Potential of the Blue Calm® food supplement in the treatment of alcohol withdrawal-induced anxiety in adult zebrafish (Danio rerio).

Alcohol use disorder (AUD) is characterized by a set of behavioral, cognitive, nutritional, and physiological phenomena derived from the uncontrolled use of alcoholic beverages. There are cases in which AUD is associated with anxiety disorder, and when untreated, it requires careful pharmacotherapy. Blue Calm® (BC) is a food supplement indicated to aid restorative sleep, which has traces of medicinal plant extracts, as well as myo-inositol, magnesium bisglycinate, taurine, and L-tryptophan as its main chemical constituents. In this context, this study aimed to evaluate the potential of the BC in the treatment alcohol withdrawal-induced anxiety in adult zebrafish (aZF). Initially, BC was submitted to antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl radical. Subsequently, the aZF (n = 6/group) were treated with BC (0.1 or 1 or 10 mg/mL; 20 µL; p.o.), and the sedative effect and acute toxicity (96 h) were evaluated. Then, the anxiolytic-like effect and the possible GABAergic mechanism were analyzed through the Light & Dark Test. Finally, BC action was evaluated for treating alcohol withdrawal-induced anxiety in aZF. Molecular docking was performed to evaluate the interaction of the major chemical constituents of BC with the GABAA receptor. BC showed antioxidant potential, a sedative effect, was not toxic, and all doses of BC had an anxiolytic-like effect and showed potential for the treatment of alcohol withdrawal-induced anxiety in aZF. In addition to the anxiolytic action, the main chemical constituents of BC were confirmed in the molecular docking, thus suggesting that BC is an anxiolytic that modulates the GABAergic system and has pharmacological potential for the treatment of alcohol withdrawal-induced anxiety.

Treating posttraumatic stress disorder and alcohol use disorder comorbidity: Current pharmacological therapies and the future of MDMA-integrated psychotherapy.

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) frequently co-occur in patients who have experienced trauma. This comorbidity leads to a vicious cycle where PTSD symptoms beget heavy drinking and vice versa. There are no FDA-approved medications to treat PTSD-AUD; therefore, individuals suffering from this comorbidity are treated with medication approved to treat the disorders separately or with off-label pharmacological interventions. However, these medications are limited in their efficacy for treating PTSD-AUD comorbidity. Emerging research on the nonclassical psychedelic drug 3,4-methylenedioxymethamphetamine (MDMA) suggests that it may be an effective drug used in conjunction with psychotherapy. The following reviews the current research for clinical pharmacotherapies, as well as MDMA-integrative psychotherapy as they pertain to PTSD and AUD in isolation and co-occurrence. Future directions for the role of psychedelic-integrative therapy for the treatment of this comorbidity are discussed.

Impact of Harm Reduction Treatment with or without Pharmacotherapy on Polysubstance Use among People Experiencing Homelessness and Alcohol Use Disorder.

OBJECTIVES: A prior randomized controlled trial showed behavioral harm reduction treatment for alcohol use disorder (AUD), or HaRT-A, was effective in improving alcohol outcomes and quality of life for people experiencing homelessness and AUD when provided with or without pharmacotherapy (ie, extended-release naltrexone). Because nearly 80% of the sample also reported baseline polysubstance use, this secondary study tested whether HaRT-A also positively impacted other substance use. METHODS: In the parent study, 308 adults with AUD and homelessness were randomized to receive HaRT-A plus intramuscular injections of 380-mg extended-release naltrexone (HaRT-A + extended-release naltrexone), HaRT-A plus placebo (HaRT-A + placebo), HaRT-A alone, or community-based services as usual (control). In this secondary study, we used random intercept models to detect changes in other substance use after exposure to any of the HaRT-A conditions. For less prevalent behaviors, outcomes included past-month use (cocaine, amphetamines/methamphetamines, opioids). For more prevalent behaviors (polysubstance, cannabis), outcomes were past-month use frequency. RESULTS: Compared with controls, participants who received HaRT-A showed significantly reduced 30-day frequency of cannabis use (incident rate ratio = 0.59, 95% CI = 0.40-0.86, P = 0.006) and polysubstance use (incident rate ratio = 0.65, 95% CI = 0.43-0.98, P = 0.040). No other significant changes were detected. CONCLUSIONS: Compared with services as usual, HaRT-A is associated with reduced cannabis and polysubstance use frequency. The benefits of HaRT-A may thus extend beyond its impact on alcohol and quality of life outcomes to positively reshape overall substance use patterns. A randomized controlled trial is needed to further investigate the efficacy of such combined pharmacobehavioral harm reduction treatment for polysubstance use.

