause blocking of physiological functions of OR. The blockage is felt by a morphine addict as withdrawal syndrome. To get rid of this harmful condition, the addict increases the dose of morphine taken. This is where tolerance manifests itself. The drug addict is forced to increase the dose of morphine from time to time because of the body responds by producing the more and more anti-OR antibodies. The immunological nature of morphine addiction is the reason for lifelong changes in the body's reactivity to the drug. An addict can be cured if he gets rid of B- and T-memory cells, which specifically react to ORs. [ABSTRACT FROM AUTHOR]

Chronic pain management remains a challenging aspect of neurosurgical care, with facet arthrosis being a significant contributor to the global burden of low back pain. This study evaluates the effectiveness of cryotherapy as a minimally invasive treatment for patients with facet arthrosis. By focusing on reducing drug dependency and pain intensity, the research aims to contribute to the evolving field of pain management techniques, offering an alternative to traditional pain management strategies. Through a retrospective longitudinal analysis of patients with facet osteoarthritis treated via cryotherapy between 2013 and 2023, we evaluated the impact on medication usage and pain levels, utilizing the Visual Analog Scale for pre- and posttreatment comparisons. The study encompassed 118 subjects, revealing significant pain alleviation, with Visual Analog Scale scores plummeting from 9.0 initially to 2.0 after treatment. Additionally, 67 patients (56.78%) reported decreased medication consumption. These outcomes underscore cryotherapy's potential as a pivotal tool in chronic pain management. The findings illuminate cryotherapy's efficacy in diminishing pain and curtailing medication dependency among patients with facet arthrosis. This study reaffirms cryotherapy's role in pain management and propels the discourse on nontraditional therapeutic avenues, highlighting the urgent need for personalized and innovative treatment frameworks. [ABSTRACT FROM AUTHOR]

Des malades atteints d'alcoolisme et de toxicomanie furent aussi soignés à Ivry par Achille Delmas. Il manifestait vis-à-vis de ces malades une attitude bienveillante et compatissante qui n'était pas orientée vers la recherche à tout prix du sevrage, comme son élève et porte-parole, le Dr Itzko Bussel, l'exposa dans sa thèse. Le séjour de Maurice Utrillo fut bénéfique car il interrompit une longue série d'hospitalisations sous contrainte dues à des ivresses délirantes. En revanche, Roger Gilbert-Lecomte, atteint d'une grave toxicomanie aux opiacés, sombra après sa sortie dans une déchéance bientôt fatale. Le séjour d'Antonin Artaud est détaillé et un parallèle est dressé entre les soins qui lui furent dispensés lors de son séjour à Rodez par Gaston Ferdière et l'attitude complaisante que Delmas manifesta à son égard. Achille Delmas also treated patients affected by alcoholism and drug addiction at the "maison de santé d'Ivry". As his student Itzko Bussel explained in his thesis, Delmas showed his patients a kindly and compassionate demeanor and did not seek to wean them off their drug at all cost. Maurice Utrillo's stay at the facility was beneficial as it ended a long series of forced hospitalizations due to delirious drunkenness. By contrast, Roger Gilbert-Lecomte, who was affected by a severe addiction to opium-containing drugs, sank into a fatal decay after his stay. Antonin Artaud's stay is detailed and a parallel is drawn between the care given to him in Rodez by Dr Gaston Ferdière and Dr Delmas' more indulgent attitude. [ABSTRACT FROM AUTHOR]

• Disrupting reconsolidation may allow new treatments for mental health disorders. • There are challenges in translating reconsolidation-based approaches to the clinic. • Understanding boundary conditions should facilitate clinical translation. Reconsolidation results in the restabilisation, and thus persistence, of a memory made labile by retrieval, and interfering with this process is thought to enable modification or weakening of the original trace. As such, reconsolidation-blockade has been a focus of research aiming to target the maladaptive memories underlying mental health disorders, including post-traumatic stress disorder and drug addiction. Current first-line therapies are not effective for all patients, and a substantial proportion of those for whom therapies are effective later relapse. A reconsolidation-based intervention would be invaluable as an alternative treatment for these conditions. However, the translation of reconsolidation-based therapies to the clinic presents a number of challenges, with arguably the greatest being the overcoming of the boundary conditions governing the opening of the reconsolidation window. These include factors such as the age and strength of memory, and can broadly be divided into two categories: intrinsic features of the targeted memory itself, and parameters of the reactivation procedure used. With maladaptive memory characteristics inevitably varying amongst individuals, manipulation of the other limitations imposed by procedural variables have been explored to circumvent the boundary conditions on reconsolidation. Although several apparently discrepant results remain to be reconciled and these limitations yet to be truly defined, many studies have produced successful results which encouragingly demonstrate that boundary conditions may be overcome using various proposed strategies to enable translation of a reconsolidation-based intervention to clinical use. [ABSTRACT FROM AUTHOR]

Substance use disorders (SUDs) are associated with a variety of co-occurring psychiatric disorders and other SUDs, which partly reflects genetic pleiotropy. Polygenic risk scores (PRSs) and phenome-wide association studies are useful in evaluating pleiotropic effects. However, the comparatively low prevalence of SUDs in population samples and the lack of detailed information available in electronic health records limit these data sets' informativeness for such analyses. We used the deeply phenotyped Yale-Penn sample (n = 10,610 with genetic data; 46.3% African ancestry, 53.7% European ancestry) to examine pleiotropy for 4 major substance-related traits: alcohol use disorder, opioid use disorder, smoking initiation, and lifetime cannabis use. The sample includes both affected and control subjects interviewed using the Semi-Structured Assessment for Drug Dependence and Alcoholism, a comprehensive psychiatric interview. In African ancestry individuals, PRS for alcohol use disorder, and in European individuals, PRS for alcohol use disorder, opioid use disorder, and smoking initiation were associated with their respective primary DSM diagnoses. These PRSs were also associated with additional phenotypes involving the same substance. Phenome-wide association study analyses of PRS in European individuals identified associations across multiple phenotypic domains, including phenotypes not commonly assessed in phenome-wide association study analyses, such as family environment and early childhood experiences. Smaller, deeply phenotyped samples can complement large biobank genetic studies with limited phenotyping by providing greater phenotypic granularity. These efforts allow associations to be identified between specific features of disorders and genetic liability for SUDs, which help to inform our understanding of the pleiotropic pathways underlying them. [ABSTRACT FROM AUTHOR]

CRISPR tiling screens offer an efficient way to identify gain-of-function mutations in targets of cancer therapy. Recently, by utilizing these screens, Kwok et al. unexpectedly discovered mutations conferring drug addiction in lymphoma, revealing a requirement for a 'just right' window of histone methylation crucial for cancer survival. [ABSTRACT FROM AUTHOR]

• Model with good predictive power that correctly classifies 91% of drivers as offenders or non-offenders. • Alcohol and drug use are key predictors of offender driver behaviour. • Offenders are systematically less likely than non-offenders to dissociate the consumption of alcohol and substances from driving. • Few women and individuals are offender drivers. • Offender drivers believe they commit fewer lapses than non-offenders. The causes underlying traffic offender behaviour might be the tip of the iceberg that represents a persistent burden on global health and serves to detect other serious social, family, work problems. Better understanding and prevention of recidivism following a First-time driving under the influence conviction and analysis of High Risk offender driver behaviors are needed. This study seeks to identify the factors that predict an offender driver profile, analysing not only drivers' general use of alcohol and/or drugs, but also their ability to dissociate the use of alcohol and other substances from driving. A total of 315 drivers — 97 offenders (95.9 % men) and 218 non-offenders (47.2 % men) responded to a battery of self-report evaluation questionnaires on: alcohol use habits (measured with the AUDIT); drug use (measured with the DAST-20); the ability of dissociating alcohol and substance use from driving; educational level; self-reported traffic violations, errors and lapses (measured with the DBQ, Driver Behaviour Questionnaire); and sociodemographic questions. The model showed good fit indicators (R2 = 0.74). It also displayed good predictive power: (1). It correctly classified 91 % of participants as offender or non-offender drivers. (2). More specifically, its sensitivity was 88 %, having correctly classified offenders as offenders. And its specificity was 92 %, having correctly classified non-offenders as non-offenders. The findings underscores that not only is alcohol use a key predictor of offending behaviour, but so is drug use. These addictions are a health problem, and their consequences are more serious when the afflicted individual drives a vehicle. This article makes evident that repeat offenders have a lower ability of dissociating alcohol and substance use from driving than do non-offender drivers. Non-offenders are shown to be more capable than offenders of dissociating consumption from driving: offender drivers are unable to dissociate the consumption of more than 5 spirit drinks, or the consumption of cannabis, from driving. More than half of non-offender drivers admitted to driving after having had 1 or 2 beers. Along these same lines, we found that offenders believe they have fewer lapses than non-offenders. This could be due to the optimism bias of bold offender drivers, who overestimate their abilities and underestimate their lapses. We also found that offender drivers have a lower educational level. Revoking the High Risk offender's driver's licence may not be enough. Instead, High Risk Offenders should be given the support they need to give up the consumption of alcohol and drugs, at least while driving. This could be achieved if they receive motivational interventions and are referred for detoxification treatment. [ABSTRACT FROM AUTHOR]

