Severe Withdrawal Research Articles

Effectiveness of the QuitSure Smartphone App for Smoking Cessation: Findings of a Prospective Single Arm Trial.

Digital therapies, especially smartphone apps for active and continuous smoking cessation support, are strongly emerging as an alternative smoking cessation therapy. In the Indian context, there is a growing interest in the use of app-based smoking cessation programs; however, there is limited evidence regarding their effectiveness in achieving long-term continuous abstinence. This study aimed to evaluate the long-term abstinence effect (up to 30-d abstinence postprogram completion) of a smartphone app, QuitSure, for smoking cessation in active smokers from India. In this prospective single-arm study, participants who signed up for the QuitSure app were enrolled in this study. The primary end point was the prolonged abstinence (PA) rate from weeks 1 to 4 (day 7 to day 30). Furthermore, data for withdrawal symptoms, relapse reasons, and reasons for not continuing the program were also assessed. The quit rate was calculated considering only the participants who followed up and completed the survey sent to them (per protocol) at day 7 and at day 30, respectively. The PA rate at day 7 was found to be 64.5% (111/172; 95% CI 56% to 72%), and the PA rate at day 30 was found to be 55.8% (72/129; 95% CI 45% to 65%). Within the 7-day abstinence period, 60.4% (67/111) of the participants did not have any withdrawal symptoms. The most common mild withdrawal symptoms were mild sleep disturbance (21/111, 18.9%), mild digestive changes (19/111, 17.1%), and coughing (17/111, 15.3%). Severe withdrawal symptoms were rare, with only 5.4% (6/111) experiencing them. For those achieving 30-day postprogram abstinence, 85% (61/72) had no mild withdrawal symptoms, and 99% (71/72) had no severe withdrawal symptoms. Among successful quitters at day 7, a total of 72.1% (80/111) reported minimal to no cravings, which increased to 88% (63/72) at day 30. Furthermore, 78% (56/72) of those with PA at day 30 reported no change in weight or reduced weight. Among participants experiencing relapse, 48% (28/58) cited intense cravings, 28% (16/58) mentioned facing a tragedy, and 26% (15/58) reported relapsing due to alcohol consumption. The PA rates as a result of the QuitSure program were found to be better than those reported in the results of other smoking-cessation app programs' studies. The QuitSure app yields high PA rates and ameliorates symptoms associated with smoking cessation. In order to obtain conclusive evidence regarding the effectiveness and efficacy of the QuitSure program, future research should include appropriate control measures. Nevertheless, the QuitSure program can serve as a valuable adjunct to a conventional smoking cessation treatment program to aid sustained abstinence.

Relevance, recovery and recuperation: A prelude to ring withdrawal

In this paper, we introduce recuperative withdrawals, belief change operators that satisfy recuperation, a postulate weaker than recovery, all the AGM postulates for contraction except recovery and another postulate which is a slightly stronger condition than conjunctive inclusion. Furthermore, we present a constructive definition for a class of operators —named ring withdrawals— which are such that the outcome of a ring withdrawal of a belief set K by a sentence α is obtained by adding to the set of most plausible models ‖K‖ all the worlds which are as close to ‖K‖ as its closest ¬α-worlds. Ring withdrawals satisfy the Lindström and Rabinowicz's interpolation thesis. We show that the classes of recuperative withdrawals and of ring withdrawals are identical. Additionally we show that the class of ring withdrawals is not contained in and does not contain the class of AGM contractions or the class of severe withdrawals. Finally we present methods for defining an operator of ring withdrawal by means of a severe withdrawal operator and by means of an AGM contraction operator, and vice-versa.

Trihexyphenidyl Alters Its Host's Metabolism, Neurobehavioral Patterns, and Gut Microbiome Feedback Loop-The Modulating Role of Anacyclus pyrethrum.