Treatment variability and its relationships to outcomes among patients with Wernicke's encephalopathy: A multicenter retrospective study.

BACKGROUND: Despite guidelines and recommendations, Wernicke's encephalopathy (WE) treatment lacks evidence, leading to clinical practice variability. AIMS: Given the overall lack of information on thiamine use for WE treatment, we analyzed data from a large, well-characterized multicenter sample of patients with WE, examining thiamine dosages; factors associated with the use of different doses, frequencies, and routes; and the influence of differences in thiamine treatment on the outcome. METHODS: This retrospective study was conducted with data from 443 patients from 21 centers obtained from a nationwide registry of the Spanish Society of Internal Medicine (from 2000 to 2012). Discharge codes and Caine criteria were applied for WE diagnosis, and treatment-related (thiamine dosage, frequency, and route of administration) demographic, clinical, and outcome variables were analyzed. RESULTS: We found marked variability in WE treatment and a low rate of high-dose intravenous thiamine administration. Seventy-eight patients out of 373 (20.9%) received > 300mg/day of thiamine as initial dose. Patients fulfilling the Caine criteria or presenting with the classic WE triad more frequently received parenteral treatment. Delayed diagnosis (after 24h hospitalization), the fulfillment of more than two Caine criteria at diagnosis, mental status alterations, and folic acid deficiency were associated significantly with the lack of complete recovery. Malnutrition, reduced consciousness, folic acid deficiency, and the lack of timely thiamine treatment were risk factors for mortality. CONCLUSIONS: Our results clearly show extreme variability in thiamine dosages and routes used in the management of WE. Measures should be implemented to ensure adherence to current guidelines and to correct potential nutritional deficits in patients with alcohol use disorders or other risk factors for WE.

The Effect of Very-Long-Chain n-3 Polyunsaturated Fatty Acids in the Central Nervous System and Their Potential Benefits for Treating Alcohol Use Disorder: Reviewing Pre-Clinical and Clinical Data.

Alcohol use poses a significant global health concern, leading to serious physical and socioeconomic issues worldwide. The current treatment options for problematic alcohol consumption are limited, leading to the exploration of alternative approaches, such as nutraceuticals. One promising target is very-long-chain n-3 polyunsaturated fatty acids (VLC n-3 PUFAs). This review aims to compile the most relevant pre-clinical and clinical evidence on the effect of VLC n-3 PUFAs on alcohol use disorders and related outcomes. The findings suggest that VLC n-3 PUFAs may alleviate the physiological changes induced by alcohol consumption, including neuroinflammation and neurotransmitter dysregulation. Additionally, they can reduce withdrawal symptoms, improve mood, and reduce stress level, all of which are closely associated with problematic alcohol consumption. However, more research is required to fully understand the precise mechanisms by which VLC n-3 PUFAs exert their function. Furthermore, PUFAs should not be considered a standalone solution, but as a complement to other therapeutic approaches. Although preliminary evidence supports the potential therapeutic effect of VLC n-3 PUFAs on problematic alcohol consumption, additional research is needed to validate these findings and determine the optimal use of PUFAs as part of a comprehensive approach to the treatment of alcohol use disorders.

Vitamin C as a potential ameliorating agent against hepatotoxicity among alcoholic abusers.

