A computational account of the development and evolution of psychotic symptoms.

The mechanisms of psychotic symptoms like hallucinations and delusions are often investigated in fully-formed illness, well after symptoms emerge. These investigations have yielded key insights, but are not well-positioned to reveal the dynamic forces underlying symptom formation itself. Understanding symptom development over time would allow us to identify steps in the pathophysiological process leading to psychosis, shifting the focus of psychiatric intervention from symptom alleviation to prevention. We propose a model for understanding the emergence of psychotic symptoms within the context of an adaptive, developing neural system. We will make the case for a pathophysiological process that begins with cortical hyperexcitability and bottom-up noise transmission, which engenders inappropriate belief formation via aberrant prediction error signaling. We will argue that this bottom-up noise drives learning about the (im)precision of new incoming sensory information because of diminished signal-to-noise ratio, causing an adaptive relative over-reliance on prior beliefs. This over-reliance on priors predisposes to hallucinations and covaries with hallucination severity. An over-reliance on priors may also lead to increased conviction in the beliefs generated by bottom-up noise and drive movement toward conversion to psychosis. We will identify predictions of our model at each stage, examine evidence to support or refute those predictions, and propose experiments that could falsify or help select between alternative elements of the overall model. Nesting computational abnormalities within longitudinal development allows us to account for hidden dynamics among the mechanisms driving symptom formation and to view established symptomatology as a point of equilibrium among competing biological forces.

Assessing pain in persons with opioid use disorder: Approaches, techniques and special considerations.

Pain and opioid use disorder (OUD) are inextricably linked, as the former can be a risk factor for the development of the latter, and over a third of persons with OUD suffer concomitant chronic pain. Assessing pain among people with OUD is challenging, because ongoing opioid use brings changes in pain responses and most pain assessment tools have not been validated for this population. In this narrative review, we discuss the fundamentals of pain assessment for populations with OUD. First, we describe the biological, psychological and social aspects of the pain experience among people with OUD, as well as how opioid-related phenomena may contribute to the pain experience in this population. We then review methods to assess pain, including (1) traditional self-reported methods, such visual analogue scales and structured questionnaires; (2) behavioural observations and physiological indicators; (3) and laboratory-based approaches, such as quantitative sensory testing. These methods are considered from a perspective that encompasses both pain and OUD. Finally, we discuss strategies for improving pain assessment in persons with OUD and implications for future research, including educational strategies for multidisciplinary teams. We highlight the substantial gaps that persist in this literature, particularly regarding the applicability of current pain assessment methods to persons with OUD, as well as the generalizability of the existing results from adjacent populations on chronic opioid therapy but without OUD. As research linking pain and OUD evolves, considering the needs of diverse populations with complex psychosocial backgrounds, clinicians will be better equipped to reduce these gaps.

From taboo to treatment: The emergence of psychedelics in the management of pain and opioid use disorder.

The rise of psychedelics in contemporary medicine has sparked interest in their potential therapeutic applications. While traditionally associated with countercultural movements and recreational use, recent research has shed light on the potential benefits of psychedelics in various mental health conditions. In this review, we explore the possible role of psychedelics in the management of chronic pain and opioid use disorder (OUD), 2 critical areas in need of innovative treatment options. Pain control remains a significant clinical challenge, particularly for individuals with OUD and those who receive long-term opioid therapy who develop marked tolerance to opioid-induced analgesia. Despite the magnitude of this problem, there is a scarcity of controlled studies investigating pain management alternatives for these populations. Drawing from preclinical and human evidence, we highlight the potential of psychedelics to act on shared neurobiological substrates of chronic pain and OUD, potentially reversing pain- and opioid-induced neuroadaptations, such as central sensitization. We elaborate on the multifaceted dimensions of the pain experience (sensory, affective and cognitive) and their intersections that overlap with opioid-related phenomena (opioid craving and withdrawal), hypothesizing how these processes can be modulated by psychedelics. After summarizing the available clinical research, we propose mechanistic insights and methodological considerations for the design of future translational studies and clinical trials, building on a shared clinical and neurobiological understanding of chronic pain and OUD. Our intention is to provide timely perspectives that accelerate the development and exploration of novel therapeutics for chronic pain and OUD amidst the escalating opioid crisis.

Leveraging neuroscience education to address stigma related to opioid use disorder in the community: a pilot study.