Trihexyphenidyl (THP)-a synthetic anticholinergic medication used to manage parkinsonism and extrapyramidal symptoms-has gained significant clinical recognition. However, there is a critical gap in understanding its withdrawal effects. This study investigates the intricate interplay between gut microbiota and oxidative stress during THP withdrawal. Furthermore, it explores the therapeutic potential of Anacyclus pyrethrum (AEAP) for alleviating the associated adverse effects. This comprehensive research combines behavioral tests, biochemical analysis, gut microbiome assessment utilizing matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and oxidative stress measures. The results reveal that the chronic administration of THP leads to severe withdrawal syndrome, marked by heightened anxiety, depressive-like behaviors, increased cortisol levels, elevated oxidative stress, and gut dysbiosis. However, the administration of AEAP alongside THP shows a significant capacity to mitigate these deleterious effects. Co-treatment and post-treatment with AEAP increased bacterial density and diversity, promoting the proliferation of beneficial bacteria associated with improved gut health. Furthermore, AEAP administration reduced cortisol levels and exhibited potent antioxidant properties, effectively countering the THP-induced oxidative damage. This study highlights the withdrawal effects of THP and underscores the therapeutic potential of AEAP for managing these symptoms. The findings reveal its promising effects in alleviating behavioral and biochemical impairments, reducing oxidative stress, and restoring gut microbiota, which could significantly impact the clinical management of THP withdrawal and potentially extend to other substance withdrawal scenarios.

Impacts of xylazine on fentanyl demand, body weight, and acute withdrawal in rats: A comparison to lofexidine

The opioid use landscape has recently shifted to include xylazine, a veterinary anesthetic, as an adulterant in the fentanyl supply. The health impacts of xylazine as an emerging fentanyl adulterant has raised alarm regarding xylazine as a public health threat, warranting research on the impacts of xylazine on fentanyl's behavioral effects. No prior studies have evaluated the effects of xylazine on fentanyl consumption at various unit doses, fentanyl demand, or withdrawal as compared to the Food and Drug Administration-approved opioid withdrawal medication, lofexidine (Lucemyra®). This is important because lofexidine and xylazine are both adrenergic α2a (A2aR) agonists, however, lofexidine is not a noted fentanyl adulterant. Here we evaluated xylazine and lofexidine combined with self-administered fentanyl doses in male and female rats and evaluated fentanyl demand, body weight, and acute withdrawal. Consumption of fentanyl alone increased at various unit doses compared to saline. Xylazine but not lofexidine shifted fentanyl consumption downward at a number of unit doses, however, both lofexidine and xylazine suppressed fentanyl demand intensity as compared to a fentanyl alone control group. Further, both fentanyl + lofexidine and fentanyl + xylazine reduced behavioral signs of fentanyl withdrawal immediately following SA, but signs increased by 12 h only in the xylazine co-exposed group. Weight loss occurred throughout fentanyl SA and withdrawal regardless of group, although the xylazine group lost significantly more weight during the first 24 h of withdrawal than the other two groups. Severity of weight loss during the first 24 h of withdrawal was also correlated with severity of somatic signs of fentanyl withdrawal. Together, these results suggest that body weight loss may be an important indicator of withdrawal severity during acute withdrawal from the xylazine/fentanyl combination, warranting further translational evaluation.

Factors Associated with Psychotic and Depressive Symptoms in Methamphetamine Users.

Objective: Methamphetamine use has been recognized as a prominent public health issue, which is associated with psychotic and depressive symptoms. This study aimed to assess factors that show a significant relation with psychotic and depressive symptoms in adults who use methamphetamine. Method : We assessed 95 patients who had used methamphetamine within the last month and were admitted to the outpatient treatment clinic. Evaluation of all patients was carried out through face-to-face interviews, and their symptoms were evaluated using different scales. The Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms were employed to assess positive and negative symptoms of psychosis, respectively. Depressive symptoms were measured using the Montgomery-Asberg Depression Rating Scale, while illness severity was evaluated using the Clinical Global Impression- Severity Scale. Additionally, functioning status was assessed using the Functioning Assessment Short Test, and withdrawal severity was measured by employing the Amphetamine Cessation Symptom Assessment Scale. Craving severity was evaluated using the Stimulant Craving Questionnaire, anxiety severity using the Hamilton Anxiety Rating Scale, and insight status using the Schedule for Assessment of Insight Expanded. Results: Among the demographic variables, working with family was associated with lower positive symptoms scores (OR = 6.31, P < 0.05). Parole/probation related admissions were associated with lower positive and depressive symptoms scores (OR = 15.06, P = 0.03; OR = 9.87, P = 0.02). Having suicide attempts, number of suicide attempts, and amount of methamphetamine used were found to show association with higher positive (OR = 13.59, P < 0.01; OR = 2.52, P < 0.05; OR = 3.48, P < 0.05, respectively) and depressive symptoms scores (OR = 10.35, P < 0.001; OR = 2.23, P < 0.01; OR = 2.3, P < 0.05). After adjusting for all variables, clinical impression and insight scores remained significantly associated with positive symptoms scores (AOR = 6.74, P < 0.05; AOR = 2.63, P < 0.001, respectively), while anxiety, amphetamine cessation, and positive symptoms scores remained associated with depressive symptoms scores (AOR = 0.48, P < 0.001; AOR = 0.11, P = 0.003; AOR = 0.36, P = 0.02, respectively). Conclusion: This study appears to be the first to examine the associations between clinical variables and both positive symptoms and depressive symptoms in methamphetamine users. Increased attention should be paid to suicide history, anxiety level, amount of methamphetamine use and loss of insight to provide effective treatment in patients with methamphetamine use.

