The Neurocircuitry of Substance Use Disorder, Treatment, and Change: A Resource for Clinical Psychiatrists.

Substance use disorder (SUD) is common in psychiatric patients and has a negative impact on health and well-being. However, SUD often goes untreated, and there is a need for psychiatrists, of all specialties, to address this pervasive clinical problem. In this review, the authors' goal is to provide a resource that describes treatments for SUD, using neuroscience as a framework. They discuss the effect of pharmacotherapy on craving, intoxication, and withdrawal and its ability to interrupt the cycle of substance use in SUD. The neuroscience of stress is reviewed, including medications targeting neurotransmitter systems activated by alarm and fear. Neuroplasticity and promising treatments that use this mechanism, including ketamine, psilocybin, and transcranial magnetic stimulation (TMS), are discussed. The authors conclude by listing resources and practice guidelines for physicians interested in learning more about treatments for SUD.

Association of Cannabis Use Reduction With Improved Functional Outcomes: An Exploratory Aggregated Analysis From Seven Cannabis Use Disorder Treatment Trials to Extract Data-Driven Cannabis Reduction Metrics.

OBJECTIVE: This exploratory analysis sought to determine whether decreases in cannabis use are associated with improvements in cannabis-related problems and functional outcomes, and if so, what percentage decrease is associated with improvement. METHODS: Data were aggregated from seven cannabis use disorder treatment trials conducted in the United States (N=920; ages 13 years and older; mean age, 25 years; 30% female, 7% Black, 11% Hispanic/Latinx). Outcome measures included the patient-reported Marijuana Problems Scale (MPS), Health-Related Quality of Life scale (HRQOL), and Pittsburgh Sleep Quality Index and the clinician-rated Clinical Global Impressions (CGI) severity and improvement scales (CGI-S and CGI-I). Generalized estimating equations tested the association between changes in 4-week cannabis use and improvements in functional outcomes. Classification and regression tree (CART) models were developed to determine what reductions in cannabis use could be used as classifiers of improvement. RESULTS: Decreases in the amount and frequency of cannabis use were significantly associated with improvements in MPS severity and total scores as well as improvements on the CGI-I and in sleep quality, but not improvements on the HRQOL. CART models performed best for CGI-I scores (72%-75% correct classification), while other outcome measures did not perform as well (40%-62% correct classification). CART models showed improvements on the CGI at 74% reduction in use amounts and 47% reduction in use days. CONCLUSIONS: Reductions in cannabis use (∼50% reduction in use days and ∼75% reduction in use amounts) were associated with clinician-assessed improvement, which suggests that cannabis use reduction may yield benefit among individuals with cannabis use disorder. These exploratory results extract a data-driven metric to inform future studies, clinicians, patients, and policy recommendations.

Another Round: Influence of Alcohol-Related Conditions and Other Drug Use-Related Disorders in Emergency Department Frequent Use - A Single-Site Matched Case-Control Study in Spain.

INTRODUCTION: Patients who make 5 or more visits per year to hospital emergency departments (EDs) are usually considered ED frequent users (FUs). This study aims to better characterize the influence of alcohol and other drug use-related disorders in this phenomenon in a European Mediterranean country with public, universal, tax-financed healthcare system. METHODS: Matched case-control study. Cases were adults between 18 and 65 years old who consulted 5 or more times the ED of a tertiary hospital in Spain between December 2018 and November 2019. Each case was assigned a control of the same age and gender, who appeared to the ED on the same day, but who made 4 visits or less to the service during the study period. The electronic record of the first ED visit during this period was used to extract the variables of interest: emergency care received, clinical and social characteristics. Predictors of frequent ED use were identified with conditional logistic regression. RESULTS: 609 case-control pairs (total n = 1,218) were selected. History of alcohol-related conditions (adjusted odds ratio [AOR] = 1.82 [95% CI: 1.26-2.64] p = 0.001) and also other drug use-related disorders (AOR = 1.50 [95% CI: 1.11-2.03] p = 0.009) significantly increased the probability of frequent use of emergency services. DISCUSSION/CONCLUSION: Alcohol-related conditions and other drug use-related disorders must be evaluated in all ED FUs. Specific action protocols to concurrently address repeated attendance and addictions in the emergency room could be a good tool to reduce frequent ED use.

