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Journal of Addiction Medicine Jun 2024Benzodiazepine-involved overdose deaths are rising, driven by increasing use of nonprescribed benzodiazepine pills. For patients who wish to stop nonprescribed...
BACKGROUND
Benzodiazepine-involved overdose deaths are rising, driven by increasing use of nonprescribed benzodiazepine pills. For patients who wish to stop nonprescribed benzodiazepine use, rapid inpatient tapers are typically the only option to treat benzodiazepine withdrawal. Substance use disorder bridge clinics can provide the high-touch care needed to manage outpatient benzodiazepine tapers in patients at high risk due to other substance use disorders.
OBJECTIVE
Describe the implementation and short-term outcomes of an outpatient benzodiazepine taper protocol to treat benzodiazepine withdrawal in a substance use disorder bridge clinic.
METHODS
The clinical team developed a 4- to 6-week intensive outpatient taper protocol using diazepam. Patients with benzodiazepine use disorder were eligible if they had benzodiazepine withdrawal, lacked a prescriber, wanted to stop benzodiazepines completely, and agreed to daily visits. For patients who initiated a taper between April 2021 and December 2022, we evaluated the proportion of patients who completed a taper (i.e., tapered to a last prescribed dose of diazepam 10 mg/d or less); likelihood of remaining on the taper over time; and seizure, overdose, or death documented at the study institution during or within 1 month of taper completion or discontinuation. Other secondary outcomes included HIV testing and prevention, hepatitis C testing, and referrals to recovery coaching or psychiatry.
RESULTS
Fifty-four patients initiated a total of 60 benzodiazepine tapers. The population was mostly male (61%) and non-Hispanic White (85%). Nearly all patients had opioid use disorder (96%), and most (80%) were taking methadone or buprenorphine for opioid use disorder before starting the taper. Patients reported using multiple substances in addition to benzodiazepines, most commonly fentanyl (75%), followed by cocaine (41%) and methamphetamine (21%). Fourteen patients (23%) completed a taper with a median duration of 34 days (IQR 27.8-43.5). Most tapers were stopped when the patient was lost to follow-up (57%), or the team recommended inpatient care (18%). Two patients had a seizure, and 4 had a presumed opioid-involved overdose during or within 1 month after the last taper visit, all individuals who did not complete a taper. No deaths occurred during or within 1 month of taper completion or discontinuation. Challenges included frequent loss to follow-up in the setting of other unstable substance use. Patients received other high-priority care during the taper including HIV testing (32%), PrEP initiation (6.7%), hepatitis C testing (30%), and referrals to recovery coaches (18%) and psychiatry (6.7%).
CONCLUSIONS
Managing benzodiazepine withdrawal with a 4- to 6-week intensive outpatient taper in patients with benzodiazepine and opioid use disorders is challenging. More work is needed to refine patient selection, balance safety risks with feasibility, and study long-term, patient-centered outcomes.
PubMed: 38922639
DOI: 10.1097/ADM.0000000000001334 -
Molecular Neurobiology Jun 2024Methamphetamine (MA) is one of the most abused drugs globally, but the mechanism of its addiction remains unclear. Several animal studies have shown that the gut...
Methamphetamine (MA) is one of the most abused drugs globally, but the mechanism of its addiction remains unclear. Several animal studies have shown that the gut microbiota (GM) influences addictive behaviors, but the pattern of GM changes during addiction in animals of different species remains unclear. The aim of this study was to explore the association between dynamic changes in GM and MA self-administration acquisition among two classical mammals, rhesus monkeys (Macaca mulatta) and rats, MA self-administration models. Male Sprague-Dawley rats and male rhesus monkeys were subjected to classical MA self-administration training, and fecal samples were collected before and after MA self-administration training, respectively. 16S rRNA sequencing was used for GM analyses. We found that GM changes were more pronounced in rats than in rhesus monkeys, as evidenced by more GM taxa producing significant differences before and after MA self-administration training in rats than in monkeys. We also found that the expression of the genus Clostridia_vadinBB60_group significantly decreased after MA self-administration training in both rats and rhesus monkeys. Lactobacillus changes were significantly negatively correlated with total MA uptake in rats (Pearson R = - 0.666, p = 0.035; Spearman R = - 0.721, p = 0.023), whereas its change was also highly negatively correlated with total MA uptake in rhesus monkeys (Pearson R = - 0.882, p = 0.118; Spearman R = - 1.000, p = 0.083), although this was not significant. These findings suggest that MA causes significant alterations in GM in both rhesus monkeys and rats and that the genus Lactobacillus might be a common therapeutic target for MA uptake prevention across the species.
PubMed: 38922485
DOI: 10.1007/s12035-024-04318-x -
Current Medicinal Chemistry Jun 2024Methamphetamine (METH), an amphetamine-type stimulant, has been extensively abused globally in the past decades. METH use causes great harm to the major systems of the...