Examining predictors of cocaine withdrawal syndrome at the end of detoxification treatment in women with cocaine use disorder

BackgroundDetoxification is frequently recommended as a treatment for moderate to severe Cocaine Use Disorder (CUD). However, the response to detoxification varies among patients, and previous studies have focused mostly on patterns of drug use behavior to test associations with treatment outcomes, overlooking the potential impact of psychosocial factors, other clinical variables, and individual life experiences. In this study we comprehensively examined several variables aiming to find the most relevant predictors to classify patients with severe versus non-severe cocaine withdrawal symptoms at the end of detoxification. Methods: Data from 284 women with CUD who enrolled in a 3-week detoxification program was used in this longitudinal study. Psychosocial, clinical, and drug use behavior characteristics were evaluated, generating a dataset with 256 potential predictors. We tested six different machine learning classification algorithms. Results: The best classification algorithm achieved an average accuracy and ROC-AUC of approximately 70%. The 16 features selected as best predictors were the severity of psychiatric, family, and social problems and the level of exposure to childhood maltreatment. Features associated with drug-use behavior included days consuming drugs and having craving symptoms in the last month before treatment, number of previous drug/alcohol-related treatments, and a composite score of addiction severity. The level of cocaine withdrawal syndrome at the beginning of detoxification was also a key feature for classification. A network analysis revealed the pattern of association between predictors. Conclusion: These variables can be assessed in real-world clinical settings, potentially helping clinicians to identify individuals with severe cocaine withdrawal that is likely to be sustained over the course of detoxification.

Does phenobarbital reduce the hospital length of stay for patients suffering from severe alcohol withdrawal? A retrospective comparison of phenobarbital to lorazepam infusions

IntroductionData suggest that phenobarbital is as effective as benzodiazepines at managing withdrawal via its direct activation of the gamma-aminobutyric acid receptor and modulating glutamate-mediated stimulation of the N-methyl-D-aspartate receptor. There are little data evaluating the effect of phenobarbital on severe withdrawal syndromes. ObjectiveThe purpose of this study was to evaluate the effect of phenobarbital compared with protocolized, symptom-driven, benzodiazepine administration on hospital length of stay (LOS) in patients experiencing severe withdrawal. MethodsThis is a retrospective chart review of patients evaluated in the emergency department for the treatment of severe alcohol withdrawal syndrome, defined as a Clinical Institute Withdrawal Assessment for Alcohol – Revised score of 20 or greater during their visit. The primary outcome measure was the difference in hospital LOS between those receiving phenobarbital and those receiving continuous lorazepam infusions. Secondary outcomes include intensive care unit (ICU) admission, ICU LOS, need for mechanical ventilation, and incidence of oversedation. ResultsIn all, 298 patients met inclusion, with 131 treated with phenobarbital and 167 initiated on a lorazepam infusion. Hospital LOS was found to be statistically significantly greater in the lorazepam infusion cohort (7.6 ± 5.3 vs. 5.2 ± 4.5 days, P < 0.001) than the phenobarbital cohort. Patients treated with lorazepam were found to have increased admissions to the ICU (risk ratio [RR] 1.79 [95% CI 1.27–2.92]) and higher rates of oversedation (RR 1.71 [95% CI 2.09–4.25]). There were no differences in ICU LOS and need for mechanical ventilation. ConclusionData from this study suggest that phenobarbital may be associated with a decrease in hospital LOS in severe alcohol withdrawal and should be considered as an alternative to benzodiazepine infusions in these patients.

