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Trials Jun 2024There are no approved pharmacotherapies for methamphetamine use disorder. Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic...
BACKGROUND
There are no approved pharmacotherapies for methamphetamine use disorder. Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic antidepressant, to be effective in reducing methamphetamine use. The proposed Tina Trial is the first phase 3 placebo-controlled randomised trial to examine the effectiveness and safety of mirtazapine as an outpatient pharmacotherapy for methamphetamine use disorder.
METHODS
This is a multi-site phase 3 randomised, double-blind, placebo-controlled parallel trial. Participants are randomly allocated (1:1) to receive either mirtazapine (30 mg/day for 12 weeks) or matched placebo, delivered as a take-home medication. The target population is 340 people aged 18-65 years who have moderate to severe methamphetamine use disorder. The trial is being conducted through outpatient alcohol and other drug treatment clinics in Australia. The primary outcome is measured as self-reported days of methamphetamine use in the past 4 weeks at week 12. Secondary outcomes are methamphetamine-negative oral fluid samples, depressive symptoms, sleep quality, HIV risk behaviour and quality of life. Other outcomes include safety (adverse events), tolerability, and health service use. Medication adherence is being monitored using MEMS® Smart Caps fitted to medication bottles.
DISCUSSION
This trial will provide information on the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder when delivered as an outpatient medication in routine clinical practice. If found to be safe and effective, this trial will support an application for methamphetamine use disorder to be included as a therapeutic indication for the prescription of mirtazapine.
TRIAL REGISTRATION
Australian and New Zealand Clinical Trials Registry ACTRN12622000235707. Registered on February 9, 2022.
Topics: Humans; Mirtazapine; Double-Blind Method; Amphetamine-Related Disorders; Methamphetamine; Adult; Middle Aged; Adolescent; Clinical Trials, Phase III as Topic; Male; Young Adult; Randomized Controlled Trials as Topic; Aged; Female; Treatment Outcome; Multicenter Studies as Topic; Australia; Time Factors; Medication Adherence; Antidepressive Agents, Tricyclic
PubMed: 38907288
DOI: 10.1186/s13063-024-08238-y -
Substance Abuse Treatment, Prevention,... Jun 2024Research demonstrates gaps in medications for opioid use disorder uptake (MOUDs; methadone, buprenorphine, and naltrexone) especially among adolescents. These gaps may...
Attitudes toward and training in medications for opioid use disorders: a descriptive analysis among employees in the youth legal system and community mental health centers.
BACKGROUND
Research demonstrates gaps in medications for opioid use disorder uptake (MOUDs; methadone, buprenorphine, and naltrexone) especially among adolescents. These gaps may be partly attributable to attitudes about and training in MOUDs among youth-serving professionals. We extended prior research by conducting descriptive analyses of attitudes regarding effectiveness and acceptability of MOUDs, as well as training in MOUDs, among youth legal system (YLS) employees and community mental health center (CMHC) personnel who interface professionally with youth.
METHODS
Using survey data from participants (n = 181) recruited from eight Midwest counties, we examined: (1) differences in MOUD attitudes/training by MOUD type and (2) by respondent demographics, and (3) prediction of MOUD attitudes/training by participant-reported initiatives to implement evidence-based practices (EBPs), workplace culture around EBPs, and workplace stress. Attitudes and training were measured in reference to five MOUD types (methadone, oral buprenorphine, injectable buprenorphine, oral naltrexone, injectable naltrexone) on three subscales (effectiveness, acceptability, training).
RESULTS
Wilcoxon signed-rank tests demonstrated that most outcomes differed significantly by MOUD type (differences observed among 22 of 30 tests). Kruskal-Wallis tests suggested MOUD differences based on demographics. For methadone, CMHC providers endorsed greater perceived effectiveness than YLS providers and age explained significant differences in perceived effectiveness. For buprenorphine, CHMC providers viewed oral or injectable buprenorphine as more effective than YLS employees, respondents from more rural counties viewed oral buprenorphine as more effective than those from less rural counties, and age explained differences in perceived effectiveness. For naltrexone, perceived gender differed by gender. Hierarchical ordinal logistic regression analysis did not find an association between personal initiatives to implement EBPs, workplace culture supporting EBPs, or workplace stress and effectiveness or acceptability of MOUDs. However, personal initiatives to implement EBPs was associated with training in each MOUD.
CONCLUSIONS
These results highlight a few key findings: effectiveness/acceptability of and training in MOUDs largely differ by MOUD type; setting, rurality, age, gender, and education explain group differences in perceived effectiveness of and training in MOUDs; and implementing EBPs is associated with training in MOUDs. Future research would benefit from examining what predicts change in MOUD attitudes longitudinally.
