Association of alcohol withdrawal severity with MTNR1A (rs34532313) and MTNR1B (rs10830963) genes polymorphisms

Alcohol withdrawal is the most threatening condition encountered in patients with alcohol use disorder. Our study aimed to investigate the association of alcohol withdrawal severity with polymorphic variants in melatonin receptor genes. Methods. The clinical study was carried out on the basis of the Republican Narcological Dispensary №1 in Ufa and the Republican Narcological Dispensary №2 in Sterlitamak. Genetic analysis was performed at the Department of Personalised Psychiatry and Neurology at the V.M. Bekhterev Research Centre, Saint Petersburg. The final sample consisted of 307 subjects. Results. Carriers of the TT genotype of the MTNR1A gene (rs34532313) were found to have less hypertension during alcohol withdrawal than carriers of the other genotypes. In comparison, carriers of the GG genotype of the MTNR1B gene (rs10830963) experienced more symptoms than other genotypes: paroxysmal sweating, visual hallucinations, anxiety, and overall CIWA-Ar score. Conclusions. Thus, it can be concluded that the TT genotype of MTNR1A gene (rs34532313) is associated with a lower risk of hypertension during alcohol withdrawal compared to carriers of other gene genotypes. The GG genotype of MTNR1B gene (rs10830963) is associated with severe withdrawal. In general, it can be concluded that melatonin receptors are involved in the pathogenesis of alcohol withdrawal and the severe of some of its symptoms.

Adverse events related to bystander naloxone administration in cases of suspected opioid overdose in British Columbia: An observational study

Introduction Take-Home Naloxone programs have been introduced across North America in response to rising opioid overdose deaths. There is currently limited real-world data on bystander naloxone administration, overdose outcomes, and evidence related to adverse events following bystander naloxone administration. Methods The research team used descriptive statistics from Take-Home Naloxone administration forms. We explored reported demographic variables and adverse events among people who received by-stander administered naloxone in a suspected opioid overdose event between August 31, 2012 and December 31, 2018 in British Columbia. We examined and contextualized differences across years given policy, program and drug toxicity changes. We used multivariate logistic regression to examine whether an association exists between number of ampoules of naloxone administered and the odds that the recipient will experience withdrawal symptoms. Results A large majority (98.1%) of individuals who were administered naloxone survived their overdose and 69.2% had no or only mild withdrawal symptoms. Receiving three (Adjusted Odds Ratio (AOR) 1.64 (95% Confidence Interval (CI): 1.08–2.48)) or four or more (AOR 2.19 (95% CI: 1.32–3.62)) ampoules of naloxone was significantly associated with odds of moderate or severe withdrawal compared to receiving one ampoule of naloxone. Conclusions This study provides evidence from thousands of bystander reversed opioid overdoses using Take-Home Naloxone kits in British Columbia, and suggests bystander-administered naloxone is safe and effective for opioid overdose reversal. Data suggests an emphasis on titration during bystander naloxone training in situations where the person experiencing overdose can be adequately ventilated may help avoid severe withdrawal symptoms. We identified a decreasing trend in the likelihood of moderate or severe withdrawal over the study period.

Clinical withdrawal symptom profile of synthetic cannabinoid receptor agonists and comparison of effects with high potency cannabis

Synthetic cannabinoid receptor agonists (SCRAs) may be used as an alternative to natural cannabis; however, they may carry a greater risk of problematic use and withdrawal. This study aimed to characterise the withdrawal symptom profile of SCRAs and compare their profile of effect with high-potency herbal cannabis. Global Drug Survey data (2015 and 2016) were used to access a clinically relevant sample of people reporting use of SCRAs >10 times in the past 12-months, a previous SCRA quit attempt, and lifetime use of high-potency herbal cannabis. Participants completed an 11-item SCRA withdrawal symptom checklist and compared SCRAs and high-potency herbal cannabis on their onset and duration of effects, speed of the development of tolerance, severity of withdrawal, and difficulty with dose titration. Participants (n = 284) reported experiencing a mean of 4.4 (95% CI: 4.1, 4.8) withdrawal symptoms after not using SCRAs for >1 day; most frequently reported were sleep issues (59.2%), irritability (55.6%), and low mood (54.2%). Withdrawal symptoms were significantly associated with frequency (>51 vs. 11–50 times per year: IRR = 1.43, 95% CI: 1.16, 1.77, p = 0.005) and quantity (grams per session: IRR = 1.13, 95% CI: 1.05, 1.22, p = 0.001) of SCRA use. Compared to high-potency herbal cannabis, SCRAs were rated as having a faster onset and shorter duration of effects, faster development of tolerance, and more severe withdrawal (p’s < 0.001). In conclusion, SCRA withdrawal symptoms are more likely to occur after greater SCRA exposure. The effects of SCRA indicate a more severe withdrawal syndrome and a greater risk of problematic use than natural cannabis.

Heart Rate Variability, Time Estimation and Internet-Dependent Behaviour in 16–17-Year-Old Adolescents: A Study in Russian Arctic

Internet-dependent behaviour in adolescents can contribute to a change in the function of the nervous system, which is reflected in the violation of time perception and autonomic regulation of the heart rate. The aim of the study was to determine groups of individuals with different risks of Internet addiction (IA) in relation to heart rate variability (HRV) parameters and the efficiency of time estimation in adolescents aged 16–17 years living in the Russian Arctic. Adolescents aged 16–17 years (n = 49–32 females, 17 males) living in Yamalo-Nenets Autonomous Okrug (Russia) were observed. Chen Scale Internet Addiction (CIAS) was used. The duration of an individual 1 min was determined. HRV parameters were determined using the "Varicard" equipment (Russia). In 16–17-year-old adolescents with different levels of risk of developing IA, including signs of IA, we revealed a high severity of symptoms of withdrawal from Internet use, difficulty in time estimation against the background of sympathicotonia and a decrease in vagal regulation of heart rate. In individuals with minimal symptoms of withdrawal from Internet use, the total HRV and vagal activity remain higher than in those with severe withdrawal symptoms, and their time estimation remains effective.