Harm Reduction for Opioid Use Disorder: Strategies and Outcome Metrics.

Tweet: The authors discuss harm reduction strategies and associated outcome metrics in relation to the ongoing opioid crisis.

Cultural Divergence in Psychedelic Use among Medical Students: An ESPAD-Adapted Survey among Poles and Iraqis.

Psychedelics can profoundly alter cognition and consciousness. Their use in Middle Eastern countries, including Iraq, is ambiguous. We aim to investigate psychedelic awareness and use among Iraqi and Polish medical students. We surveyed 739 university students from Poland (315) and Iraq (424) using 31 adapted questions from the European School Survey Project on Alcohol and Other Drugs (ESPAD). We conducted multivariable analyses based on binary logistic regression to identify the factors associated with psychedelic awareness and use. Most of the respondents were females (65.6%) and senior medical students (69.6%). Notably, the Polish students displayed a higher prevalence of psychedelic use (21.6% compared to 1.2%, p < 0.001), while the Iraqi participants exhibited a lower familiarity with psychedelics (p < 0.001). The multivariable model demonstrated a commendable level of statistical accuracy and satisfactorily conformed to the Hosmer-Lemeshow goodness-of-fit test (statistical accuracy = 91.61%, Nagelkerke R2 = 0.488, p-value = 0.848). Several factors emerged as correlates of increased psychedelic use, including lacking an intact religious belief system or commitment to its practice (OR = 7.26, 95% CI [2.33, 22.60]). Additionally, those who perceived a low risk associated with sporadic psychedelic use (3.03, [1.44, 6.36]) were likelier to engage in such behavior. Other factors included residing in Poland (2.82, [0.83, 9.55]), maintaining positive attitudes toward psychedelics (2.49, [1.20, 5.14]), frequent social nightlife activities (2.41, [1.26, 4.61]), male gender (2.05, [1.10, 3.85]), and cigarette or tobacco smoking (2.03, [1.06, 3.86]). Significant disparities exist between Poles and Iraqis, influenced by religiosity, perceptions of the usage risks, geographical location, gender, attitudes toward psychedelics, parental leniency, and social freedom, especially concerning nightlife activities. Addressing the factors influencing psychedelic usage is paramount to responsible psychedelic engagement and culturally sensitive interventions to prevent misuse.

Associations of Menstrual Cycle and Progesterone-to-Estradiol Ratio With Alcohol Consumption in Alcohol Use Disorder: A Sex-Separated Multicenter Longitudinal Study.