Topics: Humans; Male; Female; Adult; Opioid-Related Disorders; Opiate Substitution Treatment; Attitude of Health Personnel; Naltrexone; Buprenorphine; Methadone; Community Mental Health Centers; Adolescent; Middle Aged; Young Adult; Narcotic Antagonists
PubMed: 38907286
DOI: 10.1186/s13011-024-00614-w -
Biological Research Jun 2024Prenatal alcohol exposure (PAE) has serious physical consequences for children such as behavioral disabilities, growth disorders, neuromuscular problems, impaired motor...
BACKGROUND
Prenatal alcohol exposure (PAE) has serious physical consequences for children such as behavioral disabilities, growth disorders, neuromuscular problems, impaired motor coordination, and decreased muscle tone. However, it is not known whether loss of muscle strength occurs, and which interventions will effectively mitigate physical PAE impairments. We aimed to investigate whether physical alteration persists during adolescence and whether exercise is an effective intervention.
RESULTS
Using paradigms to evaluate different physical qualities, we described that early adolescent PAE animals have significant alterations in agility and strength, without alterations in balance and coordination compared to CTRL animals. We evaluated the effectiveness of 3 different exercise protocols for 4 weeks: Enrichment environment (EE), Endurance exercise (EEX), and Resistance exercise (REX). The enriched environment significantly improved the strength in the PAE group but not in the CTRL group whose strength parameters were maintained even during exercise. Resistance exercise showed the greatest benefits in gaining strength, and endurance exercise did not.
CONCLUSION
PAE induced a significant decrease in strength compared to CTRL in PND21. Resistance exercise is the most effective to reverse the effects of PAE on muscular strength. Our data suggests that individualized, scheduled, and supervised training of resistance is more beneficial than endurance or enriched environment exercise for adolescents FASD.
Topics: Fetal Alcohol Spectrum Disorders; Animals; Disease Models, Animal; Physical Conditioning, Animal; Female; Muscle Strength; Pregnancy; Male; Rats; Prenatal Exposure Delayed Effects; Rats, Wistar
PubMed: 38907274
DOI: 10.1186/s40659-024-00520-2 -
BMC Psychiatry Jun 2024The prevalence of hazardous substance use is highest in the age between 18 and 25, but few young adults enter treatment. Community Reinforcement and Family Training... (Randomized Controlled Trial)
Randomized Controlled Trial
'Before, we ended up in conflicts, now we can provide support'-Experiences of Community Reinforcement and Family Training (CRAFT) for parents of young adults with hazardous substance use.
BACKGROUND
The prevalence of hazardous substance use is highest in the age between 18 and 25, but few young adults enter treatment. Community Reinforcement and Family Training (CRAFT) is a support program for concerned significant others (CSOs) of individuals with diverse substance use disorders and is proven efficacious in promoting treatment entry. The aim of the current study was to investigate the experiences of CRAFT among parents of substance using young adults.
METHODS
We used a qualitative design conducting semi-structured interviews with 10 parents of young adults (18-24 years) with hazardous substance use. The participants were recruited from a randomized controlled trial of the CRAFT program. The transcribed interviews were analyzed using thematic analysis.
RESULTS
We divided the results into three overall domains-Reasons for entering the CRAFT program, Strengths of the CRAFT program and Limitations of the CRAFT program - with three to four themes under each domain. The parents appreciated the accessible support at a time when they needed it due to feelings of shock and powerlessness, and they described communication strategies together with positive reinforcement as the two most helpful CRAFT-sessions. Regarding limitations of CRAFT in the current population, the parents wanted more accessible support for the young adults when they were ready to enter treatment, and described difficulties to practice CRAFT-components due to changing life-circumstances and fear of aggravated health for their young adults.
CONCLUSION
The results provide arguments for the health care system to implement support programs to parents of young adults with hazardous substance use. The results show that CRAFT is suitable for the current population, but with some possible additions due to changing circumstances that are common in the young adult developmental phase emerging adulthood.
TRIAL REGISTRATION
The trial was pre-registered at isrctn.com, reference number ISRCTN12212515 date: November 7, 2018.
Topics: Humans; Substance-Related Disorders; Male; Female; Young Adult; Adolescent; Parents; Adult; Qualitative Research; Social Support; Reinforcement, Psychology; Family Therapy
PubMed: 38907237
DOI: 10.1186/s12888-024-05913-x -
Harm Reduction Journal Jun 2024Retention in substance use treatment is essential to treatment success. While programmatic factors are known to influence retention, less is known about the role of...
BACKGROUND
Retention in substance use treatment is essential to treatment success. While programmatic factors are known to influence retention, less is known about the role of involuntary discharges from drug or alcohol treatment programs. Therefore, we sought to identify the prevalence of and factors associated with involuntary discharge due to ongoing substance use.