Methamphetamine (METH), an amphetamine-type stimulant, has been extensively abused globally in the past decades. METH use causes great harm to the major systems of the human body. Specifically, METH has a negative impact on the hypothalamic- pituitary-testicular axis, testicular structure, sperm function, ovarian folliculogenesis, oocyte quality, embryo development, and newborns. However, the mechanisms underlying these toxic effects have not yet been fully described. This study reviews the evidence concerning the impact of METH on male and female reproduction in the context of the testis, sperm, ovaries, oocytes, reproductive hormones, embryo development, and newborns, discussing the potential pathophysiological mechanisms in the reproductive toxicity induced by METH.
PubMed: 38920076
DOI: 10.2174/0109298673299759240603091021 -
Brain Imaging and Behavior Jun 2024Sleep problems and impulsivity frequently occur in methamphetamine (MA) abstainers and are linked to aberrant brain function. However, the interplay between these...
Sleep problems and impulsivity frequently occur in methamphetamine (MA) abstainers and are linked to aberrant brain function. However, the interplay between these factors remains poorly understood. This study aimed to investigate the relationship between sleep, impulsivity, and regional homogeneity (ReHo) through mediation analysis in MA abstainers. 46 MA abstainers and 44 healthy controls were included. Impulsivity and sleep problems were evaluated using the Barratt Impulsivity Scale and the Pittsburgh Sleep Quality Scale, respectively. ReHo, indicative of local brain spontaneous neural activity, was assessed using resting-state functional magnetic resonance imaging. Results unveiled correlations between different dimensions of impulsivity and ReHo values in specific brain regions. Motor impulsivity correlated with ReHo values in the left postcentral gyrus and left precentral gyrus, while non-planning impulsivity was only associated with ReHo values in the left precentral gyrus. Additionally, the need for sleep medications correlated with ReHo values in the left precentral gyrus and bilateral postcentral gyrus. Also, the need for sleep medications was positively correlated with cognitive impulsivity and motor impulsivity. Mediation analysis indicated that reduced ReHo values in the left precentral gyrus mediated the association between impulsivity and the need for sleep medications. These findings imply that addressing sleep problems, especially the need for sleep medications, might augment spontaneous neural activity in specific brain regions linked to impulsivity among MA abstainers. This underscores the importance of integrating sleep interventions into comprehensive treatment strategies for MA abstainers.
PubMed: 38914808
DOI: 10.1007/s11682-024-00900-y -
Acta Pharmacologica Sinica Jun 2024Methamphetamine (METH), an abused psychostimulant, impairs cognition through prolonged or even single-dose exposure, but animal experiments have shown contradictory...
Methamphetamine (METH), an abused psychostimulant, impairs cognition through prolonged or even single-dose exposure, but animal experiments have shown contradictory effects on memory deficits. In this study we investigated the effects and underlying mechanisms of single-dose METH administration on the retrieval of object recognition memory (ORM) in mice. We showed that single-dose METH administration (2 mg/kg, i.p.) significantly impaired ORM retrieval in mice. Fiber photometry recording in METH-treated mice revealed that the activity of prelimbic cortex glutamatergic neurons (PrL) was significantly reduced during ORM retrieval. Chemogenetic activation of PrL or glutamatergic projections from ventral CA1 to PrL (vCA1-PrL) rescued ORM retrieval impairment. Fiber photometry recording revealed that dopamine (DA) levels in PrL of METH-treated mice were significantly increased, and micro-infusion of the D2 receptor (D2R) antagonist sulpiride (0.25 μg/side) into PrL rescued ORM retrieval impairment. Whole-cell recordings in brain slices containing the PrL revealed that PrL intrinsic excitability and basal glutamatergic synaptic transmission were significantly reduced in METH-treated mice, and the decrease in intrinsic excitability was reversed by micro-infusion of Sulpiride into PrL in METH-treated mice. Thus, the impaired ORM retrieval caused by single-dose METH administration may be attributed to reduced PrL activity, possibly due to excessive DA activity on D2R. Selective activation of PrL or vCA1-PrL may serve as a potential therapeutic strategy for METH-induced cognitive dysfunction.
PubMed: 38914676
DOI: 10.1038/s41401-024-01321-9 -
Rivista Di Psichiatria 2024To investigate the effects of electroacupuncture combined with paliperidone palmitate long-acting injection (PP-LAI) on withdrawal symptoms and neurotransmitters in... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To investigate the effects of electroacupuncture combined with paliperidone palmitate long-acting injection (PP-LAI) on withdrawal symptoms and neurotransmitters in methamphetamine (MA) addicts.
MATERIALS AND METHODS
A total of 109 methamphetamine addicts, who were treated in the hospital from October 2021 to October 2022, were selected. According to the random number table, the patients were divided into the study group (n=54) and the control group (n=55), in which the control group was treated with PP-LAI and the study group was treated with electroacupuncture on the basis of the control group; the methamphetamine withdrawal symptom score scale was used to assess the therapeutic effect before treatment and within 12 months after treatment; the changes of brain neurotransmitters dopamine, γ-aminobutyric acid, serotonin, acetylcholine values were compared between the two groups.