Background: The comorbidity between substance use disorder and major depressive disorder is a typical dual diagnosis in the field of substance addiction. However, the prevalence and correlates of depression in methamphetamine addicts and whether it is associated with drug craving and alexithymia have been rarely reported in the Chinese population.Methods: We recruited 585 methamphetamine-dependent males from a drug rehabilitation center in China and 203 healthy controls. Demographic and drug use data were collected. Depression was assessed using the Mini International Neuropsychiatric Interview (M.I.N·I.). Methamphetamine cravings and alexithymia were assessed using the Desire for Drugs Questionnaire (DDQ) and the Toronto Alexithymia Scale (TAS).Results: The prevalence rate of depression in methamphetamine-dependent men was 16.58 % (97/585). The scores of DDQ desire and intention, DDQ negative reinforcement, total DDQ, difficulty identifying feelings (DIF), difficulty describing feelings (DDF), and total TAS score of depressed patients were higher than those of non-depressed patients. However, only DDQ negative reinforcement score, DIF, DDF, and total TAS score remained significant after Bonferroni correction. Additionally, logistic regression analysis found that age, DIF score, and DDQ negative reinforcement score were significant factors contributing to depression in methamphetamine-dependent men.Conclusion: Our findings suggest that the prevalence of depression is significantly higher in methamphetamine-dependent men than in the healthy Chinese population. Furthermore, age, components of alexithymia and drug craving are risk factors for depression in methamphetamine addicts. [ABSTRACT FROM AUTHOR]

In 2014, we proposed that orexin signaling transformed motivationally relevant states into adaptive behavior directed toward exploiting an opportunity or managing a threat, a process we referred to as motivational activation. Advancements in animal models since then have permitted higher-resolution measurements of motivational states; in particular, the behavioral economics approach for studying drug demand characterizes conditions that lead to the enhanced motivation that underlies addiction. This motivational plasticity is paralleled by persistently increased orexin expression in a topographically specific manner—a finding confirmed across species, including in humans. Normalization of orexin levels also reduces drug motivation in addiction models. These new advancements lead us to update our proposed framework for the orexin function. We now propose that the capacity of orexin neurons to exhibit dynamic shifts in peptide production contributes to their role in adaptive motivational regulation and that this is achieved via a pool of reserve orexin neurons. This reserve is normally bidirectionally recruited to permit motivational plasticity that promotes flexible, adaptive behavior. In pathological states such as addiction, however, we propose that the orexin system loses capacity to adaptively adjust peptide production, resulting in focused hypermotivation for drug, driven by aberrantly and persistently high expression in the orexin reserve pool. This mechanistic framework has implications for the understanding and treatment of several psychiatric disorders beyond addiction, particularly those characterized by motivational dysfunction. [ABSTRACT FROM AUTHOR]

Addiction is a disease of brain-reward circuitry whereby attention, motivation, memory and emotional systems become enslaved to the goal of seeking and acquiring drug, instead of responding to the natural rewards for which these systems evolved. At the intersection of reward/limbic structures, the medial prefrontal cortex (mPFC) receives and consolidates signals regarding environment and orchestrates the most appropriate response (i.e., decision-making and attention). As such, mPFC function plays a critical role in the vulnerability or resilience to drug addiction. In our model of drug-induced reward devaluation, an outbred group of Sprague-Dawley rats parsed into two distinct drug-taking phenotypes: those, referred to as small suppressors (SS) that readily ingest a heroin-paired sweet cue and then take little drug, and those, referred to large suppressors (LS), that avoid the heroin-paired cue, but then respond greatly for the drug of abuse. In the present study, we analyzed the mPFC transcriptome of rats from these divergent groups to discover differences in gene expression that underlie these distinct phenotypes. Genes found to be differentially expressed were those associated with schizophrenia and dopamine signaling, signal transduction, development and synaptic plasticity. These genes may underlie the circumstance whereby some individuals succumb to addiction, while others do not, and may reveal new pharmacological targets for the treatment of drug addiction. [ABSTRACT FROM AUTHOR]

• Gabapentinoids have been misused to potentiate, withdraw from or substitute opioids. • Gabapentinoids are sometimes used recreationally for euphoria and relaxation. • Some describe misusing gabapentinoids to cope with pain, distress, and insomnia. • There are reports of serious psychiatric symptoms when discontinuing pregabalin. • Harms including overdose are generally reported in the context of poly-drug use. Gabapentinoids are among the most widely prescribed pain medications worldwide. However, there is growing evidence of harms associated with their use. The aim of this study was to systematically review and synthesise qualitative research exploring lived experiences of gabapentinoid (pregabalin and/or gabapentin) misuse and symptoms of dependence. Six databases (MEDLINE, Scopus, Web of Science, CINAHL, EMBASE, PsycINFO) and grey literature sources were searched from inception to September 2023. The methodological quality of included studies was appraised using a modified 11-item version of the Critical Appraisal Skills Programme qualitative checklist, and higher quality studies were prioritised in the thematic synthesis. Confidence in the overall findings of the review was assessed using the GRADE-CERQual approach. The review was prospectively registered on PROSPERO (CRD42023401832). Twenty-six articles representing 21 original studies were included. The majority used interview methods and were of high methodological quality. Motives for gabapentinoid misuse included getting high, potentiating or offsetting the effects of other drugs, self-medicating for pain, distress, insomnia, or withdrawal symptoms, and substituting for another drug. Symptoms of dependence included the rapid development of tolerance and a severe withdrawal syndrome often involving psychiatric symptoms. Harms including dissociation, loss of consciousness, and overdose were generally reported as a consequence of polysubstance use. Confidence in most of the review findings was moderate with low confidence in one finding. This review provides rich qualitative insights into the potential motives for gabapentinoid misuse as well as the diverse lived experiences of dependence symptomatology. Considering the increasing prescribing of these medications globally, and the potential for public health challenges resulting from misuse, the findings of this review can be used to develop more effective harm reduction strategies. [ABSTRACT FROM AUTHOR]

[Display omitted] • Methamphetamine (METH) substance use disorder growing public health concern, however current treatments are limited and ineffective. • There is growing interest in immunotherapies, however challenges in hapten design and low immunogenicity have stalled progress. • Here, we describe the development of a conjugated methamphetamine vaccine, using mannan as an immunogenic carrier. • The vaccines were developed and their final identity confirmed by LCMS and flash chromatography, at each step of production. • Immunogenicity studies in mice confirmed antibody response to the vaccine, with the monoamine linker compound inducing the greatest antibody response. Methamphetamine (METH) substance use disorder is a long-standing and ever-growing public health concern. Efforts to develop successful immunotherapies are ongoing with vaccines that generate strong antibody responses are an area of significant research interest. Herein, we describe the development of a METH Hapten conjugate vaccine comprised of either two short-length peptides as linkers and mannan as an immunogenic delivery carrier. Initially, Hapten 1 (with a monoamine linker) and Hapten 2 (with a diamine linker) were synthesised. Each step of the Hapten synthesis were characterized by LC-MS and purified by Flash Chromatography and the identity of the purified Haptens were confirmed by 1H NMR. Haptens were conjugated with mannan (a polymannose), and conjugation efficiency was confirmed by LC-MS, TLC, 1H NMR, and 2,4 DNPH tests. The immunogenic potential of the two conjugated vaccines were assessed in mice with a 3-dose regimen. Concentrations of anti-METH antibodies were measured by enzyme-linked immunosorbent assay. All the analytical techniques confirmed the identity of Hapten 1 and 2 during the synthetic phase. Similarly, all the analytical approaches confirmed the conjugation between the Haptens and mannan. Mouse immunogenicity studies confirmed that both vaccine candidates were immunogenic and the vaccine with the monoamine linker plus adjuvants induced the highest antibody response after the second booster. [ABSTRACT FROM AUTHOR]

