Duration Of Abstinence Research Articles

Circulating microRNA miR-137 as a stable biomarker for methamphetamine abstinence

ObjectiveStimulant use instigates abstinence syndrome in humans. miRNAs are a critical component for the pathophysiology of stimulant abstinence. Here we sought to identify a miRNA marker of methamphetamine abstinence in the circulating extracellular vesicles (cEVs).MethodsmiR-137 in the cEVs was quantified by qPCR in thirty-seven patients under methamphetamine abstinence and thirty-five age-matched healthy controls recruited from 2014 to 2016 from the general adult population in a hospital setting, Seoul, South Korea. Diagnostic power was evaluated by area under curve in the receiver-operating characteristics curve and other multiple statistical parameters.ResultsPatients under methamphetamine abstinence exhibited a significant reduction in cEV miR-137. Overall, cEV miR-137 had high potential as a blood-based marker of methamphetamine abstinence. cEV miR-137 retained the diagnostic power irrespective of the duration of methamphetamine abstinence or methamphetamine use. Interestingly, cEV miR-137 interacted with age: Control participants displayed an aging-dependent reduction of cEV miR-137, while methamphetamine-abstinent patients showed an aging-dependent increase in cEV miR-137. Accordingly, cEV miR-137 had variable diagnostic power depending on age, in which cEV miR-137 more effectively discriminated methamphetamine abstinence in the younger population. Duration of methamphetamine use or abstinence, cigarette smoking status, depressive disorder, or antidepressant treatment did not interact with the methamphetamine abstinence-induced reduction of cEV miR-137.ConclusionOur data collectively demonstrated that miR-137 in the circulating extracellular vesicles held high potential as a stable and accurate diagnostic marker of methamphetamine abstinence syndrome.

Anger and substance abuse: a systematic review and meta-analysis.

Objective:Conduct a systematic review and meta-analysis to evaluate levels of anger among substance users compared to non-user controls and to analyze the possible association between anger and psychoactive substance use (PSU).Methods:The procedures of this review followed the Meta-Analyzes of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Four electronic databases (MEDLINE, EMBASE, BIREME, PsycINFO) were searched.Results:Twelve studies were included in the meta-analysis; 10 used the State-Trait Anger Expression Inventory (STAXI) anger trait subscale and two used the Buss-Perry-Aggression Questionnaire (BPAQ) anger subscale. The sample included 2,294 users of psychoactive substances and 2,143 non-users, all male. The mean difference in anger scale scores between users and non-users was 2.151 (95%CI 1.166-3.134, p ≤ 0.00, inconsistency index [I2] = 98.83) standard deviations. Age and abstinence duration did not moderate the difference in anger between substance users and non-users.Conclusion:Users of psychoactive substances had elevated anger scores compared to non-users, which represents a high risk of relapse. It is suggested that PSU treatment programs include intensive anger management modules, focusing on factors such as dealing with daily stressors, family conflicts, frustrations, and problems.

Impaired delay discounting and time sensitivity in methcathinone use disorder.

Substance use disorder (SUD) is characterized by continued drug use despite adverse consequences. Methcathinone is a new type of psychoactive substance that is associated with high excitement and impulsive behaviors. However, it is unclear if individuals with methcathinone use disorders (MCUD) are with impaired decision-making ability. We analyzed the task performance in 45 male MCUD subjects and 35 male matched healthy controls (HC) with intertemporal decision-making task. Constant sensitivity discounting model was used to estimate potential changes in both discounting rate and time sensitivity. The results showed that MCUD individuals exhibited a higher delay discounting rate (p = 0.003, Cohen's d = 0.683) and reduced sensitivity to time (p < 0.001, Cohen's d = 1.662). The delay discounting rate was correlated to the first age for drug use (r = - 0.41, p = 0.004), and the time sensitivity was negatively correlated with the duration of abstinence (r = - 0.31, p = 0.036). We conclude that MCUD individuals are with impaired decision-making ability and time perception disturbances.

