Medical Treatment Options for Cannabis Use Disorder: An Updated Narrative Review

Background: Cannabis use disorder (CUD) is a common and growing condition in the United States and across the world. With the alteration of the legal landscape of the substance, normalization of the substance use in society, and a continual increase in frequency in recent years, more treatment options are desperately needed. CUD has been shown to be associated with various symptoms of mental illness. Most therapies to date have been psychotherapeutic in nature, involving theories such as cognitive-behavioral motivational-based methods. However, these are not always the most effective or accessible options for patients. Methods: Articles for this review were obtained by searching PubMed, Google Scholar, and the Cochrane Review database for key terms. All the studies included were human studies. Most of the included studies were randomized control trials (RCTs). Trials were prioritized for inclusion based on methodology, date, and outcome-based measures. Only papers after 2010 were considered for inclusion. Results: In recent years, many pharmacological agents have been studied, including antidepressants, mood stabilizers, GABA agents, THC-like compounds, and even some new novel agents such as N-Acetyl Cysteine (NAC), ketamine, and fatty acid amid hydrolase (FAAH) inhibitors. Of these drugs, research has found some more effective than others such as particular mood stabilizers, GABA agents, as well as THC agonists and antagonists. Newer drugs like ketamine, a FAAH inhibitor, and NAC have also been shown to be potential treatment candidates. Studies suggest other effective options may involve neuromodulation, as interventions such as transcranial magnetic stimulation (TMS) and transcranial direct-current stimulation (tDCS) have been shown to be relatively successful when targeting specific brain regions. Conclusions: While there is exciting research so far, much work must be done before there will be FDA-approved treatments on the market. Thus, we must work together to approach treatment in a multifactorial manner and prioritize the research of potential treatment options with more reliable and consistent evidence of safety and efficacy for CUD

Connectome Specific Harmonic Wave Analysis of Disordered Brain States

Background: Connectome Harmonics analysis is a novel neuroimaging framework that defines brain states as neural spatial patterns associated with different frequencies emerging within a brain. Frequencies corresponding to specific brain states, or connectome-specific harmonic waves (CSHWs), are estimated to be the building blocks of brain activity, linking cortical oscillations, functional connectivity, and structural connectivity. Using this framework, studies will examine CSHWs of patients to catalog and analyze the spatiotemporal neural dynamics of patients with disordered brain states. Methods: By using MRI (or fMRI) and DTI data extracted from MRI scans of patients, cortical surface anatomy and the underlying neural tracts can be tracked respectively and combined to generate a patient’s connectome. Once the connectome is generated, it is converted into its graphical form where Eigen decompositions of the Laplacian operator are graphed. Application of this function to the connectome’s graph results in a spectrum of harmonic brain modes corresponding to a patient’s brain’s natural resonant frequencies (eigenvalues). Results: The CSHW framework has already been used to examine brains in a variety of ways. Previous research findings show that neocortical organization and development may be shaped by the harmonic modes corresponding to the brain’s functional connectivity, Patients given classical psychedelics (LSD, Psilocybin, and DMT) display an expanded repertoire of brain states, and neuroplasticity may be underpinned by neurons shifting into metastable states that are modulated according to a brain’s CSHWs. Discussion: Common neuroimaging methods like CT scans and PET scans are important in extracting information about regional activation during tasks but fail to contextualize or explain the interconnectedness of brain activity. CSHW analysis utilizes multiple imaging techniques and mathematical functions to derive an alphabet of brain states that can be used to describe our subjective states, from mental disorders to flow states and everyday emotions. Clinical trials here at the UTRGV institute of neuroscience will apply CSHW analysis to patients suffering from bipolar disorder, depression, and alcohol withdrawal syndrome. This research will not only allow us to examine and catalog the spatiotemporal dynamics of these disorders but potentially map out treatment plans tailored to each patient’s connectome harmonics

Implementation of a Training Module on Alcohol Prevention for Promotoras on a Border Community in the Rio Grande Valley.

