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

Effect of Alcohol Consumption on Cognitive Decline among Mexicans 50 Years and Older

Background: Studies on the association between alcohol use and cognitive impairment have yielded controversial results suggesting a reduced risk of dementia in drinkers vs. nondrinkers. We aimed to examine the effect of alcohol use on cognitive trajectories among Mexican adults aged 50 and over. Methods: Data are from 5,898 cognitively normal individuals (2,512 men and 3,386 women) from the Mexican Health and Aging Study (MHAS) with a mean age of 59 years (50-90 years) at baseline (2001) and followed-up after 11 years (2012). The Cross-Cultural Cognitive Examination was the cognitive battery measuring verbal memory, visual memory, attention, and constructional praxis. Impairment was defined if scores in two or more functions were 1.5 standard deviations below the mean based on norms by age and education. Using self-reported data on frequency and quantity of alcohol consumption, as well as scores on the CAGE questionnaire, a 4-question screening tool for the detection of alcoholism, we constructed a comprehensive measure to classify alcohol use into five categories: never, mild, moderate, and heavy drinking. Those who reported they had never drunk in their life were classified as never drinkers, mild drinkers included those drinking less than one day per week, and those who drunk before and scored zero in the CAGE questionnaire, moderate drinkers included those who reported having one or two drinks each day, and as heavy drinkers, we classified those who reported having three or more drinks per day and those who drunk before and scored one or more in the CAGE questionnaire. Multivariate logistic regression models were used to analyze the predictive role of alcohol consumption in developing cognitive impairment. Sociodemographic and health variables known to increase the risk of cognitive decline (age, education, gender, locality, cardiovascular risk factors, smoking, and depressive symptoms) were included as covariates. Results: At follow-up, 4,844 participants (82.1%) remained cognitively normal, while 1,054 participants (18%) showed impaired cognition. When the more generally classified drinkers were compared to never-drinkers, they had a reduced risk of cognitive impairment (OR 0.78, 95% CI 0.64-0.95). However, when we analyzed mild, moderate, and heavy drinkers compared to never-drinkers, only mild drinkers had a significantly reduced risk of cognitive decline (OR 0.76, 95% CI 0.62-0.93). The reduced risk of cognitive impairment in moderate drinkers (OR 0.72, 95% CI; 0.49-1.05) and heavy drinkers (OR 0.90, 95%CI .70-1.16) was not significant. Conclusions: Our results suggest that among drinkers, only mild drinking has a protective effect on cognitive decline in Mexican adults aged 50 years and older

Acculturation Stress and the Rise in Alcohol Use Among Latina Women in the U.S.

Background: Epidemiological surveys and world status reports consistently indicate the gap between alcohol consumption in men and women in the United States has been closing steadily over the past 25 years. Particularly, more women now than ever are engaging in alcohol-related risk behavior such as binge drinking, catching up to those of their male counterparts. Data from national surveys conducted between 2000 and 2016 suggests that the number of people above 18 who drink each year increased for women but decreased for men. This trend is consistent amongst Latina women. College-aged, American Latinas in are drinking more frequently and more in quantity at an increasing rate as opposed to American Latinos. There is prolific and extensive research investigating the reasons for higher rates of alcohol consumption and problematic drinking amongst Latina women in the US. Most commonly, this research addresses the socioeconomic and psychological effects of acculturation into U.S. culture. Methods: This study hypothesized that being more acculturated increases alcohol risk behavior and drinking in Latina women due to stressors such as language barriers, social isolation, career difficulties, and separation from family. A literature review was conducted of studies (conducted from 2007-2021) found on PubMed, Google Scholar, and the HOLLIS Harvard Library Catalog using the search terms “Latino, “alcohol use”, and “acculturation”. These studies directly measured the relationship between acculturation of Latinos and alcohol consumption habits. The differences between male and female acculturation were then analyzed, highlighting how acculturation may impact female alcohol consumption. Acculturation, here is measured by surveys including the Acculturation Rating Scale for Mexican Americans (ARSMA) and the Bi-dimensional Acculturation Scale for Hispanics, utilizing the proxies of English/Spanish proficiency and place of birth. Results: Our review revealed that high acculturation scores are more strongly related to increased drinking in Latino women than men. A national sample found that Latinas in the top tercile of acculturation are almost 6 times more likely to drink than Latinas in the bottom tercile. The studies labeled such drinking as a coping mechanism for previously mentioned acculturation stressors of academics and career matters. However, they also described the behavior as a sign of adjustment to new cultural norms and discovery. The discouragement of health-risk behavior such as excessive drinking in women is prevalent in Latino communities, where gender expectations stress female temperance and self-control. Young environment such as a bustling American college where drinking is normalized can cause these women to experiment and risk-take more frequently. Conclusions: The results of our review indicate that acculturation stress is related to increased alcohol use among young Latinas. Further research should aim at developing a comprehensive understanding of these stressors within the context of acculturation, as well as within the broader context of sociocultural and gender norm differences. This perspective is particularly relevant for studies focused on the Rio Grande Valley, a unique area in terms of acculturation and Latino/American cultural mixing. Future research should aim to develop targeted preventative interventions that address these nuanced factors to effectively reduce alcohol-related risk behaviors in this population