• Exercise is highly feasible and acceptable, significantly contributing to the reduction of drug cravings among individuals with drug dependency. • The specific type of exercise appears to be a key determinant of the intervention's effectiveness. Aerobic exercises were more effective than resistance exercises. • This study is the first systematic review of exercise improving cravings in individuals with drug dependency. This systematic review aims to assess the feasibility, acceptability, and efficacy of exercise-based interventions in reducing craving levels among individuals with drug dependency. This study included randomized controlled trials that investigated the effects of exercise on craving levels in individuals with drug dependence. We searched for relevant literature in PubMed, Web of Science, EMbase, The Cochrane Library, CNKI, China Biomedicine, Wanfang, and VIP databases from their inception until July 2024. Two researchers independently reviewed the literature. The quality of the studies was assessed using the PEDro scale, and the GRADE profiler software was utilized to evaluate the strength of the evidence. A qualitative synthesis was performed to describe the findings. We included 26 studies involving a total of 1381 participants, with 787 in the experimental group and 594 in the control group. These studies were mainly conducted in China, the United States, and the United Kingdom, and were published mostly after 2018. The participants had typically been dependent on drugs for more than 5 years. The review found that exercise interventions were feasible and well-accepted, and effectively reduced drug cravings. Among the 26 studies, 22 showed positive outcomes in reducing cravings. The type of exercise appears to be a crucial factor. Aerobic exercises were more effective than resistance exercises. Out of 18 studies that included aerobic exercises, 17 reported significant reductions in cravings. In contrast, among the 4 studies that included resistance exercises, 3 did not find a significant impact on cravings. Exercise is highly feasible and acceptable, significantly contributing to the reduction of drug cravings among individuals with drug dependency. The specific type of exercise appears to be a key determinant of the intervention's effectiveness. Aerobic exercises were more effective than resistance exercises. The evidence supporting these findings is of high quality, with an average score of 6.92 on the PEDro scale. The research was supported by the Shanghai Key Laboratory of Human Performance, with the project number 11DZ2261100. Registration details can be found on PROSPEO under the number CRD42024525700 at www.crd.york.ac.uk. [ABSTRACT FROM AUTHOR]

• Heroin and methadone directly suppress human T cell function in vitro. • Methadone exhibits stronger inhibitory effects on T cells compared to heroin. • Methadone additionally interferes with in vitro Treg induction and expansion. Opioid addiction presents a relevant health challenge, with chronic heroin use linked to detrimental effects on various aspects of physical, mental, and sociological health. Opioid maintenance therapy (OMT), particularly using methadone, is the primary treatment option for heroin addiction. Previous studies using blood samples from current heroin addicts and OMT patients have shown immunomodulatory effects of heroin and methadone on T cell function. However, various additional factors beyond heroin and methadone affect these results, including the consumption of other substances, a stressful lifestyle, comorbid psychological and somatic disorders, as well as additional medications. Therefore, we here investigated the direct effects of heroin and methadone on purified human T cells in vitro. Our results reveal that both, heroin and methadone directly suppress T cell activation and proliferation. Strikingly, this inhibitory effect was markedly stronger in the presence of methadone, correlating with a decrease in secretion of pro-inflammatory cytokines. While heroin did not interfere with the in vitro differentiation and expansion of regulatory T cells (Tregs), methadone significantly impaired the proliferation of Tregs. Overall, our findings suggest a direct inhibitory impact of both opioids on effector T cell function in vitro , with methadone additionally interfering with Treg induction and expansion in contrast to heroin. [ABSTRACT FROM AUTHOR]

[Display omitted] • ICH guidelines bases method validation. • HPTLC based method used for to check in vitro based method to check Acacia activity. • Method in future used to estimation of nicotine in blood plasma. • Babbul (Acacia nilotica) was seen effective against tobacco toxicity as evidenced by HPTLC method. Tobacco (Nicotiana tobacum) and tobacco products are the most critical public health challenges today across the globe. Nicotine is the main chemical composition of tobacco and is associated with withdrawal syndrome. A laboratory animal is commonly employed as a model to investigate nicotine toxicity, drug dependence, reinforcing effects, and the protective effects of samples against nicotine-induced toxicity. The first in-vitro model was developed to prove the protective effect of Babbul (Acacia nilotica Linn.) against nicotine poisoning caused by consumption of tobacco products. The HPTLC method for estimating the protective effect against nicotine poisoning was performed by taking the solvent systems dichloromethane, methanol, and liquid ammonia (25 %)(9:1:0.04v/v/v). This in-vitro approach was done by treating the bark of the Acacia nilotica extract with a standard solution of nicotine, which reduced the concentration of nicotine by 39.12 %. The prescribed HPTLC method can be used successfully to assess Acacia nilotica's protective impact against nicotine toxicity caused by intake of nicotine containing tobacco products. [ABSTRACT FROM AUTHOR]

To study the effects of resveratrol on heroin addiction-related behaviors and to preliminarily explore the possible intervention mechanism of resveratrol in heroin dependence. The effects of resveratrol on heroin withdrawal symptoms were observed by naloxone; The effect of resveratrol on heroin reward memory acquisition was detected by CPP paradigm; The effect of resveratrol on the mental excitability of heroin was tested by open field experiment; The effect of resveratrol on heroin spatial learning and memory was tested by water maze test. Western blot was used to detect Sirtuin 1 (SIRT1) Expression of brain-derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF), and postsynaptic density protein (PSD95). The behavioral results showed that the withdrawal behavior of the resveratrol intervention group was reduced compared with the heroin chronic dependence group (P <0.05), and the shift score of the conditioned place preference test of the resveratrol intervention group was reduced compared with the heroin chronic dependence group (P <0.05) The spatial learning and memory ability of the water maze in the resveratrol intervention group was improved compared with the heroin chronic dependence group (P <0.05), and the mental excitability of the resveratrol intervention group was lower than that of the heroin chronic dependence group (P <0.05), but higher than that of the saline group (P <0.05); SIRT1 The expression levels of BDNF, GDNF and PSD95 protein were significantly increased (P <0.05). The behavioral results of this study suggest that resveratrol can be used as a potential drug to treat heroin dependence. At the same time, SIRT1 The expression of BDNF, GDNF, and PSD95 increased; SIRT1, BDNF, GDNF, and PSD95 play an essential role in heroin addiction. [ABSTRACT FROM AUTHOR]

In contrast to G protein-coupled receptors or receptor tyrosine kinases, the mechanism underlying ERK activation through nicotine acetylcholine receptors (nAChRs), members of the ligand-gated ion channel family, remains poorly elucidated. This study aimed to delineate the signaling pathway responsible for ERK activation by the α4β2 nAChR subtype, which is implicated in nicotine addiction and various mental disorders. Loss-of-function strategies and mutants of arrestin2/PKCβII with distinct functional characteristics were employed to identify the cellular components and processes involved in ERK activation. ERK activation via α4β2 nAChR was observed within the nucleus and necessitated the nuclear translocation of arrestin2 and PKCβII, which exhibited mutual augmentation. Activation of PKCβII by α4β2 nAChR stimulation facilitated the nuclear translocation of arrestin2 by enhancing its interaction with importin β1. Apart from scaffolding ERK activation in the nucleus, arrestin2, in cooperation with GRK2, facilitated the activation of the Src/Syk/PKCβII signaling cascade, leading to the nuclear entry of PKCβII in a Gβγ-dependent manner. Upon nuclear localization, PKCβII underwent ubiquitination by Mdm2 and interacted with MEK1, resulting in ERK activation. In summary, α4β2 nAChR-mediated ERK activation in the nucleus involves the nuclear translocation of arrestin2 and PKCβII, which is reciprocally facilitated via positive feedback augmentation. As α4β2 nAChRs play a pivotal role in various cellular processes including drug addiction and mental disorders, our findings will offer insights into understanding the pathogenesis of α4β2 nAChR-related disorders and may facilitate the development of targeted therapeutic interventions. [Display omitted] [ABSTRACT FROM AUTHOR]

Chronic antipsychotic use among nursing home (NH) residents carries risks with uncertain benefits. Despite guidelines recommending restricted use, these agents remain widely prescribed. This study investigates chronic antipsychotic use in Belgian NHs. We examined the evolution of chronic antipsychotic use, associated NH resident profiles, impact of NH admissions, and variation among Belgian NHs in a retrospective dynamic cohort study between 2017 and 2022. Antipsychotic dispensation rates were extracted for members of the Independent Health Insurance Funds in NHs. Prescription trends and resident profiles were evaluated for around 15,000 residents yearly (n = 14,733-15,451) from 2017 to 2022 and variation was assessed among 59 NHs. The impact of NH admission was analyzed for 9647 admissions between 2020 and 2022, and variation was evaluated among 22 NHs. For 22 antipsychotics identified at the ATC3 level, chronic use was defined as ≥80 defined daily doses (DDD) and/or ≥16 weekly dispensations per year. We analyzed changes in the 4 most frequently used antipsychotics (haloperidol, olanzapine, quetiapine, risperidone) on NH admission, with chronic use defined as ≥80 minimal prescribed doses (MPD) annually. The prevalence of chronic antipsychotic use among NH residents decreased from 24% in 2017 to 22.5% in 2022 (P =.002). Factors associated with higher antipsychotic use included younger age, greater dependency, and lower socioeconomic status. Upon NH admission, 30% (n = 818 of 2723) of residents discontinued treatment, while in 33% (n = 949 of 2854) treatment was initiated, predominantly with quetiapine or risperidone. This led to a small but significant increase of 1.4% after admission (P <.001). Defining chronic use as ≥80 MPD annually appeared to be more sensitive in measuring chronic antipsychotic use. Chronic antipsychotic use remains widespread in Belgian NHs, with care transition as an important decision point. Further research should explore effects of safer (de)prescribing strategies on patient well-being. [ABSTRACT FROM AUTHOR]