Retrospective analysis on the effect of duration of ejaculatory abstinence on fertilization, embryo development, and pregnancy rates in patients undergoing conventional in vitro fertilization

Aim: This study aims to find out how different sexual abstinence period influences semen parameters, fertilization, embryo development, and pregnancy rates in patients undergoing conventional in vitro fertilization. Setting and designs: A retrospective analysis was conducted at a tertiary level infertility care clinic. Materials and methods: The clinical study included 532 patients between January 2017 and July 2021 who had been treated with conventional in vitro fertilization. The effect of sexual abstinence on primary outcomes such as semen volume, total sperm concentration, total motile sperm concentration, sperm morphology, and secondary outcomes such as fertilization rate, cleavage rate, top quality day 3 and day 5 embryo development rate, implantation and clinical pregnancy rate between fresh versus frozen embryo transfer on day 3 and day 5 of conventional in vitro fertilization under three groups, that is, sexual abstinence of less than or equal to 1, 2 to 5, and 6 to 7 days was evaluated. Statistical analysis used: Chi-square test was used to evaluate the qualitative variables whereas one-way analysis of variance was used to evaluate the quantitative variables. Results: Group II with 2 to 5 days of abstinence, observed a positive correlation between abstinence period and semen volume, total sperm concentration, total motile sperm concentration, and morphology. Fertilization rate was higher in groups II and III than group I (P = 0.21) with no significant difference in cleavage rate (P = 0.4) and embryo development on day 3 (P = 0.1057). The formation of AA grade blastocyst between group I and group II was 27.54 % and 23.47 %, respectively, with a P-value of 0.007154. Both fresh and frozen embryo transfers of groups II and III of abstinence period had implantation and clinical pregnancy rates of 23.39% and 43.83%, respectively. Conclusion: Our study did not find any significant difference in primary and secondary outcomes of conventional in vitro fertilization between the three groups. We recommend further prospective large randomized control studies to prove any association between duration of abstinence and pregnancy outcomes.

Efficacy and Safety of Baclofen for Treatment of Alcohol Dependence: An Updated Meta-Analysis and Meta-Regression Study

Baclofen is increasingly used for alcohol dependence treatment but its use remains controversial. Therefore, this study aimed to assess the efficacy and safety of baclofen use on alcohol dependence. This is systematic review and meta-analysis of randomized controlled trials. PubMed, Science Direct, Scopus and Thai databases were systematically searched. Randomized controlled trials investigating efficacy and safety of baclofen on alcohol dependence were included. Study selection, data extraction and quality assessment were performed independently by two reviewers. The clinical therapeutic efficacy and adverse events of baclofen were assessed and were pooled using a random-effects model. Heterogeneity was assessed by I2 and chi-squared test. Sixteen studies with 1539 alcohol dependence patients were included. Baclofen increased risk of abstinence (risk ratio=1.32; 95 % confidence interval: 1.12, 1.55; p=0.0006) and abstinence duration (standard mean difference=1.07 d (95 % confidence interval: 0.13, 2.01; p=0.04) significantly. Moreover, baclofen significantly decreased heavy drinking days (standard mean difference=-1.14 d; 95 % confidence interval:-1.95, -0.34; p=0.007). However, there were no significant effects on times to relapse, craving and number of alcohol drinks. No serious adverse event associated with baclofen was reported during treatments. The meta-regression found baclofen dose was significantly associated with craving. This meta-analysis indicated that baclofen treatment in alcohol dependence patients is associated with better outcomes in risk of abstinence, abstinence duration and heavy drinking days. However, larger welldesigned studies are required to confirm these conclusions.

Association of Psychological Distress with Smoking Cessation, Duration of Abstinence from Smoking, and Use of Non-Combustible Nicotine-Containing Products: A Cross-Sectional Population Survey in Great Britain

Association of Psychological Distress with Smoking Cessation, Duration of Abstinence from Smoking, and Use of Non-Combustible Nicotine-Containing Products: A Cross-Sectional Population Survey in Great Britain

Common gray matter loss in the frontal cortex in patients with methamphetamine-associated psychosis and schizophrenia