OBJECTIVE: Drug and substance abuse remains a major medical problem globally. Alcohol consumption, particularly heavy drinking, is an important risk factor for many health problems and is a major contributor to the global burden of disease. Vitamin C has proven to be defensive against toxic substances and provides antioxidant and cytoprotective activity to hepatocytes. The aim of this study was to investigate vitamin C as a potential ameliorating agent against hepatotoxicity among alcohol abusers. PATIENTS AND METHODS: This study was a cross-sectional study that included eighty male hospitalized alcohol abusers and twenty healthy people as a control group. Alcohol abusers received standard treatment plus vitamin C. Total protein, albumin, total Bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and 8-hydroxhguanosine (8-OHdG) were investigated. RESULTS: This study reported that, in the alcohol abuser group, there was a significant increase in the total protein, bilirubin, AST, ALT, ALP, TBARS, SOD and 8-OHdG; on the other hand, there was a significant decrease in albumin, GSH and CAT compared with the control group. The alcohol abuser group treated with vitamin C showed a significant decrease in total protein, bilirubin, AST, ALT, ALP, TBARS, SOD and 8-OHdG; on the other hand, there was a significant increase in albumin, GSH and CAT compared with the control group. CONCLUSIONS: This study's findings suggest that alcohol abuse induces significant alterations in various hepatic biochemical parameters and oxidative stress and that vitamin C has a partial protective role in countering alcohol abuse-induced hepatotoxicity. Using vitamin C as an adjunctive supplement to standard treatment may be helpful in minimizing the toxic side effects of alcohol abuse.

Magnesium in the treatment of alcohol withdrawal syndrome: a multicenter randomized controlled trial.

OBJECTIVE: Alcohol withdrawal syndrome (AWS) is a frequent and potentially life-threatening condition experienced in alcohol use disorder. Since hypomagnesemia is involved in AWS's severity, we conducted a multicenter double-blind randomized placebo-controlled trial to examine the efficacy of oral magnesium supplementation as an adjuvant therapy of AWS. MATERIAL AND METHODS: Inpatients were recruited in six different centers if they had a baseline score higher than eight on the Revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar). The experimental treatment was magnesium lactate dehydrate, administrated three times per day providing a total of 426.6 mg per day and up to 15 days. The primary endpoint was the significant between-group difference of the CIWA-Ar total score change from baseline to 3 days later. The treatment group and baseline score were introduced as covariables in an analysis of covariance. RESULTS: A total of 98 inpatients were included {71.4% of men; mean age of 49.1 years [standard deviation (SD): 10.3]}. In the intention-to-treat population, the mean reduction of the CIWA-Ar score in the experimental group between baseline and 3 days later was 10.1 (SD: 5.2), whereas it was 9.2 (SD: 3.9) in the control group. The absolute difference of the adjusted mean in the experimental group compared with the control group was -0.69 (SD: 0.72), which did not correspond to a significant between-group difference (P = 0.34). Per-protocol analysis and sensitivity analyses also supported this result. Supplementary analyses found no significant difference regarding benzodiazepine consumption, magnesium blood concentration, and satisfaction to care. CONCLUSIONS: The present study does not support the rationale of systematic oral magnesium supplementation in patients with AWS.

Further evidence of relationship between thiamine blood level and cognition in chronic alcohol-dependent adults: Prospective Pilot Study of an inpatient detoxification with oral supplementation protocol.

BACKGROUND: The relationship between thiamine blood level (TBL) and cognition remains uncertain, including among alcohol-dependent persons (ADP). AIM: To evaluate this relationship during protocol-driven inpatient alcohol detoxification treatment including thiamine supplementation (AD + Th). METHODS: Prospective 3-week study with 100 consecutively admitted detoxification-seeking ADP (47.7 ± 11 years old, 21% females) without superseding comorbidities requiring treatment. TBL and Montreal Cognitive Assessment (MoCA) were measured at admission (t1, pre-AD + Th) and discharge (t3, post-AD + Th). Frontal Assessment Battery (FAB) was performed at t1. AD + Th included abstinence, pharmacological alcohol withdrawal syndrome treatment, and oral thiamine supplementation (200 mg/day for 14 days). Regression and mediation analyses assessed TBL-cognition relationships. RESULTS: We found no cases of Wernicke Encephalopathy (WE) and only one case of thiamine deficiency. Both MoCA and TBL significantly improved across AD + Th (with medium-to-large effect sizes). At t1, TBL significantly predicted MoCA and FAB sum scores (medium effect sizes; extreme and very strong evidence, respectively). The clear TBL-MoCA association disappeared at t3. In multivariate regression and mediation analyses exploring key influential factors of cognition (identified by LASSO regression), the TBL-MoCA interactions did not relevantly change at t1 and t3. Age, serum transaminases, vitamin D levels, drinking-years, and depression score weakly modified the relationship. CONCLUSION: TBL was a robust predictor of pre-detoxification cognitive impairment, and both TBL and cognition improved significantly during AD + Th (including abstinence) in our ADP population, supporting routine thiamine supplementation for ADP, even those at low WE-risk. The TBL-cognition relationship was minimally confounded by age, alcohol-toxicity proxies, mood, and vitamin D levels.