OBJECTIVE: Alcohol use disorder (AUD) constitutes a critical public health issue and has sex-specific characteristics. Initial evidence suggests that progesterone and estradiol might reduce or increase alcohol intake, respectively. However, there is a need for a better understanding of how the menstrual cycle in females and the ratio of progesterone to estradiol in females and males influence alcohol use patterns in individuals with AUD. METHODS: In this sex-separated multicenter longitudinal study, the authors analyzed 12-month data on real-life alcohol use (from 21,460 smartphone entries), menstrual cycle, and serum progesterone-to-estradiol ratios (from 667 blood samples at four individual study visits) in 74 naturally cycling females and 278 males with AUD between 2020 and 2022, using generalized and general linear mixed modeling. RESULTS: Menstrual cycle phases were significantly associated with binge drinking and progesterone-to-estradiol ratio. During the late luteal phase, females showed a lower predicted binge drinking probability of 13% and a higher predicted marginal mean of progesterone-to-estradiol ratio of 95 compared with during the menstrual, follicular, and ovulatory phases (binge drinking probability and odds ratios vs. late luteal phase, respectively: 17%, odds ratio=1.340, 95% CI=1.031, 1.742; 19%, odds ratio=1.523, 95% CI=1.190, 1.949; and 20%, odds ratio=1.683, 95% CI=1.285, 2.206; difference in progesterone-to-estradiol ratios, respectively: -61, 95% CI=-105.492, -16.095; -78, 95% CI=-119.322, -37.039; and -71, 95% CI=-114.568, -27.534). In males, a higher progesterone-to-estradiol ratio was related to lower probabilities of binge drinking and of any alcohol use, with a 10-unit increase in the hormone ratio resulting in odds ratios of 0.918 (95% CI=0.843, 0.999) and 0.914 (95% CI=0.845, 0.988), respectively. CONCLUSIONS: These ecologically valid findings suggest that high progesterone-to-estradiol ratios can have a protective effect against problematic alcohol use in females and males with AUD, highlighting the progesterone-to-estradiol ratio as a promising treatment target. Moreover, the results indicate that females with AUD may benefit from menstrual cycle phase-tailored treatments.

Predictors and Correlates of Positive Urine Drug Screening in a Retrospective Cohort Analysis of Child and Adolescent Psychiatry Inpatients Throughout the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVES: Youth substance use is associated with significant psychological, neurological, and medical complications. Risk factors for substance use among children and adolescents in the general population include peer and/or parental substance use, certain psychiatric illnesses (eg, Attention-Deficit/Hyperactivity Disorder, depression), and history of maltreatment. Co-occurring substance use and psychiatric illness have been associated with increased suicidality, but few prior studies have characterized substance use among child/adolescent inpatients. As such, it remains unclear how substance use contributing to acute psychiatric presentations has changed since the start of the COVID-19 pandemic. METHODS: This is a retrospective cohort study of 816 unique child/adolescent psychiatry inpatients with urine drug screening (UDS) results from a diverse urban setting. Charts of patients hospitalized between June 1, 2018 and November 30, 2021 were reviewed for sociodemographic characteristics, indication for admission, psychiatric history, hospital course, treatment plan, and discharge diagnosis. Differences in sociodemographic and clinical characteristics, such as age, race, and diagnoses, between patients with and without positive UDS were explored throughout various periods of the COVID-19 pandemic. Descriptive and comparative statistics were performed, as well as a logistic regression model to identify the predictors of positive UDS. RESULTS: Of the study sample, 18% had a positive UDS. Older age, diagnosis of impulsive or behavioral disorder, and a history of violence were found to be predictors of positive UDS. Asian/South Asian or Hispanic/LatinX race and history of a developmental or intellectual disability were found to be negative predictors. The frequency of positive UDS in this population did not change based on COVID-19. DISCUSSION AND CONCLUSIONS: Multiple factors may predispose children and adolescents to substance use. Though no impact of COVID-19 was found in this sample, longer-term studies are needed. SCIENTIFIC SIGNIFICANCE: This study identifies independent predictors of active substance use in the child and adolescent psychiatric inpatient population.

Association of Cortico-Striatal Engagement During Cue Reactivity, Reappraisal, and Savoring of Drug and Non-Drug Stimuli With Craving in Heroin Addiction.