METHODS
Data were derived from two community-recruited prospective cohort studies of people who use drugs in Vancouver, Canada. Generalized estimating equation (GEE) analyses were used to identify variables associated with involuntary discharge from treatment programs due to ongoing substance use.
RESULTS
Between June 2017 and March 2020, 1487 participants who accessed substance use treatment and completed at least one study interview were included in this study. Involuntary discharge from a treatment program due to ongoing substance use was reported by 41 (2.8%) participants throughout the study, with 23 instances reported at baseline and another 18 reported during study follow-up. In a multivariable GEE analysis, involuntary discharge was positively associated with homelessness (Adjusted Odds Ratio [AOR] = 3.22, 95% Confidence Interval [95% CI]: 1.59-6.52), daily injection drug use (AOR = 1.87, 95% CI 1.06-3.32) and recent overdose (AOR = 2.50, 95% CI 1.38-4.53), and negatively associated with age (AOR = 0.93, 95% CI 0.90-0.96). In sub-analyses, participants have most commonly been discharged from in-patient treatment centres (52.2%), recovery houses (28.3%) and detox programs (10.9%), and for using heroin (45.5%) and/or crystal methamphetamine (36.4%).
CONCLUSIONS
While involuntary discharge was a relatively rare occurrence, those who were discharged due to active substance use possessed several markers of risk, including high-intensity injection drug use, homelessness, and recent non-fatal overdose. Our findings highlight the need for increased flexibility within treatment programs to account for those who re-initiate or continue to use substances during treatment.
Topics: Humans; Male; Female; Adult; Middle Aged; Ill-Housed Persons; Substance-Related Disorders; Prospective Studies; Canada; British Columbia; Substance Abuse Treatment Centers; Patient Discharge; Cohort Studies
PubMed: 38907209
DOI: 10.1186/s12954-024-01036-4 -
Communications Biology Jun 2024Tuberous sclerosis complex 2 (TSC2) crucially suppresses Rheb activity to prevent mTORC1 activation. However, mutations in TSC genes lead to mTORC1 overactivation,...
Tuberous sclerosis complex 2 (TSC2) crucially suppresses Rheb activity to prevent mTORC1 activation. However, mutations in TSC genes lead to mTORC1 overactivation, thereby causing various developmental disorders and cancer. Therefore, the discovery of novel Rheb inhibitors is vital to prevent mTOR overactivation. Here, we reveals that the anti-inflammatory cytokine IL-37d can bind to lysosomal Rheb and suppress its activity independent of TSC2, thereby preventing mTORC1 activation. The binding of IL-37d to Rheb switch-II subregion destabilizes the Rheb-mTOR and mTOR-S6K interactions, further halting mTORC1 signaling. Unlike TSC2, IL-37d is reduced under ethanol stimulation, which results in mitigating the suppression of lysosomal Rheb-mTORC1 activity. Consequently, the recombinant human IL-37d protein (rh-IL-37d) with a TAT peptide greatly improves alcohol-induced liver disorders by hindering Rheb-mTORC1 axis overactivation in a TSC2- independent manner. Together, IL-37d emerges as a novel Rheb suppressor independent of TSC2 to terminate mTORC1 activation and improve abnormal lipid metabolism in the liver.
Topics: Mechanistic Target of Rapamycin Complex 1; Ras Homolog Enriched in Brain Protein; Humans; Animals; Mice; Signal Transduction; Tuberous Sclerosis Complex 2 Protein; Liver Diseases, Alcoholic; Interleukin-1; Mice, Inbred C57BL; Male; HEK293 Cells
PubMed: 38907105
DOI: 10.1038/s42003-024-06427-8 -
Child Abuse & Neglect Jun 2024Effective classification of individuals who commit sexual offences is important for their assessment, treatment, and risk management. Victim age has often been used as a...
BACKGROUND
Effective classification of individuals who commit sexual offences is important for their assessment, treatment, and risk management. Victim age has often been used as a distinguishing factor between perpetrators.
OBJECTIVE
This study aimed to analyse the distinctive psychopathological and criminological characteristics of contact sexual offenders with adult and minor victims.
PARTICIPANTS AND SETTING
The study involved 97 adult males who were serving a prison sentence in Spain for at least one contact sexual offence against an adult or a minor.
METHODS
Researchers gathered data on criminological variables concerning the offender, victim, and modus operandi from prison records and interviews. Participants completed the Millon Clinical Multiaxial Inventory-III (MCMI-III) in a second session, and between-group differences were analysed.