• Mortality risk of primary brain abscess persists in the postinfection period. • Patients with identified causative bacteria had higher survival rates. • Early mortality is significantly associated with intravenous drug use. • Involvement of the temporal lobe is linked with late-stage mortality. • Patients with intravenous drug use or malignancy had shorter survival. This study of 331 primary brain abscess (PBA) patients aimed to understand infecting agents, predisposing factors, and outcomes, with a focus on factors affecting mortality. Data were collected from 39 centers across 16 countries between January 2010 and December 2022, and clinical, radiological, and microbiological findings, along with their impact on mortality, were analyzed. The patients had a mean ± SD age of 46.8 ± 16.3 years, with a male predominance of 71.6%. Common symptoms included headache (77.9%), fever (54.4%), and focal neurological deficits (53.5%). Gram-positive cocci were the predominant pathogens, with Viridans group streptococci identified as the most frequently isolated organisms. All patients received antimicrobial therapy and 71.6% underwent interventional therapies. The 42-day and 180-day survival rates were 91.9% and 86.1%, respectively. Significant predictors of 42-day mortality included intravenous drug addiction (HR: 6.02, 95% CI: 1.38-26.26), malignancy (HR: 3.61, 95% CI: 1.23-10.58), confusion (HR: 2.65, 95% CI: 1.19-5.88), and unidentified bacteria (HR: 4.68, 95% CI: 1.76-12.43). Significant predictors of 180-day mortality included malignancy (HR: 2.70, 95% CI: 1.07-6.81), confusion (HR: 2.14, 95% CI: 1.11-4.15), temporal lobe involvement (HR: 2.10, 95% CI: 1.08-4.08), and unidentified bacteria (HR: 3.02, 95% CI: 1.49-6.15). The risk of death in PBA extends beyond the infection phase, with different factors influencing the 42-day and 180-day mortality rates. Intravenous drug addiction was associated with early mortality, while temporal lobe involvement was associated with late mortality. [ABSTRACT FROM AUTHOR]

People who use drugs face entrenched stigma, which fosters shame, restricts service access, and exacerbates inequalities. The use of mass media in anti-stigma interventions offers an opportunity to challenge stigmatising attitudes at scale. There are, however, inconsistencies in messaging approaches used in mass media anti-stigma interventions, and how authors conceptualise and measure 'stigma'. This scoping review maps literature on the development and/or evaluation of mass media interventions intended to reduce stigma towards people who use drugs. We systematically searched seven databases for reports about: (i) people who use drugs, (ii) stigma, (iii) mass media. We charted data about intervention (i) subjects and recipients, (ii) format, (iii) authors, (iv) content; and (v) conceptualisation and measurement of stigma. We narratively synthesised findings with qualitative content analyses. From 14,256 records, we included 49 reports about 35 interventions. 25/35 were from the last five years and 19/35 were from the United States. Intended recipients included the public and/or specified sub-populations, often including healthcare workers. Most interventions were intended to reduce stigma towards people with patterns of drug use perceived to be problematic, as opposed to people who use drugs in general. Interventions ranged from single pieces of media to complex multi-format campaigns. People who use(d) drugs contributed to 22/35 interventions. Professionals working in medical disciplines co-authored 29/35 interventions. Intervention content often had a medical focus, describing dependence as a 'disease' or medical issue, and emphasised the benefits of recovery. Other interventions, however, criticised medical framings. In some interventions drug use and people who use drugs were described in markedly negative terms. 'Stigma' was often under-theorised, and measurement approaches were inconsistent, with 42 instruments used to measure phenomena associated with stigma across 19 quantitative evaluations. We found inconsistencies in approaches to reduce and measure stigma, potentially reflecting different motivations for intervention development. The primary motivation of many interventions was seemingly to promote drug service engagement and recovery. [ABSTRACT FROM AUTHOR]

The problem of drug addiction has become a profound societal problem worldwide. A better understanding of the neurobiological basis of addiction and the discovery of more effective treatments are needed. Recent studies have shown that many mechanisms that underlie addiction exist in more primitive organisms, including the nematode Caenorhabditis elegans (C. elegans). C. elegans is also hypothesized to possess a functional opioid-like system, including the endogenous opioid-like peptide NLP-24 and opioid-like receptor NPR-17. Opioids, such as morphine, are thought to cause addiction-like behavior by activating dopamine nerves in C. elegans via the opioid-like system. Accumulating evidence suggests that C. elegans is an excellent animal model for identifying molecular mechanisms of addiction. • Addictive substances cause addiction-like behaviors in Caenorhabditis elegans. • C.elegans is hypothesized to have a functional endogenous opioid-like system. • Morphine could exert addiction-like effects by activating dopaminergic neurons in C. elegans. [ABSTRACT FROM AUTHOR]

A systematic review of functional neuroimaging studies on drug (self-) administration in rodents is lacking. Here, we summarized effects of acute or chronic drug administration of various classes of drugs on brain function and determined consistency with human literature. We performed a systematic literature search and identified 125 studies on in vivo rodent resting-state functional magnetic resonance imaging (n = 84) or positron emission tomography (n = 41) spanning depressants (n = 27), opioids (n = 23), stimulants (n = 72), and cannabis (n = 3). Results primarily showed alterations in the striatum, consistent with the human literature. The anterior cingulate cortex and (nonspecific) prefrontal cortex were also frequently implicated. Upregulation was most often found after shorter administration and downregulation after long chronic administration, particularly in the striatum. Importantly, results were consistent across study design, administration models, imaging method, and animal states. Results provide evidence of altered resting-state brain function in rodents upon drug administration, implicating the brain's reward network analogous to human studies. However, alterations were more dynamic than previously known, with dynamic adaptation depending on the length of drug administration. • Rodent brain function upon drug administration implicates the reward network. • Upregulation of brain function was consistently seen after short drug administration. • Long chronic administration resulted in downregulation, particularly in the striatum. • Results highlight the utility of preclinical models for neuroimaging substance use. [ABSTRACT FROM AUTHOR]

• Nonaccidental fractures are the most common signs of physical abuse in children. • Physical abuse was reported in 22.4% of the patients. • The most common form of physical abuse was hitting (94.3%). • Most abused children experience single-bone fractures. • The most common fracture observed in abused children is upper limb fracture. Child physical abuse, a type of child maltreatment (CM), poses a significant global public health concern. Nonaccidental fractures and soft tissue injuries, which encompass any action that directly or indirectly harms a child, are the primary indicators of physical abuse in children. This study aimed to investigate the prevalence, risk factors, and outcomes of accidental and nonaccidental skeletal fractures in a sample of Egyptian children. A cross-sectional analytical study was conducted between March 2022 and August 2022. A total of 156 children who presented with skeletal injuries and attended Mobarak Central Hospital were enrolled. Patients were subjected to full history taking, complete examination, and investigations. A structured questionnaire was administered to all the legal guardians. Physical abuse was reported in 22.4 % of cases, while medical neglect was reported in 19.9 % of cases. The incidence of physical abuse was notably higher among children whose fathers were smokers and/or drug addicts (p ≤ 0.05). The most common form of physical abuse was hitting (94.3 %). Among skeletal injuries, fractures were predominant (94.3 %), primarily closed fractures associated with contusions. Fractures of the upper limb accounted for the highest incidence (94.3 %) of skeletal injuries, and 60 % of physically abused children experienced moderate-severity injuries. The most common fracture observed in abused children is the upper limb fracture, typically involving a single bone. Clinicians should be more vigilant in suspecting abuse, even in cases where there is an isolated fracture, and advocate for the development of parental training programs. [ABSTRACT FROM AUTHOR]