N-acetylcysteine does not alter neurometabolite levels in non-treatment seeking adolescents who use alcohol heavily: A preliminary randomized clinical trial.

Current treatments for adolescent alcohol use disorder (AUD) are mainly psychosocial and limited in their efficacy. As such, pharmacotherapies are being investigated as potential adjunctive treatments to bolster treatment outcomes. N-acetylcysteine is a promising candidate pharmacotherapy for adolescent AUD because of its tolerability and demonstrated ability to modulate glutamatergic, GABAergic, and glutathione systems. The primary objective of this double-blind, placebo-controlled, within-subjects crossover preliminary investigation was to measure potential changes within glutamate + glutamine (Glx), GABA, and glutathione levels in the dorsal anterior cingulate cortex (dACC) using proton magnetic resonance spectroscopy during 10-days of N-acetylcysteine (1200 mg twice daily) compared to 10-days of placebo in non-treatment seeking adolescents who use alcohol heavily (N = 31; 55% female). Medication adherence was confirmed via video. Effects on alcohol use were measured using Timeline Follow-Back as an exploratory aim. Linear mixed effects models controlling for baseline metabolite levels, brain tissue composition, alcohol use, cannabis use, and medication adherence found no significant differences in Glx, GABA, or glutathione levels in the dACC after N-acetylcysteine compared to placebo. There were also no measurable effects on alcohol use; however, this finding was underpowered. Findings were consistent in the subsample of participants who met criteria for AUD (n = 19). The preliminary null findings in brain metabolite levels may be due to the young age of participants, relatively low severity of alcohol use, and non-treatment seeking status of the population investigated. Future studies can use these findings to conduct larger, well-powered studies within adolescents with AUD.

N-acetylcysteine improves impulse control and attenuates relapse-like alcohol intake in long-term drinking rats.

Increasing evidence suggests that individuals with alcohol use disorder (AUD) present with a disrupted glutamatergic system that underlies core components of addictive disorders, including drug relapse and low impulse control. N-acetylcysteine (NAC) is a cystine prodrug that has been found to promote glutamate homeostasis and drug abstinence. However, no studies to date have evaluated NAC's effect on impulsivity in substance use disorders. Here we determined whether NAC would decrease alcohol-intake behaviors, in addition to improving impulse control, in long-term alcohol drinking male Wistar-Han rats. Before the start of the experiments, all rats were exposed to long-term intermittent access to 20% ethanol for at least seven weeks. Next, in different groups of rats, the effect of NAC (60 and/or 90 mg/kg) was evaluated on (i) voluntary alcohol drinking using a two-bottle free choice paradigm, (ii) the motivation to self-administer alcohol under a progressive ratio schedule of reinforcement, and (iii) relapse-like drinking using the alcohol deprivation effect model. Finally, (iv) NAC's effect on impulse control was evaluated using the five-choice serial reaction time task. Results showed that NAC administration at 90 mg/kg significantly reduced relapse-like drinking and improved impulse control. In contrast, NAC had no effect on levels of alcohol drinking or motivation to drink alcohol. In conclusion, our findings continue to support the use of NAC as an adjuvant treatment for the maintenance of abstinence in AUD. Moreover, we provide evidence for NAC's efficacy in improving impulse control following drinking, which warrants further investigation in substance use settings.

Pregnenolone effects on provoked alcohol craving, anxiety, HPA axis, and autonomic arousal in individuals with alcohol use disorder.