RESULTS
Sex offenders with minor victims (SOMV) had significantly lower scores than sex offenders with adult victims (SOAV) on the Antisocial (r = -0.283, p = .005) and Sadistic (r = -0.209, p = .04) personality subscales, and on the Alcohol (r = -0.426, p < .001) and Drug dependence (r = -0.332, p = .001) syndrome subscales. SOAV were also more likely to use violence and/or intimidation, use a weapon, offend against female victims, offend against an intimate partner, commit their offences in public places, serve other ongoing prison sentences, and report a history of alcohol and substance abuse. SOMV were older and more likely to offend against family members.
CONCLUSIONS
These results suggest that there are key differences between SOAV and SOMV that should be considered in tailored prevention programmes for each subgroup of offenders.
PubMed: 38906041
DOI: 10.1016/j.chiabu.2024.106896 -
Medicine Jun 2024Gegensan (GGS) has been reported for the treatment of alcoholic liver disease (ALD), but its therapeutic mechanism is still unclear. This paper aims to determine the...
Gegensan (GGS) has been reported for the treatment of alcoholic liver disease (ALD), but its therapeutic mechanism is still unclear. This paper aims to determine the therapeutic mechanism and targets of action of GGS on alcoholic liver disease utilizing network pharmacology and bioinformatics. The active ingredients in GGS were screened in the literature and databases, and common targets of ALD were then obtained from public databases to construct the network diagram of traditional Chinese medicine-active ingredient targets. Based on the common targets, Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to find target enrichment pathways, and the core targets were screened out by combining differential analysis and protein-protein interaction network analysis. Molecular docking was performed to verify the binding effect between the core targets and the corresponding active ingredients. ALD and GGS have 84 common targets, corresponding to 91 active ingredients. After subsequent differential analysis and protein-protein interaction network analysis, 10 core targets were identified. Gene Ontology and KEGG enrichment analyses showed that the main BPs corresponding to the common targets included the response to lipopolysaccharide, inflammatory response, etc. The KEGG pathways involved in the regulation of the common targets included the lipid-atherosclerosis pathway and the alcoholic liver disease pathway, etc. Further molecular docking showed that the core targets CYP1A1, CYP1A2, CXCL8, ADH1C, MMP1, SERPINE1, COL1A1, APOB, MMP1, and their corresponding 4 active ingredients, Naringenin, Kaempferol, Quercetin, and Stigmasterol, have a greater docking potential. The above results suggest that GGS can regulate lipid metabolism and inflammatory response in the ALD process, and alleviate the lipid accumulation and oxidative stress caused by ethanol. This study analyzed the core targets and mechanisms of action of GGS on ALD, which provides certain theoretical support for the further development of GGS in the treatment of ALD, and provides a reference for the subsequent research on the treatment of ALD.
Topics: Liver Diseases, Alcoholic; Network Pharmacology; Humans; Molecular Docking Simulation; Drugs, Chinese Herbal; Computational Biology; Protein Interaction Maps; Medicine, Chinese Traditional; Gene Ontology
PubMed: 38905402
DOI: 10.1097/MD.0000000000038315 -
JAMA Network Open Jun 2024
Topics: Humans; United States; Clinical Trials as Topic; Consent Forms; Databases, Factual; Registries
PubMed: 38904965
DOI: 10.1001/jamanetworkopen.2024.18895 -
Cureus May 2024The abuse of inhalants like nitrous oxide (NO), readily available worldwide, has remained a prominent public health problem during the last few decades. Literature...
The abuse of inhalants like nitrous oxide (NO), readily available worldwide, has remained a prominent public health problem during the last few decades. Literature reveals increased use during the previous pandemic, particularly regarding recreational use. There is limited evidence-based data available to relate the abuse of NO with psychosis. Therefore, this case report of a 22-year-old adult with no previous psychiatry history, reportedly abusing 75-100 canisters of NO per day during the last pandemic COVID-19 lockdown, highlights the relationship between (NO) abuse and the symptoms evolved including delusions, auditory hallucinations, and disorganized cognition. All the laboratory findings and results from imaging modalities were inconsistent for any organic cause of the symptoms. The case then underwent treatment with antipsychotic medications and a multidisciplinary model, which improved the symptoms gradually. The case, in particular, discusses NO abuse, which is widespread in European Union countries, including the UK and the Republic of Ireland, and its chronic use puts one at a higher risk of developing psychosis, personality changes, affective lability, anxiety, depression, cognitive impairment, and myeloneuropathy. The sale of NO for its psychoactive properties is prohibited in many countries, including the Republic of Ireland, as per legislation. However, NO is not a controlled drug, meaning it is not a crime to possess NO. This case report manifests the psychopathy caused by abuse of NO, which would further attract specialists in the field to conduct epidemiological studies for prevention at the primary level.
PubMed: 38903353
DOI: 10.7759/cureus.60634