• The link between cannabis and anhedonia is devastating for mental health. • A bidirectional relationship between cannabis and anhedonia is suggested. • Effects of cannabis on anhedonia: (THC) increases it and (CBD) decreases it. • Isolating cannabidiol (CBD) might be promising for the treatment of anhedonia. • Early detection of anhedonia prevents the decrease of the orbitofrontal cortex. This paper employs a systematic review to examine the correlation between anhedonia and marijuana use, exploring whether individuals with anhedonia use marijuana as a coping mechanism or if marijuana use plays a role in the onset of anhedonia. The search utilised PubMed and Web of Science databases, following PRISMA guidelines for paper selection. A total of 21 papers were selected to address this inquiry, and assessments were carried out using the Risk of Bias in Non-randomized Studies of Exposures (ROBINS-E) tool. The results revealed that 17 studies exhibited moderate and low risk of bias. The evaluation encompassed a total of 12,427 participants, including both animals and humans. Experimental animal studies focused on exploring the association between cannabidiol (CBD) and anhedonia, while human studies primarily employed observational research, examining various forms of anhedonia in individuals with or without mental disorders such as depression or psychosis. These studies also delved into understanding the effects of anhedonia during adolescence and explored the causal relationship between these concepts. The findings indicate a reciprocal rather than unidirectional relationship, establishing that initial anhedonia predisposes individuals to cannabis use, and subsequent consumption significantly intensifies the anhedonia experienced. Particularly, the studies placed special emphasis on adolescents and individuals with mental disorders. [ABSTRACT FROM AUTHOR]

The dual mechanisms of control (DMC) framework is important for portraying two temporally distinct modes of cognitive control. In parallel with this model, understanding emotion regulation (ER) from a dual-mechanism perspective becomes plausible since cognitive control is a crucial element of ER. The present study characterized reactive and proactive ER based on a dual mechanisms framework to identify their distinct temporal dynamics using electroencephalography (EEG) recordings. The reappraisal cue, compared with the watch-cue and no-cue conditions, evoked a larger fronto-central P3a magnitude, suggesting that participants could adaptively distribute their attention resources to prepare for strategy use. To track the cognitive effort that supports the ER process, we measured the frontal late positive potential (LPP). The results indicated that the reactive group, compared with the proactive group, used more effort to complete the reappraisal task when participants were subjected to decreased negative-emotional experiences to the same degree. Furthermore, decoding analysis showed that proactive ER starts earlier than reactive ER. These findings highlight the advantages of proactive ER. Further understanding of the modes of ER will help elucidate the control mechanisms underlying ER, which can then be applied to a variety of conditions, such as alcoholism, gambling, and drug addiction, to avert self-regulation failures caused by negative emotions. • ERPs can decode the activity of reactive and proactive emotion regulation (ER). • Proactive ER starts earlier and consumes less cognitive effort than reactive ER. • Proactive ER should be recommended to manage emotion in self-regulation. [ABSTRACT FROM AUTHOR]

Drug addiction is a major problem in many countries, with rehabilitation and treatment clinics playing a critical role in aiding drug addicts' recovery. Thus, the issue requires an effective automated system that can predict the likelihood of relapse in addicts. The system uses a dataset to train and test a machine learning algorithm for the automatic classification of drug patients. Nonetheless, the problem in training a machine learning classifier includes imbalanced classes, which can increase problems of overfitting and hinder generalization performance. The study proposed an association feature rule to combine the two most common over-sampling techniques: Synthetic Minority Over-Sampling Technique (SMOTE) and Random Over-Sampling Technique (ROSE) to balance the number of samples between classes, extending the problem feature space. Accordingly, the Random Forest algorithm is employed to classify new instances. The cross-experiments results on the Validi drug relapse dataset showed that the proposed combination approach outperforms the popular over-sampling and under-sampling approaches, indicating that the selected set of association features help the relapse classification tasks. [ABSTRACT FROM AUTHOR]

Impaired behavioral inhibition is a critical factor in drug addiction and relapse. Repetitive transcranial magnetic stimulation (rTMS) reduces the craving of heroin-addicted individuals for drug-related cues. However, it is unclear whether this technique also improves impaired behavioral inhibition and how improved behavioral inhibition affects craving. The intermittent theta-burst stimulation (iTBS) has been recently shown to be non-inferior relative to rTMS for depression. Here, we aim to investigate the effect of iTBS on heroin-addicted individuals' behavioral inhibition and cue-induced craving and the relationship between the alteration of behavioral inhibition and craving. 42 of 56 initially recruited individuals with the heroin-use disorder in the abstinent-course treatment were randomized to undergo active or sham iTBS to the left dorsolateral prefrontal cortex and received three daily iTBS treatments for 10 consecutive days. We measured participants' performance during a two-choice oddball task (80% standard and 20% deviant trials) and heroin-related cue-induced craving before and immediately after treatment. The group that received active iTBS showed significantly improved two-choice oddball task performance after 10 days of intervention compared to both pre-intervention and the group who received sham iTBS. Similarly, a significant reduction in cue-induced craving was observed after following the intervention in the active iTBS group but not the sham iTBS group. The moderation model indicated that iTBS categories play a significant moderating role in the relationship between accuracy cost changing and altered cue-induced craving. The iTBS treatment protocol positively affects behavioral inhibition in patients with heroin addiction. Improvements in behavioral inhibition can substantially reduce craving. • iTBS treatment protocol can enhance behavioral inhibition of heroin use disorder. • iTBS targeting prefrontal cortex reduce cue-induced craving in heroin use disorder. • Improvements in behavioral inhibition can be a predictive factor of treatment outcome. • Improving cognitive control functions could have therapeutic implications in drug addiction. [ABSTRACT FROM AUTHOR]

While there is evidence that mental health problems are more prevalent in people with borderline intellectual functioning (BIF) compared to the general population, it is not known to what extent this has varied or changed over time and whether there have been changes in access to services. This paper compares the prevalence rates of psychiatric disorders and monitors trends in treatment and services in this population compared to the general population. We conducted secondary analysis on the Adult Psychiatric Morbidity Surveys carried out in England in 2000, 2007 and 2014. The total sample analysed included 21,796 participants, with 12.8% of individuals identified with BIF (n = 2786). Regression models were used to examine trends in psychiatric disorders, treatment and service use across the three datasets. People with BIF had significantly higher odds of developing mood and anxiety disorders, psychosis, drug dependence and suicidal behaviour than the general population, increasing at each subsequent timepoint. They received significantly more pharmacological treatments than the general population but have had increasingly more access to general practitioners, community care and daycare services over time. This study shows increasing prevalence rates of several mental disorders in people with BIF. Access to day-care, community care and healthcare services has increased over time for this group but not formal psychiatric care. These changes over time underline some of the problems this population faces, emphasizing a need to recognize that this is a population often overlooked in research and clinical practice. [ABSTRACT FROM AUTHOR]

Plusieurs recherches se développent pour soutenir les théorisations des addictions aux substances psychoactives. Parmi les pistes, le paradigme de l'attachement et la thèse des psychotraumatismes éclairent davantage la problématique. Cette étude vise à examiner l'influence de l'attachement et des psychotraumatismes dans l'étiologie des addictions aux substances psychoactives. Elle a porté sur 120 participants, dont 60 sujets dépendants aux drogues (âge moyen = 33,67 ans et écart-type = 13,47) et 60 de leurs frères et/ou sœurs (âge moyen = 25,37 ans et écart-type = 5,79) sans antécédents addictifs, y compris les addictions sans drogues. Les résultats démontrent que les sujets qui développent les troubles liés à l'utilisation aux substances psychoactives disposent des styles d'attachement insécure évitant et désorganisé. En outre, le nombre élevé de psychotraumatismes semble influencer la consommation de drogues (autres que le tabac et l'alcool). Ces résultats corroborent la contribution des perspectives attachementiste et psychotraumatique de la problématique addictive. Cependant, il faut se garder des généralisations contextuelles et s'ouvrir à d'autres modèles d'explications. Many researches are developed to support theorizations of drug addiction. Among the tracks, the attachment paradigm and the psychotrauma thesis shed more light on the problem. This study aims to examine the influence of attachment and psychotrauma in the etiology of the addictions of psychoactive substances. It involved 120 participants including 60 drug dependent subjects (average age = 33.67 years and standard deviation = 13.47) and 60 of their brothers and/or sisters (average age = 25.37 years and standard deviation = 5.79) with no addictive history, including drug-free addictions. The results show that subjects, who develop disorders linked to the use of psychoactive substances, have styles of insecure avoidance and disorganized attachment. In addition, the number of psychotraumas seems to influence the use of drugs (other than tobacco and alcohol). These results corroborate the contribution of attachmentist and psychotraumatic perspectives of addictive problem. However, we must beware of contextual generalizations and open up to other models of explanations. [ABSTRACT FROM AUTHOR]