Establishing the safety of phenobarbital treatment of alcohol withdrawal syndrome on general medical wards: A retrospective cohort study

IntroductionConcern about adverse effects from phenobarbital limits its use in treating alcohol withdrawal syndrome (AWS) on general medical wards. Benzodiazepines are the recommended treatment for inpatient management of AWS, yet a subset of patients have an inadequate response or experience complications of AWS despite treatment with benzodiazepines. Data supporting an alternative treatment are needed. We set out to estimate the rate of serious adverse events (SAEs) of phenobarbital treatment for AWS on general medical wards. MethodsRetrospective cohort study of all general medical ward patients hospitalized at a single tertiary urban VA Medical Center from October 2018–May 2021 who received phenobarbital for treatment of AWS. Primary outcomes were SAEs attributed to phenobarbital and treatment failure. SAEs were defined as ICU transfer or intubation for over-sedation, pneumonia, and death. Treatment failure was defined as progression of withdrawal resulting in seizure, ICU transfer, behavioral emergencies, or death. ResultsDuring the study period, phenobarbital was administered in 29% (244) of all AWS hospitalizations. Among them, 93% had a history of AWS hospitalization and 68% had a history of complicated AWS. Fifty-three percent of patients met criteria for moderate, severe, or complicated withdrawal prior to phenobarbital initiation. The mean cumulative dose of phenobarbital per patient was 966.5 mg (13.6 mg/kg). SAEs occurred in 1 of 244 hospitalizations (0.4%): there were no intubations, ICU transfers for oversedation, or deaths due to phenobarbital or AWS. One case of pneumonia was possibly attributable to phenobarbital. Treatment failures (6 ICU transfers, 9 behavioral emergencies) were identified during 12 of 244 hospitalizations (4.9%). ConclusionsSAEs and treatment failures were infrequent among 148 patients treated with phenobarbital across 244 hospitalizations with a mean cumulative dose of 966.5 mg per patient. Our findings suggest that phenobarbital is a safe alternative treatment of AWS in general medical ward patients.

Rapid appearance of negative emotion during oral fentanyl self-administration in male and female rats.

Opioid use disorder has become an epidemic in the United States, fuelled by the widespread availability of fentanyl, which produces rapid and intense euphoria followed by severe withdrawal and emotional distress. We developed a new preclinical model of fentanyl seeking in outbred male and female rats using volitional oral self-administration (SA) that can be readily applied in labs without intravascular access. Using a traditional two-lever operant procedure, rats learned to take oral fentanyl vigorously, escalated intake across sessions, and readily reinstated responding to conditioned cues after extinction. Oral SA also revealed individual and sex differences that are essential to studying substance use risk propensity. During a behavioural economics task, rats displayed inelastic demand curves and maintained stable intake across a wide range of fentanyl concentrations. Oral SA was also neatly patterned, with distinct 'loading' and 'maintenance' phases of responding within each session. Using our software DeepSqueak, we analysed ultrasonic vocalizations (USVs), which are innate expressions of current emotional state in rats. Rats produced 50 kHz USVs during loading then shifted quickly to 22 kHz calls despite ongoing maintenance of oral fentanyl taking, reflecting a transition to negative reinforcement. Using fibre photometry, we found that the lateral habenula differentially processed drug cues and drug consumption depending on affective state, with potentiated modulation by drug cues and consumption during the negative affective maintenance phase. Together, these results indicate a rapid progression from positive to negative reinforcement occurs even within an active drug taking session, revealing a within-session opponent process.

"Alone Again, Naturally": Mental Health Problems, Level of Personality Functioning, Social Withdrawal and Loneliness in Adolescents Admitted as Acute Inpatients in the Aftermath of the COVID-19 Pandemic.