Background: Complications due to unhealthy alcohol use are widely spread, and there is a significant unmet need for prevention and treatment in the community. The South Texas-Mexico border region consists of over ninety percent of Hispanics and suffers from a significant shortage of physicians. Alcohol-related problems are highly unrecognized and untreated in this large Hispanic population due to the shortage of healthcare providers, low education levels, and limited trust in the health care system. Prevention efforts should be designed to prevent or reduce the risk of developing alcohol addiction. Methods: The proposed module focuses on enhancing the Promotoras or Community Health Worker (CHW) ability to screen and recognize unhealthy alcohol use and the need for referral for care. We use a survey to follow and record the experience of a subset of these Promotoras who will educate Hispanic families from their communities. Results: This module provides data that will significantly contribute to our understanding of the barriers in knowledge, access to services, and care for people with alcohol problems. The study consists of a train-the-trainer module designed by the Institute of Neuroscience at the University of Texas Rio Grande Valley (UTRGV) specifically for Promotoras. CHW aimed at increasing their knowledge concerning general health practices among ethnic minorities, specifically in terms of alcohol abuse prevention. The initial workshop trained 44 Promotoras from Cameron and Hidalgo counties. Each Promotora was assessed using pre-and post-test questionnaires. Conclusions: The research team assessed Promotora\u27s alcohol knowledge and prevention strategies with plotted data. In summary, the study provided a measurable unit of our training module in enhancing understanding of screening and the need for intervention for alcohol-related problems by Community Health Workers

Pro- and Anti-inflammatory Biomarkers as Predictors of Response to Valproate in Patients with Comorbid Alcohol Use and Bipolar Disorder-Preliminary Findings

Objective/Hypothesis: Bipolar disorder (BD) has the highest association with alcohol and other substance use disorders compared to other major psychiatric disorders. This patient population is particularly challenging to treat. We have previously shown that some patients with co-occurring alcohol use and bipolar disorders respond to the GABAergic agonist valproate (VPA), which is known to modulates the dopaminergic system, and also as an epigenetic modifier. Predictors of therapeutic response to VPA in patients with AUD/BD are not known, and the subgroup which would benefit from VPA is still to be identified. Recent evidence suggests that AUD promotes a pro-inflammatory state while VPA increases levels of anti-inflammatory factors. We hypothesized that VPA has an anti-inflammatory effect and that patients with AUD/BD who respond to VPA have higher baseline inflammatory indices. Methods: Nine patients with DSM-IV-defined diagnoses of AUD and BD (AUD/BD) were enrolled in the study. Patients received a course of VPA for 3 months at an average dose of 1000 mg a day in addition to receiving either naltrexone of 50 mg daily or placebo. Blood was collected prior to the initiation of VPA and throughout the treatment study. Liver function tests and trough VPA serum concentrations were evaluated periodically. Alcohol use outcome was assessed using the Timeline Follow-Back for Recent Drinking. The use of other drugs was monitored through regular urine drug screen. The primary alcohol use outcome was changes in proportion of weekly heavy drinking days (defined as ³ 5 drinks per day for men and ³ 4 drinks per day for women). Plasma levels of cytokines were measured using Multiplex Immunoassay, in accordance to the manufacturers’ recommendations. Results: We found that about one half of enrolled patients responded to VPA. Screening of pro- and anti-inflammatory cytokines showed that responders had higher levels of the chemokine SDF-1a/CXCL12a and the pro-inflammatory marker C-reactive protein (CRP) and lower levels of anti-inflammatory factor matrix metalloproteinase-10 (MMP-10) (p \u3c 0.05). Screening of cytokines in samples before and after treatment with VPA showed that VPA increased levels of anti-inflammatory factors interleukin-10 (IL-10) and MMP-10 (p \u3c 0.05) and tended to decrease levels of pro-inflammatory CRP (p \u3e 0.05). Discussion: Pro- and anti-inflammatory biomarkers may serve as predictors of treatment response to VPA in patients with combined AUD/BD. Our preliminary results also suggest that therapeutic effect of VPA may be in part due to anti-inflammatory action of VPA. Larger studies may be indicated to validate these findings

Representation of Racial and Ethnic Minorities and Their Preferences for Mood Stabilizing Treatment Selection for Bipolar Disorder: A Systematic Review

