Substance Use Disorders Research Articles

Genome-wide meta-analyses of cross substance use disorders in European, African, and Latino ancestry populations.

Genetic risks for substance use disorders (SUDs) are due to both SUD-specific and SUD-shared genes. We performed the largest multivariate analyses to date to search for SUD-shared genes using samples of European (EA), African (AA), and Latino (LA) ancestries. By focusing on variants having cross-SUD and cross-ancestry concordant effects, we identified 45 loci. Through gene-based analyses, gene mapping, and gene prioritization, we identified 250 SUD-shared genes. These genes are highly expressed in amygdala, cortex, hippocampus, hypothalamus, and thalamus, primarily in neuronal cells. Cross-SUD concordant variants explained ~ 50% of the heritability of each SUD in EA. The top 5% individuals having the highest polygenic scores were approximately twice as likely to have SUDs as others in EA and LA. Polygenic scores had higher predictability in females than in males in EA. Using real-world data, we identified five drugs targeting identified SUD-shared genes that may be repurposed to treat SUDs.

Which pediatric practices use substance use consultation services?

Substance use disorders (SUD) are common in adolescents and young adults, though few youth with SUD receive treatment, and rates of medication for substance use disorder treatment are much lower in youth compared to adults. Pediatric primary care could present an opportunity for youth with SUD to access medication, though pediatric providers may need support. Massachusetts has provided a substance use consultation line for pediatric providers since 2018. One large network of independent primary care practices within the state has been further supported by access to resources provided through a grant from the Substance Abuse and Mental Health Services Administration. In this paper, we describe the services provided in Massachusetts and examine whether additional resources are associated with increased use of the consultation line as a marker of provider engagement in SUD treatment.

Evaluating the Efficacy of Transcranial Magnetic Stimulation in Symptom Relief and Cognitive Function in Obsessive–Compulsive Disorder, Substance Use Disorder, and Depression: An Insight from a Naturalistic Observational Study

The utilization of non-invasive neurostimulation techniques, such as transcranial magnetic stimulation (TMS), is increasingly prevalent in psychiatry due to their efficacy and safety. Although the precise therapeutic mechanisms remain partially unclear, repetitive TMS, particularly high-frequency stimulation, may enhance cognitive functions, contributing to therapeutic benefits. This within-subjects study examined the impact of TMS on cognitive and symptomatic outcomes in patients with obsessive–compulsive disorder (OCD), substance use disorder (SUD), and major depressive disorder (MDD). A total of 44 patients underwent cognitive tests and symptom assessments before and after an intensive four-week TMS treatment phase, followed by a four-week maintenance phase. Cognitive assessments included Raven’s matrices, verbal fluency, and digit span tests, while symptom severity was measured using the Italian version of the SCL-90-R. Decision-making performance was also evaluated by administering a delay discounting (DD) test. Principal component analysis was used to generate a dimensional characterization of subjects along cognitive and symptom-related axes before and after treatment. The results indicated that TMS significantly improved symptom scores, but no significant cognitive enhancement was observed. Statistical analysis based on linear mixed-effects models confirmed these findings, showing a significant fixed effect of TMS treatment on symptoms but not on cognitive performance. DD metrics remained unchanged. These findings suggest that while TMS effectively alleviates clinical symptoms, it does not produce consistent or appreciable enhancement of cognitive functions in these protocols. This study highlights the need for more personalized and combined therapeutic approaches to maximize the benefits of TMS, potentially incorporating cognitive enhancement strategies. Future studies will be useful to explore whether the results we obtained are valid for other pathologies, cognitive tests, and stimulation protocols.