Background and hypothesisMethamphetamine (MA)-associated psychosis has become a public concern. However, its mechanism is not clear. Investigating similarities and differences between MA-associated psychosis and schizophrenia in brain alterations would be informative for neuropathology. Study designThis study compared gray matter volumes of the brain across four participant groups: healthy controls (HC, n = 53), MA users without psychosis (MA, n = 22), patients with MA-associated psychosis (MAP, n = 34) and patients with schizophrenia (SCZ, n = 33). Clinical predictors of brain alterations, as well as association of brain alterations with psychotic symptoms and attention impairment were further investigated. Study resultsCompared with the HC, the MAP and the SCZ showed similar gray matter reductions in the frontal cortex, particularly in prefrontal areas. Moreover, a stepwise extension of gray matter reductions was exhibited across the MA – MAP – SCZ. Duration of abstinence was associated with regional volumetric recovery in the MAP, while this amendment in brain morphometry was not accompanied with symptom’s remission. Illness duration of psychosis was among the predictive factors of regional gray matter reductions in both psychotic groups. Volume reductions were found to be associated with attention impairment in the SCZ, while this association was reversed in the MAP in frontal cortex. ConclusionsThis study suggested MA-associated psychosis and schizophrenia had common neuropathology in cognitive-related frontal cortices. A continuum of neuropathology between MA use and schizophrenia was tentatively implicated. Illness progressions and glial repairments could both play roles in neuropathological changes in MA-associated psychosis.

The Relationship Between Cannabis, Cognition, and Schizophrenia: It's Complicated.

The consequences of cannabis use, especially in the context of schizophrenia, have gained increased importance with the legalization of cannabis in North America and across the globe. Cannabis use has multifaceted impacts on cognition in schizophrenia patients and healthy subjects. Healthy subjects, particularly those who initiated cannabis use at earlier ages and used high-potency cannabis for longer durations, exhibited poorer cognition mainly in working memory and attention. Cannabis use in schizophrenia has been associated with symptom exacerbation, longer and more frequent psychotic episodes, and poorer treatment outcomes. However, cannabis-using patients have better overall cognitive performance compared to patients who were not cannabis users. Interestingly, these effects were only apparent in lifetime cannabis users, but not in current (or within last 6months) users. Moreover, higher frequency and earlier age of cannabis use initiation (i.e., before 17years of age) were associated with better cognitive performance, although they had an earlier illness onset. Three possible hypotheses seem to come forward to explain this paradox. First, some components of cannabis may have antipsychotic or cognitive-enhancing properties. Secondly, chronic cannabis use may alter endocannabinoid signaling in the brain which could be a protective factor for developing psychosis or cognitive impairments. A third explanation could be their representation of a phenotypically distinct patient group with more intact cognitive functioning and less neurodevelopmental pathology. Multiple factors need to be considered to understand the complex relationship between cannabis, cognitive function, and schizophrenia. In short, age at initiation, duration and rate of cannabis use, abstinence duration, co-use of substances and alcohol, prescribed medications, relative cannabinoid composition and potency of cannabis, presence of genetic and environmental vulnerability factors are prominent contributorsto the variability in outcomes. Animal studies support the disruptive effects of Δ9-tetrahydrocannabinol (THC) administration during adolescence on attention and memory performance. They provide insights about interaction of cannabinoid receptors with other neurotransmitter systems, such as GABA and glutamate, and other regulatory molecules, such as PSD95 and synaptophysin. Cannabidiol (CBD), on the other hand, can improve cognitive deficits seen in neurodevelopmental and chemically-induced animal models of schizophrenia. Future studies focusing on bridging the translational gaps between human and animal studies, through the use of translationally relevant methods of exposure (e.g., vaping), consistent behavioral assessments, and congruent circuit interrogations (e.g., imaging) will help to further clarify this complex picture.

Effectiveness of incorporating contingency management into a public treatment program for people who use crack cocaine in Brazil. A single-blind randomized controlled trial.

Smoked cocaine (i.e., crack use) is a severe health problem in Brazil, with the country being reported as having the largest crack market in the world. The objective of this study was to evaluate the effectiveness of incorporating Contingency Management targeting cocaine abstinence into a public treatment program in Brazil. Single-blind randomized controlled trial conducted at Unidade Recomeço Helvétia (URH), a public ambulatory treatment program for persons who use crack and live in the "Crackland" region in downtown São Paulo, Brazil. In total, 98 treatment-seeking individuals who use crack were randomized to one of two treatment conditions. Participants allocated to the control condition (n=48) received 12 weeks of the standard treatment provided at URH. Participants allocated to the experimental condition (n=50) received the same treatment in combination with Contingency Management (URH+CM). In URH+CM, participants were provided with vouchers with monetary value for submission of negative cocaine urinalysis twice weekly. Compared to the URH group, the URH+CM group was significantly more likely to submit a negative cocaine urinalysis during treatment, with odds ratios ranging from 4.17 to 6.78, depending on how missing data was accounted for (p<0.01). Participants receiving Contingency Management also had higher odds of achieving three or more weeks of continuous abstinence (OR= 8.07; 95% CI [2.48, 26.24]), achieved longer durations of abstinence (B=2.14; 95% CI [0.67, 3.61]), submitted a higher percentage of negative urinalysis (B=19.85; 95% CI [6.89, 32.82]), and were retained in treatment for a longer period (B=3.00; 95% CI [1.04, 4.97]), compared to those receiving URH alone (p<0.01 for all). The incorporation of Contingency Management was effective in promoting cocaine abstinence and treatment retention. The large-scale dissemination of Contingency Management may be an effective strategy to treat Brazilians with cocaine use disorders.