OBJECTIVE: The authors investigated cortico-striatal reactivity to drug cues (as compared with neutral and food cues), drug cue reappraisal, food cue savoring, and their correlations with heroin craving in individuals with heroin use disorder compared with healthy control subjects. METHODS: Cross-sectional changes in functional MRI blood-oxygen-level-dependent signal during a novel cue reactivity task were assessed in 32 individuals with heroin use disorder (mean age, 40.3 years; seven women) and 21 age- and sex-matched healthy control subjects (mean age, 40.6 years; eight women). RESULTS: Drug cue reactivity (vs. neutral cues) was significantly higher in the nucleus accumbens in the heroin use disorder group compared with the control group and nominally significantly higher in the orbitofrontal cortex (OFC); ventromedial prefrontal cortex (vmPFC) activity positively correlated with drug craving. Drug cue reactivity (vs. salient food cues) was also higher in the inferior frontal gyrus (IFG) in the heroin use disorder group compared with the control group. Drug reappraisal and food savoring (vs. passive viewing) showed increased IFG and supplementary motor area activity in all participants; in the heroin use disorder group, higher IFG/dorsolateral PFC (dlPFC) activity during drug reappraisal and rostral anterior cingulate cortex (ACC) activity during food savoring were associated with lower drug cue-induced craving and longer treatment, respectively. A direct comparison of regulation of reactivity to both salient cues revealed widespread group differences such that drug reappraisal activity was higher in the heroin use disorder group and food savoring activity was higher in the control group in both cortical (e.g., OFC, IFG, ACC, vmPFC, and insula) and subcortical (e.g., dorsal striatum and hippocampus) regions. Higher drug reappraisal versus food savoring in the dlPFC was associated with higher self-reported methadone dosage in the heroin use disorder group. CONCLUSIONS: The results demonstrate cortico-striatal upregulation during drug cue exposure and impaired reactivity during processing of alternative non-drug rewards in the heroin use disorder group. Normalizing cortico-striatal function by reducing drug cue reactivity and enhancing natural reward valuation may inform therapeutic mechanisms for reducing drug craving and seeking in heroin addiction.

The Long-Term Relationship Between Cannabis and Heroin Use: An 18- to 20-year Follow-Up of the Australian Treatment Outcome Study (ATOS).

OBJECTIVE: Cannabis use is common among individuals with opioid use disorder, but it remains unclear whether cannabis use is associated with an increase or a reduction in illicit opioid use. To overcome limitations identified in previous longitudinal studies with limited follow-ups, the authors examined a within-person reciprocal relationship between cannabis and heroin use at several follow-ups over 18 to 20 years. METHODS: The Australian Treatment Outcome Study (ATOS) recruited 615 people with heroin dependence in 2001 and 2002 and reinterviewed them at 3, 12, 24, and 36 months as well as 11 and 18-20 years after baseline. Heroin and cannabis use were assessed at each time point using the Opiate Treatment Index. A random-intercept cross-lagged panel model analysis was conducted to identify within-person relationships between cannabis use and heroin use at subsequent follow-ups. RESULTS: After accounting for a range of demographic variables, other substance use, and mental and physical health measures, an increase in cannabis use 24 months after baseline was significantly associated with an increase in heroin use at 36 months (estimate=0.21, SE=0.10). Additionally, an increase in heroin use at 3 months and 24 months was significantly associated with a decrease in cannabis use at 12 months (estimate=-0.27, SE=0.09) and 36 months (estimate=-0.22, SE=0.08). All other cross-lagged associations were not significant. CONCLUSIONS: Although there was some evidence of a significant relationship between cannabis and heroin use at earlier follow-ups, this was sparse and inconsistent across time points. Overall, there was insufficient evidence to suggest a unidirectional or bidirectional relationship between the use of these substances.

Converging Evidence for Frontopolar Cortex as a Target for Neuromodulation in Addiction Treatment.

Noninvasive brain stimulation technologies such as transcranial electrical and magnetic stimulation (tES and TMS) are emerging neuromodulation therapies that are being used to target the neural substrates of substance use disorders. By the end of 2022, 205 trials of tES or TMS in the treatment of substance use disorders had been published, with heterogeneous results, and there is still no consensus on the optimal target brain region. Recent work may help clarify where and how to apply stimulation, owing to expanding databases of neuroimaging studies, new systematic reviews, and improved methods for causal brain mapping. Whereas most previous clinical trials targeted the dorsolateral prefrontal cortex, accumulating data highlight the frontopolar cortex as a promising therapeutic target for transcranial brain stimulation in substance use disorders. This approach is supported by converging multimodal evidence, including lesion-based maps, functional MRI-based maps, tES studies, TMS studies, and dose-response relationships. This review highlights the importance of targeting the frontopolar area and tailoring the treatment according to interindividual variations in brain state and trait and electric field distribution patterns. This converging evidence supports the potential for treatment optimization through context, target, dose, and timing dimensions to improve clinical outcomes of transcranial brain stimulation in people with substance use disorders in future clinical trials.