Workforce estimate to treat mental disorders in the Kingdom of Saudi Arabia

BackgroundMental, neurological, and substance abuse (MNS) disorders describe a range of conditions that affect the brain and cause distress or functional impairment. In the Middle East and North Africa (MENA), MNS disorders make up 10.88 percent of the burden of disease as measured in disability-adjusted life years. The Kingdom of Saudi Arabia (KSA) is one of the main providers of mental health services and one of the largest contributors to mental health research in the region. Within the past decade, mental health resources and services has increased.MethodsWe employ a needs-based workforce estimate as a planning exercise to arrive at the total number of psychiatrists, nurses, and psychosocial care providers needed to meet the epidemiological need of mental health conditions of the population of KSA. Estimates for a potential mental health workforce gap were calculated using five steps: Step 1—Quantify target population for priority mental health conditions. Step 2—Identify number of expected cases per year. Step 3—Set target service coverage for each condition. Step 4—Estimate cost-effective health care service resource utilization for each condition. Step 5—Estimate service resources needed for each condition.ResultsThe planning exercise indicates an epidemiologic need for a total of 17,100 full-time-equivalent (FTE) health care providers to treat priority MNS disorders. KSA appears to have a need-based shortage of 10,400 health workers to treat mental disorders. A total of 100 psychiatrists, 5700 nurses, and 4500 psychosocial care providers would be additionally needed (that is, above and beyond current levels) to address the priority mental health conditions. The shortfall is particularly severe for nurses and psychosocial workers who make up 98.9 percent of the shortfall. This shortage is substantial when compared to other high-income countries. Overall, the workforce needed to treat MNS conditions translates to 49.2 health workers per 100,000 population.ConclusionChallenges to addressing the shortfall are Saudi specific which includes awareness of cultural customs and norms in the medical setting. These challenges are compounded by the lack of Saudi nationals in the mental health workforce. Saudi nationals make up 29.5 percent of the physician workforce and 38.8 percent of the nursing workforce. Policymakers and planners supplement this shortfall with non-Saudi providers, who must be mindful of Saudi-specific cultural considerations. Potential solutions to reducing the shortfall of mental health care workers includes nurse task shifting and training of general practitioners to screen for, and treat, a subset of MNS disorders.

Substance Use Disorder as Risk Factor for Intubation in Angioedema: A Nationwide Cohort Study.

Individuals with angioedema (AE) are at high risk for airway compromise and often require endotracheal intubation. Patient factors predisposing one to airway compromise are not well described. The objective of this study is to examine whether substance use disorder (SUD) in patients with AE is associated with need for airway intervention. This population-based retrospective cohort study compared AE patients with SUD versus propensity-matched control groups. Outcomes were hospitalization, intubation, and tracheotomy. Using the TriNetX National Database, this study included 28,931 patients with SUD and 117,509 patients without SUD who presented with AE. Among patients with AE, those with each subtype of SUD (alcohol, cannabis, cocaine, tobacco, and opioids) were found to have higher risk of severe AE compared to propensity-matched non-SUD cohorts. Rate of hospitalization after cohort matching ranged from 20.4% for tobacco use disorder to 30.4% for cocaine use disorder, all significantly higher than the 8.0% in a population without SUD. Each SUD subtype was associated with a higher rate of intubation compared with matched non-SUD groups, with cannabis use disorder having the highest relative risk (RR) of 3.67 (95% CI: 2.69-5.02). Tobacco (RR = 2.45, 95% CI: 1.79-3.34) and alcohol (RR = 2.82, 95% CI: 1.73-4.58) use disorders were both associated with significantly higher risk of tracheotomy. These data suggest that patients with SUD, regardless of subtype, and after propensity matching for demographics and comorbidities are at higher risk for adverse outcomes when presenting with AE. This study highlights clinically relevant predictors of airway compromise. Level 3 Laryngoscope, 2024.

A Source Control Model for Treatment-Resistant Substance Use Disorder.

We propose applying the "source control" model of infectious disease treatment to the management of treatment-resistant substance use disorder (SUD). We believe that this conceptual framework complements other models for understanding SUD, fills a gap in our current understanding of treatment-resistant SUD, and advances the destigmatization of SUD by reinforcing SUD as a disease similar to other medical conditions. The model also harmonizes the need for multimodal treatment and novel interventions for both acute supportive care and long-term treatment of SUD. In this manuscript, we discuss the justification for, as well as the strengths and limitations of, the "source control" model for the management of treatment-resistant SUD. We also discuss the model's potential to direct innovative research questions and therapeutic interventions.

