Systematic review and meta-analysis: Combining transcranial magnetic stimulation or direct current stimulation with pharmacotherapy for treatment of substance use disorders.

BACKGROUND AND OBJECTIVES: Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have evidence for their potential in the treatment of substance use disorders (SUD). Medication for addiction treatment (MAT) is underutilized and not always effective. We identified randomized controlled trials (RCTs) and case studies that evaluated the effectiveness of TMS or tDCS used concurrently with MAT in SUD treatment. METHODS: A systematic review of published literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted on 6/1/2023 by a medical librarian. Craving-related scales were extracted for an effect size calculation. The Physiotherapy Evidence Database (PEDro) scale assessed study quality. RESULTS: Eight studies (7 RCT, 1 case) including 253 individuals were published from 2015 to 2022, 5 of which had available data for meta-analysis. TMS or tDCS combined with MAT significantly reduced craving-related measures relative to sham stimulation (Hedges' g = -0.42, confidence interval: -0.73 to -0.11, p < .01). Opioid use disorder, methadone, and the dorsolateral prefrontal cortex were the most commonly studied SUD, MAT, and target region. DISCUSSION AND CONCLUSIONS: Our results show a significant effect; however, is limited by a small number of studies with heterogeneous methodology across intervention methods and SUDs. Additional trials are needed to fully assess the clinical impact and mechanisms of combined brain stimulation and pharmacotherapy. We discuss a possible mechanism for synergism from these treatment combinations. SCIENTIFIC SIGNIFICANCE: Adds the first systematic review of combination treatment with TMS or tDCS and MAT in SUD patients to the literature and estimates its overall effect size.

Tribal Reservation Adolescent Connections Study: A study protocol using mixed methods for examining social networks and associated outcomes among American Indian youth on a Northern Plains reservation.

BACKGROUND: Rich cultural and traditional practices make interpersonal relationships vital for American Indian (AI) youth. Social relations and multigenerational networks (i.e., peer, family, kinship, and community) remain a salient fixture of AI culture, survival and thriving in reservation communities. Research in other populations has demonstrated how social networks impact youth risk and resilience, but data are lacking on AI adolescent networks. Intergenerational trauma from settler colonialism leads some AI youth to early initiation of substance use and subsequent substance misuse, along with disproportionately high risk for suicide and vulnerability to witnessing and experiencing violence. Using network data to develop prevention strategies among this population is a promising new avenue of research. In this study protocol paper, we describe the rationale and methodology of an exploratory study to be conducted with American Indian 9th and 10th graders at three schools on a Northern Plains reservation. METHODS: This mixed methods study will collect quantitative social network surveys (N = 300) and qualitative interviews (n = 30). The study will examine the extent to which existing social network theories and data metrics adequately characterize AI youth networks or how they may need to be expanded for this population. Associations of network characteristics with risk and protective factors for substance use, exposure to violence, and suicide will also be examined. DISCUSSION: This innovative methodological approach holds promise for informing the development of effective preventive approaches to address co-occurring risks for substance use, violence and suicide among AI adolescents. Understanding processes that impact social networks among AI adolescents can promote culturally resonant social relationships that may support better outcomes for youth.

Translating the nuanced risk for substance use among adolescents treated for attention-deficit/hyperactivity disorder (ADHD) into clinical practice: a commentary on McCabe et al. (2023).

In their recent examination of the Monitoring the Future (MTF) data, McCabe et al. (Journal of Child Psychology and Psychiatry, 2023) address the complex, longstanding, and clinically valuable questions of whether and how stimulant medication treatment for adolescents with ADHD relates to their risk for substance use. Here, we expand on the authors' interpretations of their nuanced findings of increased risk for illicit stimulant use and non-prescribed stimulant medication use for youth with later age of medication treatment initiation and shorter treatment duration. We particularly focus on highlighting tangible clinical implications, and we recommend ways future research can build on the authors' findings to further clarify this important issue.

Association Between Marijuana Use and Clinical Outcomes After Coronary Artery Bypass Grafting.