Altered Fecal Microbiota Correlated With Systemic Inflammation in Male Subjects With Methamphetamine Use Disorder.

Methamphetamine use disorder (MUD) is a major public health problem worldwide with limited effective treatment options. Previous studies have reported methamphetamine-associated alterations in gut microbiota. A potential role of gut microbiota in regulating methamphetamine-induced brain dysfunction through interactions with the host immune system has been proposed, but evidence for this hypothesis is limited. The present study aimed to investigate the alterations in the fecal microbiota and explore its relationship with systemic inflammation in MUD. Fecal samples were obtained from 26 male subjects with MUD and 17 sex- and age- matched healthy controls. Fecal microbial profiles were analyzed by 16S rRNA sequencing. Plasma inflammatory markers were measured using enzyme-linked immunosorbent assay. Associations between fecal microbiota, systemic inflammatory markers and clinical characteristics were examined by Spearman partial correlation analysis while controlling for possible confounders. Compared with healthy controls, individuals with MUD showed no difference in fecal microbial diversity, but exhibited differences in the relative abundance of several microbial taxa. At the genus level, a higher abundance of Collinsella, Odoribacter and Megasphaera and lower levels of Faecalibacterium, Blautia, Dorea and Streptococcus were detected in subjects with MUD. More importantly, altered fecal microbiota was found to be correlated with plasma levels of CRP, IL-2, IL-6 and IL-10. The order Lactobacillales, exhibiting lower abundance in participants with MUD, was positively related to the duration of methamphetamine abstinence and the plasma level of anti-inflammatory cytokine IL-10. This study is the first to provide evidence for a link between altered fecal microbiota and systemic inflammation in MUD. Further elucidation of interactions between gut microbiota and the host immune system may be beneficial for the development of novel therapeutic approaches for MUD.

Indirect Relationship between Alcoholics Anonymous Spirituality and Their Hopelessness: The Role of Meaning in Life, Hope, and Abstinence Duration

Spiritual growth is a significant factor in Alcoholics Anonymous treatment process. In the literature, there is an observable lack of research regarding spiritual mechanisms of recovery in alcohol addicted individuals who are participants of self-help groups. The study purpose was to examine the potential mechanisms indirectly influencing participants of Alcoholics Anonymous (AA) and to determine the effects of spiritual experiences on their feelings of hopelessness through finding meaning in life, improving hope, and longer abstinence duration. The study was conducted using a cross-sectional design. Participants were AA meeting attenders from Poland. According to the obtained results, the relationship between spiritual experiences and feelings of hopelessness was indirect through meaning in life, hope, and abstinence duration. Additionally, the moderated mediation effect was positively verified. Meaning in life moderated the relationship between hope and feelings of hopelessness. In a group of AA participants with less-than-average and average levels of meaning in life, hope protected against feelings of hopelessness. Among AA participants with higher-than-average meaning in life, hope was not related to their depression symptoms. The spiritual mechanisms, which led to reduced feelings of hopelessness among AA participants, and the role of meaning in life, hope, and duration of abstinence were confirmed.

Mate Retention Behavior and Ejaculate Quality in Humans.

Males of some species use mate retention behavior and investment in ejaculate quality as anti-cuckoldry tactics concurrently while others do so in a compensatory fashion. Leivers, Rhodes, and Simmons (2014) reported that men who performed mate retention less frequently produced higher-quality ejaculates, suggesting that humans use these tactics compensatorily. We conducted a conceptual replication of this research in a sample of 41 men (18-33years; M = 23.33; SD = 3.60). By self-report, participants had not had a vasectomy and had never sought infertility treatment. We controlled for several covariates known to affect ejaculate quality (e.g., abstinence duration before providing an ejaculate) and found no statistically significant relationships between mate retention behavior and four components of ejaculate quality: sperm velocity, sperm concentration, slow motility, and ejaculate volume. The present results provide little support for the hypothesis that human males deploy mate retention behavior and ejaculate quality investment compensatorily. We discuss the limitations of this study and highlight the need for research to address questions about the nature of anti-cuckoldry tactic deployment in humans, especially concerning investment in ejaculate quality.