The weight of weights: Causal impact of overweight on major depressive disorder and its disparate association with suicide attempts in over 450,000 individuals of European ancestry (AM-SRNMA 003)

AimSome studies and societal discussions have suggested a potential link between overweight and a higher risk of mental disorders and suicidal ideation. However, the causal relationships between these factors remain unclear. This study aims to assess the bidirectional causal associations between overweight and mental disorders, including suicidal attempts. MethodWe conducted a Two-Sample Mendelian Randomization study utilizing data from over 450,000 individuals of European ancestry sourced from a comprehensive Genome-Wide Association Study database. We chose single-nucleotide polymorphisms as instrumental variables. ResultsOur analyses consistently supported a unidirectional causal association of overweight with the increased risk of major depressive disorder (MDD, β = 0.152, se = 0.069, P = 0.027), bipolar affective disorders (BD, β = 0.197, se = 0.092, P = 0.033), and attention-deficit / hyperactivity disorder (ADHD, β = 0.308, se = 0.080, P = 1.366 × 10−4). We observed no significant causal relationships for the exposure of overweight to anxiety disorder (AD), manic episode (MA), panic disorder (PD), schizophrenia (SZ), substance use disorder (SUD), autism spectrum disorder (ASD), ever attempted suicide, recent thoughts of suicide or self-harm, and suicide or other intentional self-harm events. ConclusionThis study has provided evidence for the causal relationship between overweight and MDD, BD, ADHD, with no observed relationship between overweight and AD, MA, PD, SZ, SUD, ASD, ever attempted suicide, recent thoughts of suicide or self-harm, and suicide or other intentional self-harm events.

Maternal mental health as a major contributor to maternal mortality

Perinatal mental health conditions affect up to 20 % of pregnant or postpartum individuals, and nearly 15 % of pregnant individuals meet criteria for substance use disorder (SUD). All providers taking care of pregnant or postpartum individuals will encounter patients in these scenarios. Maternal Mortality Review Committees (MMRCs) have determined maternal mental health conditions, including SUD, to be the leading cause of preventable maternal death during pregnancy or in the first year postpartum. Lessons learned from MMRCs to prevent these deaths include the recommendation that screening and identification of mental health conditions need to be linked with evidence-based, patient-centered, and accessible treatments. Obstetricians and gynecologists, midwives, family medicine providers, and pediatricians, are in unique positions not only to screen and diagnose, but also to treat individuals with mental health concerns, including SUD, during pregnancy and postpartum.

Examining the Psychological Measures and Feasibility of Recreational Trail Rides in Reducing Cravings for Addictive Substances among Veterans: A Replication Pilot Study.

Equine-assisted services have been gaining popularity as complementary therapies for a variety of populations with a diversity of diagnoses. Interventions using equines might benefit the military Veteran population through building therapeutic alliance as well as reducing symptoms. This pilot observational study is primarily aimed to investigate safety, feasibility, and acceptability of equine-assisted services for Veterans with substance abuse disorders. It is the second pilot observational study, the first being completed in 2022. Secondary outcomes included recording the impact of trail riding on psychological measures among Veterans at a large Veterans Administration medical center. The study included a total of 32 Veterans who participated in trail riding sessions from May 4, 2022 to August 31, 2022. The study utilized the Positive and Negative Affect Scale, Adult Hope Scale, and Craving Experience Questionnaire to assess changes in positive affect, negative affect, hope components, and substance craving. The results indicated significant reductions in negative affect and substance craving after the first session, with positive effects observed in subsequent sessions. However, demographic and diagnostic variables did not predict significant changes in psychological instruments. Overall, the study demonstrated that trail riding was a safe and feasible intervention and may have potential benefits for improving emotional well-being and reducing substance cravings among Veterans. It is recommended that future studies research mechanisms of action, as well as conduct more rigorous investigations, including controlled trials using larger sample sizes and longitudinal research, to best determine lasting effects of these types of complementary therapies.