Effect of Alcohol Consumption on Cognitive Decline among Mexican Adults

Background: Studies on the association between alcohol use and cognitive impairment have yielded controversial results suggesting a reduced risk of dementia in drinkers vs. nondrinkers. We aimed to examine the effect of alcohol use on cognitive trajectories among Mexican adults aged 50 and over. Methods: Data are from 5,898 cognitively normal individuals (2,512 men and 3,386 women) from the Mexican Health and Aging Study (MHAS) with a mean age of 59 years (50-90 years) at baseline (2001) and followed-up after 11 years (2012). The Cross-Cultural Cognitive Examination was the cognitive battery measuring verbal memory, visual memory, attention, and constructional praxis. Impairment was defined if scores in two or more functions were 1.5 standard deviations below the mean based on norms by age and education. Using self-reported data on frequency and quantity of alcohol consumption, as well as scores on the CAGE questionnaire, a 4-question screening tool for the detection of alcoholism, we constructed a comprehensive measure to classify alcohol use into five categories: never, mild, moderate, and heavy drinking. Those who reported they had never drunk in their life were classified as never drinkers, mild drinkers included those drinking less than one day per week, and those who had drunk before and scored zero in the CAGE questionnaire, moderate drinkers included those who reported having one or two drinks each day, and as heavy drinkers, we classified those who reported having three or more drinks per day and those who drunk before and scored one or more in the CAGE questionnaire. Multivariate logistic regression models were used to analyze the predictive role of alcohol consumption in developing cognitive impairment. Sociodemographic and health variables known to increase the risk of cognitive decline (age, education, gender, locality, cardiovascular risk factors, smoking, and depressive symptoms) were included as covariates. Results: At follow-up, 4,844 participants (82.1%) remained cognitively normal, while 1,054 participants (18%) showed impaired cognition. When the more generally classified drinkers were compared to never-drinkers, they had a reduced risk of cognitive impairment (OR 0.78, 95% CI 0.64-0.95). However, when we analyzed mild, moderate, and heavy drinkers compared to never-drinkers, only mild drinkers had a significantly reduced risk of cognitive decline (OR 0.76, 95% CI 0.62-0.93). The reduced risk of cognitive impairment in moderate drinkers (OR 0.72, 95% CI; 0.49-1.05) and heavy drinkers (OR 0.90, 95%CI .70-1.16) was not significant. Conclusions: Our results suggest that among drinkers, only mild drinking has a protective effect on cognitive decline in Mexican adults aged 50 years and olde

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

Human Papilloma Viruses Infection and Pre-Malignant Lesions in Women on the Texas Mexico Border

Background: In United States, 24-40 million women have had at least one Human Papillomavirus (HPV) infection. While HPV infection is responsible for over 93% of cervical cancer cases worldwide, it is relatively uncommon in US given screening programs and the introduction of the Papanicolaou test. In Texas, where cervical screening and uptake of the HPV vaccine is lower, the incidence of cervical cancer is 12 cases per 100,000 women. Along the border with Mexico the incidence of cervical cancer rises to 16 cases per 100,000 women, mirroring Mexico’s public health problem: cervical cancer is the leading cause of death in women. Despite successful screening programs and declining incidence of cervical cancer in the US and other high-income countries, HPV infection and cervical cancer are still very formidable public health issues in the lower income countries such as Mexico and the US-Mexico border. Methods: Women were recruited from a specialty clinic in Valle Hermoso, Tamaulipas, a border city in Mexico. Women were eligible to participate in the study if were over the age of 18, reported being sexually active, were not pregnant and had never had a hysterectomy or cervical cancer (n=212). Each participant was given a self-administered questionnaire to be completed prior to having the conventional Pap smear examination. The questionnaire obtained demographic, lifestyle and reproductive histories for participants and their partners. History of diabetes mellitus, tobacco, alcohol use. Examinations were performed using the standard method by placing the woman on an examination table in the lithotomy position. Results: Participants median age was 38 years old (91%), had greater than or equal to a high school education (54%), were married (84%), reported only having had only one sexual partner (93%), reported using at least one contraceptive method (96%), and approximately 14% reported having had a history of a sexually transmitted infection. For those women whose specimens were available for analyses (n=200), sixty-four percent were found to be HPV infected and 17% were found to have multiple types of HPV. Tested positive for an HPV infection, 39% were infected with high risk types 16 (n=45) and 18 (n=33). When including other HPV high-risk types associated with cancer, the percentage of women infected with a high-risk HPV jumped to 66%. Conclusion: These data raise important issues about the needs for cervical cancer screening and HPV vaccination Mexican women; particularly those living along the US-Mexico border. Data collected during the same time period among women working in a nearby maquiladora found that only 7% of employed woman were infected with a high-risk HPV type despite similar demographic, lifestyle and reproductive histories. Another area of concern is that high-risk HPV infections may be just as high among Hispanic women living along the US-Mexico border. More studies are needed to document the burden of HPV among these underserved populations

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