BACKGROUND: Worldwide, three million deaths each year are reported due to the harmful use of alcohol. To date, only a few drugs have been approved for the treatment of Alcohol Use Disorder (AUD). This systematic review and meta-analysis aim to assess the long-term efficacy and safety of sodium oxybate (SMO) treatment in patients with AUD.
METHODS: We followed the PRISMA statement guidelines and searched PubMed and ISI Web of Science to retrieve the studies of interest. In total, 13 studies on long-term (>12 weeks) SMO administra- tion in patients with AUD were included in this systematic review, and 7 were included in the meta- analysis.
RESULTS: Overall, the abstinence rate after 12 weeks of treatment was similar in the SMO and placebo groups, while it was significantly in favour of SMO compared to Naltrexone (NTX). The completion rate was similar in all three conditions. Mean corpuscular volume (MCV) levels favoured SMO over NTX, while Alcohol Craving Scale (ACS) scores did not favour SMO. The incidence of adverse reactions varied widely between studies.
CONCLUSIONS: SMO in the chronic treatment of patients with AUD showed no superiority to placebo in our analysis of published RCTs, although many observational studies reported its beneficial effect in the long term. On the contrary, SMO was superior to NTX treatment on abstinence. The rate of study completion was similar in the three groups. Safety was not an issue in any of the studies included. Further studies are needed to better assess SMO efficacy and safety in the long term.

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BACKGROUND: Pharmacist-led smoking cessation programs in pre-admission clinics (PAC) have shown to increase quit attempts and achieve abstinence by the day of surgery (DOS).
OBJECTIVE: To evaluate the feasibility of Pharmacist E-script Transcription Service (PETS) initiated nicotine replacement therapy (NRT) in PAC, including smoking cessation on DOS.
METHODS: A single centre, pre and post-intervention pilot study conducted at an Australian public hospital PAC. In a two-month intervention period, PAC nursing staff invited smokers (≥1 cigarette/day) to see a smoking cessation PET pharmacist. Pharmacist-initiated NRT and Quitline© referrals were offered. Cessation outcomes were compared with the preceding two-month control period.
METHODS: feasibility of intervention.
RESULTS: DOS smoking abstinence rates and three-months post-surgery.
RESULTS: PAC nurses identified 112 smokers over 4 months; 53 during pre-intervention period, and 59 during intervention period. Twenty-two intervention patients (37%) accepted seeing the pharmacist, with 16 subsequent Quitline© referrals (73%) and 11 NRT prescriptions (50%) written. The median nursing smoking status documentation time increased in the intervention period (1 min vs. 4, p < .001). The intervention did not impact pharmacist\'s workload. Verified abstinence increased from 8.5% (4/47) pre-intervention to 9.4% (5/53) post-intervention, p =1.00. Relapse rates in the intervention period increased (20% vs. 50%) at three-months post-surgery.
CONCLUSIONS: A PETS-initiated NRT program in PAC is feasible and increased preoperative use of NRT and Quitline© with minimal impact on smoking cessation. SO WHAT?: This study has highlighted the importance of implementing a multidisciplinary smoking cessation program in PAC however, larger studies are needed to determine the true impact of the program on smoking cessations.

BACKGROUND: Anxiety during early alcohol abstinence, likely resulting from neural changes caused by chronic alcohol use, contributes to high relapse rates. Studies in rodents show heightened activation during early abstinence in the bed nucleus of the stria terminalis (BNST)-a neural hub for anxiety-and its extended anxiety-related corticolimbic network. Despite the clinical importance of early abstinence, few studies investigate the underlying neural mechanisms.
METHODS: To address this gap, we investigated brain function in early alcohol abstinence (EA = 20, 9 women) relative to controls (HC = 20, 11 women) using an unpredictable threat task shown to engage the BNST and corticolimbic brain regions involved in anxiety and alcohol use disorder (AUD). Group, anxiety, and sex were predictors used to determine whole-brain activation and BNST functional connectivity.
RESULTS: We found widespread interactions of group × anxiety and group × anxiety × sex for both activation and BNST connectivity during unpredictable threat. In the EA group, higher anxiety was correlated with activation in the BNST, rostral anterior cingulate cortex (ACC), insula (men only), and dorsal ACC (men only). In the HC group, higher anxiety was negatively correlated with activation in the BNST, nucleus accumbens, thalamus, and insula (men only). For connectivity, anxiety was positively correlated in EA and negatively correlated in HC, between the BNST and the amygdala, ventromedial prefrontal cortex (PFC), and dorsomedial PFC; EA men showed stronger BNST-vmPFC connectivity than HC men.
CONCLUSIONS: These novel findings provide preliminary evidence for alterations in the BNST and anxiety-related corticolimbic brain regions in early alcohol abstinence, adding to growing literature in humans supporting the BNST\'s role in anxiety and sex-dependent effects of chronic alcohol use.