T124 - Assessing Amygdala Habituation as it Relates to Substance-Use Disorder Vulnerability, Using Data From the ABCD Study®

T124 - Assessing Amygdala Habituation as it Relates to Substance-Use Disorder Vulnerability, Using Data From the ABCD Study®

Neurocognitive and clinical profile of male patients with substance use disorder in early remission phase with and without comorbid depression

Substance Use Disorder (SUD) represents one of the most frequent conditions worldwide which commonly coexists with major depressive disorder (MDD). This comorbidity (SUD + MDD) is one of the most prevalent with patients showing certain social and clinical characteristics that could lead to a worsening of their cognitive performance. However, despite these particularities, only a few studies have addressed the possible differences in cognitive performance between patients with SUD + MDD compared with those with SUD-only patients. Therefore, the aim of this study is to examine the clinical and cognitive profile of patients with SUD + MDD vs. SUD-only who are in early remission phase. For this purpose, 271 male patients underwent a clinical and neuropsychological assessment (SUD + MDD group: N = 101; SUD-only group: N = 170). Results indicated that SUD + MDD patients showed worse cognitive performance than SUD in visuospatial reasoning, verbal memory and learning, recognition, and processing speed even after a 3-month period of abstinence. Furthermore, these patients exhibited more self-reported prefrontal symptoms, as well as worse social and clinical conditions. This study indicates that the neurocognitive and clinical profile of patients with SUD + MDD could represent a risk since their characteristics have been associated with poorer recovery and prognosis. Our results could be helpful in clinical practice highlighting the need for cognitive remediation strategies in these populations, providing information that would allow the implementation of more appropriate treatments and preventive strategies.

Associations between delay discounting and unhealthy behaviors in substance use recovery

BackgroundResearch on delay discounting (DD) is mixed on whether DD is a domain-specific component related to specific behaviors or a domain-general process that cuts across various behaviors. A pivotal group to test the associations between DD and unhealthy behaviors is individuals in recovery from substance use disorders (SUD), as they are moving away from a disorder toward a healthier state. MethodsIndividuals in SUD recovery (n = 317) completed the Temptation Scale, the Health Behaviors Questionnaire, and an Adjusting Delay Discounting Task. An exhaustive model space search was performed using linear regression to examine associations between DD with temptation, engagement in unhealthy behaviors, and the total number of unhealthy behaviors participants engage in. We also tested whether remission status is associated with the total number of unhealthy behaviors participants engage in. ResultsResults revealed that DD was positively associated with poor eating (p<.001), physical inactivity (p=.003), financial irresponsibility (p<.001), risky behaviors (p<.001), lack of personal development goals (p<.001), lack of household savings (p=.004), and lack of health behaviors (p=.003). DD was also positively associated with the total number of unhealthy behaviors participants engage in (p<.001). Participants who were not in remission engaged in more unhealthy behaviors compared to those who were in remission (p<.001). ConclusionIn a sample of individuals in recovery from SUD, DD is not domain-specific and undergirds engagement in several maladaptive health behaviors that can negatively impact recovery. Thus, DD can be a target for interventions aiming to reduce other maladaptive behaviors in SUD recovery.

Partitioning the Genomic Components of Behavioral Disinhibition and Substance Use (Disorder) Using Genomic Structural Equation Modeling.