RATIONALE: Chronic alcohol intake down-regulates GABAergic transmission and reduces levels of neuroactive steroids. These changes are associated with greater stress dysregulation and high alcohol craving which in turn increases relapse risk. OBJECTIVES: This study tested whether potentiation of the neurosteroid system with pregnenolone (PREG), a precursor to neuroactive steroids and known to increase GABAergic transmission, will normalize chronic alcohol-related stress adaptations in the hypothalamic-pituitary-adrenal (HPA) axis and autonomic responses and reduce alcohol craving to significantly impact relapse risk. METHODS: Forty-three treatment-seeking individuals with alcohol use disorder (AUD) were randomized to placebo (PBO) or supraphysiologic pregnenolone doses of 300 mg or 500 mg treatment using a parallel-between subject design as part of a larger 8-week pilot clinical trial. In week 2, they participated in a 3-day laboratory experiment where on each day they self-administered the assigned study drug in the laboratory and were then exposed to 5-min personalized guided imagery provocation of stress, alcohol, or neutral/relaxing cues, one condition per day on separate days, in a random, counterbalanced order. Repeated assessments of alcohol craving, anxiety, HPA axis, heart rate (HR), systolic (SBP), and diastolic blood pressure (DBP) and serum pregnenolone levels were made on each day. RESULTS: Pregnenolone levels were significantly increased in the PREG groups versus PBO. PREG treatment decreased stress- and alcohol cue- induced craving and dose-specifically reduced stress-induced anxiety in the 300 mg/day group. Both PREG doses compared to PBO also normalized CORT/ACTH and increased stress-induced HR, stress- and cue-induced SBP, and in the 300 mg PREG group cue-induced DBP responses relative to neutral condition. CONCLUSIONS: Findings indicate that pregnenolone decreases stress- and alcohol cue-provoked craving and normalizes HPA axis and autonomic arousal in individuals with AUD, thereby supporting the need for further assessment of pregnenolone in the treatment of AUD.

Sodium Butyrate Supplementation Modulates Neuroinflammatory Response Aggravated by Antibiotic Treatment in a Mouse Model of Binge-like Ethanol Drinking.

Growing evidence supports the pivotal role of the bidirectional interplay between the gut microbiota and the central nervous system during the progression of alcohol use disorder (AUD). In our previous study, supplementation with sodium butyrate (SB) in C57BL/6J mice prevented increased ethanol consumption in a binge-like drinking paradigm (DID) as a result of treatment with a non-absorbable antibiotic cocktail (ABX). In this study, we tested the hypothesis that SB protection against enhanced ABX-induced ethanol consumption in mice is partially due to modulation of neuroinflammatory responses. Pro- and anti-inflammatory cytokines, as well as changes in microglia and astrocytes were analyzed in hippocampus tissues from ABX-, SB-, ABX+SB-treated mice subjected to 4-week DID. We found that ethanol without or with ABX treatment increased mRNA levels of key brain cytokines (MCP-1, TNF-α, IL-1ß, IL-6 and IL-10) while SB supplementation prevented these changes. Additionally, SB supplementation prevented changes in microglia, i.e., increase in Iba-1 positive cell number and morphology, and in astrocytes, i.e., decrease in GFAP-positive cell number, induced by combination of ethanol and ABX treatments. Our results suggest that gut microbiota metabolites can influence drinking behavior by modulation of neuroinflammation, highlighting the potential for microbiome-targeting strategies for treatment or prevention of AUD.

Effectiveness of a pharmacist-delivered primary care telemedicine intervention to increase access to pharmacotherapy and specialty treatment for alcohol use problems: Protocol for the alcohol telemedicine consult cluster-randomized pragmatic trial.

