The prevalence of methamphetamine use disorder is increasing in North America. Well-evidenced treatment options are currently limited to behavioural interventions, with contingency management (CM) regarded as the most effective approach. Psychostimulants have been identified as a potentially promising treatment for methamphetamine use disorder, particularly at higher doses. This study was designed to examine the effectiveness of a high-dose daily psychostimulant (lisdexamfetamine; LDX) and CM, both alone and in combination, in addition to treatment-as-usual (TAU) for the treatment of moderate-to-severe methamphetamine use disorder.

The ASCME study is a multicentre, four-arm, blinded, randomized, placebo-controlled clinical trial examining the effectiveness of adding LDX (250 mg) and CM, alone or in combination, to TAU in reducing days of methamphetamine use among adults with moderate-to-severe methamphetamine use disorder. A total of 440 participants will be randomized across 5 sites to 12 weeks of 1) LDX + TAU + CM; 2) LDX + TAU; 3) placebo + CM + TAU; and 4) placebo + TAU. The primary outcome is reduction in days of self-reported methamphetamine use, with secondary outcomes including treatment retention, sustained abstinence, safety, medication adherence, satisfaction, and quality of life.

This study will be the largest study to date examining the effectiveness of a prescribed psychostimulant in the treatment of methamphetamine use disorder, and the first of its kind to employ a four-arm approach to evaluate the added benefit of its combination with CM on psychostimulant treatment. The development of pharmacologic treatments for methamphetamine use disorder remains an urgent research goal.

Novel strategies are needed to engage people who use stimulants into the continuum of addiction care. Contingency management (CM) is the most effective intervention for stimulant use disorder and may engage non-treatment-seeking populations, especially when delivered by peer recovery support specialists (peers). We describe development and training for a novel peer-delivered CM program for stimulant use harm reduction and treatment engagement.

We used a community based participatory research (CBPR) process to develop a CM program focused on self-identified goals for harm reduction and treatment engagement. A steering committee of peers guided study design, CM rewards, schedule, and incentivized goals. Peers completed coaching-to-criterion of six CM skills based on the CM Competence Scale (CMCS), then completed a one-on-one roleplay with a standardized patient. Coaches rated peer performance of each CMCS skill according to its Likert scale (1 = Very Poor to 7 = Excellent) and an a priori rating criterion of 4 ('adequate'). Roleplays included feedback and a 'replay' of skills, if necessary.

The steering committee devised two CM interventions: an enhanced standard-of-care incentivizing peer visits ($20 for weekly peer visits) and an intervention that additionally incentivized self-directed goals ($20 for weekly peer visits and $30 for completed goal-related activities). Self-identified goal-related activities were chosen through a collaborative process and organized into 6 domains: (1) overdose/overamping prevention (2) substance use supports/treatment (3) daily living/housing (4) education/employment (5) mental/physical/spiritual health (6) social relationships. Forty-seven peers across nine peer-led organizations (three rural and six urban organizations across Oregon) completed CM training. All 47 peers met the a priori criterion in their roleplay, with seventeen (36%) requiring a 'replay' of a skill. Mean CMSC summary scores were 28.51 (SD 4.73) on the first attempt and 29.62 (SD 4.01) on the second attempt.

PEER-CM (Peers Expanding Engagement in Stimulant Harm Reduction with Contingency Management) is among the first trials to use peer-delivered CM for stimulant use, incentivizing peer engagement and self-identified goals for harm reduction and treatment engagement. A CBPR approach strengthened the study design by incorporating peer guidance. Peers in this large, multisite sample demonstrated adequate CM delivery skills with acceptable fidelity following training. Trial Registration This study is registered at ClinicalTrials.gov (NCT05700994). Registered 26 January, 2023.

Methamphetamine abuse is a growing global health concern, recognized for its highly addictive properties and severe effects on the human body. Commonly referred to as crystal, chalk, or ice, methamphetamine is a synthetic stimulant that can be administered in various ways. Methamphetamine abuse is associated with a spectrum of oral health issues known as "meth mouth," including rampant teeth caries, extensive occlusal tooth wear, periodontal diseases, xerostomia, bruxism, and poor oral hygiene. Despite the significant oral health impact, the exact pathogenesis remains unclear due to the limited number of reported cases and comprehensive studies performed. This case series details changes in oral and general health of different severity associated with methamphetamine abuse, highlighting unusual presentations such as the generalized decrease in teeth sensitivity, which can be associated with aseptic tooth pulp necrosis, hairy black tongue, rampant arrested caries, decreased periodontal inflammation, specific sunflower seed abrasions on antagonistic central incisors, pityriasis rosea skin lesion and palmar erythema. The clinical management was presented in detail and justified, which entails conservative dental, periodontal and oral mucosae treatments and highlighted the need for a comprehensive complex examination of these patients and financial consideration in treatment planning. This case series underscores the need to recognize the diverse oral and general health effects of methamphetamine abuse, which vary with duration and individual symptoms. Patients often withhold substance use, leading to delayed diagnosis until severe manifestations arise. Enhanced awareness among healthcare providers can improve diagnosis and management, offering valuable insights into underlying mechanisms and enabling better care for this high-risk population.