Externalizing behaviors encompass manifestations of risk-taking, self-regulation, aggression, sensation-/reward-seeking, and impulsivity. Externalizing research often includes substance use (SUB), substance use disorder (SUD), and other (non-SUB/SUD) "behavioral disinhibition" (BD) traits. Genome-wide and twin research have pointed to overlapping genetic architecture within and across SUB, SUD, and BD. We created single-factor measurement models-each describing SUB, SUD, or BD traits-based on mutually exclusive sets of European ancestry genome-wide association study (GWAS) statistics exploring externalizing variables. We then assessed the partitioning of genetic covariance among the three facets using correlated factors models and Cholesky decomposition. Even when the residuals for indicators relating to the same substance were correlated across the SUB and SUD factors, the two factors yielded a large correlation (rg=0.803). BD correlated strongly with the SUD (rg=0.774) and SUB (rg=0.778)factors. In our initial decompositions, 33% of total BD variance remained after partialing out SUD and SUB. The majority of covariance between BD and SUB and between BD and SUD was shared across all factors, and, within these models, only a small fraction of the total variation in BD operated via an independent pathway with SUD or SUB outside of the other factor. When only nicotine/tobacco, cannabis, and alcohol were included for the SUB/SUD factors, their correlation increased to rg=0.861; in corresponding decompositions, BD-specific variance decreased to 27%. Further research can better elucidate the properties of BD-specific variation by exploring its genetic/molecular correlates.

Exploring the Nexus of Climate Change and Substance Abuse: A Scoping Review.

The increase in average air temperature and multiple extreme weather events, such as heatwaves and droughts, pose significant health risks to humans. This scoping review aims to examine the current state of the existing literature concerning the potential relationship between substance abuse and climate change, along with the aspects it encompasses. The review followed PRISMA guidelines for methodological rigor, aiming to identify studies on drug abuse. Searches were conducted across the primary databases using specific search strings. Quality assessment involved evaluating the research question's clarity, search strategy transparency, consistency in applying the inclusion/exclusion criteria, and reliability of data extraction. Most studies were conducted in the USA. They included observational and retrospective quantitative studies, as well as qualitative and prospective observational ones. Research examined the correlation between extreme weather and some substance abuse. All studies analyzed the adverse effects of climate change, especially heatwaves, on both physiological and pathological levels. The scoping review notes the scarcity of studies about the correlation between substance abuse and climate change, and emphasizes the threats faced by individuals with substance abuse and mental health disorders due to climate change.

Managing Substance Use Disorders and Addiction: How to Integrate Professionalism and Ethics with the Complexity of Diagnosis and Therapy

Physicians and other healthcare staff who work with the patients having substance use disorders (SUDs) and addiction have to deal with different and complex scenario invariably in comparison to other healthcare providers dealing with regular medical services sought by the patients. Hence, the unconventional nature of practice regarding patients of SUDs and addiction and the diverse range of backgrounds among substance use workers, e.g., psychiatrist, general physician, nurse, psychotherapist, counsellor, social worker, and public health specialist highlights the universal relevance of being more professional and more ethical in practice. They are expected to demonstrate a variety of ethical and professional competences to safeguard themselves and others involved. Clinical team engaged in such activities requires specific ethical training that can help them face specific ethical dilemmas and guide through deeper consideration of those pressing and complex issues, using specific framework, professional guidelines, or institutional management approaches. Professional societies and accrediting institutions should apply their authority to establish practice standards, competencies, regulatory procedures, and codes of ethics to help guide practice and protect public trust and confidence. For the team involved in practice, it is important to become familiar with and adhere to the principles and values that define professionalism and ethical conduct in care for patients suffering from SUDs and addiction. The review paper aims to examine the intersection of professionalism and ethics with the complexity of diagnosis and therapy in this specific area of practice. Besides, some frameworks will be highlighted which may help healthcare providers to foster ethical decision making. It is also a modest effort to show some new insights for improving the quality of care in addiction and mental health by the professional team and healthcare organization from both clinical and operational viewpoint. Mugda Med Coll J. 2024; 7(1): 42-47

Mental Health Hospitalizations in Canadian Children, Adolescents, and Young Adults Over the COVID-19 Pandemic