We report that environmental context can have a major impact on morphine locomotor behavior and ERK effects. We manipulated environmental context in terms of an environmental novelty/ familiarity dimension and measured morphine behavioral effects in both acute and chronic morphine treatment protocols. Wistar rats (n=7 per group) were injected with morphine 10 mg/kg or vehicle (s.c.), and immediately placed into an arena for 5 min, and locomotor activity was measured after one or 5 days. The morphine treatments were initiated either when the environment was novel or began after the rats had been familiarized with the arena by being given 5 daily nondrug tests in the arena. The results showed that acute and chronic morphine effects were strongly modified by whether the environment was novel or familiar. Acute morphine administered in a novel environment increased ERK activity more substantially in several brain areas, particularly in reward-associated areas such as the VTA in comparison to when morphine was given in a familiar environment. Repeated morphine treatments initiated in a novel environment induced a strong locomotor sensitization, whereas repeated morphine treatments initiated in a familiar environment did not induce a locomotor stimulant effect but rather a drug discriminative stimulus dis-habituation effect. The marked differential effects of environmental novelty/familiarity and ongoing dopamine activity on acute and chronic morphine treatments may be of potential clinical relevance for opioid drug addiction. • Environmental novelty is a modulator of acute and repeated effects of morphine. • In a novel environment, repeated MOR induced sensitization. • In a familiar environment, repeated MOR did not induce sensitization • In a novel environment acute MOR increased ERK activity. • MOR can reinforce prepotent behavior in a novel environment. [ABSTRACT FROM AUTHOR]

Sexual minority (e. g., bisexual, gay, lesbian, queer) and gender minority (e. g., transgender, non-binary, gender expansive) individuals (SGMI) experience higher rates of alcohol and other substance use disorders than their heterosexual and cisgender (i. e., non-transgender) counterparts. 12-Step programs are currently the most common source of support for alcohol and other substance use-related problems in the United States. Little is known about rates and levels of participation and outcomes of SGMI in 12-Step programs. Examining SGMI with a lifetime alcohol or other substance use disorder, this study aims to: 1) describe lifetime attendance rates (any vs. none) and levels of participation (number of program activities) in 12-Step groups among SGMI overall and compare rates of attendance and levels of participation across sexual and gender minority identities and 2) determine how lifetime level of participation in 12-Step programs relates to past-year alcohol and other substance use outcomes. We used data collected through The PRIDE Study, a national, large-scale, longitudinal health study of adult SGMI, administering supplemental questions to assess alcohol and other substance use disorders and 12-step participation. Zero-Inflated Negative Binomial models (N = 1353) run with sexual and gender identities as predictors of lifetime 12-step attendance (yes/no) and level of 12-Step participation determine if greater levels of 12-Step participation were associated with lower levels of past-year Alcohol and Substance Use Disorder (AUD & SUD) symptoms. The study ran models for those with lifetime AUD (n = 1074) and SUD (n = 659) separately. Participants who engaged in greater levels of 12-Step participation had lower levels of past-year AUD and SUD symptoms. Gay and queer respondents with AUD were more likely and lesbian respondents with SUD were less likely than other participants to have ever participated in 12-Step programs. All other associations between sexual/gender identities and 12-Step participation disappeared when age was added to the model. This study provides preliminary evidence that 12-Step participation may be an effective resource for reducing AUD and SUD symptoms among SGMI. Younger SGMI and SGMI holding sexual/gender identities other than gay and queer may require additional support to initiate participation in 12-Step programs. • This is the only known study examining substance use outcomes of 12-Step participation among SGMI. • Greater 12-Step participation was associated with lower levels of past year AUD/SUD severity. • Gay and queer respondents with AUD were more likely to have ever participated in 12-Step programs. • Lesbian respondents with SUD were less likely to have ever participated in 12-Step programs. [ABSTRACT FROM AUTHOR]

Emergency department (ED)-based peer recovery coach (PRC) programs can improve access to substance use disorder treatment (SUD) for ED patients. As literature on early stages of PRC implementation is limited, we conducted a qualitative assessment of ED PRC program implementation from several US-based PRC programs focusing on barriers and facilitators for implementation and providing recommendations based on the findings. We collected qualitative data from 39 key informants (peer recovery coaches, PRC program managers, ED physicians and staff, representatives of community-based organizations) via 6 focus groups and 21 interviews in February–December 2023. We transcribed audio-recordings and analyzed data using codebook thematic analysis. We identified the following major themes related to specific barriers and recommendations to address them. To facilitate timely linkage to PRCs , programs would regularly inform ED staff about the program and its linkage procedures, establish trust between PRC and ED staff, streamline the linkage procedures, and choose an "opt-out" linkage approach. To address barriers related to external referrals, programs use "warm handoff" and "warm line" strategies, maintain and update a comprehensive catalog of resources, and familiarize peer coaches with local service providers. Telehealth services implementation requires addressing logistical barriers, ensuring patients' privacy, and training peer coaches on building trust and rapport online. Peer coaches' wellness and quality of services can be improved by limiting PRC's workload, prioritizing quality over quantity, facilitating self-, peer- and professional care to mitigate stress and burnout; and, importantly, by providing supportive supervision and training to peer coaches and advocating for PRC team as an equal partner in the ED settings. To facilitate PRC program adoption and sustainment program managers engage local communities and program champions, seek diverse sources of funding, and advocate for structural changes to accommodate recruitment and retention of peer recovery coaches. We compiled a wealth of best practices used by PRC programs to address numerous implementation barriers and challenges. These recommendations are intended for PRC program planners, managers and champions, hospital leadership, and state and local public health agencies leading SUD epidemic response. • Emergency department (ED) peer recovery coach (PRC) programs can improve access to substance use disorder services. • We examined barriers and best practices for early stage implementaiton of ED PRC programs. • Practical solutions address linkage to and quality of services, staff wellness, and program sustainment. [ABSTRACT FROM AUTHOR]

Substance dependence represents a pervasive global concern within the realm of public health. Presently, it is delineated as a persistent and recurrent neurological disorder stemming from drug-triggered neuroadaptations in the brain's reward circuitry. Despite the availability of various therapeutic modalities, there has been a steady escalation in the mortality rate attributed to drug overdoses. Substantial endeavors have been directed towards the exploration of innovative interventions aimed at mitigating cravings and drug-induced repetitive behaviors. Within this review, we encapsulate the most auspicious contemporary treatment methodologies, accentuating meta-analyses of efficacious pharmacological and non-pharmacological approaches: including gabapentin, topiramate, prazosin, physical exercise regimens, and cerebral stimulation techniques. • Brain stimulation and exercise are effective to attenuate substance craving. • Gabapentin and prazosin efficiently reduce alcohol intake in alcohol use disorder. • Topiramate shows better effects than approved pharmacotherapy for alcoholism. • Crocin and S. alopecuroides attenuate withdrawal syndrome in abstinence periods. • Novel interventions have been developed to revert drug-induced neuroplasticity. [ABSTRACT FROM AUTHOR]

Biological sex disparities manifest at various stages of drug addiction, including craving, substance abuse, abstinence, and relapse. These discrepancies are underpinned by notable distinctions in neurobiological substrates, encompassing brain structures, functions, and neurotransmitter systems implicated in drug addiction. Neuronal biomarkers, such as neurotransmitters, signaling proteins, and genes may be associated with the diagnosis, prognosis, and treatment outcomes in both biological sexes afflicted by drug abuse. Sex differences in the neural reward system, mainly through dopaminergic transmission during drug abuse, can be attributed to modifications in neurotransmitter systems and signaling pathways. This results in distinct patterns of neural activation and responsiveness to addictive substances in males and females. Sex hormones, the estrus/menstrual cycle, and cerebral neurochemistry contribute to the progression of psychological and physiological dependence in both male and female individuals grappling with addiction. Moreover, the alteration of sex hormone balance and neurotransmitter release plays a pivotal role in substance use disorders, subsequently modulating cognitive functions pertinent to reward, including memory formation, decision-making, and locomotor activity. Comparative investigations reveal distinctions in brain region volume, gene expression, neuronal firing, and circuitry in substance use disorders affecting individuals of both biological sexes. This review examines prevalent substance use disorders to elucidate the impact of sex hormones as therapeutic biomarkers on the mesocorticolimbic neurotransmitter systems via diverse mechanisms within the addicted brain. We underscore the imperative necessity of considering these variations to gain a deeper comprehension of addiction mechanisms and potentially discern sex-specific neuronal biomarkers for tailored therapeutic interventions. • Physiological and psychological sex differences affect various stages of drug addiction. • Sex differences in drug abuse arise from the sexually dimorphic development of the brain. • Neurotransmitters involved in reward pathways mediate gender-related addictive behaviors. • The consequences of drug abuse disorders are different based on gender. • Neuronal biomarkers based on gender are valuable therapeutic targets for drug addiction. [ABSTRACT FROM AUTHOR]