Opioid use disorder (OUD) and overdose deaths are a public health crisis. One contributing factor is stigma towards people who use opioids. We developed and conducted a public-facing, half-day educational event designed to challenge misperceptions about OUD from a contemporary neuroscience perspective. Participants engaged with three different resources on the neurobiology of addiction, and, at the end of the event, they rated its effectiveness. We also collected and compared pre- and post-event composite OUD stigma scales. Participants rated our approach and the overall event as highly effective. Additionally, OUD stigma scores were lower immediately following the event, and this decrease was primarily driven by decreased internalized stigma. Here, we demonstrate an effective proof-of-concept that an accessible, public-facing, neuroscience education event may reduce OUD stigma in the community.

Digital Dialogue-How Youth Are Interacting With Chatbots.

This Viewpoint describes the use of large language model chatbots in social, educational, and therapeutic settings and the need to assess when children are developmentally ready to engage with them.

Diagnosis and treatment of Wernicke's encephalopathy: A systematic literature review.

BACKGROUND: Wernicke's encephalopathy (WE) is a serious neurological disorder that is underdiagnosed. Despite limited clinical guidelines, the standard use of intravenous (IV) thiamine is underutilized and remains an area of research deserving much attention. OBJECTIVES: We conducted a systematic review using Medline, Embase, and CENTRAL databases to identify and summarize the literature on IV thiamine treatment in WE. Human studies with WE patients who received ≥100 mg of thiamine IV met inclusion criteria. Randomized controlled trials, cross-sectional studies, and case reports were included. RESULTS: A total of 27 studies were included: 20 case reports, five retrospective studies, one prospective study and one randomized control trial. Of the case reports, 11 (55%) cases were female, and the average age of all cases was 45 years (SD = 15). The other seven studies included 688 patients; the average age was 52 years (SD = 9), and 266 (38.7%) were female. Among the case reports, neurological and clinical findings were used to diagnose WE in 16 (80%) cases. MRI was utilized to diagnose 15 (75%) cases. 500 mg IV thiamine TID was reported in 12 case reports (60%). 18 (90%) of case reports had partial or complete resolution of symptoms following IV thiamine. CONCLUSION: IV thiamine can alleviate neurological symptoms, cognitive dysfunction, and brain imaging lesions associated with WE. We found key limitations in the evidence for IV thiamine and diagnostic standards for WE. Future targeted research should establish clear diagnostic and treatment guidelines for WE to prevent this serious condition from being underdiagnosed or undertreated.

Emergency services utilization by patients with alcohol-associated hepatitis: An analysis of national trends.

BACKGROUND: Hospitalization and mortality in patients with alcohol-associated hepatitis (AH), a severe form of liver disease, continue to increase over time. Given the severity of the illness, most hospitalized patients with AH are admitted from the emergency department (ED). However, there are no data on ED utilization by patients with AH. Thus, the Nationwide Emergency Department Sample (NEDS) dataset was analyzed to determine the ED utilization for AH. METHODS: Temporal trends (2016-2019) and outcomes of ED visits for AH were determined. Primary or secondary AH diagnoses were based on coding priority. Numbers of patients evaluated in the ED, severity of disease, complications of liver disease, and discharge disposition were analyzed. Crude and adjusted rates were examined, and temporal trends evaluated using logistic regression with orthogonal polynomial contrasts for each year. RESULTS: There were 466,014,370 ED visits during 2016-2019, of which 448,984 (0.096%) were for AH, 85.0% of which required hospitalization. The rate of visits for AH (primary and secondary) between 2016 and 2019 increased from 85 to 106.8/100,000 ED visits. The rate of secondary AH increased more than the rate of primary AH (from 68.6 to 86.5 vs. from 16.4 to 20.3/100,000 ED visits). Patients aged 45-64 years had the highest rate of ED visits for AH, which decreased during the study period, while the rate of ED visits for AH increased in those aged 25-44 years (from 38.5% to 42.9%). The severity of disease (ascites, hepatic encephalopathy, and acute kidney injury) also increased over time. Medicaid and private insurance were the most common payors for patients seeking care in the ED for AH. CONCLUSIONS: Temporal trends show an overall increase in ED utilization rates for AH, more patients requiring hospitalization, and an increase in the proportion of younger patients presenting to the ED with AH.

All a-BORG! The Dangerous Drinking Trend Steamrolling Across Social Media and College Campuses.

ABSTRACT: Black out rage gallons (BORGs) are a troublesome drinking pattern emerging on social media platforms. The prevalence of BORGs has been increasing on college campuses and is demonstrating significant consequences. There is no known research on BORGs in addiction treatment settings. We suggest that future research will be necessary to understand their implication. Troublesome binge drinking is not a new problem among colleges. However, social media has seemed to ignite such trends.