Amphetamine-type stimulants are the second-most used illicit drugs globally, yet there are no US Food and Drug Administration (FDA)-approved treatments for amphetamine-type stimulant use disorders (ATSUD). The aim of this study was to utilize a drug discovery framework that integrates artificial intelligence (AI)-based drug prediction, clinical corroboration and mechanism of action analysis to identify FDA-approved drugs that can be repurposed for treating ATSUD.

An AI-based knowledge graph model was first utilized to prioritize FDA-approved drugs in their potential efficacy for treating ATSUD. Among the top 10 ranked candidate drugs, ketamine represented a novel candidate with few studies examining its effects on ATSUD. We therefore conducted a retrospective cohort study to assess the association between ketamine and ATSUD remission using US electronic health record (EHR) data. Finally, we analyzed the potential mechanisms of action of ketamine in the context of ATSUD.

ATSUD patients who received anesthesia (n = 3663) or were diagnosed with depression (n = 4328) between January 2019 and June 2022. The outcome measure was the diagnosis of ATSUD remission within one year of the drug prescription.

Ketamine for anesthesia in ATSUD patients was associated with greater ATSUD remission compared with other anesthetics: hazard ratio (HR) = 1.58, 95% confidence interval (CI) = 1.15-2.17. Similar results were found for ATSUD patients with depression when comparing ketamine with antidepressants and bupropion/mirtazapine with HRs of 1.51 (95% CI = 1.14-2.01) and 1.68 (95% CI = 1.18-2.38), respectively. Functional analyses demonstrated that ketamine targets several ATSUD-associated pathways including neuroactive ligand-receptor interaction and amphetamine addiction.

There appears to be an association between clinician-prescribed ketamine and higher remission rates in patients with amphetamine-type stimulant use disorders.

Novel interventions are urgently needed to treat methamphetamine use disorder (MUD), for which there are no FDA-approved treatments. Previous studies in patients with MUD suggest transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (L. dlPFC) decreases craving for methamphetamine. Theta burst stimulation (TBS), which includes intermittent TBS and continuous TBS (cTBS), is increasingly being used for substance use disorders, including MUD. Previous reviews of TMS in MUD performed sub-group meta-analyses of studies that delivered TBS in MUD. However, these meta-analyses included studies with overlapping participant cohorts. Given the absence of prior meta-analyses or reviews examining TBS in MUD using unique participant cohorts, we reviewed randomized controlled trials (RCTs) from three databases (PubMed/Medline, EMBASE, Google Scholar) until September 1, 2024, comparing the impact of TBS versus sham TBS on cue-induced methamphetamine cravings in patients with MUD. We performed a meta-analysis with four eligible RCTs that delivered iTBS. Results suggest iTBS was more effective in reducing cue-induced methamphetamine cravings than sham iTBS (standardized mean difference [SMD] in change = 1.04; 95% CI [0.16, 1.92]). Our systematic review included two additional RCTs that did not have sham comparator arms; one of these demonstrated a significant reduction in methamphetamine craving with accelerated iTBS. Future studies should examine if iTBS can impact clinical outcome measures other than craving, such as methamphetamine use, by measuring return to drug use. It is also pertinent to explore accelerated iTBS and cTBS for MUD and study their effects on relevant biomarkers for MUD.

Substance use disorders (SUDs) are a public health issue, with only some having FDA-approved indicated treatments and these having high attrition. Consequently, there has been interest in novel interventions (e.g. psychedelics that target 5-HT2A receptors) with some promising results. In this narrative review, we aim to focus on the role of the 5-HT2A receptors on the effectiveness of the treatment of SUDs.

We evaluated the clinical evidence of the treatment of SUDs with non-psychedelic medications with a primary affinity for the 5-HT2A receptor.

The reviewed literature showed some positive effects on craving and abstinence but, overall, results were mixed. Comparison of this work with work on psychedelic agents suggests that mixed results are not unique to non-psychedelic agents. Both psychedelic and non-psychedelic drugs with 5-HT2A affinity are not exclusively selective for 5-HT2A receptors. The observation that most agents reviewed are 5-HT2A receptor antagonists instead of agonists and that psychedelics (typically 5-HT2A receptor agonists) may have more homogenous positive results gives more support to 5-HT2A receptor agonists as a promising group for treating SUDs. Mechanisms may target a common denominator across SUDs (e.g. chronic hypodopaminergic states).

Methamphetamine and other stimulant use are increasing across Mexico while treatment options and public funding remain scarce for substance use treatment. This study examined the attitudes and perspectives of service providers who work with persons who use stimulants in Mexico.