Assessing combinatorial effects of HIV infection and former cocaine dependence on cognitive control processes: A functional neuroimaging study of response inhibition

Individuals with a diagnosis of co-morbid HIV infection and cocaine use disorder are at higher risk of poor health outcomes. Active cocaine users, both with and without HIV infection, show clear deficits in response inhibition and other measures of executive function that are instrumental in maintaining drug abstinence, factors that may complicate treatment. Neuroimaging and behavioral evidence indicate normalization of executive control processes in former cocaine users as a function of the duration of drug abstinence, but it is unknown to what extent co-morbid diagnosis of HIV affects this process. To this end, we investigate the combinatorial effects of HIV and cocaine dependence on the neural substrates of cognitive control in cocaine-abstinent individuals with a history of cocaine dependence. Blood-oxygen level dependent signal changes were measured as 86 participants performed a Go/NoGo response inhibition task while undergoing functional magnetic resonance imaging (fMRI). Four groups of participants were selected based on HIV and cocaine-dependence status. Participants affected by both conditions demonstrated the lowest response accuracy of all participant groups. In a region of interest analysis, hyperactivation in the left putamen and midline-cingulate hyperactivation was observed in individuals with both HIV and cocaine dependence relative to individuals with only one condition. Results of a whole-brain analysis indicate response inhibition-related hyperactivation in the bilateral supplementary motor area, bilateral hippocampi, bilateral primary somatosensory areas, right dorsal anterior cingulate, and left insula in the CD+/HIV+ group relative to all other groups. These results indicate complex and interactive alterations in neural activation during response inhibition and highlight the importance of examining the neurocognitive effects of co-morbid conditions.

English

BACKGROUND Alcohol use disorder is one of the dangerous public health burden. The construct of impulsivity and its various dimensions in relation with aggression are relevant for understanding alcohol dependence and relapse. The goal of the study is to describe the role of impulsivity and aggression in the context of alcohol dependence. The purpose and implications of this study was to understand the human factors contributing to aggression and impulsivity and in providing advanced treatment programs. METHODS This cross-sectional study was discussed in detail and approved by the ethical committee of the Madras Medical College. The cases were selected consecutively from all the patients attending the outpatients as well as inpatient for the same after fulfilling the inclusion and exclusion criteria, within seven days of last intake of alcohol. The diagnosis was made according to International Classification of Diseases (ICD-10) criteria after ruling out psychotic disorder and other comorbid medical illnesses. Informed consent was obtained from all the patients and caregivers. Descriptive statistics used meticulously to measure the magnitude. RESULTS This study found significant positive correlation (P &lt; 0.001) between impulsivity, aggression subtypes with alcohol dependence. Various subsets in Barrett impulsivity scale (BIS) and subsets of Buss Perry aggression scales (BPAS) had positive correlations. We found that as severity of dependence increases, impulsivity and aggression scores increases and vice versa. The comparison of means of illness variables within groups showed that there was no significant difference between groups in terms of age of onset of illness, last alcohol intake, number of hospital admissions, duration of abstinence and frequency of relapse. CONCLUSIONS This study describes the important role of behavioural model and disease model of alcoholism, 1,2 greatly stresses the inability to control the quantity and frequency of the drinking behaviour. There is higher level of connectivity between alcohol dependence with biological and behavioural indicators of impulsivity and aggression. 3 It supports that relapse is an acquired behaviour in which the individual is able to control his substance taking pattern through adequate cognitive behavioural techniques in addition to pharmacological treatment and also suggest more research needed in future to focus on causality and intervention. KEY WORDS Impulsivity, Aggression, Alcohol dependence, Relapse

Sperm donor lifestyle survey: modifiable risk factors for potential sperm donors.