Civil commitment for opioid misuse: do short-term benefits outweigh long-term harms?

In response to a sharp rise in opioid-involved overdose deaths in the USA, states have deployed increasingly aggressive strategies to limit the loss of life, including civil commitment—the forcible detention of individuals whose opioid use presents a clear and convincing danger to themselves or others. While civil commitment often succeeds in providing short-term protection from overdose, emerging evidence suggests that it may be associated with long-term harms, including heightened risk of severe withdrawal, relapse and opioid-involved mortality. To better assess and mitigate these harms, states should collect more robust data on long-term health outcomes, decriminalise proceedings and stays, provide access to medications for opioid use disorder and strengthen post-release coordination of community-based treatment.

Personal Growth and Well-Being in the Time of COVID: An Exploratory Mixed-Methods Analysis

The physical distancing measures necessitated by COVID-19 have resulted in a severe withdrawal from the patterns of daily life, necessitating significantly reduced contact with other people. To many, such withdrawal can be a major cause of distress. But, to some, this sort of withdrawal is an integral part of growth, a pathway to a more enriching life. The present study uses a sequential explanatory QUAN-qual design to investigate whether people who felt that their lives had changed for the better after being forced to engage in physical distancing, what factors predicted such well-being, and how they spent their time to generate this sense of well-being. We invited 614 participants who reported closely following physical distancing recommendations to complete a survey exploring this topic. Our analyses, after controlling for all other variables in the regression model, found a greater positive association between presence of meaning in life, coping style, and self-transcendent wisdom and residualized current well-being accounting for retrospective assessments of well-being prior to physical distancing. An extreme-case content analysis of participants' personal projects found that participants with low self-transcendent wisdom reported more survival-oriented projects (e.g., acquiring groceries or engaging in distracting entertainments), while participants reporting high self-transcendent wisdom reported more projects involving deepening interactions with other people, especially family. Our findings suggest a more nuanced pathway from adversity to a deeper sense of well-being by showing the importance of not merely coping with adversity, but truly transcending it.

High-dose benzodiazepine dependence among health-care professionals: A neglected phenomenon

Chronic use of benzodiazepines (BDZs) is a widespread phenomenon which can lead to side effects such as tolerance, dependence and cognitive impairment, as well as resulting in accidents at work. High-dose BDZ dependence (HD-BDZ) is little studied, and it is mainly attributed to major psychiatric disorders and polydrug abuse. To date, few studies have investigated HD-BDZ among active workers, with none among health-care professionals (HPs). Tapering from high doses of BDZs can cause severe withdrawal symptoms, including seizures. The Addiction Unit of the University Hospital in Verona uses a protocol based on flumazenil slow infusion (FLU-SI), the safest and most effective treatment for HD-BDZ. Since 2003, 1281 patients have been detoxified from long-term use of high doses of BDZ using FLU-SI. The sample includes 139 (10.8%) HPs. Mean daily doses were 336 mg diazepam equivalent among HPs and 365 mg diazepam equivalent among non-HPs (no statistically significant difference). HPs are at higher risk of sleep disorders and work-related stress. Most of these HPs experience difficulties at work due to cognitive impairment, but they are often afraid of the potential legal implications and too ashamed to ask for help. It is important to study the prevalence of HD-BDZ among HPs and to investigate the impact on their working skills and working eligibility.

Neural bases for attenuation of morphine withdrawal by Heantos-4: role of l-tetrahydropalmatine

Severe withdrawal symptoms triggered by cessation of long-term opioid use deter many individuals from seeking treatment. Opioid substitution and α2-adrenergic agonists are the current standard of pharmacotherapy for opioid use disorder in western medicine; however, each is associated with significant complications. Heantos-4 is a non-opioid botanical formulation used to facilitate opioid detoxification in Vietnam. While ongoing clinical use continues to validate its safety and effectiveness, a mechanism of action accounting for these promising effects remains to be specified. Here, we assess the effects of Heantos-4 in a rat model of morphine-dependence and present evidence that alleviation of naloxone-precipitated somatic withdrawal signs is related to an upregulation of mesolimbic dopamine activity and a consequent reversal of a hypodopaminergic state in the nucleus accumbens, a brain region implicated in opioid withdrawal. A central dopaminergic mechanism is further supported by the identification of l-tetrahydropalmatine as a key active ingredient in Heantos-4, which crosses the blood–brain barrier and shows a therapeutic efficacy comparable to its parent formulation in attenuating withdrawal signs. The anti-hypodopaminergic effects of l-tetrahydropalmatine may be related to antagonism of the dopamine autoreceptor, thus constituting a plausible mechanism contributing to the effectiveness of Heantos-4 in facilitating opioid detoxification.

Ambulatory detoxification in alcohol use disorder and opioid use disorder

Ambulatory detoxification in alcohol use disorder and opioid use disorder is an important component in the management of patients experiencing withdrawal symptoms from alcohol or opioids. The goal of withdrawal management is ultimately to provide each patient with comfort and safety. Having the knowledge of the possible signs and symptoms of intoxication and withdrawal assists providers to institute the most appropriate treatment protocol and setting for the patient. Pharmacists play a vital role in choosing appropriate therapeutic management options for common or complex clinical situations involving ambulatory detoxification from alcohol and opioids. Ambulatory detoxification serves as an appealing option to many patients and helps save the limited inpatient resources that many institutions have for those patients with more severe withdrawal presentations.