A person-centered approach to capture health disparities and multidimensional impact of COVID-related stressors.

The COVID-19 pandemic has influenced people's lives in diverse ways. The authors utilized latent class analysis (LCA), a person-centered approach, to examine distinct patterns of COVID-related stressors and their associations with alcohol-related, mental health, and quality of life outcomes. Participants were 463 adults who completed the baseline assessment of the National Institute on Alcohol Abuse and Alcoholism COVID-19 Pandemic Impact on Alcohol Study from June 2020 to January 2022. Using cross-sectional data, three analytic methods (continuous sum score, categorical grouping, and LCA) were applied to model 17 COVID-related stressors. Regression analyses indicated higher COVID-related stress and endorsement of four or more COVID-related stressors were generally associated with worse health-related outcomes. LCA revealed four classes: Class 1: Minimal COVID-Related Impact (51.6%); Class 2: Work Interruptions (24.8%); Class 3: Family/Friends Affected by COVID (14.5%); and Class 4: Serious Financial Stress (9.1%). Racial/ethnic minorities were more likely to be in Class 3, whereas individuals with more years of education and higher income were less likely to be in Class 4. Individuals with a history of alcohol use disorder were more likely to be in Classes 2 and 4. Compared with Class 1, Class 4 reported highest levels of perceived stress, problematic alcohol use, anxiety symptoms, depressive symptoms, alcohol craving, loneliness, drinking to cope, and lowest levels of physical, psychological, social, and environment quality of life. COVID-related stressors disproportionately affected minority and vulnerable groups. Individuals who experienced multiple financial stressors had the greatest risk for negative health-related outcomes and may benefit from holistic interventions and community outreach. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Suggestibility is associated with alcohol self-administration, subjective alcohol effects, and self-reported drinking behavior.

BACKGROUND: Suggestibility, defined as an individual's inclination to accept and internalize messages, has not been studied in relation to alcohol use. Peer conformity, a component of suggestibility, may be related to alcohol use, as peer groups show similarities in patterns of alcohol use. Few studies have assessed how suggestibility and peer conformity relate to alcohol self-administration or to reinforcing effects of alcohol. AIMS: This study assessed whether suggestibility and peer conformity were associated with drinking behavior, alcohol self-administration, subjective response to alcohol, and drinking motives and expectancies. METHODS: Study 1 participants were alcohol drinkers (n=20), who completed a laboratory study of free-access intravenous alcohol self-administration. Study 2 participants were adolescents and young adults, age 14-25 (n=150), with lifetime alcohol use. Participants completed surveys of suggestibility and drinking patterns (Study 1 and 2), subjective alcohol effects (Study 1 only), and alcohol motives and expectancies (Study 2 only). RESULTS/OUTCOMES: In Study 1, participants with higher levels of suggestiblity self-administered more alcohol, and reported greater subjective alcohol effects. Peer conformity, though correlated with suggestibility, was not related to these measures. In Study 2, participants with higher suggestiblity reported more alcohol consumption, higher drinking motives and alcohol expectancies. Peer conformity was not related to alcohol consumption, but was related to coping and enhancement drinking motives, and all expectancies measures. CONCLUSIONS/INTERPRETATION: Results indicate that suggestibility, beyond peer conformity, may be a critical factor to study when examining alcohol consumption behavior, and may provide insight into the development of alcohol use disorder.

Stress vulnerability and alcohol use and consequences: From human laboratory studies to clinical outcomes.

It is well known that vulnerability to stress is a risk factor for alcohol use disorder (AUD). Chronic alcohol use can result in neuroadaptations in cortico-striatal pathways and hypothalamic pituitary adrenal (HPA) axis function that are manifested in altered behavioral and cognitive control functions contributing to alcohol craving, compulsive motivation, consumption, and consequences. This symposium brings together studies utilizing novel approaches to help improve our understanding of stress - past, acute, and chronic - on alcohol seeking and consumption and related outcomes using a combination of human laboratory models, neuroimaging, and clinical measures. Examining factors that determine vulnerability as well as resilience to stress are of particular interest in the study of AUD because, in addition to increasing our understanding of the risk factors for AUD, such knowledge can be used to develop more effective treatments. Dr. Stangl presented a novel human experimental model that demonstrates, for the first time, stress-induced increases in alcohol self-administration in binge drinkers using a guided imagery paradigm combined with intravenous alcohol self-administration (IV-ASA). Dr. Blaine presented data demonstrating that glucocorticoid response to stress drives compulsive alcohol motivation and intake in binge/heavy drinkers. Dr. Plawecki presented data examining sex differences in the effect of two distinct stress paradigms - mood induction and abstinence - on IV-ASA in moderate drinkers. Dr. Schwandt presented clinical data providing a new perspective on the relationship between childhood trauma and AUD by suggesting possible underlying mechanisms that confer resilience, rather than vulnerability, to severe early life stress exposure.

The endocannabinoid system as a target for addiction treatment: Trials and tribulations.

Addiction remains a major public health concern, and while pharmacotherapies can be effective, clinicians are limited by the paucity of existing interventions. Endocannabinoid signaling is involved in reward and addiction, which raises the possibility that drugs targeting this system could be used to treat substance use disorders. This review discusses findings from randomized controlled trials evaluating cannabinergic medications for addiction. Current evidence suggests that pharmacotherapies containing delta-9-tetrahydrocannabinol, such as dronabinol and nabiximols, are effective for cannabis withdrawal. Dronabinol may also reduce symptoms of opioid withdrawal. The cannabinoid receptor 1 (CB1) inverse agonist rimonabant showed promising effects for smoking cessation but also caused psychiatric side effects and currently lacks regulatory approval. Few trials have investigated cannabinergic medications for alcohol use disorder. Overall, the endocannabinoid system remains a promising target for addiction treatment. Development of novel medications such as fatty acid amide hydrolase inhibitors and neutral CB1 antagonists promises to extend the range of available interventions. This article is part of the Special Issue entitled "A New Dawn in Cannabinoid Neurobiology".