(1) Background: Adolescents admitted as acute inpatients belong to a particularly psychosocially vulnerable population. This study aimed to examine the clinical characteristics of an affected population in Germany using a theory-based approach. (2) Methods: We assessed the mental health problems, levels of personality functioning, and the severity of social withdrawal and loneliness in n = 62 adolescents admitted to an acute psychiatric inpatient unit. Cases were investigated cross-sectionally utilizing standardized psychometric questionnaires from the perspective of the patients and clinical experts. (3) Results: Mental health, level of impaired personality functioning, social withdrawal, and loneliness were all positively associated with the need for acute admission. Further analyses revealed that the level of personality functioning fully mediated the positive association between social withdrawal and mental health problems. In contrast, level of personality functioning only partially mediated the positive association between loneliness and mental health problems. (4) Conclusions: Our results suggest that more impairment in personality functioning might lead to poorer mental health when adolescents socially withdraw in the aftermath of the COVID-19 pandemic. Loneliness, social withdrawal, and the level of personality functioning may help identifying essential characteristics of adolescents admitted to acute psychiatric inpatient units and guide the development of specific interventions.

Adverse childhood experiences: impacts on adult mental health and social withdrawal.

Adverse childhood experiences (ACEs) have been found to negatively impact adult mental health outcomes. Numerous studies have highlighted on ACEs in family and community settings. However, few have examined the impact of ACEs in school settings, despite the potential influence on social participation. Hikikomori, characterized by severe social withdrawal, was first studied in Japan and has gained recognition in recent years. The present study aims to present the concept of ACEs specific to schools and investigate the impact of both school ACEs and traditional ACEs on adult mental health and Hikikomori. A total of 4,000 Japanese adults, aged 20-34, were recruited through an Internet survey form. All data were obtained in October 2021. Participants answered questions regarding their ACEs in the family (10 items), school ACEs (five teacher-related items and two bullying-related items), depressive/anxiety symptoms, and Hikikomori (remaining at home for more than 6 months). A significant association with depressive/anxiety symptoms was shown in both ACEs and school ACEs. An increase of one point in the ACE scores was associated with a 24% increase in the risk of depressive/anxiety symptoms. School ACE scores also demonstrated a significant association with depressive/anxiety symptoms, with an increase of one point associated with a 44% increase in the risk of these symptoms. As for Hikikomori, a significant association was shown in the school ACEs only: a 29% increased risk of Hikikomori for every one-point increase in school ACE scores. Both school ACE scores for teacher-related and bullying-related factors revealed a significant association with Hikikomori; the rates of increased risk were 23 and 37%, respectively. These results suggest that school ACEs, rather than ACEs in the family, are associated with the risk of Hikikomori. School ACEs are important for social adaptation, and reducing traumatic experiences in school settings may have the potential to prevent problems in later life, specifically in terms of social participation.

Hikikomori (Severe Social Withdrawal) in Italian Adolescents: Clinical Features and Follow-Up.

Severe social withdrawal, including staying alone in one's bedroom, non-attendance at school or work, and minimal or absent social contacts, sometimes only through electronic devices, can be found in several psychiatric disorders, or in a 'primary' form, firstly defined in Japan as 'Hikikomori'. The distinction between primary and secondary forms is questionable, as it prevalently depends on the quality of psychiatric assessment. To date, few studies specifically explored Hikikomori in an adolescent population outside Japan. The aim of the present study is to describe clinical features of a consecutive group of 80 referred youth (13 to 18 years, 57 males) with social isolation, of which 40 were followed up on for 4-6 months, to characterize clinical features and outcome. All the participants presented psychiatric comorbid disorders, prevalently anxiety disorders, mood disorders, and autism spectrum disorder. Suicidality (ideation and behavior) was reported in 32.5% of the participants, and 20% of the participants attempted suicide. More than half of the participants exceeded the cut-off of the Internet Addiction Test, and 42.4% met the criteria for the Internet Gaming Disorder. At the follow-up appointment, an improvement of social withdrawal was reported in 75% of the sample; 67.5% of the participants significantly improved according to the CGI-improvement scale; and 55% of the participants had an improvement of functioning according to the C-GAS. Our findings suggest that Hikikomori is a transnosographic entity, with high rates of suicidality and Internet addiction, and that can it improve when it is timely diagnosed and treated.