BACKGROUND: Alcohol use problems are associated with serious medical, mental health and socio-economic consequences. Yet even when patients are identified in healthcare settings, most do not receive treatment, and use of pharmacotherapy is rare. This study will test the effectiveness of the Alcohol Telemedicine Consult (ATC) Service, a novel, personalized telehealth intervention approach for primary care patients with alcohol use problems. METHODS: This cluster-randomized pragmatic trial, supplemented by qualitative interviews, will include adults with a primary care visit between 9/10/21-3/10/23 from 16 primary care clinics at two large urban medical centers within Kaiser Permanente Northern California, a large, integrated healthcare system. Clinics are randomized to the ATC Service (intervention), including alcohol pharmacotherapy and SBIRT (screening, MI (Motivational Interviewing)-based brief intervention and referral to addiction treatment) delivered by clinical pharmacists, or the Usual Care (UC) arm that provides systematic alcohol SBIRT. Primary outcomes include a comparison of the ATC and UC arms on 1) implementation outcomes (alcohol pharmacotherapy prescription rates, specialty addiction treatment referrals); and 2) patient outcomes (medication fills, addiction treatment initiation, alcohol use, healthcare services utilization) over 1.5 years. A general modeling approach will consider clustering of patients/providers, and a random effects model will account for intra-class correlations across patients within providers and across clinics. Qualitative interviews with providers will examine barriers and facilitators to implementation. DISCUSSION: The ATC study examines the effectiveness of a pharmacist-provided telehealth intervention that combines pharmacotherapy and MI-based consultation. If effective, the ATC study could affect treatment models across the spectrum of alcohol use problems. CLINICAL TRIALS REGISTRATION: This study has been registered on ClinicalTrials.gov (NCT05252221).

Spironolactone as a potential new pharmacotherapy for alcohol use disorder: convergent evidence from rodent and human studies.

Evidence suggests that spironolactone, a nonselective mineralocorticoid receptor (MR) antagonist, modulates alcohol seeking and consumption. Therefore, spironolactone may represent a novel pharmacotherapy for alcohol use disorder (AUD). In this study, we tested the effects of spironolactone in a mouse model of alcohol drinking (drinking-in-the-dark) and in a rat model of alcohol dependence (vapor exposure). We also investigated the association between spironolactone receipt for at least 60 continuous days and change in self-reported alcohol consumption, using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), in a pharmacoepidemiologic cohort study in the largest integrated healthcare system in the US. Spironolactone dose-dependently reduced the intake of sweetened or unsweetened alcohol solutions in male and female mice. No effects of spironolactone were observed on drinking of a sweet solution without alcohol, food or water intake, motor coordination, alcohol-induced ataxia, or blood alcohol levels. Spironolactone dose-dependently reduced operant alcohol self-administration in dependent and nondependent male and female rats. In humans, a greater reduction in alcohol consumption was observed among those who received spironolactone, compared to propensity score-matched individuals who did not receive spironolactone. The largest effects were among those who reported hazardous/heavy episodic alcohol consumption at baseline (AUDIT-C ≥ 8) and those exposed to ≥ 50 mg/day of spironolactone. These convergent findings across rodent and human studies demonstrate that spironolactone reduces alcohol use and support the hypothesis that this medication may be further studied as a novel pharmacotherapy for AUD.

[Prospects for the development of new prolonged forms of valproic acid derivatives for the relief of convulsive syndrome]. / Perspektivy razrabotki novykh prolongirovannykh form proizvodnykh val'proevoi kisloty dlya kupirovaniya sudorozhnogo sindroma.

Poisoning with pesticides containing convulsive substances is the cause of death of thousand people in the world. Convulsive syndrome can also develop with infection of the central nervous system, intracranial hemorrhages and strokes, alcohol withdrawal syndrome, eclampsia. Up to 10% of all of the people on the Earth had experienced seizures. The most common cause of seizures is epilepsy. Existing drugs are not always effective and have side effects. Alternative therapies are being developed. Valproates (derivatives of valproic acid) are one of the most studied drugs of choice for epilepsy and other variants of convulsive syndrome, have many years of experience in use, are included in international and Russian clinical guidelines for the treatment of epilepsy. The antiepileptic, mood stabilizing and neuroprotective properties of valproate due to pre- and postsynaptic modulation of GABA-ergic transmission, regulation of glutamate activity, serotonin and dopamine levels in the hippocampus, modulation of sodium, calcium and potassium channels, epigenetic effects on the body are described. However, valproates have a number of undesirable side effects, usually associated with high doses of drugs used for a long time. Attempts to reduce the risk through the development of drugs with controlled release of the active substance are not always effective - the high individual sensitivity of about 15% of patients with epilepsy makes standard doses toxic, the pharmacokinetics and effectiveness of the developed generics are significantly inferior to the original imported drug. An alternative could be the development of Russian preparations containing a proactive component from which valproic acid is gradually released during the metabolism.