Semistructured qualitative interviews were conducted with 20 service providers in diverse cities in the northern and central regions of Mexico, from healthcare centers and harm reduction community-based organizations (CBOs). All interviews were audio-recorded, transcribed, and de-identified. We conducted a thematic analysis to identify and compare common themes and patterns among participants, including portrayal of persons who use stimulants, dynamics of use, attitudes toward persons who use stimulants, and treatment availability and effectiveness.

First, service providers considered that persons who use stimulants have more complex backgrounds than others who use other substances. Second, although most providers mentioned trauma, pain, and the risk environment, CBO providers also stressed the importance of accounting for hedonism for understanding stimulant use trajectories. Third, treatment options are based on the type of services the institutions provide, usually constrained to guidelines for any substance use. In a few cases, cocaine treatment guidelines are used regardless of the type of stimulant used. Fourth, although health care services are abstinence-based, providers acknowledge the effectiveness of harm reduction approaches. In contrast, CBOs provide person-centered options.

Overall, although service providers are aware of the increase in stimulant use, stigmatizing attitudes are prominent among some of them. However, providers in CBOs were more sensitized to their communities' specific needs. Public policy recommendations include training to eliminate institutional stigmatization, the importance of first-person language, harm reduction effectiveness, and implementing community-based interventions to improve stimulant use-related services.

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.

Herbal medicine Ja-Geum-Jeong (JGJ) has been used for the treatment of detoxification in Eastern Asia. However, the mechanisms involved are not clearly defined. The purpose of the present study was to investigate if herb medication inhibits Methamphetamine (METH)'s reinforcing effect and also examined if a combination of herb medication and acupuncture produces a synergistic effect on METH.

Male Sprague-Dawley rats were given acute METH intraperitoneally and the locomotor activity and ultrasonic vocalization (USV) calls were measured. Rats were administered JGJ orally and acupuncture was given at HT7 or SI5. Monosodium glutamate (MSG) and gamma-aminobutyric acid (GABA) agonists were injected into the Central amygdala (CeA) to investigate a possible neuroscientific mechanism. Tyrosine hydroxylase (TH) and fast scan cyclic voltammetry (FSCV) were measured to immunohistochemically and electrically confirm the behavioral data.

Locomotor activity and USV calls were increased by METH (P < 0.05) and these increases were inhibited by JGJ (P < 0.05). Also, JGJ had no effect on the normal group given saline, and acupuncture at SI5 acupoint, but not at HT7 acupoint, produced a synergistic effect when combined with JGJ (P < 0.05). The JGJ's inhibition was blocked by the inactivation of CeA (P < 0.05), and MSG mimicked JGJ (P < 0.05). TH and FSCV measures showed the same pattern with the behavioral data (P < 0.05).

Results of the present study suggest that JGJ had inhibitory effects on the METH which was mediated through the activation of CeA and that combination of acupuncture and herb produced synergistic effect.

Stimulant use is a growing problem, but little is known about service utilization among patients with stimulant use disorder (StUD). In the context of the overdose crisis, much research has focused on patients with opioid use disorder (OUD). It is unclear how the characteristics, treatment receipt, and hospitalization of patients with StUD differ from patients with OUD.

Electronic health record data were extracted for national Veterans Health Administration patients with a visit from March 1, 2020, to February 28, 2021 with StUD and/or OUD (N = 132,273). We compared patients with StUD without OUD to those with (1) co-occurring StUD + OUD and (2) OUD without StUD. Patient characteristics, substance use disorder treatment, and hospitalizations in the year following patients' first study period visit were descriptively compared. Treatment and hospitalization were also compared in adjusted regression models.

Compared with patients with OUD + StUD, those with StUD without OUD were less likely to receive outpatient (adjusted odds ratio [aOR] 0.49, 95% confidence interval [CI] 0.47-0.50) or any treatment (aOR 0.47, 95% CI 0.46-0.49). Compared with patients with OUD without StUD, those with StUD without OUD were less likely to receive outpatient (aOR 0.51, 95% CI 0.49-0.52) or any treatment (aOR 0.56, 95% CI 0.54-0.58) and more likely to receive residential treatment (aOR 2.18, 95% 2.05-2.30) and to be hospitalized (aOR 1.62, 95% 1.56-1.69).

Patients with StUD may be less likely to receive treatment and more likely to be hospitalized than patients with OUD. Efforts focused on mitigating hospitalization and increasing treatment receipt for patients with StUD are needed.

This epigenomics sub-study embedded within a randomized controlled trial examined whether an evidenced-based behavioral intervention model that decreased stimulant use altered leukocyte DNA methylation (DNAm).