INTRODUCTION: Though marijuana use has been linked to an increase in heart failure admissions, no prior study has explored the association between its use and outcomes after coronary artery bypass grafting (CABG). This study examines the relationship between marijuana use and postoperative outcomes in CABG patients. METHODS: We utilized data from the National Inpatient Sample database from 2008 to 2018 for CABG patients ≥18 y old. Patients were divided into two groups based on marijuana use (abuse/dependency versus nonuse). Primary outcomes include in-hospital mortality, favorable discharge, and length of stay (LOS). Secondary outcomes include acute kidney injury (AKI), acute myocardial infarction (AMI), and transient ischemic attack (TIA)/stroke. A multivariable model, adjusted for confounding variables, was utilized for each outcome. RESULTS: A total of 343,796 patients met inclusion criteria for the study, 590 of which were marijuana users. In both marijuana user and nonuser groups, most patients were male and White with an average age of 56.0 and 66.3 y, respectively. There was a nonsignificant decreased odds of in-hospital mortality among marijuana users (odds ratio [OR] = 0.41, [0.141-1.124]). Marijuana users exhibited significantly decreased odds of home discharge (OR = 1.50, [1.24-1.81]), and increased odds of longer LOS (mean 10.4 d versus 9.8 d; OR = 1.14, [1.09-1.20]), AKI (OR = 1.40, [1.11-1.78]), AMI (OR = 1.56, [1.32-1.84]), and TIA/stroke (OR = 1.64, [1.21-2.22]). CONCLUSIONS: Marijuana use and dependency are associated with increased nonhome discharge, AKI, AMI, TIA/stroke, and longer LOS. Further studies are needed to delineate the pathophysiologic derangements that contribute to these unfavorable post-CABG outcomes.

Managing substance use in patients receiving therapeutic repetitive transcranial magnetic stimulation: A scoping review.

Repetitive Transcranial Magnetic Stimulation (rTMS) is an invaluable treatment option for neuropsychiatric disorders. Co-occurring recreational and nonmedical substance use can be common in those presenting for rTMS treatment, and it is unknown how it may affect the safety and efficacy of rTMS for the treatment of currently approved neuropsychiatric indications. This scoping review aimed to map the literature on humans receiving rTMS and had a history of any type of substance use. The search identified 274 articles providing information on inclusion/exclusion criteria, withdrawal criteria, safety protocols, type of rTMS and treatment parameters, adverse events and effect on primary outcomes that related to substance use. There are neurophysiological effects of substance use on cortical excitability, although the relevance to clinical rTMS practice is unknown. The current literature supports the safety and feasibility of delivering rTMS to those who have co-occurring neuropsychiatric disorder and substance use. However, specific details on how varying degrees of substance use alters the safety, efficacy, and mechanisms of rTMS remains poorly described.

Dysfunction of the Neurovascular Unit by Psychostimulant Drugs.

'Drug abuse' has been recognized as one of the most pressing epidemics in contemporary society. Traditional research has primarily focused on understanding how drugs induce neurotoxicity or degeneration within the central nervous system (CNS) and influence systems related to reward, motivation, and cravings. However, recent investigations have increasingly shifted their attention toward the detrimental consequences of drug abuse on the blood-brain barrier (BBB). The BBB is a structural component situated in brain vessels, responsible for separating brain tissue from external substances to maintain brain homeostasis. The BBB's function is governed by cellular interactions involving various elements of the 'neurovascular unit (NVU),' such as neurons, endothelial cells, astrocytes, pericytes, and microglia. Disruption of the NVU is closely linked to serious neurodegeneration. This review provides a comprehensive overview of the harmful effects of psychostimulant drugs on the BBB, highlighting the mechanisms through which drugs can damage the NVU. Additionally, the review proposes novel therapeutic targets aimed at protecting the BBB. By understanding the intricate relationships between drug abuse, BBB integrity, and NVU function, researchers and clinicians may uncover new strategies to mitigate the damaging impact of drug abuse on brain health.

Effects of transcranial magnetic stimulation on cocaine addiction: A systematic review of randomized controlled trials.

OBJECTIVE: While pharmacological strategies appear to be ineffective in treating long-term addiction, repetitive transcranial magnetic stimulation (rTMS) is emerging as a promising new tool for the attenuation of craving among multiple substance dependent populations. METHOD: A systematic review of randomized controlled trials (RCTs) was conducted on the efficacy and tolerability of rTMS in treating cocaine use disorder (CUD). Relevant papers published in English through November 30th 2022 were identified, searching the electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Library. RESULTS: Eight studies matched inclusion criteria. The best findings were reported by the RCTs conducted at high-frequency (≥5 Hz) multiple sessions of rTMS delivered over the left dorsolateral prefrontal cortex (DLPFC): a significant decrease in self-reported cue-induced cocaine craving and lower cocaine craving scores and a considerable amelioration in the tendency to act rashly under extreme negative emotions (impulsivity) were found in the active group compared to controls. CONCLUSION: Although still scant and heterogeneous, the strongest evidence so far on the use of rTMS on individuals with CUD support the high frequency stimulation over the left DLPFC as a well tolerated treatment of cocaine craving and impulsivity.