Effect of Extract of Black Sticky Rice with Giant Embryo on Alcohol Cravings of Korean Social Drinkers: A 12-Week Randomized, Placebo-Controlled Trial.

We investigated the effect of black sticky rice with giant embryo (BSRGE) extract known to contain high levels of gamma-aminobutyric acid (GABA) on alcohol cravings in social drinkers. A total of 41 subjects were divided into a BSRGE extract group (G group: n = 21) and a placebo group (P group: n = 20), and a randomized placebo-controlled experiment was performed for 12 weeks. The G group took the BSRGE extracts that contained 30 mg of GABA per day. (1) In the Pennsylvania Alcohol Craving Scale, there was a tendency for time and group interaction between the two groups (P = .087) on the total score. (2) In the Obsessive-Compulsive Drinking Scale (OCDS), there was a significance for time and group interaction between the G and P groups (P = .011) on the obsessive subscale. The total score of the OCDS showed significant time and group interactions between the G and P groups (P = .011). Our results showed that the extract of BSRGE containing a high level of GABA significantly reduced alcohol cravings in Korean social drinkers.

Sustained drug delivery strategies for treatment of common substance use disorders: Promises and challenges.

Substance use disorders (SUDs) are a leading cause of death and other ill health effects in the United States and other countries in the world. Several approaches ranging from detoxification, behavioral therapy, and the use of antagonists or drugs with counter effects are currently being applied for its management. Amongst these, drug therapy is the mainstay for some drug abuse incidences, as is in place specifically for opioid abuse or alcohol dependence. The severity of the havocs observed with the SUDs has triggered constant interest in the discovery and development of novel medications as well as suitable or most appropriate methods for the delivery of these agents. The chronic need of such drugs in users warrants the need for their prolonged or sustained systemic availability. Further, the need to improve patient tolerance to medication, limit invasive drug use and overall treatment outcome are pertinent considerations for embracing sustained release designs for medications used in managing SUDs. This review aims to provide an overview on up-to-date advances made with regards to sustained delivery systems for the drugs for treatment of different types of SUDs such as opioid, alcohol, tobacco, cocaine, and cannabis use disorders. The clinical relevance, promises and the limitations of deployed sustained release approaches along with future opportunities are discussed.

Early treatment with thiamine and mortality among patients with alcohol use disorder who are hospitalized for pneumonia.

BACKGROUND: The paucity of research linking thiamine treatment with improved outcomes may be driving its underutilization among patients at risk for Wernicke encephalopathy. OBJECTIVE: To assess relationships of thiamine usage to outcomes of patients hospitalized with alcohol use disorder and pneumonia. DESIGN, SETTING AND PARTICIPANTS: This is a retrospective cohort study of adult patients hospitalized with pneumonia who also have alcohol use disorder and were treated with benzodiazepines during the initial two hospital days, between 2010 and 2015 at hospitals participating in the Premier Healthcare Database. EXPOSURE: Any thiamine treatment, and, among those treated, high-dose thiamine treatment, during the initial two hospital days. MAIN OUTCOME AND MEASURES: Death on days 3-14 of hospitalization (primary); discharge home; transfer to intensive care unit; length of stay (LOS). We used propensity-weighted models to estimate treatment effects. RESULTS: Among 36,732 patients from 625 hospitals, 26,520 (72.2%) patients received thiamine, with mortality of 6.5% and 8.1% among recipients and nonrecipients, respectively. With propensity score adjustment, thiamine was associated with reduced mortality (odds ratio [OR]: 0.80, 95% confidence interval [CI]: 0.75-0.85) and more frequent discharges to home (OR: 1.10, 95% CI: 1.06-1.14). Other outcomes were similar. Relative to low-dose thiamine, high-dose thiamine was not associated with mortality (adjusted OR: 0.99, 95% CI: 0.89-1.10), but LOS was longer (ratio of means: 1.06, 95% CI: 1.04-1.08), and discharges to home were less frequent (OR: 0.92, 95% CI: 0.87-0.97). CONCLUSION: Thiamine is not reliably given to patients with pneumonia and alcohol use disorder receiving benzodiazepines. Improving thiamine administration may represent an opportunity to save lives in this high-risk group of inpatients.