Sexual minority men with HIV who use methamphetamine were randomized to a five-session positive affect intervention (n = 32) or an attention-control condition (n = 21), both delivered during three months of contingency management for stimulant abstinence. All participants exhibited sustained HIV virologic control - an HIV viral load less than 40 copies/mL at baseline and six months post-randomization. The Illumina EPIC BeadChip measured leukocyte methylation of cytosine-phosphate-guanosine (CpG) sites mapping onto five a priori candidate genes of interest (i.e., ADRB2, BDNF, FKBP5, NR3C1, OXTR). Functional DNAm pathways and soluble markers of immune dysfunction were secondary outcomes.

Compared to the attention-control condition, the positive affect intervention significantly decreased methylation of CpG sites on genes that regulate β2 adrenergic and oxytocin receptors. There was an inconsistent pattern for the direction of the intervention effects on methylation of CpG sites on genes for glucocorticoid receptors and brain-derived neurotrophic factor. Pathway analyses adjusting for the false discovery rate (padj < 0.05) revealed significant intervention-related alterations in DNAm of Reactome pathways corresponding to neural function as well as dopamine, glutamate, and serotonin release. Positive affect intervention effects on DNAm were accompanied by significant reductions in the self-reported frequency of stimulant use.

There is an epigenetic signature of an evidence-based behavioral intervention model that reduced stimulant use, which will guide the identification of biomarkers for treatment responses.

The aim of the current study was to assess the accuracy of expert predictions, which were derived using a Delphi panel foresight study between 2009 and 2011, on a variety of drug-related topics in Finland in 2020.

The material used to evaluate the accuracy of the predictions consists of published reports on statistics, survey results, official register data, wastewater analyses and official documents. Whenever possible, we used multiple information sources to ascertain possible changes related to the predictions.

Between 2009 and 2011, the majority - but not all - of the experts accurately predicted an increase in drug use. Indeed, more people experimented with or used drugs, and more drug residues were found in wastewater monitoring. The experts also correctly predicted an increase in population-level approval of drug use, but this development has been rather slow. Contrary to predictions, there was no marked increase in the use of new synthetic drugs. However, the misuse of buprenorphine increased during the 2010s. In the drug market, unit prices were surprisingly stable over the ten-year period. There were no changes in legislation related to the legal status of drugs, as was foreseen by the experts. However, enforcement moved in the direction foreseen by the experts: more lenient measures have been taken against users. Drug care system reforms favored a combination of mental health and addiction care units between 2009 and 2011, and 2020, as foreseen by the experts.

It seems to have been easier for the experts to foresee the continuation of existing trends, e.g., increasing use of drugs or widening approval of drugs, than to predict possible changes in the popularity of distinct groups of drugs such as new psychoactive substances (NPS). Even armed with the prediction that drug imports and wholesale would increasingly fall into the domain of organized crime, this undesirable development could not be stopped. Expert disagreement can also be seen as a valuable indication of uncertainty regarding the future. Foresight related to drug-related issues can produce relatively accurate and realistic views of the future at least up to ten years ahead.

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.

Amphetamine and other substances induced psychotic disorder and associated suicidal risk among hospitalized US veterans is not clear.

To understand the demographic profile, substance use trends, psychotic disorders and suicide attempts in veterans hospitalized with acute Mental Health Conditions (MHC).

Veterans Affairs Informatics and Computing Infrastructure Database (ICD) and codes were used to identify veterans hospitalized with MHC diagnosis between 1999 and 2022. Laboratory records used to determine types of substances used hospitalization frequency, all-cause mortality, suicide attempts and suicide outcomes. SAS was used for statistical analysis.

Among veterans with MHC, psychosis, manic-bipolar and PTSD were common diagnosis. Psychosis was comparatively less among males above 50 years of age, but prevalent among Hispanics. In general, substances use was significantly higher, and amphetamines were most used, followed by cannabis codeine, morphine, cocaine, barbiturates, fentanyl, and PCP among veterans with MHC. Amphetamine induced psychotic disorder persisted in 22.28% and other substance induced psychotic disorder persisted in 77.72% of veterans hospitalized with MHC. Psychosis was associated with higher rates of hospitalization, suicide attempts, and suicide death.

Among US Veterans with MHC, amphetamine was most used substance associated with higher rates of psychotic disorders, hospitalization, suicide attempts, and death.

There has been a significant increase in methamphetamine use and methamphetamine use disorder (Meth UD) in the United States, with evolving racial and ethnic differences.

This secondary analysis explored racial and ethnic differences in baseline sociodemographic and clinical characteristics as well as treatment effects on a measure of substance use recovery, depression symptoms, and methamphetamine craving among participants in a pharmacotherapy trial for Meth UD.

The ADAPT-2 trial (ClinicalTrials.gov number, NCT03078075; N=403; 69% male) was a multisite, 12-week randomized, double-blind, trial that employed a two-stage sequential parallel design to evaluate the efficacy of combination naltrexone (NTX) and oral bupropion (BUP) vs. placebo for Meth UD. Treatment effect was calculated as the weighted mean change in outcomes in the NTX-BUP minus placebo group across the two stages of treatment.