The COVID-19 pandemic resulted in multiple socially restrictive public health measures and reported negative mental health impacts in youths. Few studies have evaluated incidence rates by sex, region, and social determinants across an entire population. To estimate the incidence of hospitalizations for mental health conditions, stratified by sex, region, and social determinants, in children and adolescents (hereinafter referred to as youths) and young adults comparing the prepandemic and pandemic-prevalent periods. This Canadian population-based repeated ecological cross-sectional study used health administrative data, extending from April 1, 2016, to March 31, 2023. All youths and young adults from 6 to 20 years of age in each of the Canadian provinces and territories were included. Data were provided by the Canadian Institute for Health Information for all provinces except Quebec; the Institut National d'Excellence en Santé et en Services Sociaux provided aggregate data for Quebec. The COVID-19-prevalent period, defined as April 1, 2020, to March 31, 2023. The main outcome measures were the prepandemic and COVID-19-prevalent incidence rates of hospitalizations for anxiety, mood disorders, eating disorders, schizophrenia or psychosis, personality disorders, substance-related disorders, and self-harm. Secondary measures included hospitalization differences by sex, age group, and deprivation as well as emergency department visits for the same mental health conditions. Among Canadian youths and young adults during the study period, there were 218 101 hospitalizations for mental health conditions (ages 6 to 11 years: 5.8%, 12 to 17 years: 66.9%, and 18 to 20 years: 27.3%; 66.0% female). The rate of mental health hospitalizations decreased from 51.6 to 47.9 per 10 000 person-years between the prepandemic and COVID-19-prevalent years. However, the pandemic was associated with a rise in hospitalizations for anxiety (incidence rate ratio [IRR], 1.11; 95% CI, 1.08-1.14), personality disorders (IRR, 1.21; 95% CI, 1.16-1.25), suicide and self-harm (IRR, 1.10; 95% CI, 1.07-1.13), and eating disorders (IRR, 1.66; 95% CI, 1.60-1.73) in females and for eating disorders (IRR, 1.47; 95% CI, 1.31-1.67) in males. In both sexes, there was a decrease in hospitalizations for mood disorders (IRR, 0.84; 95% CI, 0.83-0.86), substance-related disorders (IRR, 0.83; 95% CI, 0.81-0.86), and other mental health disorders (IRR, 0.78; 95% CI, 0.76-0.79). This cross-sectional study of Canadian youths and young adults found a rise in anxiety, personality disorders, and suicidality in females and a rise in eating disorders in both sexes in the COVID-19-prevalent period. These results suggest that in future pandemics, policymakers should support youths and young adults who are particularly vulnerable to deterioration in mental health conditions during public health restrictions, including eating disorders, anxiety, and suicidality.

The human VGLUT3-pT8I mutation elicits uneven striatal DA signaling, food or drug maladaptive consumption in male mice

Cholinergic striatal interneurons (ChIs) express the vesicular glutamate transporter 3 (VGLUT3) which allows them to regulate the striatal network with glutamate and acetylcholine (ACh). In addition, VGLUT3-dependent glutamate increases ACh vesicular stores through vesicular synergy. A missense polymorphism, VGLUT3-p.T8I, was identified in patients with substance use disorders (SUDs) and eating disorders (EDs). A mouse line was generated to understand the neurochemical and behavioral impact of the p.T8I variant. In VGLUT3T8I/T8I male mice, glutamate signaling was unchanged but vesicular synergy and ACh release were blunted. Mutant male mice exhibited a reduced DA release in the dorsomedial striatum but not in the dorsolateral striatum, facilitating habit formation and exacerbating maladaptive use of drug or food. Increasing ACh tone with donepezil reversed the self-starvation phenotype observed in VGLUT3T8I/T8I male mice. Our study suggests that unbalanced dopaminergic transmission in the dorsal striatum could be a common mechanism between SUDs and EDs.

Association between genital gender-affirming surgery and psychiatric comorbidities in individuals with gender incongruence.