RESULTS
1) There was no statistical difference in MA withdrawal symptom scores between the two groups before treatment (p>0.05); 2) MA withdrawal symptom scores have a statistically significant difference between the study group and the control group after 3 and 6 months of treatment; 3) dopamine levels in the study group were significantly higher than those in the control group after 6 months of completion of treatment, and γ-aminobutyric acid values and 5- serotonin values in the study group were significantly lower than those in the control group (p<0.05).
CONCLUSIONS
Electroacupuncture combined with PP-LAI can partially improve the withdrawal symptoms and anxiety of methamphetamine addicts. This is a potential treatment for preventing relapse of withdrawal symptoms.
Topics: Humans; Paliperidone Palmitate; Substance Withdrawal Syndrome; Methamphetamine; Male; Adult; Electroacupuncture; Amphetamine-Related Disorders; Female; Neurotransmitter Agents; Combined Modality Therapy; Delayed-Action Preparations; Dopamine; Serotonin; gamma-Aminobutyric Acid; Middle Aged; Treatment Outcome; Antipsychotic Agents
PubMed: 38912759
DOI: 10.1708/4288.42698 -
Lancet Regional Health. Americas Aug 2024Manitoba saw the highest number of new HIV diagnoses in the province's history in 2021 and is the only Canadian province not meeting any of the previous UNAIDS 90-90-90...
Sex differences in houselessness, injection drug use, and mental health conditions among people newly diagnosed with HIV in Manitoba, Canada from 2018 to 2021: a retrospective cohort study.
BACKGROUND
Manitoba saw the highest number of new HIV diagnoses in the province's history in 2021 and is the only Canadian province not meeting any of the previous UNAIDS 90-90-90 targets. Our goal was to describe sex differences and syndemic conditions within an incident HIV cohort in Manitoba, and the HIV treatment initiation and undetectable viral load outcomes.
METHODS
This was a retrospective cohort study of all people 18 years and older newly diagnosed with HIV in Manitoba, Canada between January 1st, 2018 and December 31st, 2021. Data was collected as follows: : chlamydia, gonorrhoea, syphilis, and/or hepatitis C antibodies. : age, sex, gender, race/ethnicity, sexual orientation. : CD4 counts, viral load, HIV treatment, hospitalizations, and number of visits to HIV care. Main exposures evaluated: methamphetamine use, injection drug use, houselessness, and mental health conditions. Outcomes: started antiretroviral treatment and achieved an undetectable viral load. A descriptive statistical analysis was used.
FINDINGS
There were 404 new HIV diagnoses in Manitoba from 2018 to 2021; 44.8% were female, 55.2% male; 76.% self-identified as Indigenous, 13.4% white/European, 4.7% African/black; 86.6% cis-gender; 60.9% heterosexual, 13.4% gay, bisexual and men who have sex with men, and 1.7% lesbian. Injection drug use was reported by 71.8% and 43.5% of females and males respectively. Methamphetamine was the most frequently injected drug (62.4%). Amongst females, 81.8% experienced at least one of the following: houselessness (43.1%), mental health comorbidities (46.4%), and injection drug use (71.8%). Only 64.9% of all individuals had an undetectable viral load (61.1% females and 67.9% males), 56.5% among people experiencing houselessness, 59% among young people (≤29 years), and 60.1% among people who inject drugs.
INTERPRETATION
People newly diagnosed with HIV in Manitoba are disproportionately experiencing houselessness, mental illness, and injection drug use (mostly methamphetamine). This pattern is more pronounced for female individuals. These findings highlight the need for syndemic and gender-specific approaches, simultaneously addressing social and health conditions, to treat HIV.
FUNDING
This work was supported by the Canadian Institutes of Health Research, The Manitoba Medical Service Foundation, The James Farley Memorial Fund and the Canada Research Chairs Program.
PubMed: 38912328
DOI: 10.1016/j.lana.2024.100805 -
Psychiatry Research Jun 2024Attention deficit hyperactive disorder (ADHD) medication use rises among women of childbearing age and during pregnancy. Little is known on the safety of amphetamine...
Attention deficit hyperactive disorder (ADHD) medication use rises among women of childbearing age and during pregnancy. Little is known on the safety of amphetamine stimulants for ADHD treatment during breastfeeding. Most data on the safety of these medications are from recreational abuse of methamphetamine. This study followed children (N = 13) exposed to amphetamine stimulants during breastfeeding. Assessments by Pediatric Quality of Life and Denver Developmental Scale evaluated neurodevelopment and outcomes. Study results showed normal neurodevelopment with no significant adverse effects. Findings suggest amphetamines are likely compatible with breastfeeding; however larger studies are needed.
PubMed: 38908263
DOI: 10.1016/j.psychres.2024.116047 -
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 -
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