Of the 403 participants in the ADAPT-2 trial, the majority (65%) reported non-Hispanic White, while 14%, 11% and 10% reported Hispanic, non-Hispanic Black, and non-Hispanic other racial and ethnic categories respectively. At baseline non-Hispanic Black participants reported less severe indicators of methamphetamine use than non-Hispanic White. Treatment effects for recovery, depression symptoms and methamphetamine cravings did not significantly differ by race and ethnicity.

Although we found racial and ethnic differences at baseline, our findings did not show racial and ethnic differences in treatment effects of NTX-BUP on recovery, depression symptoms and methamphetamine cravings. However, our findings also highlight the need to expand representation of racial and ethnic minority groups in future trials.

While the majority of people with cocaine use disorders (CUD) also co-use tobacco/nicotine, most preclinical cocaine research does not include nicotine. The present study examined nicotine and cocaine co-use under several conditions of intravenous drug self-administration in monkeys, as well as potential peripheral biomarkers associated with co-use. In Experiment 1, male rhesus monkeys (N = 3) self-administered cocaine (0.001-0.1 mg/kg/injection) alone and with nicotine (0.01-0.03 mg/kg/injection) under a progressive-ratio schedule of reinforcement. When nicotine was added to cocaine, there was a significant leftward/upward shift in the number of injections received. In Experiment 2, socially housed female and male cynomolgus monkeys (N = 14) self-administered cocaine under a concurrent drug-vs-food choice schedule of reinforcement. Adding nicotine to the cocaine solution shifted the cocaine dose-response curves to the left, with more robust shifts noted in the female animals. There was no evidence of social rank differences. To assess reinforcing strength, delays were added to the presentation of drug; the co-use of nicotine and cocaine required significantly longer delays to decrease drug choice, compared with cocaine alone. Blood samples obtained post-session were used to analyze concentrations of neuronally derived small extracellular vesicles (NDE); significant differences in NDE profile were observed for kappa-opioid receptors when nicotine and cocaine were co-used compared with each drug alone and controls. These results suggest that drug interactions involving the co-use of nicotine and cocaine are not simply changing potency, but rather resulting in changes in reinforcing strength that should be utilized to better understand the neuropharmacology of CUD and the evaluation of potential treatments.

Methamphetamine abuse results in a host of social and medical issues. Methamphetamine use disorder (MUD) can hinder the brain and impair cognitive functions and mental health. Transcranial magnetic stimulation (TMS) is a non-invasive approach in the treatment of MUD. Recent studies have demonstrated encouraging and positive effects of TMS on the craving, affective symptoms, sleep quality, and cognitive functions in individuals with MUD. The regulation of specific brain activities through TMS has also been found to be a contributing factor to these positive outcomes. It is essential to employ more techniques, participants, and stimulation parameters and targets in the future.

Stimulant use disorder is a continuously growing medical and social burden without approved medications available for its treatment. Psychosocial interventions could be a valid approach to help people reduce or cease stimulant consumption. This is an update of a Cochrane review first published in 2016.

To assess the efficacy and safety of psychosocial interventions for stimulant use disorder in adults.

We searched the Cochrane Drugs and Alcohol Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, three other databases, and two trials registers in September 2023. All searches included non-English language literature. We handsearched the references of topic-related systematic reviews and the included studies.

We included randomised controlled trials (RCTs) comparing any psychosocial intervention with no intervention, treatment as usual (TAU), or a different intervention in adults with stimulant use disorder.

We used the standard methodological procedures expected by Cochrane.