BACKGROUND: Previous research literature reported different results regarding the long-term effects that cannabis use can exert on the frontal lobe neurocognitive functions of its users. Another body of research suggested that cannabis use negatively affects the person\'s general level of occupational and psychosocial functioning consequently to these alterations. Some other research results did not support these findings. To date, it is still debatable whether chronic cannabis use triggers negative neurocognitive effects in chronic users even after a period of abstinence. Research data exploring consequent adverse outcomes on the general individual occupational and psychosocial functioning is not yet conclusive.
RESULTS: We conducted this study to examine the residual neurocognitive effects of cannabis use, whether it is affected by duration of cannabis use before abstinence, and its relation to individual\'s global assessment of functioning exhibited in the person\'s occupational and social life whether it\'s family or friends. Our sample comprised 80 male participants (18-45 years old) who were grouped into 4 groups (3 groups with different durations of use and a control group), with no significant difference between the four studied groups regarding age, education, and socioeconomic level. The Kruskal Wallis test was used to test the significance of differences in the distribution of total frontal lobe battery results and the general assessment of function scores using GAF scores between study groups. Post hoc testing was performed to adjust for multiple comparisons using Bonferroni method.
CONCLUSIONS: Data analysis showed that cannabis users experienced general functional disturbances that encompass impairments in social and occupational life aspects. These impairments in function are correlated with the presence of neurocognitive deficits even after a period of abstinence. Both having significant positive correlation with longer duration of cannabis use.

In recent years, astrocytes have been increasingly implicated in cellular mechanisms of substance use disorders (SUD). Astrocytes are structurally altered following exposure to drugs of abuse; specifically, astrocytes within the nucleus accumbens (NAc) exhibit significantly decreased surface area, volume, and synaptic colocalization after operant self-administration of cocaine and extinction or protracted abstinence (45 days). However, the mechanisms that elicit these morphological modifications are unknown. The current study aims to elucidate the molecular modifications that lead to observed astrocyte structural changes in rats across cocaine abstinence using astrocyte-specific RiboTag and RNA-seq, as an unbiased, comprehensive approach to identify genes whose transcription or translation change within NAc astrocytes following cocaine self-administration and extended abstinence. Using this method, our data reveal cellular processes including cholesterol biosynthesis that are altered specifically by cocaine self-administration and abstinence, suggesting that astrocyte involvement in these processes is changed in cocaine-abstinent rats. Overall, the results of this study provide insight into astrocyte functional adaptations that occur due to cocaine exposure or during cocaine withdrawal, which may pinpoint further mechanisms that contribute to cocaine-seeking behavior.

Opioid use disorder is marked by a progressive change in the motivation to administer the drug even in the presence of negative consequences. After long periods of abstinence, the urge to return to taking the drug intensifies over time, known as incubation of craving. Conditioned responses to drug-related stimuli, can acquire motivational properties and exert control over motivated behaviors leading to relapse. Although, preclinical data suggest that the behavioral expression of opioid use is similar between male and female rodents, we do not have conclusive results on sex differences on craving and relapse across abstinence periods. Here, we investigated the effects of abstinence from oxycodone self-administration on neurotransmission in the paraventricular thalamus (PVT) to nucleus accumbens shell (NAcSh) pathway in male and female rats. Using optogenetics and ex vivo electrophysiology, we assessed synaptic strength and glutamate release probability in this pathway, as well as NAcSh medium spiny neurons (MSN) intrinsic excitability, in slices from rats which were subjected to either 1 (acute) or 14 (prolonged) days of forced abstinence after self-administration. Our results revealed no sex differences in oxycodone self-administration or somatic withdrawal symptoms following acute abstinence. However, we found a sex-specific enhancement in cue-induced relapse after prolonged, but not acute, abstinence from oxycodone self-administration, with females exhibiting higher relapse rates. Notably, prolonged abstinence led to similar increases in synaptic strength at PVT-NAcSh inputs compared to saline controls in both sexes, which was not observed after acute abstinence. Thus, prolonged abstinence results in a time-dependent increase in PVT-NAcSh synaptic strength and sex-specific effects on cue-induced relapse rates. These findings suggest that prolonged abstinence leads to significant synaptic changes, contributing to heightened relapse vulnerability, highlighting the need for targeted therapeutic strategies in opioid use disorder.

The increasing prevalence of substance misuse in modern culture is contributing to the growth in neonatal abstinence syndrome (NAS) cases in India. NAS can be challenging to diagnose due to nonspecific symptoms and maternal suppression of drug history. Only a few reports of NAS have been published from India. This is a case series of three newborns from India who all had symptoms like restlessness, high-pitched crying, excessive sweating, vigorous sucking, tremors, and diarrhea. The investigations did not lead to any conclusions. In the first case, the mother was treated with a combination of psychotropic medications, including selective serotonin reuptake inhibitors (SSRIs), atypical antipsychotics, and tricyclic antidepressants. In the second case, the mother was a nicotine addict, while in the third case, the mother had an opiate addiction. It was only after being asked several times that the abuse background of the last two cases was revealed. As a result, three cases of NAS were diagnosed, successfully managed with phenobarbitone, and discharged.