Previous studies present mixed evidence on the relationship between psychiatric comorbidities and genital gender-affirming surgery (GGAS) in individuals with gender incongruence (GI). This research aims to investigate the psychiatric comorbidity rates post-GGAS in the GI population-namely, depressive disorders, anxiety disorders, posttraumatic stress disorders, substance abuse disorder, and suicidality. Based on the TriNetX health care database, an international database with >250 million patients, a cross-sectional study was executed comparing psychiatric comorbidity rates among cases of GI with and without GGAS. Individuals were matched for demographic and health-related variables, which included history of cardiovascular disease, diabetes, and obesity. The main focus was to establish the rates and changes in psychiatric comorbidities following GGAS. Among individuals with GI, the study identified 4061 with GGAS and 100 097 without. At 1 year post-GGAS, there was a significant decrease in depression (odds ratio [OR], 0.748; 95% CI, 0.672-0.833; P < .0001), anxiety (OR, 0.730; 95% CI, 0.658-0.810; P < .0001), substance use disorder (OR, 0.730; 95% CI, 0.658-0.810; P < .0001), and suicidality (OR, 0.530; 95% CI, 0.425-0.661; P < .0001), and these reductions were maintained or improved on at 5 years, including posttraumatic stress disorder (OR, 0.831; 95% CI, 0.704-0.981; P = .028). The findings indicate that GGAS may play a crucial role in diminishing psychiatric comorbidities among individuals with GI. This is the largest known study to evaluate the effect of GGAS on psychiatric comorbidities in the GI population, offering robust evidence. The reliance on the precision of CPT and ICD-10 codes for data extraction poses a limitation due to potential coding inaccuracies. The evidence suggests a significant association between GGAS and reduced psychiatric comorbidities in individuals with GI.

Disrupting Substance Use Disorder: The Chemistry of Iboga Alkaloids

The iboga alkaloids are a family of monoterpene indole alkaloids first discovered from the root of Tabernanthe iboga. The major alkaloid constituent in the root, ibogaine, has garnered interest for its anti‐addictive properties. Ibogaine has been shown to reduce opiate, amphetamine, alcohol, and nicotine self‐administration in rodents. However, ibogaine itself is less than optimal as a treatment in humans for Substance Abuse Disorder (SUD) due to its cardiotoxicity and hallucinogenic potential. Alternatively, it is an attractive lead for drug discovery efforts. Several notable programs have been launched to both elucidate ibogaine’s mechanism of action and reduce its toxicity. While there have been over twenty total syntheses of ibogamine, ibogaine, and closely related family members, there are far fewer syntheses of recently isolated iboga alkaloids. In this targeted review, we discuss the synthetic strategies applied to the synthesis of classical and non‐classical iboga alkaloids.

The Impact of Medicaid Institutions for Mental Disease Exclusion Waivers on the Availability of Substance Abuse Treatment Services and the Varying Effect by Ownership Type.

Access to integrated care for those with co-occurring mental health (MH) and substance use disorders (SUDs) has been limited because of an exclusion in Medicaid on paying for SUD care for those in institutions for mental disease (IMDs). Starting in 2015, the federal government encouraged states to pursue waivers of this exclusion, and by the end of 2020, 28 states had done so. It is unclear what impact these waivers have had on the availability of care for co-occurring disorders and the characteristics of any facilities that expanded care because of them. Using data from the National Survey of Substance Abuse Treatment Services, we estimate a two-stage residual inclusion model including time- and state-fixed effects to examine the effect of state IMD SUD waivers on the percentage of facilities offering co-occurring MH and SUD treatment, overall and for residential facilities specifically. Separate analyses are conducted by facility ownership type. Results show that the adoption of an IMD SUD waiver is associated with 1.068 greater odds of that state having facilities offering co-occurring MH and substance abuse (SA) treatment a year or more later. The adoption of a waiver increases the odds of a state's residential treatment facility offering co-occurring MH and SA treatment by 1.129 a year or more later. Additionally, the results suggest 1.163 higher odds of offering co-occurring MH/SA treatment in private for-profit SA facilities in states that adopt an IMD SUD waiver while suggesting no significant impact on offered services by private not-for-profit or public facilities. Our study findings suggest that Medicaid IMD waivers are at least somewhat effective at impacting the population targeted by the policy. Importantly, we find that there are differential responses to these IMD waivers based on facility ownership, providing new evidence for the literature on the role of ownership in the provision of health care.