We included a total of 64 RCTs (8241 participants). Seventy-three percent of studies included participants with cocaine or crack cocaine use disorder; 3.1% included participants with amphetamine use disorder; 10.9% included participants with methamphetamine use disorder; and 12.5% included participants with any stimulant use disorder. In 18 studies, all participants were in methadone maintenance treatment. In our primary comparison of any psychosocial treatment to no intervention, we included studies which compared a psychosocial intervention plus TAU to TAU alone. In this comparison, 12 studies evaluated cognitive behavioural therapy (CBT), 27 contingency management, three motivational interviewing, one study looked at psychodynamic therapy, and one study evaluated CBT plus contingency management. We also compared any psychosocial intervention to TAU. In this comparison, seven studies evaluated CBT, two contingency management, two motivational interviewing, and one evaluated a combination of CBT plus motivational interviewing. Seven studies compared contingency management reinforcement related to abstinence versus contingency management not related to abstinence. Finally, seven studies compared two different psychosocial approaches. We judged 65.6% of the studies to be at low risk of bias for random sequence generation and 19% at low risk for allocation concealment. Blinding of personnel and participants was not possible for the type of intervention, so we judged all the studies to be at high risk of performance bias for subjective outcomes but at low risk for objective outcomes. We judged 22% of the studies to be at low risk of detection bias for subjective outcomes. We judged most of the studies (69%) to be at low risk of attrition bias. When compared to no intervention, we found that psychosocial treatments: reduce the dropout rate (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.74 to 0.91; 30 studies, 4078 participants; high-certainty evidence); make little to no difference to point abstinence at the end of treatment (RR 1.15, 95% CI 0.94 to 1.41; 12 studies, 1293 participants; high-certainty evidence); make little to no difference to point abstinence at the longest follow-up (RR 1.22, 95% CI 0.91 to 1.62; 9 studies, 1187 participants; high-certainty evidence); probably increase continuous abstinence at the end of treatment (RR 1.89, 95% CI 1.20 to 2.97; 12 studies, 1770 participants; moderate-certainty evidence); may make little to no difference in continuous abstinence at the longest follow-up (RR 1.14, 95% CI 0.89 to 1.46; 4 studies, 295 participants; low-certainty evidence); reduce the frequency of drug intake at the end of treatment (standardised mean difference (SMD) -0.35, 95% CI -0.50 to -0.19; 10 studies, 1215 participants; high-certainty evidence); and increase the longest period of abstinence (SMD 0.54, 95% CI 0.41 to 0.68; 17 studies, 2118 participants; high-certainty evidence). When compared to TAU, we found that psychosocial treatments reduce the dropout rate (RR 0.79, 95% CI 0.65 to 0.97; 9 studies, 735 participants; high-certainty evidence) and may make little to no difference in point abstinence at the end of treatment (RR 1.67, 95% CI 0.64 to 4.31; 1 study, 128 participants; low-certainty evidence). We are uncertain whether they make any difference in point abstinence at the longest follow-up (RR 1.31, 95% CI 0.86 to 1.99; 2 studies, 124 participants; very low-certainty evidence). Compared to TAU, psychosocial treatments may make little to no difference in continuous abstinence at the end of treatment (RR 1.18, 95% CI 0.92 to 1.53; 1 study, 128 participants; low-certainty evidence); probably make little to no difference in the frequency of drug intake at the end of treatment (SMD -1.17, 95% CI -2.81 to 0.47, 4 studies, 479 participants, moderate-certainty evidence); and may make little to no difference in the longest period of abstinence (SMD -0.16, 95% CI -0.54 to 0.21; 1 study, 110 participants; low-certainty evidence). None of the studies for this comparison assessed continuous abstinence at the longest follow-up. Only five studies reported harms related to psychosocial interventions; four of them stated that no adverse events occurred.

This review's findings indicate that psychosocial treatments can help people with stimulant use disorder by reducing dropout rates. This conclusion is based on high-certainty evidence from comparisons of psychosocial interventions with both no treatment and TAU. This is an important finding because many people with stimulant use disorders leave treatment prematurely. Stimulant use disorders are chronic, lifelong, relapsing mental disorders, which require substantial therapeutic efforts to achieve abstinence. For those who are not yet able to achieve complete abstinence, retention in treatment may help to reduce the risks associated with stimulant use. In addition, psychosocial interventions reduce stimulant use compared to no treatment, but they may make little to no difference to stimulant use when compared to TAU. The most studied and promising psychosocial approach is contingency management. Relatively few studies explored the other approaches, so we cannot rule out the possibility that the results were imprecise due to small sample sizes.

As overdose rates increase for multiple substances, policymakers need to identify geographic patterns of substance-specific deaths. In this study, we describe county-level opioid and psychostimulant overdose patterns and how they correlate with county-level social vulnerability measures.

A cross-sectional observational study, we used nationwide 2016-2018 restricted access Centers for Disease Prevention and Control county-level mortality files for 1,024 counties. We estimated quartiles of opioid and psychostimulant overdose mortality and provided estimates of their association with county-level Social Vulnerability Index (SVI) percentile.

There was high opioid and psychostimulant overdose mortality in the Middle Atlantic, South Atlantic, East North Central, and Mountain regions. The Central US had the lowest opioid and psychostimulant overdose mortality rates. Counties with higher SVI scores (i.e. higher social vulnerability) were significantly more likely to experience high opioid and high psychostimulant overdose (high-high) mortality. A 10-percentile increase in SVI score was associated with a 3.1 percentage point increase in the likelihood of being a high-high county (p < 0.001) in unadjusted models and a 1.5 percentage point increase (p < 0.05) in models adjusting for region.

Our results illustrated the heterogenous geographic distribution of the growing concurrent opioid and psychostimulant overdose crisis. The substantial regional variation we identified highlights the need for local data to guide policymaking and treatment planning. The association of opioid-psychostimulant overdose mortality with social vulnerability demonstrates the critical need in impacted counties for tailored treatment that addresses the complex medical and social needs of people who use both opioids and psychostimulants.