Understanding the Mechanisms of Action and Effects of Drugs of Abuse.

AIM: Drug abuse and addiction are major public health concerns, with millions of people worldwide affected by the negative consequences of drug use. To better understand this complex issue, a review was conducted to examine the mechanisms of action and effects of drugs of abuse, including their acute and chronic effects, the symptoms of abstinence syndrome, as well as their cardiovascular impacts. METHODS: The analyzed data were obtained after surveying an electronic database, namely PubMed, with no time limit, grey literature sources, and reference lists of relevant articles. RESULTS: The review highlights the different categories of drugs of abuse, such as opioids, stimulants, depressants, hallucinogens, and cannabis, and discusses the specific ways that each drug affects the brain and body. Additionally, the review explores the short-term and long-term effects of drug abuse on the body and mind, including changes in brain structure and function, physical health problems, and mental health issues, such as depression and anxiety. In addition, the review explores the effects of drug abuse on cardiovascular health, focusing on electrocardiogram changes. Moreover, the analysis of relevant literature also highlighted possible genetic susceptibility in various addictions. Furthermore, the review delves into the withdrawal symptoms that occur when someone stops using drugs of abuse after a period of chronic use. CONCLUSION: Overall, this review provides a comprehensive overview of the current state of knowledge on drug abuse and addiction. The findings of this review can inform the development of evidence-based prevention and intervention strategies to address this critical public health issue.

Non-alcohol substance use disorder after bariatric surgery in the prospective, controlled Swedish Obese Subjects study.

OBJECTIVE: The goal of this study was to investigate whether bariatric surgery is associated with substance use disorder (SUD) with substances other than alcohol. METHODS: The prospective, controlled Swedish Obese Subjects study enrolled 2010 patients with obesity who underwent bariatric surgery (gastric bypass n = 265; vertical banded gastroplasty n = 1369; gastric banding n = 376) and 2037 matched control individuals receiving usual obesity care. Participants with SUD other than alcohol use disorder were identified using International Statistical Classification of Diseases (ICD) codes from the Swedish National Patient Register (covering treatment in hospital but not primary care). Those with a history of non-alcohol SUD were excluded. Median follow-up was 23.8 years. RESULTS: During follow-up, non-alcohol SUD incidence rates per 1000 person-years with 95% CI were 1.6 (0.8-3.1), 0.8 (0.5-1.2), 1.1 (0.5-2.2), and 0.6 (0.4-0.8) for gastric bypass, vertical banded gastroplasty, gastric banding, and control individuals, respectively. Only gastric bypass was associated with increased incidence of non-alcohol SUD (adjusted hazard ratio 2.54 [95% CI: 1.14-5.65], p = 0.022) compared with control participants. CONCLUSIONS: Gastric bypass surgery was associated with increased risk of non-alcohol SUD, and this should be considered in long-term postoperative care.

The effect of marijuana use on short-term outcomes with bariatric surgery.

BACKGROUND: Despite increasing marijuana use nationwide, there are limited data on implications of marijuana use on bariatric surgery outcomes. OBJECTIVE: We investigated associations between marijuana use and bariatric surgery outcomes. SETTING: Multicenter statewide study utilizing data from the Michigan Bariatric Surgery Collaborative, a payor-funded consortium including over 40 hospitals and 80 surgeons performing bariatric surgery statewide. METHODS: We analyzed data from the Michigan Bariatric Surgery Collaborative clinical registry on patients who underwent a laparoscopic sleeve gastrectomy or Roux-en-Y gastric bypass between June 2019 and June 2020. Patients were surveyed at baseline and annually on medication use, depression symptoms, and substance use. Regression analysis was performed to compare 30-day and 1-year outcomes between marijuana users and nonusers. RESULTS: Of 6879 patients, 574 reported baseline marijuana use and 139 reported use at baseline and 1 year. Marijuana users were more likely to be current smokers (14% versus 8%, P < .0001), screen positive for alcohol use disorder (20.0% versus 8.4%, P < .0001), and score higher on the Patient Health Questionnaire-8 (6.1 versus 3.0, P < .0001). There were no statistically significant differences in 30-day outcomes or co-morbidity remission at 1 year. Marijuana users had higher adjusted total mean weight loss (47.6 versus 38.1 kg, P < .0001) and body mass index reduction (17 versus 14 kg/m2, P < .0001). CONCLUSIONS: Marijuana use is not associated with worse 30-day outcomes or 1-year weight loss outcomes and should not be a barrier to bariatric surgery. However, marijuana use is associated with higher rates of smoking, substance use, and depression. These patients may benefit from additional mental health and substance abuse counseling.