The Zero Suicide Model in Addiction Treatment Settings: Recognizing the Need for Feasibility and Implementation Data.

The Zero Suicide (ZS) model is a promising approach for preventing all suicides across health care settings. ZS provides guidelines for health care systems to implement best practices in suicide prevention. Patients with substance use disorders are at increased risk for suicide, but no known research has investigated how to integrate the ZS model into addiction treatment settings. This Open Forum encourages clinicians and researchers to integrate ZS into such settings and to study its feasibility and effectiveness. ZS integration into addiction treatment may improve both suicide and addiction outcomes, but additional research is needed.

Dysregulation of the endogenous cannabinoid system following opioid exposure.

Rates of opioid-related deaths and overdoses in the United States are at record-high levels. Thus, novel neurobiological targets for the treatment of OUD are greatly needed. Given the close interaction between the endogenous opioid system and the endocannabinoid system (ECS), targeting the ECS may have therapeutic potential in OUD. The various components of the ECS, including cannabinoid receptors, their lipid-derived endogenous ligands (endocannabinoids [eCBs]), and the related enzymes, present potential targets for developing new medications in OUD treatment. The purpose of this paper is to review the clinical and preclinical literature on the dysregulation of the ECS after exposure to opioids. We review the evidence of ECS dysregulation across various study types, exposure protocols, and measurement protocols and summarize the evidence for dysregulation of ECS components at specific brain regions. Preclinical research has shown that opioids disrupt various ECS components that are region-specific. However, the results in the literature are highly heterogenous and sometimes contradictory, possibly due to variety of different methods used. Further research is needed before a confident conclusion could be made on how exposure to opioids can affect ECS components in various brain regions.

Phencyclidine Positivity on Urine Drug Screening in Patients Treated for Alcohol Withdrawal on a Dual-diagnosis Medically Assisted Withdrawal Unit.

OBJECTIVES: Little contemporary research has explored phencyclidine (PCP) use in people with alcohol use disorder. Therefore, we sought to determine the prevalence of PCP positivity on urine toxicology screening among patients admitted for alcohol withdrawal, identify correlates of PCP positivity, and investigate PCP positivity's relationship to length of stay (LOS) and risk of facility readmission. METHODS: This was a retrospective study of patients admitted to a dual-diagnosis medically assisted withdrawal unit for alcohol withdrawal from 2014 to 2019. Univariate tests and logistic regression were used to investigate potential correlates of PCP positivity on admission toxicology screening (primary outcome). Multivariable linear regression models and survival analyses analyzing LOS and risk of readmission (secondary outcomes) were also developed. RESULTS: Ninety of 3731 patients (2.4%) screened positive for PCP. There were significant associations on univariate testing between PCP positivity and age, race, homeless status, and urine toxicology positivity for amphetamines, benzodiazepines, barbiturates, cocaine, tetrahydrocannabinol, and oxycodone. On multivariate logistic regression, only tetrahydrocannabinol, barbiturates, and cocaine positivity were associated with PCP positivity. Multivariate logistic regression and survival analysis found no statistically significant associations between PCP positivity and LOS or risk of readmission. CONCLUSIONS: This study provides rare analysis of contemporary data on PCP use among patients undergoing medically assisted alcohol withdrawal. Phencyclidine positivity was uncommon, but use appears considerably higher among this patient population than the general population. There was no significant association between PCP positivity and LOS or readmission risk.

Race, economic status, and disparities in the receipt of benzodiazepine prescriptions in a large primary care sample.

OBJECTIVE: To evaluate the relationship between race, economic status, and patient characteristics with benzodiazepine prescribing in an urban and suburban primary care context. METHOD: This retrospective study used data from a previously described cohort of patients seen in a large Ohio healthcare system's primary care clinics from 2019 to 2020. Associations and interactions between race, economic status (using median income of patient ZIP code as a proxy), patient characteristics, and prescription of benzodiazepines were assessed using multivariable logistic regression. RESULTS: 455,537 patients had 1,643,473 primary care visits, and 5.8% of patients were prescribed a benzodiazepine. White patients were prescribed benzodiazepines more often than Multiracial/Multicultural, African American and Asian American patients (6.5%, 3.8%, 2.7% and 2.0% respectively). Patients from lower income ZIP codes were less likely to receive a prescription. Interaction effects were observed between race, patient economic status, gender, insurance status, and diagnoses (general anxiety disorder, insomnia, and panic disorder). The largest prescribing disparities by race were among patients with these three diagnoses. The largest disparity in prescription by income was seen in African American patients. CONCLUSION: African American, Multicultural/Multiracial and Asian American patients were less likely than White patients to receive benzodiazepine prescriptions. Middle and lower-income patients are particularly susceptible to this prescribing disparity.