Individuals with mental illness have a high incidence of comorbid substance use, with one of the most prevalent being alcohol use disorder (AUD). Naltrexone, FDA-approved for AUD, decreases reward associated with alcohol-related social cues. This study aimed to determine if a pharmacist-driven screening tool would increase the use of extended-release naltrexone (XR-NTX) in patients with AUD and a comorbid psychiatric condition. Pharmacists screened and recommended XR-NTX for adults admitted to the inpatient psychiatric unit, who had a DSM-5 diagnosis of AUD, a negative urine drug screen for opioids, and were hospitalized for at least 1 day. Endpoints evaluated included the number of XR-NTX doses administered during the screening period to the prescreening period, 30-day readmission rates, recommendation acceptance rates, and reasons for not administering XR-NTX. Pharmacists identified 66 of 641 screened patients who met the inclusion criteria and were candidates for XR-NTX. Compared to the preintervention period, more patients received XR-NTX for AUD (2 vs. 8). Readmission rates were similar between those with AUD who received XR-NTX and those who did not. Pharmacist-driven screening for AUD led to greater administration of XR-NTX when compared to the same 4-month period the year prior to initiating the study.

Psychoactive drug combinations are increasingly contributing to overdose deaths among White and Black Americans. To understand the evolving nature of overdose crisis, inform policies, and develop tailored and equitable interventions, this study provides a comprehensive assessment of polysubstance mortality trends by race and sex during the opioid epidemic.

We used serial cross-sectional US mortality data for White and Black populations from 1999 through 2018 to calculate annual age-adjusted death rates (AADR) involving any opioid, opioid subtypes, benzodiazepines, cocaine, psychostimulants, or combinations of these drugs, stratified by race and sex. Trend changes in AADR were analyzed using joinpoint regression models and expressed as average annual percent change (AAPC) during each period of the three waves of the opioid epidemic: 1999-2010 (wave 1), 2010-2013 (wave 2), and 2013-2018 (wave 3). Prevalence measures assessed the percent co-involvement of an investigated drug in the overall death from another drug.

Polysubstance mortality has shifted from a modest rise in death rates due to benzodiazepine-opioid overdoses among White persons (wave 1) to a substantial increase in death rates due to illicit drug combinations impacting both White and Black populations (wave 3). Concurrent cocaine-opioid use had the highest polysubstance mortality rates in 2018 among Black (5.28 per 100,000) and White (3.53 per 100,000) persons. The steepest increase in death rates during wave 3 was observed across all psychoactive drugs when combined with synthetic opioids in both racial groups. Since 2013, Black persons have died faster from cocaine-opioid and psychostimulant-opioid overdoses. Between 2013 and 2018, opioids were highly prevalent in cocaine-related deaths, increasing by 33% in White persons compared to 135% in Blacks. By 2018, opioids contributed to approximately half of psychostimulant and 85% of benzodiazepine fatal overdoses in both groups. The magnitude and type of drug combinations with the highest death rates differed by race and sex, with Black men exhibiting the highest overdose burden beginning in 2013.

The current drug crisis should be considered in the context of polysubstance use. Effective measures and policies are needed to curb synthetic opioid-involved deaths and address disparate mortality rates in Black communities.

Addiction is a chronic disease with limited pharmacological options for intervention. Focusing on reducing glutamate levels in the brain seems to be a promising strategy in addiction treatment research. Our research aimed to evaluate the effects of CNQX, an antagonist that targets AMPA and kainate glutamatergic receptors while also exhibiting affinity for the NMDA receptor, especially by modulating its glycine site. We conducted this assessment on the self-administration of nicotine and methamphetamine via intravenous (IV) administration in rats.

An operant IV self-administration model was used in male Wistar rats. When animals maintained a stable intake of nicotine or methamphetamine, we administered a single injection of CNQX (in the dose of 3 or 6 mg/kg IV) to evaluate its effect on drug intake. Subsequently, the rats were forced to abstain by staying in their home cages for 2 weeks. The period of abstinence was followed by a context-induced relapse-like session before which animals were pretreated with the injection of CNQX (3 or 6 mg/kg IV) to evaluate its effect on drug seeking.

CNQX significantly reduced nicotine intake during the maintenance phase, but no effect was revealed on nicotine seeking after forced abstinence. CNQX did not affect methamphetamine taking or seeking.

The effect of reducing nicotine taking but not seeking could be explained by different involvement of glutamatergic receptors in various stages of nicotine dependence.

Methamphetamine Toxicities and Clinical ManagementMethamphetamine increases the release and blocks the uptake of norepinephrine, serotonin, and dopamine. This article reviews the morbidity and mortality associated with methamphetamine use and discusses prevention and treatment strategies.