[Anxiolytics: Appropriate Use of Benzodiazepine Receptor Agonists].

Anxiolytics are a class of drugs that include benzodiazepine receptor agonists and serotonin 1A receptor partial agonists. Although benzodiazepine receptor agonists have anxiolytic, sedative-hypnotic, muscle relaxant, and anticonvulsant effects, their use should be carefully monitored due to their potential for paradoxical reactions, withdrawal symptoms, and dependence. On the other hand, serotonin 1A receptor partial agonists have a slower onset, and their use also presents challenges. In clinical practice, having a thorough understanding of the various types of anxiolytics and their unique features is crucial.

Associations among discrimination, psychological functioning, and substance use among US Black adults aged 18-28: Moderation by racial attribution and sex.

INTRODUCTION: Discrimination is associated with poor mental health and substance use among Black Americans, but research is needed on mediators and moderators of these relationships. This study tested whether: 1) discrimination is associated with current alcohol, tobacco (cigarette or e-cigarette), and cannabis use among US Black emerging adults; 2) psychological distress (PD) and positive well-being (PW) are mediators of discrimination-substance use relationships; and 3) these relationships are moderated by sex and attributions to discrimination (racial vs. nonracial). METHODS: Using data from a 2017 US nationally representative survey, we conducted bivariate and multiple-group moderated mediation analyses among 1118 Black American adults aged 18-28. The study assessed discrimination and attribution to discrimination using the Everyday Discrimination scale, past 30-day PD with the Kessler-6 scale, and past 30-day PW with the Mental Health Continuum Short Form. We utilized probit regression for all structural equation models and adjusted final models for age. RESULTS: Discrimination was positively associated with past 30-day cannabis and tobacco use directly and indirectly through PD in the overall model. Among males who reported race as the sole/main attribution to discrimination, discrimination was positively associated with alcohol, cannabis, and tobacco use through PD. Among females who reported race as the sole/main attribution to discrimination, discrimination was positively associated with cannabis use through PD. Discrimination was positively associated with tobacco use among those who reported nonracial attributions to discrimination and with alcohol use among those whose attribution was not assessed. Discrimination was positively associated with PD among those who reported race as a secondary attribution to discrimination. CONCLUSIONS: Discrimination specifically attributed to race may contribute to greater PD and in turn alcohol, cannabis, and tobacco use among Black emerging adults, especially males. Future substance use prevention and treatment efforts targeted to Black American emerging adults may benefit from addressing racial discrimination and PD.

Problematic alcohol use in post-bariatric patients - a qualitative study. / Problematisk alkoholbruk etter fedmekirurgi ­ en kvalitativ studie.

BACKGROUND: Research shows an increased risk of alcohol use disorders in post-bariatric patients. This study aims to gain insight into what post-bariatric patients receiving treatment for substance use think are the possible causes for developing problematic alcohol consumption after surgery. MATERIAL AND METHOD: Ten in-depth interviews were held with post-bariatric patients receiving treatment for substance use in 2020 (six men and four women). The data material was transcribed and analysed using the stepwise deductive-inductive (SDI) method. RESULTS: The participants first started to experience problematic alcohol consumption after bariatric surgery. They described new, intense feelings of intoxication and how their body responded differently to alcohol. Alcohol now functioned as an appetite stimulant, pain reliever and food replacement. Most participants had positive experiences during the initial post-operative period, but they described an ambivalence towards their bodily changes and an increased mental vulnerability in the years following the surgery. INTERPRETATION: The new effect and function of alcohol after the procedure may have made the participants more vulnerable to problematic alcohol consumption.

Exploring Drug De-addiction Treatment in Unani Medicine.

Background: Drug addiction, or substance abuse disorder, has a long history. The use of a drug that causes dependence has been used in various religious and tribal initiation ceremonies. Currently, recreational use or peer modelling leads an individual to substance abuse. The magnitude of the problem of addiction increases multifold in the presence of stressors like broken families, joblessness, occupational stress, etc. Objectives: The de-addiction process is used to relieve an individual's craving for the drug. It is a painful process, as several effects of withdrawal compel a person to return to the drugs again and again. Our aim is to explore the available literature on the use of Unani medicine for de-addiction. Methodology: We surveyed various classical books from the available literature for drug de-addiction in Unani medicine. Indexed journals were also surveyed for the available related material using various keywords like "opium addiction" and "Unani medicine and de-addiction " and the information was filtered for this review. Results: We observed that there was an elaborate scheme for de-addiction in opium addiction and the process is so general that it could serve as a framework for the de-addiction process for other similar drugs. Conclusion: Unani medicine is significant in the literature as being among the the available de-addiction addiction processes and may furnish several leads for various herbal drugs that may be used for de-addiction in the future.