Prenatal Substance Abuse: a 1-Year Single-Center Experience at a Tertiary Neonatal Intensive Care Unit

Objective: Eight newborns diagnosed with prenatal substance abuse were evaluated for the clinical course of neonatal abstinence syndrome depending on the type of substances used by their mothers during pregnancy. Material and Methods: A retrospective study of neonates with prenatal substance abuse admitted to our tertiary care university hospital’s Neonatal Intensive Care Unit (NICU) was conducted between February 2022 and March 2023. Demographic data, withdrawal symptoms, need for pharmacological treatment, and duration of hospitalization were collected. Newborns exposed to substances were divided into two groups: opioid and non-opioid (methamphetamine, Bonsai, marijuana). Results: Eight infants were included in the study. Four cases (50%) were in the group exposed to opioids. Pregnant users of opioids were older (28±6.73) than non-opioid substance users (21±4.83). The mean birth weight of newborns exposed to opioids (2541 g) was lower than that of the non-opioid group (3020 g). The average length of hospital stay was longer in the opioid group (34 days) compared to the non-opioid group (10 days). All newborns exposed to substances were born preterm (&amp;lt;37 gestational weeks). Withdrawal symptoms were observed in all cases in the opioid group and three cases in the non-opioid group to varying degrees. Medical treatment was required in three out of the seven cases with withdrawal symptoms. All patients requiring treatment were in the opioid group. All infants were discharged in good health. Conclusion: Substance exposure during the prenatal period is a significant cause of preterm birth in neonates. Many of these substances can cause varying degrees of withdrawal syndrome in newborns. Replacement therapies used during pregnancy containing heroin and naloxone can lead to a more severe, prolonged, and treatment-requiring neonatal withdrawal syndrome than other substances. In cases where morphine and methadone are unavailable, the symptoms of withdrawal syndrome can be managed with phenobarbital. It is crucial to monitor all newborns with prenatal exposure to substances early because it allows for appropriate intervention and treatment.

Assessment of alcohol withdrawal syndrome: new perspectives

Alcohol withdrawal syndrome is one of the most important consequences of alcohol use disorder, a complex neuropsychiatric disorder, which is firstly treated in non-specific and secondly in psychiatric/addictive in- or outpatient units. On the other hand, alcohol withdrawal syndrome is one of the most important outcomes of the severity of alcohol use disorder, further, it can lead to the development of alcohol-related seizure and delirium tremens. Hence, early recognition and optimal treatment of alcohol withdrawal syndrome have a critical importance. Therefore, the main goal of the present review was - by systematically summarizing the scientific data published during the past two decades - to form a unique diagnostic and therapeutic algorithm. During the recognition and the course of alcohol withdrawal syndrome, the Clinical Institute Withdrawal Assessment for Alcohol, Revised scale, while in the risk assessment the Prediction of Alcohol Withdrawal Severity Scale are the recommended psychometric tools. Benzodiazepines are the key elements of the pharmacotherapy of alcohol withdrawal syndrome. Many studies have evaluated that diazepam, chlordiazepoxide, lorazepam and oxazepam with distinct indications have sufficient evidence in the treatment of alcohol withdrawal syndrome. However, in the past few years some authors have recommended the importance of non-benzodiazepine medications. The efficacy of propofol, phenobarbital, carbamazepin, oxcarbamazepin and alpha-2 receptor agonists in the treatment of alcohol withdrawal syndrome have been revealed. Furthermore, it has been evaluated that benzodiazepines are recommended in the treatment of alcohol-related seizure and delirium tremens. In the present review, our aim was to construct a unique, up-to-date diagnostic and therapeutic algorithm by summarizing the related papers published during the past two decades. Hence this scheme may be useful in the optimal treatment of patients diagnosed with alcohol use disorder and it could help to conduct further clinical researches. Orv Hetil. 2023; 164(38): 1487-1496.

Predictors of Escalation to Intensive Care Unit Level of Care Among Admissions for Alcohol Withdrawal.