To examine the association between modifiable lifestyle factors and the main semen parameter values, the number of qualified sperm donors, and to provide some sensible guidance for sperm donors. Healthy men screened as potential sperm donors were recruited in the Hunan Province Human Sperm Bank of China from March 2019 to December 2019. Participants were invited to complete interviewer-assisted questionnaires on eleven items of information. Univariate and multivariate analyses were conducted to analyze which lifestyle factors collected by the questionnaire had an impact on the eligibility and main semen parameters of sperm donors. The eligibility of men as sperm donors was strongly influenced by the duration of abstinence (P = 0.002). The rate of eligibility sperm donors increased significantly with the number of days of abstinence. In addition, semen volume increased with abstinence time (P = 0.000). Exercise frequency (P = 0.025) and abstinence time (P = 0.000) were positively correlated with sperm concentration, and masturbation frequency was negatively correlated with sperm concentration (P = 0.013). Progressive sperm motility was significantly affected by abstinence time (P = 0.000) and bedtime (P = 0.047). Abstinence time was highly associated with semen parameters and donor qualification. Increase the abstinence time before donation may be meaningful in improving the proportion of eligible sperm donors.

Citalopram for treatment of cocaine use disorder: A Bayesian drop-the-loser randomized clinical trial

BackgroundMedication development research for cocaine use disorder (CUD) has been a longstanding goal in addiction research, but has not resulted in an FDA-approved treatment. Rising cocaine use rates underscore the need for efficient adaptive designs. This study compared differences between two doses of the selective serotonin reuptake inhibitor (SSRI) citalopram (versus placebo) on duration of cocaine abstinence and applied adaptive decision rules to select the ‘best efficacy’ dose. MethodsA double-blind, placebo-controlled, randomized Bayesian drop-the-loser (DTL) trial with three arms compared placebo to citalopram 20 mg and 40 mg. Adults (N = 107) with CUD attended thrice-weekly clinic visits for 9 weeks. The primary outcome was longest duration of abstinence (LDA), based on continuous cocaine-negative urine drug screens (UDS). The secondary outcome was probability of cocaine-negative UDS during treatment. A planned interim analysis performed at approximately 50% of recruitment dropped the least-effective active medication. Bayesian inference was used for all analyses with a pre-specified posterior probability (PP) threshold PP ≥ 95% considered statistically reliable evidence ResultsCitalopram 40 mg satisfied interim efficacy criteria and was retained for the second half of the trial. For LDA, analyses indicated PP = 82% and PP = 65% of benefit for 40 mg and 20 mg, respectively (each relative to placebo). The odds of having cocaine-negative UDS decreased in all groups over 9 weeks but remained higher for 40 mg (PP = 97.4%) ConclusionsNeither dose met the 95% PP threshold for the primary outcome; however, 40 mg provided moderate-to-strong evidence for positive effects on LDA and cocaine-negative UDS. The 40 mg dose was declared the “winner” in this DTL trial.

Comparison of naltrexone implant and oral buprenorphine-naloxone in the treatment of opiate use disorder.

We aimed to compare the effectiveness of extended-release naltrexone (XR-NTX) implant and sublingual buprenorphine-naloxone (BUP-NX) in relapse prevention in opiate use disorder (OUD). Medical records of 400 patients who were treated for OUD between 2016 and 2020 were retrospectively evaluated concerning sociodemographic and clinical characteristics and abstinence duration with either BUP-NX (192 patients) or XR-NTX (208 patients) as maintenance treatments. The median age of patients using BUP-NX was 25.00, and the median age of patients using XR-NTX was 25.50 (p=.785). The ratio of female patients in the BUP-NX group and the XR-NTX group was 7.3% (n=14) and 6.7% (n=14), respectively. A significantly higher abstinence time was observed in the BUP-NX group (median=4months) than in the XR-NTX group (median=3months) (p=.015). Liver function tests were within the normal ranges at the three time points, which were just before the beginning and in the first and third months of treatment. These findings suggest that BUP-NX might be more effective than XR-NTX in preventing relapse in OUD and both drugs are safe for the liver. Prospective randomized studies are needed to replicate our results.

Baseline severity and the prediction of placebo response in clinical trials for alcohol dependence: A meta-regression analysis to develop an enrichment strategy.