Association of topiramate prescribed for any indication with reduced alcohol consumption in electronic health record data.

BACKGROUND AND AIMS: Topiramate is a medication that is widely prescribed to treat a variety of conditions, including alcohol use disorder (AUD). We used electronic health record (EHR) data to measure topiramate's effects on drinking in individuals differentiated by a history of AUD. DESIGN: Parallel-groups comparison of patients prescribed topiramate and a propensity score-matched comparison group. SETTING: A large US integrated health-care system. PARTICIPANTS: Patients with Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) scores prior to and after a minimum of 180 days of topiramate prescription for any indication and a propensity score-matched group. The sample included 5918 patients with an electronic health record diagnosis of alcohol use disorder at any time (AUD-hx-pos) (1738 topiramate-exposed and 4180 controls) and 23 614 patients with no EHR diagnosis of AUD (AUD-hx-neg) (6324 topiramate-exposed and 17 290 controls). MEASUREMENTS: Regression analyses compared difference-in-difference (DiD) estimates, separately by AUD history. DiD estimates represent exposure-group (i.e. topiramate versus control) differences on the pre-post difference in AUDIT-C score. Effects of baseline AUDIT-C score and daily topiramate dosage were also tested. FINDINGS: AUD-hx-neg patients who received topiramate had a greater reduction in AUDIT-C score (-0.11) than matched controls (-0.04). This yielded a DiD score of -0.07 [95% confidence interval (CI) = -0.11,-0.03; P = 0.002], with the greatest effect among AUD-hx-neg patients with a baseline AUDIT-C score of 4+ (DiD = -0.35, 95% CI = -0.49, -0.21; P < 0.0001) and those prescribed > 150 mg/day of the medication (DiD = -0.15, 95%CI = -0.23, -0.07; P < 0.001). DISCUSSION: Among individuals with no history of alcohol use disorder, topiramate appears to be associated with reduced drinking. This small effect is most evident among patients with higher baseline drinking levels and at a higher average daily topiramate dosage.

S3 Guideline "Smoking and Tobacco Dependence: Screening, Diagnosis, and Treatment" - Short Version.

INTRODUCTION: In addition to the prevention of tobacco consumption, the establishment and assurance of high-quality treatment for harmful use and dependence on tobacco products remains an important health-related task in Germany. Regular updating of the Association of the Scientific Medical Societies (AWMF) S3 guideline "Smoking and Tobacco Dependence: Screening, Diagnosis, and Treatment" (Tobacco Guideline) offers a sustainable and reputable source of knowledge on smoking cessation. METHODS: Under the auspices of the German Society for Psychiatry, Psychotherapy, Psychosomatics, and Neurology (DGPPN) and the German Society for Addiction Research and Addiction Therapy (DG-Sucht), the Tobacco Guideline was revised in 2019-2020 by 63 experts, who were involved in the development process of the text, in 11 working groups. Undue influence of conflicts of interest on the guideline could be minimized through careful conflict of interest management. Delegates from 50 professional societies discussed the 80 guideline recommendations and voted online. RESULTS: In addition to recommendations for screening and diagnostics, the Tobacco Guideline takes a positive stance towards the use of low-threshold counseling and support services. If, due to the severity of the tobacco-related disorder, brief counseling, telephone counseling, or internet- or smartphone-based methods are not sufficiently effective, individual or group behavioral therapy, possibly in combination with medication, is indicated. If nicotine replacement therapy is not effective, varenicline or bupropion should be offered. Alternative strategies with a lower level of recommendation are hypnotherapy, mindfulness-based treatments, or medication with cytisine. In adolescents and pregnant women, the use of medication should be limited to well-specified exceptions and nicotine replacement. The mean agreement with the recommendations reached a value of 98%. A general overview of the treatment recommendations of the Tobacco Guideline is provided by three clinical algorithms.