Background: The use of second-generation antipsychotics for bipolar disorder (BD) has increased in the past years1Concerns on potential serious medical side effects and need for blood level monitoring of some traditional mood stabilizers along with other factors have influenced this change. Shared decision-making (SDM) strategies have been implemented in clinical settings due to their ability to engage patients in the process of treatment selection.2 Within minority groups with mental illnesses, socioeconomic factors, individual concerns, and cultural variations in clinical presentations, are often overlooked or misrepresented when assessing the patient’s treatment preferences. Although several studies evaluating the effectiveness of SDM interventions in BD, the representation of patients that belong to minority groups and how their preferences and outcomes differ from those belonging to non-minority groups is unknown. The primary aim of this is to assess the inclusion of minority patients in studies assessing SDM strategies in patients with BD. Methods: After the systematic search, screening and data extraction will be conducted in a duplicate and independent manner. We will include interventional studies implementing strategies for SDM in patients diagnosed with bipolar disorder. Data on the proportion of minorities included in the studies, as well as on quality indicators for the clinical encounter regarding SDM, treatment adherence, and clinical outcomes will be extracted. Results and Conclusion: We have no results yet, but the relevance of the expected results is discussed. Compared to non-Hispanic white patients, patients from minority racial/ethnic groups have lower odds of receiving classic mood stabilizers and higher rates of antipsychotic prescription.3 Patients that belong to minority groups are also at higher risk of misdiagnosis -with subsequent delay in the diagnosis-, and of mistreatment.4 These disparities have been associated with potential cognitive biases that lead to symptom misattribution, inadequate treatment regimens and omission of patient’s sociocultural background.5 Patient-centered care could also benefit the assessment of risk factors that are common to specific groups (e.g., metabolic risk in Hispanic patients).6,7 Moreover, SDM can help understand better the values, preferences for treatment choices and help evaluate if patient engagement can be translated into clinical benefits and an improved quality of life

Creativity and bipolar disorder: Touched by fire or burning with questions?

Substantial literature has linked bipolar disorder with creative accomplishment. Much of the thinking in this area has been inspired by biographical accounts of poets, musicians, and other highly accomplished groups, which frequently document signs of bipolar disorder in these samples. A smaller literature has examined quantitative measures of creativity among people with bipolar disorder or at risk for the disorder. In this paper, we provide a critical review of such evidence. We then consider putative mechanisms related to the link of bipolar disorder with creativity, by drawing on literature outside of bipolar disorder on personality, motivational, and affective predictors of creativity. Because so little research has directly evaluated whether these factors could help explain the elevations of creativity in bipolar disorder, we conclude with an agenda for future research on the theoretically and clinically compelling topic of creativity in bipolar disorder

A Person-centered Approach to Diagnosis and Care for Bipolar Disorder and Alcoholism

Person-centered Medicine proposes the whole person in context, as the center and goal of clinical care and public health. Person-centered Integrative Diagnosis (PID) is an emerging model for conceptualizing the process of clinical diagnosis and care implementing the vision and goals of person-centered medicine. Person-centered Integrative Diagnosis entails a broader and deeper notion of diagnosis, beyond the restricted concept of nosological diagnosis and intends to provide the informational basis for person-centered organization of health care. It involves the dynamic integration of both positive health and ill health and emphasizes the formulation of the health status through true partnership with interactive participation and engagement of clinicians, patients, and families using all relevant descriptive tools (categorization, dimensions, and narratives). The applicability of this model to chronic, complex comorbidity with emphasis on the recovery process and health restoration is particularly pertinent. This paper focuses on the applicability of the PID to the challenging comorbidity of bipolar disorder and alcoholism. The PID provides an integrated formulation of multiple complex problems as well as positive aspects of health and strengths that are key to formulating and implementing personalized treatment and recovery plans

Substance Abuse and Schizophrenia: Impediments to Optimal Care

ABSTRACT With lifetime prevalence estimates of substance abuse among schizophrenics as high as 47.01 %, there is an increasing awareness of the importance of this dual diagnosis and the global deficiencies in our knowledge about this comorbid condition. Patients with substance abuse disorders and schizophrenia are problematic from a clinical, economic, and health care systems perspective. The lack of systematic research into phenomenology, etiology, and treatment approaches (both psychotherapeutic and psychopharmacologic) has hindered the development of an adequate strategy to care for the needs of these patients. Thus, these patients place a significant burden on the mental health delivery system through chronic disability, social dysfunction, frequent rehospitalizations, and poor overall treatment compliance. The authors critically review the contemporary literature relevant to concurrent substance abuse and schizophrenia, highlight major deficiencies in our knowledge, and call for research to reduce the individual, economic, and social costs of this condition

Person Centered Medicine: Core and Diversity

In the conceptualization of Person Centered Medicine (PCM) one can recognize core concepts as well as diversity at multiple levels. The core concepts convey vision and depth. Diversity displays plurality, richness and scope. And both are intertwined and articulated through the unfolding process and journey that the construction of PCM represents. This paper briefly elaborates on these complementary perspectives of PCM. And ends introducing a set of papers that illustrate its core and diversity