According to the 2019 National Survey on Drug Use and Health, 14.5 million people ages 12 and older had alcohol abuse disorder. Alcohol withdrawal syndrome (AWS) can be defined as a collection of physical symptoms experienced due to abrupt cessation of alcohol after long-term dependence. In instances where regular inpatient management fails to control AWS symptoms, patients are shifted to intensive care units (ICUs) for closer monitoring and prevention of life-threatening complications like withdrawal seizures and delirium tremens (DTs), labeled as severe alcohol withdrawal syndrome (SAWS). Although this represents a significant healthcare burden, minimal studies have been conducted to determine objective predictors. In this study, we aim to determine the effect of patient demographics, socio-economic status, biochemical parameters, and clinical factors on the need for escalation to ICU level of care among admissions for AWS. Our study showed that factors such as a history of DTs or alcohol-related seizures, the initial protocol of management, degree of reported alcohol usage, activation of rapid response teams, mean corpuscular value, alcohol level on admission, highest Clinical Institute Withdrawal Assessment Alcohol Revised (CIWA-Ar) scored during the hospital stay, and the total amount of sedatives used were significantly associated with escalation to ICU level of care. Clinicians must use these objective parameters to identify high-risk patients and intervene early. We encourage further studies to establish a scoring algorithm incorporating biochemical parameters to tailor management algorithms that might better suit high-risk patients.

Sex Differences in Cannabis Use and Effects

Cannabis, the most widely used illicit substance globally, has seen a significant increase in usage, driven by the growth of the cannabis industry and evolving public opinion on potential risks. Understanding the differential effects of cannabis on males and females is becoming increasingly significant. This paper aims to investigate the sex differences in cannabis use, including patterns, motivations, and physiological responses, and their impact on health and well-being. Usage patterns exhibit variations between genders, with men using cannabis more frequently, in larger quantities, and starting at a younger age. Conversely, women tend to experience a "telescoping effect," progressing more rapidly from initial use to dependence. Sex differences are observed in the effects of cannabis, including increased heart rate and heightened sensitivity in women, and long-term consequences like Cannabis Use Disorder (CUD) and cognitive impairment in men. Cannabis use has also been linked to negative effects on reproductive health in women, as well as sexual function and testosterone levels in men. Mental health concerns are also prevalent, with women at a higher risk of developing dependence and experiencing severe withdrawal symptoms. Conversely, heavy cannabis use may exacerbate anxiety and depression in men. Further research is imperative to inform the general population and the healthcare industry, enabling informed decision-making regarding the potential benefits and risks of cannabis use. This knowledge will facilitate the development of gender-specific prevention and treatment strategies for cannabis use disorders, promoting the overall well-being of individuals.

A Comparison of Injectable Diazepam and Lorazepam in the Goal-Directed Management of Severe Alcohol Withdrawal.

Benzodiazepines are the gold standard for treatment of alcohol withdrawal, yet the selection of a preferred benzodiazepine is limited due to a lack of comparative studies. The primary objective of this study was to compare the efficacy and safety of injectable lorazepam (LZP) and diazepam (DZP) in the treatment of severe alcohol withdrawal syndrome (AWS). Retrospective cohort study of adult patients admitted to an intensive care unit with a primary diagnosis of AWS. Subjects who received at least 12 LZP equivalent units (LEU) of injectable DZP or LZP within 24 hours of initiation of the severe AWS protocol were included. The primary outcome was time with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scores at goal over the first 24 hours of treatment. A total of 191 patients were included (DZP n = 89, LZP n = 102). Time with CIWA-Ar scores at goal during the first 24 hours was similar between groups (DZP 12 hours [interquartile range, IQR, = 9-15] vs LZP 14 hours [IQR = 10-17]), P = 0.06). At 24 hours, LEU requirement was similar (DZP 40 [IQR = 22-78] vs LZP 32 [IQR = 18-56], P = 0.05). Drug cost at 24 hours was higher in the DZP group ($204.6 [IQR = 112.53-398.97] vs $8 [IQR = 4.5-14], P < 0.01). DZP or LZP are equally efficacious for the treatment of severe AWS. LZP may be preferred due to cost but both medications can be used interchangeably based on availability.