Morphine addiction poses a significant challenge to global healthcare. Current opioid substitution therapies, such as buprenorphine, naloxone and methadone are effective but often lead to dependence. Thus, exploring alternative treatments for opioid addiction is crucial. We have developed a novel vaccine that presents morphine and Pam3Cys (a TLR-2 agonist) on the surface of Acr1 nanoparticles. This vaccine has self-adjuvant properties and targets TLR-2 receptors on antigen-presenting cells, particularly dendritic cells. Our vaccination strategy promotes the proliferation and differentiation of morphine-specific B-cells and Acr1-reactive CD4 T-cells. Additionally, the vaccine elicited the production of high-affinity anti-morphine antibodies, effectively eliminating morphine from the bloodstream and brain in mice. It also reduced the expression of addiction-associated μ-opioid receptor and dopamine genes. The significant increase in memory CD4 T-cells and B-cells indicates the vaccine's ability to induce long-lasting immunity against morphine. This vaccine holds promise as a prophylactic measure against morphine addiction. [ABSTRACT FROM AUTHOR]

Effective classification of individuals who commit sexual offences is important for their assessment, treatment, and risk management. Victim age has often been used as a distinguishing factor between perpetrators. This study aimed to analyse the distinctive psychopathological and criminological characteristics of contact sexual offenders with adult and minor victims. The study involved 97 adult males who were serving a prison sentence in Spain for at least one contact sexual offence against an adult or a minor. Researchers gathered data on criminological variables concerning the offender, victim, and modus operandi from prison records and interviews. Participants completed the Millon Clinical Multiaxial Inventory-III (MCMI-III) in a second session, and between-group differences were analysed. Sex offenders with minor victims (SOMV) had significantly lower scores than sex offenders with adult victims (SOAV) on the Antisocial (r = −0.283, p =.005) and Sadistic (r = −0.209, p =.04) personality subscales, and on the Alcohol (r = −0.426, p <.001) and Drug dependence (r = −0.332, p =.001) syndrome subscales. SOAV were also more likely to use violence and/or intimidation, use a weapon, offend against female victims, offend against an intimate partner, commit their offences in public places, serve other ongoing prison sentences, and report a history of alcohol and substance abuse. SOMV were older and more likely to offend against family members. These results suggest that there are key differences between SOAV and SOMV that should be considered in tailored prevention programmes for each subgroup of offenders. • This study analysed the psychopathological/criminological traits of sex offenders. • Participants were divided into two groups by victim's age (adult vs. minor). • Sex offenders with minor victims scored lower in antisocial and sadistic traits. • Those with adult victims were more likely to use violence and offend their partner. • These results should be translated into tailored prevention programs. [ABSTRACT FROM AUTHOR]

Racial and ethnic inequities persist in receipt of prenatal care, mental health services, and addiction treatment for pregnant and postpartum individuals with substance use disorder (SUD). Further qualitative work is needed to understand the intersectionality of racial and ethnic discrimination, stigma related to substance use, and gender bias on perinatal SUD care from the perspectives of affected individuals. Peer interviewers conducted semi-structured qualitative interviews with recently pregnant people of color with SUD in Massachusetts to explore the impact of internalized, interpersonal, and structural racism on prenatal, birthing, and postpartum experiences. The study used a thematic analysis to generate the codebook and double coded transcripts, with an overall kappa coefficient of 0.89. Preliminary themes were triangulated with five participants to inform final theme development. The study includes 23 participants of diverse racial/ethnic backgrounds: 39% mixed race/ethnicity (including 9% with Native American ancestry), 30% Hispanic or Latinx, 26% Black/African American, 4% Asian. While participants frequently names racial and ethnic discrimination, both interpersonal and structural, as barriers to care, some participants attributed poor experiences to other marginalized identities and experiences, such as having a SUD. Three unique themes emerged from the participants' experiences: 1) Participants of color faced increased scrutiny and mistrust from clinicians and treatment programs; 2) Greater self-advocacy was required from individuals of color to counteract stereotypes and stigma; 3) Experiences related to SUD history and pregnancy status intersected with racism and gender bias to create distinct forms of discrimination. Pregnant and postpartum people of color affected by perinatal SUD faced pervasive mistrust and unequal standards of care from mostly white healthcare staff and treatment spaces, which negatively impacted their treatment access, addiction medication receipt, postpartum pain management, and ability to retain custody of their children. Key clinical interventions and policy changes identified by participants for antiracist action include personalizing anesthetic plans for adequate peripartum pain control, minimizing reproductive injustices in contraceptive counseling, and addressing misuse of toxicology testing to mitigate inequitable Child Protective Services (CPS) involvement and custody loss. • Birthing people of color with SUD face increased scrutiny and mistrust. • Interpersonal discrimination and structural racism are frequent barriers to care. • Greater self-advocacy was required to counteract stereotypes and stigma • Racial and ethnic discrimination intersect with gender bias and stigma due to SUD. [ABSTRACT FROM AUTHOR]

• It described the electrophysiological characteristics of addiction nuclei at the single-cell level in humans. • The burst neurons account for highest (90 %) in NAc. • Among different nuclei, the mean firing rate (MFR) was the highest (1.94 Hz) in NAc. • MFR increased after entering the NAc and decreased after entering the ALIC. • The single-cell level electrophysiological characteristics of the different nuclei were found to be distinct along the surgical trajectory. The nucleus accumbens (NAc) and the anterior limb of internal capsule (ALIC) are effective targets for treating addiction using deep brain stimulation (DBS). However, there have been no reports on the electrophysiological characteristics of addiction nuclei at the single-cell level in humans. This study aimed to investigate the electrical activity characteristics of neurons in the NAc and ALIC using microelectrode recording (MER) during DBS surgery in patients with addiction, and six patients with addiction were included (five with heroin addiction and one with alcohol addiction). The microelectrode recording trajectories were reconstructed and recording sites at different depths were determined by merging the pre- and post-operative images in the FrameLink system. The results showed that among the 256 neurons, 204 (80 %) were burst neurons. NAc neurons accounted for the majority (57 %), and the mean firing rate (MFR) was the highest (1.94 Hz). ALIC neurons accounted for the least (14 %), and MFR was the lowest (0.44 Hz). MFR increased after entering the NAc and decreased after entering the ALIC. In the patients with addiction treated using DBS, the single-cell level electrophysiological characteristics of the different nuclei were found to be distinct along the surgical trajectory. [ABSTRACT FROM AUTHOR]

While there is extensive research on alcohol dependence, the factors that make an individual vulnerable to developing alcoholism haven't been explored much. In this study, we aim to investigate how neonatal exposure to sex hormones affects alcohol intake and the regulation of the mesolimbic pathway in adulthood. The study aimed to investigate the impact of neonatal exposure to a single dose of testosterone propionate (TP) or estradiol valerate (EV) on ethanol consumption in adult rats. The rats were subjected to a two-bottle free-choice paradigm, and the content of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens (NAcc) was measured using HPLC-ED. The expression of critical DA-related proteins in the mesolimbic pathway was evaluated through RT-qPCR and western blot analysis. Supraphysiological neonatal exposure to EV or TP resulted in increased ethanol intake over four weeks in adulthood. In addition, the DA and DOPAC content was reduced and increased in the NAcc of EV and TP-treated rats, and β-endorphin content in the hypothalamus decreased in EV-treated rats. The VTA μ receptor and DA type 2 form short receptor (D 2S) expression were significantly reduced in EV and TP male rats. Finally, in an extended 6-week protocol, the increase in ethanol consumption induced by EV was mitigated during the initial two hours post-naloxone injection. Neonatal exposure to sex hormones is a detrimental stimulus for the brain, which can facilitate the development of addictive behaviors, including alcohol use disorder. • Sex hormones modulate dopamine neurons. • Neonatal administration to sex hormones increases ethanol intake from adolescence to early adulthood. • The ethanol intake and neonatal administration to sex hormones produce long-term hypodopaminergia. • Neonatal administration to sex hormones is a vulnerability factor to develop risky behaviors such as alcohol dependence. [ABSTRACT FROM AUTHOR]