Prescribing of Z-Drugs With and Without Opioid Coprescribing to Primary Care Patients in a Large Health Care System From 2019-2020.

Objective: This study aimed to characterize Z-drug prescribing with and without opioid coprescribing pre- and post-COVID-19 lockdown in the primary care clinics of a large health care system.Methods: A retrospective, cross-sectional study was conducted that measured the prevalence of Z-drug prescribing with and without opioids for adults aged ≥ 18 years that were seen in the primary care clinics of a large health care system in 2019 and 2020. The pre-COVID time period was defined as March 24, 2019-December 31, 2019, and the post-lockdown time period was defined as March 24, 2020-December 31, 2020.Results: Among 455,537 adult patients, 6,743 (1.48%) were prescribed a Z-drug during the study period. In addition, 1,064 (0.2%) were coprescribed a Z-drug and an opioid at least once, constituting 15.78% of patients receiving a Z-drug prescription. There was no change in the rate of Z-drug prescription post-lockdown (odds ratio [OR] = 0.978, 95% confidence interval [CI] = 0.942-1.010, P = .233), though odds of coprescribing decreased (OR = 0.883, 95% CI = 0.789-0.988, P = .031). Important correlates of receiving a Z-drug prescription during the study period were older age, White race, and diagnosis of opioid use disorder. Older age and a diagnosis of opioid use disorder were also associated with coprescribing. Receiving a de novo Z-drug prescription post-lockdown was associated with increased age, White race, and diagnosis of bipolar disorder, generalized anxiety disorder, and insomnia.Conclusions: Rates of Z-drug prescribing were unchanged post-lockdown, while rates of Z-drug with opioid coprescribing decreased. Some patient populations vulnerable to Z-drug adverse effects were at heightened risk of Z-drug prescription, while racial disparities in Z-drug prescribing were observed.

Clinical Presentations and Treatment of Phenibut Toxicity and Withdrawal: A Systematic Literature Review.

OBJECTIVES: This systematic review aimed to identify published articles that evaluated all phenibut toxicity and withdrawal cases to understand better their clinical presentations and treatments. METHODS: A comprehensive literature search was conducted using Medline (Ovid), Embase (Ovid), and Cochrane Library databases to capture all published cases on the presentations and management of phenibut toxicity or withdrawal. RESULTS: Sixty-two cases from 36 studies on presentation and management of phenibut toxicity or phenibut withdrawal were identified. Of all subjects, 80.7% were male. The average age was 30.9 years (SD, 13.2 years; range, 0-71 years). A total of 86.8% reported obtaining phenibut online, and 63.2% reported concomitant substance use with other addictive agents; benzodiazepines and alcohol were the most combined drugs. The average length of hospital stay was 5.0 days (n = 25; SD, 5.4 days; range, 1-25 days) for phenibut toxicity and 7.7 days (n = 20; SD, 7.8 days; range, 0-30 days) for phenibut withdrawals. The most common symptoms reported during phenibut toxicity were altered mental status, somnolence, psychosis, and movement disorders. Of the phenibut toxicity cases, 48.7% required intubation. Benzodiazepines and antipsychotics were most used to treat phenibut toxicity. For phenibut withdrawal cases, 95.7% reported daily use. The most common symptoms reported during phenibut withdrawals were anxiety, irritability or agitation, insomnia, and psychosis. Sixteen (69.6%) of phenibut withdrawal cases required multiple medications for treatment. Benzodiazepines, baclofen, atypical antipsychotics, gabapentanoids, and barbiturates were commonly used to treat phenibut withdrawals. CONCLUSIONS: The seriousness of presentations, combined with the assortments of medications used for both syndromes, reflects the potential dangers of phenibut use and the need for systematized treatment protocols.

Three Cases of Reported Improvement in Microsmia and Anosmia Following Naturalistic Use of Psilocybin and LSD.