Examining the unique and additive effect of trauma and racial microaggressions on substance use risk among Black young adults.

OBJECTIVE: Exposure to traumatic events is linked to adverse health outcomes, including substance use. Contemporary models have conceptualized racism, including racial microaggressions, as a form of trauma. However, few studies have been conducted examining the unique and additive effect of racial microaggressions within models that include exposure to traditional forms of trauma on substance use outcomes, as well as whether effects vary by gender. METHOD: Three hundred and ninety-nine Black young adults between 18 and 29 (61% female, mean age 20.7) completed measures on problem alcohol and cannabis use, and experiences of trauma and racial microaggressions. RESULTS: Controlling for age, gender, income, race (i.e., monoracial vs. multiracial), and recruitment source, regression analyses showed that racial microaggressions predicted problem substance use above the effect of trauma exposure. Moreover, exoticization/assumptions of similarity and workplace/school microaggressions primarily accounted for the effect of racial microaggressions on substance use risk. One gender effect was found, with trauma exposure associated with lower cannabis use for Black males and a nonsignificant effect found for Black females. CONCLUSIONS: Racial microaggressions provide unique and additive understanding in risk for substance use outcomes among Black young adults above effects observed from exposure to traditional forms of trauma. This finding highlights the significance of racial microaggression on health outcomes for Black young adults and can inform future research in the area of trauma exposure and substance use risk among this population of young people. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Religious affiliation protects against alcohol/substance use initiation: A prospective study among healthy adolescents.

BACKGROUND: A substantial volume of the literature suggests that religious factors buffer against alcohol/substance use among adults, but research among adolescents is sparse. Further, few studies in this area have been prospective, and therefore it is unclear how religion may impact less alcohol/substance use among adolescents. METHOD: We prospectively evaluated effects of religious affiliation on initiation of alcohol/substance use in a sample of 81 psychiatrically healthy 13-14-year-olds from New England, over a 3-year period (from November 2015 to January 2019). Known risk factors were also evaluated including anxiety, depression, and impulsivity; family history of mental illness and alcohol/substance misuse; and volume of brain regions implicated in adolescent alcohol/substance misuse (assessed by Magnetic Resonance Imaging). RESULTS: Religiously affiliated adolescents were significantly less likely to initiate use of alcohol/substances (hazard ratio [HR] = 0.38). The addition of family history of alcohol/substance misuse to the model increased the predictive value of religious affiliation (HR = 0.34). Other risk factors did not diminish nor increase observed effects. CONCLUSIONS: These findings support and extend the current research by suggesting that religious affiliation protects against initiation of alcohol/substance use during early adolescence, particularly in individuals with elevated risk.

Dual action of ketamine confines addiction liability.

Ketamine is used clinically as an anaesthetic and a fast-acting antidepressant, and recreationally for its dissociative properties, raising concerns of addiction as a possible side effect. Addictive drugs such as cocaine increase the levels of dopamine in the nucleus accumbens. This facilitates synaptic plasticity in the mesolimbic system, which causes behavioural adaptations and eventually drives the transition to compulsion1-4. The addiction liability of ketamine is a matter of much debate, in part because of its complex pharmacology that among several targets includes N-methyl-D-aspartic acid (NMDA) receptor (NMDAR) antagonism5,6. Here we show that ketamine does not induce the synaptic plasticity that is typically observed with addictive drugs in mice, despite eliciting robust dopamine transients in the nucleus accumbens. Ketamine nevertheless supported reinforcement through the disinhibition of dopamine neurons in the ventral tegmental area (VTA). This effect was mediated by NMDAR antagonism in GABA (γ-aminobutyric acid) neurons of the VTA, but was quickly terminated by type-2 dopamine receptors on dopamine neurons. The rapid off-kinetics of the dopamine transients along with the NMDAR antagonism precluded the induction of synaptic plasticity in the VTA and the nucleus accumbens, and did not elicit locomotor sensitization or uncontrolled self-administration. In summary, the dual action of ketamine leads to a unique constellation of dopamine-driven positive reinforcement, but low addiction liability.