Despite extensive preclinical research over the years, a significant gap remains in our understanding of the specific effects of methamphetamine (METH) and amphetamine (AMPH) withdrawal. Understanding these differences could be pivotal to unveiling the unique pathophysiology underlying each stimulant. This may facilitate the development of targeted and effective treatment strategies tailored to the specific characteristics of each substance. Following PRISMA guidelines, this systematic review was conducted to examine alterations in spontaneous locomotor activity, specifically horizontal activity, in animals experiencing withdrawal from extended and repeated administration of AMPH or METH. Original articles were retrieved from four electronic databases, supplemented by a review of the references cited in the published papers. A total of thirty-one full-length articles (n = 31) were incorporated in the analysis. The results indicated that six studies documented a significant increase in horizontal activity among animals, seven studies reported decreased locomotion, and eighteen studies (8 AMPH; 10 METH) reported no significant alterations in the animals\' locomotor activity. Studies reporting heightened locomotion mainly employed mice undergoing withdrawal from METH, studies reporting diminished locomotion predominantly involved rats undergoing withdrawal from AMPH, and studies reporting no significant changes in horizontal activity employed both rats and mice (12 rats; 6 mice). Drug characteristics, routes of administration, animal models, dosage regimens, duration, and assessment timing seem to influence the observed outcomes. Despite more than 50% of papers enlisted in this review indicate no significant changes in the locomotion during the stimulant withdrawal, the unique reactions of animals to withdrawal from METH and AMPH reported by some underscore the need for a more nuanced understanding of stimulant withdrawal.

BACKGROUND: Wearable technology for objective, continuous, and reliable alcohol monitoring has been developed. These are known as transdermal alcohol sensors (TASs). They can be worn on the wrist or ankle with the sensor pressed against the skin and can measure sweat vapors being emitted from the skin, to record transdermal alcohol concentration (TAC). Previous studies have investigated the accuracy and acceptability of the available TAS brands, but there has been little research into their use in people with alcohol use disorders (AUD).
OBJECTIVE: This feasibility randomized controlled trial aims to explore the feasibility, strengths, and limitations of using a TAS to monitor alcohol consumption in individuals in treatment for AUD with or without contingency management (CM) to promote abstinence or low-level alcohol consumption.
METHODS: The target sample size is 30 (15 randomized to each group). Participants will be recruited through poster adverts at alcohol services. Both groups (control and CM) will wear the TAS (BACtrack Skyn) for 2 weeks in the context of their usual treatment, meeting with the researcher every other weekday. In the last meeting, the participants will complete a postwear survey on their experience of wearing the TAS. The CM group will also receive small financial incentives for low or no alcohol consumption, as measured by the TAS. On days where the TAC peak is below a set threshold (<115.660 g/L), CM group participants will be rewarded with a £5 (US $6.38) voucher. There are financial bonuses if this target is achieved on consecutive days. The researcher will monitor TAC for each day of the study at each research visit and allocate financial incentives to participants according to a set reinforcement schedule.
RESULTS: The first participant was enrolled in June 2023, and the last in December 2023. Data analysis is underway and is estimated to be completed by June 2024. A total of 32 participants were enrolled.
CONCLUSIONS: Most TAS brands have had limited application in clinical settings, and most studies have included healthy adults rather than people with AUD. TAS has the potential to enhance treatment outcomes in clinical alcohol treatment. The accuracy, acceptability, and feasibility of TAS for people with AUD in clinical settings need to be investigated. This is the first study to use TAS in specialized alcohol services with diagnosed AUD individuals currently receiving treatment from a south London alcohol service.
BACKGROUND: ISRCTN Registry ISRCTN46845361; https://www.isrctn.com/ISRCTN46845361.
UNASSIGNED: DERR1-10.2196/57653.

Alcohol Use Disorder (AUD) is a growing problem worldwide, causing an incredible burden on health and the economy. Though AUD impacts people of all backgrounds and demographics, increasing evidence has suggested robust sex differences in alcohol drinking patterns and AUD-induced negative emotionality or hyperkatifeia. Rates of problematic drinking have significantly risen among women, and women face more severe negative emotional consequences in abstinence such as increased risk of comorbidity with an anxiety or mood disorder and more severe symptoms of depression. As such, a bevy of preclinical literature using contingent methods of alcohol (ethanol) consumption has amassed in recent years to better understand sex as a biological variable in alcohol drinking and abstinence-induced negative emotionality. Mice are widely used to model alcohol drinking, as they are conducive to genetic manipulation strategies, and many strains will voluntarily consume alcohol. Sex-specific results from these mouse studies, however, have been inconsistent. Therefore, this review aims to summarize the current knowledge on sex differences in AUD-related contingent ethanol drinking and abstinence-induced negative emotionality in mice. Various contingent mouse drinking models and negative emotional-based behavioral paradigms are introduced and subsequently discussed in the context of sex differences to show increasing indications of sex specificity in mouse preclinical studies of AUD. With this review, we hope to inform future research on potential sex differences in preclinical mouse models of AUD and provide mounting evidence supporting the need for more widespread inclusion of preclinical female subjects in future studies.