BackgroundThere is considerable unexplained variability in alcohol abstinence rates (AR) in the placebo groups of randomized controlled trials (RCTs) for alcohol dependence (AD). This is of particular interest because placebo responses correlate negatively with treatment effect size. Recent evidence suggests that the placebo response is lower in very heavy drinkers who show no “spontaneous improvement” prior to treatment initiation (high‐severity population) than in a mild‐severity population and in studies with longer treatment duration. We systematically investigated the relationship between population severity, treatment duration, and the placebo response in AR to inform a strategy aimed at reducing the placebo response and thereby increasing assay sensitivity in RCTs for AD.MethodsWe conducted a systematic literature review on placebo‐controlled RCTs for AD.We assigned retained RCTs to high‐ or mild‐severity groups of studies based on baseline drinking risk levels and abstinence duration before treatment initiation. We tested the effects of population severity and treatment duration on the placebo response in AR using meta‐regression analysis.ResultsAmong the 19 retained RCTs (comprising 1996 placebo‐treated patients), 11 trials were high‐severity and 8 were mild‐severity RCTs. The between‐study variability in AR was lower in the high‐severity than in the mild‐severity studies (interquartile range: 7.4% vs. 20.9%). The AR in placebo groups was dependent on population severity (p = 0.004) and treatment duration (p = 0.017) and was lower in the high‐severity studies (16.8% at 3 months) than the mild‐severity studies (36.7% at 3 months).ConclusionsPharmacological RCTs for AD should select high‐severity patients to decrease the magnitude and variability in the placebo effect and and improve the efficiency of drug development efforts for AD.

Adults with a history of recreational cannabis use have altered speech production

Stereotypical depictions of speech in cannabis users often suggest slow, laboured output, yet objective evidence supporting this assumption is extremely limited. We know that depressants or hallucinogenic drugs such as cannabis can cause acute changes in communication and speech rate, but the long-lasting effects of cannabis use on speech are not well described. The aim of this study was to investigate speech in individuals with a history of recreational cannabis use compared to non-drug-using healthy controls. Speech samples were collected from a carefully described cohort of 31 adults with a history of cannabis use (but not use of illicit stimulant drugs) and 40 non-drug-using controls. Subjects completed simple and complex speech tasks including a monologue, a sustained vowel, saying the days of the week, and reading a phonetically balanced passage. Audio samples were analysed objectively using acoustic analysis for measures of timing, vocal control, and quality. Subtle differences in speech timing, vocal effort, and voice quality may exist between cannabis and control groups, however data remain equivocal. After controlling for lifetime alcohol and tobacco use and applying a false discovery rate, only spectral tilt (vocal effort and intensity) differed between groups and appeared to change in line with duration of abstinence from cannabis use. Differences between groups may reflect longer term changes to the underlying neural control of speech. Our digital analysis of speech shows there may be a signal differentiating individuals with a history of recreational cannabis use from healthy controls, in line with similar findings from gait and hand function studies.

Neurophysiological correlate of incubation of craving in individuals with methamphetamine use disorder.

Previous studies both in laboratory animals and humans have reported that abstinence induces incubation of cue-induced drug craving for nicotine, alcohol, cocaine, and methamphetamine. However, current experimental procedures utilized to study incubation of methamphetamine craving do not incorporate the temporal dynamics of neuropsychological measures and electrophysiological activities associated with this incubation process. This study utilized the high-density electroencephalogram (EEG) signals as a rapid, inexpensive, and noninvasive measure of cue-induced craving potential. A total of 156 male individuals with methamphetamine use disorder (MUD) enrolled in this multisite, cross-sectional study. Structured clinical interview data, self-report questionnaires (cued craving, quality of sleep, impulsivity, anxiety, and depression) and resting-state, eye-closed 128 high-density channel EEG signals were collected at 5 abstinence duration time points (<1, 1-3, 3-6, 6-12, and 12-24 months) to track the neuropsychological and neurophysiological signatures. Cue-induced craving was higher after 1-3 months than after the other time points. This incubation effect was also observed for sleep quality but not for anxiety, depression, and impulsivity symptoms, along with exhibited decreased power spectrum for theta (5.5-8 Hz) and alpha (8-13 Hz), and increased in beta (16.5-26.5 Hz) frequency band. Source reconstructed resting-state EEG analysis showed increased synchronization of medial prefrontal cortex (MPFC) for the beta frequency band in 1-3 months abstinent MUD group, and associated with the incubation of craving. Remarkably, the robust incubation-related abnormalities may be driven by beta-band source space connectivity between MPFC and bilateral orbital gyrus (ORB). Our findings suggest the enhancement of beta activity in the incubation period most likely originates from a dysfunction involving frontal brain regions. This neurophysiological signature of incubation of craving can be used to identify individuals who might be most susceptible to relapse, providing a potential insight into future therapeutic interventions for MUD via neuromodulation of beta activity.