FAAH Gene Variation Moderates Stress Response and Symptom Severity in Patients with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence.

BACKGROUND: A common single nucleotide polymorphism (C385A) in the human fatty acid amide hydrolase (FAAH) gene has been associated with decreased distress responses in healthy volunteers, but its role in psychiatric disorders remains unknown. Here, we obtained genotypes and carried out a secondary analysis of subjects from a trial of comorbid posttraumatic stress disorder (PTSD) and alcohol dependence (AD). We evaluated the effects of C385A variation on behavioral and biochemical biomarkers of distress responses. METHODS: Forty-nine patients with PTSD and AD were admitted for 4 weeks to an experimental medicine unit at the National Institutes of Health Clinical Center. Following detoxification, stress reactivity and peripheral endocannabinoid (eCB) levels were assessed in response to a challenge session using personalized auditory guided imagery. Over the course of the study, subjects were also evaluated for changes in PTSD symptom severity. RESULTS: FAAH C385A allele carriers showed a marked increase in serum anandamide levels at baseline and throughout the stress challenge procedure compared with C allele homozygotes, while levels of eCBs primarily metabolized through other enzymatic activity, such as 2-arachidonoylglycerol, did not differ between genotype groups. FAAH C385A carriers also had decreased subjective anxiety responses to the stress challenge. Similar effects of FAAH C385A genotype were found at the level of clinical PTSD symptom severity, in particular in the arousal domain. CONCLUSIONS: This is to our knowledge the first study showing that FAAH C385A variation modulates stress responses in subjects with disorders characterized by increased stress reactivity. These findings point to the eCB pathway as a promising target for future antistress therapeutics.

Effects of Sex, Drinking History, and Omega-3 and Omega-6 Fatty Acids Dysregulation on the Onset of Liver Injury in Very Heavy Drinking Alcohol-Dependent Patients.

BACKGROUND: Heavy alcohol consumption frequently causes liver inflammation/injury, and certain fatty acids (FAs) may be involved in this liver pathology. In this study, we evaluated the association of heavy drinking and the changes in the FA levels involved in the ω-6 (pro-inflammatory) and ω-3 (anti-inflammatory) state in alcohol-dependent (AD) patients who had no clinical manifestations of liver injury. We aimed to identify sex-based differences in patients with mild or no biochemical evidence of liver injury induced by heavy drinking. METHODS: A total of 114 heavy drinking AD female and male patients aged 21 to 65 years without clinical manifestations of liver injury, who were admitted to an alcohol dependence treatment program, were grouped by the alanine aminotransferase (ALT) levels: ≤40 IU/l, as no liver injury (GR.1), and >40 IU/l, as mild liver injury (GR.2). Patients were actively drinking until the day of admission. Comprehensive metabolic panel, comprehensive FA panel, and drinking history data were evaluated. RESULTS: Elevated ALT and aspartate aminotransferase (AST) showed close association with markers of heavy alcohol intake. In the patients with mild biochemical liver injury (GR.2), females showed significantly higher AST level than males. Significant association of AST and total drinks in past 90 days (TD90) in females, and AST and heavy drinking days in past 90 days (HDD90) in males was observed. The ω-6:ω-3 ratio showed a significant pro-inflammatory response only in females with mild liver injury (GR.2) when adjusted by drinking history marker, TD90. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were increased in males with liver injury, while females did not show any comparable rise in EPA; and DHA levels were lower. CONCLUSIONS: Measures of heavy drinking, TD90 and HDD90, predicted changes in liver injury. Changes in the ω-3 and ω-6 FA levels and the ω-6:ω-3 ratio showed a pro-inflammatory shift in patients with biochemical liver injury with a significant effect in females. Changes in FAs involved in the inflammatory state may represent one mechanism for liver inflammation/injury in response to heavy alcohol drinking.

Methods for inducing alcohol craving in individuals with co-morbid alcohol dependence and posttraumatic stress disorder: behavioral and physiological outcomes.

Alcohol addiction is a chronic relapsing disorder that presents a substantial public health problem, and is frequently co-morbid with posttraumatic stress disorder (PTSD). Craving for alcohol is a predictor of relapse to alcohol use, and is triggered by cues associated with alcohol and trauma. Identification of reliable and valid laboratory methods for craving induction is an important objective for alcoholism and PTSD research. The present study compares two methods for induction of craving via stress and alcohol cues in individuals with co-morbid alcohol dependence (AD) and PTSD: the combined Trier social stress test and cue reactivity paradigm (Trier/CR), and a guided imagery (Scripts) paradigm. Outcomes include self-reported measures of craving, stress and anxiety as well as endocrine measures. Subjects were 52 individuals diagnosed with co-morbid AD and PTSD seeking treatment at the National Institute on Alcohol Abuse and Alcoholism inpatient research facility. They participated in a 4-week inpatient study of the efficacy of a neurokinin 1 antagonist to treat co-morbid AD and PTSD, and which included the two challenge procedures. Both the Trier/CR and Scripts induced craving for alcohol, as well as elevated levels of subjective distress and anxiety. The Trier/CR yielded significant increases in adrenocorticotropic hormone and cortisol, while the Scripts did not. Both paradigms are effective laboratory means of inducing craving for alcohol. Further research is warranted to better understand the mechanisms behind craving induced by stress versus alcohol cues, as well as to understand the impact of co-morbid PTSD and AD on craving.