The gut microbiome contributes to somatic morphine withdrawal behavior and implicates a TLR2 mediated mechanism

ABSTRACT The ongoing opioid epidemic has left millions of people suffering from opioid use disorder due to the over-prescription of highly addictive substances. Chronic opioid exposure leads to dependence, where the absence of the drug results in negative symptoms of withdrawal, often driving patients to continue drug use; however, few therapeutic strategies are currently available to combat the cycle of addiction and the severity of morphine withdrawal. This study investigates the microbiome as a potential therapeutic target for morphine withdrawal, as gut dysbiosis caused by morphine use has been proven to contribute to other aspects of opioid use disorders, such as tolerance. Results show that although the microbiome during morphine withdrawal trends toward recovery from morphine-induced dysbiosis, there continues to be a disruption in the alpha and beta diversity as well as the abundance of gram-positive bacteria that may still contribute to the severity of morphine withdrawal symptoms. Germ-free mice lacking the microbiome did not develop somatic withdrawal symptoms, indicating that the microbiome is necessary for the development of somatic withdrawal behavior. Notably, only TLR2 but not TLR4 whole-body knockout models display less withdrawal severity, implicating that the microbiome, through a gram-positive, TLR2 mediated mechanism, drives opioid-induced somatic withdrawal behavior.

Associations Between Childhood Trauma and Tobacco Use Outcomes in Adults after Overnight Abstinence.

Childhood trauma is known to be associated with nicotine dependence, yet limited smoking outcomes have been examined and few studies have assessed associations between specific trauma subscales and smoking. Additionally, sex differences in trauma-smoking relations are understudied. This study examined associations between childhood trauma and several smoking-related outcomes in adults who smoke after overnight abstinence. People who smoke (N = 205) completed self-report and biochemical assessments evaluating childhood trauma, affect, nicotine dependence, smoking urges, withdrawal, and plasma cortisol and cotinine levels. Smoking outcomes were compared between those with and without a history of moderate to severe childhood trauma among the total sample and by sex. Relative to those with no to minimal abuse, those with moderate to severe abuse had higher negative affect, withdrawal severity, and plasma cotinine levels. Exploratory analyses revealed that women were more likely than men to have urges to smoke for negative reinforcement and have higher withdrawal severity, but no interactions between abuse group and sex were observed. Examining specific trauma subscales, the moderate to severe emotional abuse group had more severe nicotine dependence, negative affect, and withdrawal compared to the no to minimal group. The moderate to severe sexual abuse group had more severe nicotine dependence and withdrawal compared to the no to minimal group. Exposure to childhood trauma is associated with more severe nicotine dependence, negative affect, withdrawal, and higher plasma cotinine levels. Findings also indicate that different types of trauma may differentially affect smoking behaviors. This study of adults who smoke finds that childhood trauma history may be a marker for smoking susceptibility and suggests that individuals with experiences of emotional and sexual abuse may require targeted forms of smoking cessation interventions. Moreover, findings suggest that smoking risks may differ for men and women. Findings inform public health interventions intended to reduce cigarette use in individuals with exposure to childhood trauma.

Interactive effects of financial strain and distress tolerance on prequit tobacco withdrawal symptoms in smokers preparing to initiate a quit attempt.

Smokers experiencing greater financial strain are less likely to successfully quit smoking, possibly due to greater severity of tobacco withdrawal. However, limited research has explored whether individual-level psychological factors (i.e., distress tolerance) may buffer the deleterious effects of financial strain on withdrawal. This study examined the main and interactive effects of financial strain and distress tolerance on tobacco withdrawal experienced prior to quitting smoking among smokers preparing to initiate a quit attempt. Fifty-nine adult smokers completed a baseline session including a financial strain measure and subjective and behavioral assessments of distress tolerance. Participants were then instructed to initiate a quit attempt, without any behavioral or pharmacological assistance, 14 days following baseline. Prequit tobacco withdrawal symptoms were assessed once per day for 3 days prior to quit date. Linear regression models tested main and interactive effects between financial strain and distress tolerance on experiences and perceptions of prequit withdrawal. Findings demonstrated significant interactions between financial strain, distress tolerance, and perceptions of tolerating withdrawal. Negative associations found between higher distress tolerance and lower perceptions of tobacco withdrawal and negative mood as being "intolerable" prior to quitting were stronger for those experiencing greater levels of financial strain. Financial strain may negatively impact one's perceived ability to tolerate mood- and tobacco-related withdrawal prior to quitting. Yet, higher distress tolerance may buffer the effects of financial strain on smoking cessation processes. Psychosocial interventions designed to promote tolerance of distress from both internal and external stressors may benefit cessation efforts among smokers experiencing high financial strain. (PsycInfo Database Record (c) 2023 APA, all rights reserved).