Scientific advances continue to broaden our understanding of the biological, developmental, and environmental elements underlying drug use and addiction and to accelerate efforts to develop targeted strategies for their prevention and treatment. At the same time, the challenges confronting the addiction field have grown both in number and in magnitude. This presentation will highlight such challenges as the growing use of fentanyl by itself or in combination with other opioids or stimulant drugs like cocaine and methamphetamine and the staggering number of overdose deaths that result. It will also focus on how NIH researchers have been using scientific advances to address the opioid crisis which has been further exacerbated by the COVID pandemic, including the development of new medications and formulations to help treat opioid use disorders and overdoses; prevention strategies to mitigate an individual's vulnerability to addiction; and implementation science to guide optimal deployment of therapeutic interventions including the use of telehealth in diverse settings (healthcare, justice setting, rural communities). [ABSTRACT FROM AUTHOR]

Involving individuals with lived experience of substance use disorders (LESUD) in research is increasingly recognized as a critical strategy to reduce stigma, develop effective personalized interventions, and enhance policy recommendations. Individuals with LESUD are well-positioned to identify research challenges and intended outcomes, perform outreach activities, develop referrals, foster trust, and disseminate findings to the community. Accordingly, several organizations (e.g., SAMHSA and NIDA) now strongly encourage researchers to engage individuals with LESUD and their families in all steps of research process including grant proposal development, implementation, and review. The College of Problems on Drug Dependence Human Research Committee presents a forum focusing on guiding principles to ensure purposeful engagement of individuals with LESUD in SUD research. Forum speakers will give overviews of effective collaborations with organizations representing individuals with SUD, study planning, data collection methods and analysis, and dissemination of findings. The forum will provide attendees with different perspectives and best practices to collaborate with individuals with LESUD to design effective and responsive research programs and enhance clinical practice and public policy. [ABSTRACT FROM AUTHOR]

As opioid-related deaths have increased nationally, so too has policy attention toward addressing the problem. However, there are questions concerning public perceptions of the latest proposals to address opioid misuse and more generally, current regulatory practices. To what extent do Americans support these new reforms: safe consumption sites, greater availability of Narcan, and expanding addiction treatment services? Relatedly, how does the public view the present level of oversight toward the pharmaceutical industry? What factors—concern about drug addiction and associated problems, direct experiences with opioids, trust in the pharmaceutical industry, and personal health indicators—affect policy preferences and views of current regulation efforts? Drawing on a 2023 nationally representative survey, this study examines these research questions. Anxiety about crime-related social disorder, direct experiences with opioid addiction, the extent of confidence in the drug industry, and other factors are tied to policy views among the public. Implications of these findings are discussed. • Public opinion in the context of addressing the "opioid epidemic" is studied. • We examined national poll data from 2023. • The study found that most of the public supports new reforms. • Most Americans also believe regulation of the drug industry is too lax. • There were also significant divides in experiences, perceptions, and attitudes. [ABSTRACT FROM AUTHOR]

In this essay we want to foreground a question: what happens to 'addiction' when we take seriously cultural scripts informing its trajectories? Can this bring us to unthink addiction as problematic notion and move it onto new paradigms that fit better the now acknowledged fluidity and pluralistic episteme of 'addiction' and more broadly of chronic life conditions? Indeed, 'addiction' has become a pivotal concept in the contemporary world. A powerful diagnostic framework in interpreting human behaviour, for some 'addiction' has become the 'new normal' with chronic relations with different things such as food, sex, gambling, and mind-altering substances touching upon the lifestyle of a majority of individuals, making everyone 'addicts in practice'. Perhaps this has something to do with the constituent force that 'habit' – as in 'addiction' – has in defining our present and future. Though 'addiction' goes beyond the question of mind-altering drugs, the politics of 'addiction' is intimately tied to substances such as opioids and opiates, cocaine, cannabis, and psychedelics that have been the object of durable systemic political control and security repression. Contextually the line between licit/illicit substances is softening and blurring, the 'dual' purpose that drugs serve is now recognised in scientific and popular analysis moving the question of 'addiction' beyond the medicine/drug dichotomy. Yet, culture is generally absent in understanding 'addiction.' When it is referred to, this happens in diminutive terms limited to Anglo-American modern culture. Culture matters and it matters with different weights and measures as it moves across the world. There are cultural environments of health informed by practices and epistemologies of well-being that have evolved in lines opposites from or only intersecting with the Anglo-American, and generally Western, world. Exploring these spaces and cultural scripts enables our scholarship on drugs and 'addiction' to move the barycentre of discussion towards novel considerations around the historical trajectories and potential futures of our diagnostic terms and policy interventions. [ABSTRACT FROM AUTHOR]

Behavioral therapies are considered best practices in the treatment of substance use disorders (SUD) and used as first-line approaches for SUDs without FDA-approved pharmacotherapies. Decades of research on the neuroscience of drug reward and addiction have informed the development of current leading behavioral therapies that, while differing in focus and technique, have in common the overarching goal of shifting reward responding away from drug and toward natural non-drug rewards. This review begins by describing key neurobiological processes of reward in addiction, followed by a description of how various behavioral therapies address specific reward processes. Based on this review, a conceptual 'map' is crafted to pinpoint gaps and areas of overlap, serving as a guide for selecting and integrating behavioral therapies. • Many theories posit addiction as a disorder of reward. • Correspondingly, behavior therapies for addiction operate on reward mechanisms. • The neurobiology of reward reveals there are several separable reward processes. • We examine which reward processes are addressed by behavior therapies for addiction. [ABSTRACT FROM AUTHOR]

The ventral pallidum is a prominent structure within the basal ganglia, regulating reward and motivational processes. Positioned at the interface between motor and limbic structures, its function is crucial to the development and maintenance of substance use disorders. Chronic drug use induces neuroplastic events in this structure, leading to long-term changes in VP neuronal activity and synaptic communication. Moreover, different neuronal populations within the VP drive drug-seeking behavior in opposite directions. This review explores the role of the VP as a hub for reward, motivation, and aversion, establishing it as an important contributor to the pathophysiology of substance use disorders. • Long-term plasticity induced by addictive drugs in VP underlies drug-seeking behavior. • Cocaine alters NAc-VP synaptic transmission to induce cocaine-seeking. • Activation of VP GABAergic neurons potentiates while inhibition of VP GABAergic neurons inhibits drug-seeking behavior. • Transcriptomic data uncovered Drd3 in VP and Nr4a1 in VP-MDT neurons as key molecules for cocaine-seeking. [ABSTRACT FROM AUTHOR]

Relapse to drug use during abstinence is a defining feature of addiction. To date, however, results from studies using rat relapse/reinstatement models have yet to result in FDA-approved medications for relapse prevention. To address this translational gap, we and others have developed rat models of relapse after voluntary abstinence from drug self-administration. One of these models is the electric barrier conflict model. Here, we introduce the model, and then review studies on behavioral and neuropharmacological mechanisms of cue-induced relapse and incubation of drug seeking (time-dependent increase in drug seeking during abstinence) after electric barrier-induced abstinence. We also briefly discuss future directions and potential clinical implications. One major conclusion of our review is that the brain mechanisms controlling drug relapse after electrical barrier-induced voluntary abstinence are likely distinct from those controlling relapse after homecage forced abstinence. • Drug craving and relapse during abstinence are defining features of drug addiction. • Classical animal models of relapse do not capture human voluntary abstinence. • Electric barrier-induced voluntary abstinence mimics this feature of human addiction. • Ventral subiculum is a critical brain area for relapse after electric barrier-induced abstinence. • The electric barrier model can be used to study individual differences in relapse vulnerability. [ABSTRACT FROM AUTHOR]

World Drug Report 2023 concluded that 296 million people abused drugs, 39.5 million became addiction and 494,000 died as a direct or indirect result of addiction. Addiction has become a growing problem that affects individuals, their families, societies, countries and even the world. However, treatment for addiction is only limited to some developed countries because of the high cost, difficult implementation, and time consuming. Therefore, there is an urgent need to develop a low-cost, effective drug for the development of addiction treatment in more countries, which is essential for the stability and sustainable development of the world. In this review, it provided an overview of the abuse of common addictive drugs, related disorders, and current therapeutic regimen worldwide, and summarized the mechanisms of drug addiction as reward circuits, neuroadaptation and plasticity, cognitive decision-making, genetics, and environment. According to their chemical structure, 43 natural products and 5 herbal combinations with potential to treat addiction were classified, and their sources, pharmacological effects and clinical trials were introduced. It was also found that mitragine, ibogine, L-tetrahydropalmatine and crocin had greater potential for anti-addiction. [Display omitted] • Overview of addictive drugs abuse, related disorders and current therapeutic regimen. • Summary on the mechanisms of addiction. • Some natural products showed the potential to treat addiction. • Mitragine, ibogaine, l-THP and crocin are used for anti-addiction in clinical trials. [ABSTRACT FROM AUTHOR]