An online global survey and follow-up expert groups on the scope and needs related to training, research, and mentorship among early-career addiction medicine professionals.

Addiction medicine is a rapidly growing field with many young professionals seeking careers in this field. However, early-career professionals (ECPs) face challenges such as a lack of competency-based training due to a shortage of trainers, limited resources, limited mentorship opportunities, and establishment of suitable research areas. The International Society of Addiction Medicine (ISAM) New Professionals Exploration, Training & Education (NExT) committee, a global platform for early-career addiction medicine professionals (ECAMPs), conducted a two-phase online survey using a modified Delphi-based approach among ECAMPs across 56 countries to assess the need for standardized training, research opportunities, and mentorship. A total of 110 respondents participated in Phase I (online key informant survey), and 28 respondents participated in Phase II (online expert group discussions on three themes identified in Phase I). The survey found that there is a lack of standardized training, structured mentorship programs, research funding, and research opportunities in addiction medicine for ECAMPs. There is a need for standardized training programs, improving research opportunities, and effective mentorship programs to promote the next generation of addiction medicine professionals and further development in the entire field. The efforts of ISAM NExT are well-received and give a template of how this gap can be addressed.

Primary Care at the Intersection of Lifestyle Interventions and Unhealthy Substance Use.

Primary care physicians are well-positioned to integrate lifestyle interventions into the management of patients with unhealthy substance use, who may also have mental and physical chronic health comorbidities. However, the COVID-19 pandemic exacerbated the U.S.'s poor state of health, revealing that its current approach to chronic disease management is neither effective nor sustainable. Today's full spectrum comprehensive care model requires an expanded toolkit. Lifestyle interventions broaden current treatment approaches and may enhance Addiction Medicine care. Primary care providers have the potential to have the greatest impact on unhealthy substance use care because they are experts in chronic disease management and their frontline accessibility minimizes healthcare barriers. Individuals with unhealthy substance use are at an increased risk of chronic physical conditions. Incorporating lifestyle interventions with unhealthy substance use care at every level of medicine, from medical school through practice, normalizes both as part of the standard care of medicine and will drive evidence-based best practices to support patients through prevention, treatment, and reversal of chronic diseases.

Psychoactive substance use in patients diagnosed with attention-deficit/hyperactivity disorder: an exploratory study.

Introduction: Attention-deficit/hyperactivity disorder (ADHD) was originally treated as a neurodevelopmental disorder that occurs mainly in children and tends to diminish or disappear with age, but we now know that symptoms persist into adulthood in over 50% of ADHD patients. Undiagnosed individuals often turn to psychoactive substance to minimize the negative aspects of functioning and improve quality of life. Methods: The study was conducted online using random sampling through a Facebook group administered by physicians and targeted to patients diagnosed with ADHD. The study was naturalistic and exploratory, therefore no hypothesis was made. 438 correctly completed questionnaires were received. Analysis of the results showed that people with ADHD turn to psychoactive substances relatively frequently. Results: The most commonly used stimulants include alcohol, marijuana, 3,4-methylenedioxymethamphetamine (MDMA), amphetamine/methamphetamine, and psilocybin. In the study population, methylphenidate is the most commonly used drug among patients. After treatment with psychostimulants, the majority of respondents note a decrease in symptoms of hyperactivity disorder, especially in male patients. Conclusion: It is necessary to perform proper diagnostics and actively look for ADHD symptoms in patients who tend to use psychoactive substances.