Cultural awareness of anosmia and microsmia has recently increased due to their association with COVID-19, though treatment for these conditions is limited. A growing body of online media claims that individuals have noticed improvement in anosmia and microsmia following classic psychedelic use. We report what we believe to be the first three cases recorded in the academic literature of improvement in olfactory impairment after psychedelic use. In the first case, a man who developed microsmia after a respiratory infection experienced improvement in smell after the use of 6 g of psilocybin containing mushrooms. In the second case, a woman with anosmia since childhood reported olfactory improvement after ingestion of 100 µg of lysergic acid diethylamide (LSD). In the third case, a woman with COVID-19-related anosmia reported olfactory improvement after microdosing 0.1 g of psilocybin mushrooms three times. Following a discussion of these cases, we explore potential mechanisms for psychedelic-facilitated improvement in olfactory impairment, including serotonergic effects, increased neuroplasticity, and anti-inflammatory effects. Given the need for novel treatments for olfactory dysfunction, increasing reports describing improvement in these conditions following psychedelic use and potential biological plausibility, we believe that the possible therapeutic benefits of psychedelics for these conditions deserve further investigation.

Antemortem Health System Utilization in People Experiencing Homelessness Who Died in the Emergency Department.

People experiencing homelessness (PEH) have high rates of mortality, medical and psychiatric comorbidities, and emergency department utilization. In this study, a health system's emergency department encounters were evaluated to identify PEH who died in the emergency department. Patient demographics, medical history, prehospital and emergency department characteristics, and health care utilization patterns were collected. Descriptive statistics were calculated. We identified 48 PEH pronounced dead in the emergency department; mean age at death was 46.5. Forty-four (92%) decedents presented in cardiac arrest, 12 (25%) of which were substance use-related; 4 (8%) presented with trauma. Out of 44 patients presenting in cardiac arrest, (20.5%) had bystander cardiopulmonary resuscitation (CPR) performed before arrival of emergency medical services. In the year prior to death, 15 (32%) decedents had no documented health care utilization, while 16 (33%) had 10 or more emergency department/outpatient visits. Our study is the first to characterize PEH who died in the emergency department, analyzing the pre-hospital and in-hospital characteristics and antemortem health system utilization in this population. A sizeable proportion of deceased PEH had no health system contact in the 12 months prior to death, suggesting that those with high mortality risk may underutilize health services. Conversely, a similar proportion of decedents had extensive (more than 10) health system utilization in the year prior to death, representing possible opportunities to reduce mortality.

Cognitive, imaging, and psychiatric changes associated with chronic toluene use: case report and literature review.

Inhalant misuse and inhalant use disorder are global public health concern that impacts adolescents but can occur throughout life. Toluene is the most commonly misused inhalant. Toluene use leads to significant neuroanatomic, cognitive, and psychiatric deficits. The purpose of this study was to review and summarize the effects of toluene and present a case of a middle-aged patient with an inhalant use disorder. A literature review was conducted to evaluate imaging, neurocognitive, and psychiatric consequences of toluene misuse. The common imaging findings amongst those who misuse toluene were cerebral and cerebellar atrophy, ventricular dilation, loss of gray-white matter differentiation, corpus callosum thinning, and diffuse white matter changes. Concerning cognition, toluene misusers were shown to have deficits in intelligence, attention, memory, visuospatial function, and complex cognition. In addition, toluene users also commonly presented with apathy, flat affect, hallucinations, delusions, anxiety, depression, and insomnia. The neuroanatomical, neurocognitive, and psychiatric effects of toluene misuse are profound. These deficits can make inhalant use disorder difficult to treat. Therefore, evidence-based treatments that recognize and address these domain-specific neurocognitive deficits are needed.

Methamphetamine-associated catatonia: Case series and systematic review of the literature from 1943-2020.

BACKGROUND: Catatonia due to a general medical condition may result from a variety of causes, including substance intoxication and withdrawal. Stimulants are occasionally associated with catatonia, though there has been little investigation of methamphetamine's relationship to catatonia. Here we present 5 cases of catatonia associated with methamphetamine use and a systematic review of the associated literature from 1943 to 2020. METHODS: We performed a systematic review of the literature and present 5 cases of catatonia evaluated using the Bush-Francis Catatonia Rating Scale and KANNER catatonia rating scale. RESULTS: Methamphetamine use was associated with catatonia in a small number of cases in the literature. However, some of these reports included other possible etiologies. The patients in our case series met DSM-5 criteria for catatonia due to a general medical condition, with all reporting recent methamphetamine use and testing positive for amphetamines on urine drug screen. CONCLUSIONS: Given the ongoing rise in methamphetamine use in the United States, it is important that clinicians understand that methamphetamine use can be associated with catatonia. Patients with methamphetamine-associated catatonia may respond favorably to lorazepam and require shorter hospital stays than other catatonic patients. Lastly, methamphetamine-associated catatonia highlights how alteration in dopamine function and projections may be a critical neural mechanism underlying catatonia in general.