Trace amine-associated receptor 1 (TAAR1), the founding member of a nine-member family of trace amine receptors, is responsible for recognizing a range of biogenic amines in the brain, including the endogenous β-phenylethylamine (β-PEA)1 as well as methamphetamine2, an abused substance that has posed a severe threat to human health and society3. Given its unique physiological role in the brain, TAAR1 is also an emerging target for a range of neurological disorders including schizophrenia, depression and drug addiction2,4,5. Here we report structures of human TAAR1-G-protein complexes bound to methamphetamine and β-PEA as well as complexes bound to RO5256390, a TAAR1-selective agonist, and SEP-363856, a clinical-stage dual agonist for TAAR1 and serotonin receptor 5-HT1AR (refs. 6,7). Together with systematic mutagenesis and functional studies, the structures reveal the molecular basis of methamphetamine recognition and underlying mechanisms of ligand selectivity and polypharmacology between TAAR1 and other monoamine receptors. We identify a lid-like extracellular loop 2 helix/loop structure and a hydrogen-bonding network in the ligand-binding pockets, which may contribute to the ligand recognition in TAAR1. These findings shed light on the ligand recognition mode and activation mechanism for TAAR1 and should guide the development of next-generation therapeutics for drug addiction and various neurological disorders.

This meta-analysis (PROSPERO-ID: CRD42022362962), pooled effect estimates of outcomes, from placebo-controlled randomized clinical trials (RCTs) examining bupropion efficacy and safety for amphetamine-type stimulant use disorder (ATSUD) treatment.

Electronic databases were searched for records published to October 31st, 2022, including MEDLINE, CINAHL, PsycINFO, EBM Reviews, EMBASE, PubMed, Web of Science, trial registries. Inclusion criteria were RCTs comparing bupropion to placebo in ATSUD. Cochrane RoB2 tool and GRADE evidence certainty assessment were employed. Outcomes included amphetamine-type stimulant (ATS) use by urinalysis, retention in treatment, treatment adherence, ATS craving, addiction severity, depressive symptom severity, drop-out following adverse events (AEs), and serious AEs. Random-effect meta-analysis was conducted presenting standardized mean difference (SMD), risk ratio (RR), and risk difference (RD).

Eight RCTs (total N=1239 participants) were included. Bupropion compared to placebo was associated with reduced ATS use (RR: 0.90; 95% CI: 0.84, 0.96), end-of-treatment ATS craving (SMD: -0.38; 95%CI: -0.63, -0.13), and adherence (RR: 0.91; 95%CI: 0.84, 0.99). Subgroup analysis showed greater reduction in ATS use with longer trial duration (12 weeks) (RR: 0.85; 95%CI: 0.78, 0.93) and greater reduction in end-of-treatment ATS craving in studies with mixed ATS use frequency (SMD: -0.46; 95%CI: -0.70, -0.22) and male-only samples (SMD: -1.26; 95%CI: -1.87, -0.65).

Bupropion showed a significant modest reduction in ATS use and ATS craving (both rated as very low-quality evidence), larger in males (craving), and with longer treatment (ATS use). These results may inform future studies. More research is warranted on who might benefit from bupropion as ATSUD treatment.

Amphetamine injection is expanding in North America and has been associated with male homosexuality among people who inject drugs (PWID). Applying subcultural evolution theory, we examined overall and gender-stratified trends in amphetamine injection and assessed sexual orientation as a gender-specific predictor of initiation among PWID in Montreal, Canada.

Data were from HEPCO, an open prospective cohort of PWID. Gender and sexual orientation were self-identified at enrolment. Interviewer-administered questionnaires at three-monthly (HCV RNA-negative participants) or yearly (RNA-positive) intervals captured past three-month amphetamine injection and covariates. Annual prevalence and linear trends in amphetamine injection were estimated using GEE. Incidence was computed among naïve individuals and hazard ratios for initiation estimated using gender-stratified, time-varying Cox regression models.

803 participants contributed 8096 observations between March 2011 and December 2019. Annual prevalence of amphetamine injecting increased from 3.25% [95%CI: 2.06-4.43%] to 12.7% [9.50-16.0] (trend p<0.001). Bivariate Cox regression models suggested similar and divergent predictors of initiation by gender. Incidence was 3.27 per 100 person-years [95%CI: 2.51-4.18] among heterosexual men, 7.18 [3.50-13.2] among gay/bisexual men, 1.93 [0.78-4.02] among heterosexual women and 5.30 [1.69-12.8] among gay/bisexual women. Among men, gay/bisexual identity doubled risk of initiation after adjusting for age, ethnicity, calendar year (aHR 2.16 [1.07-4.36]) and additional covariates (2.56 [1.24-5.30]). Among women, evidence for an association with gay/bisexual identity was inconclusive (aHR 2.63 [0.62-11.2]) and sample size precluded further adjustment CONCLUSIONS: Prevalence of amphetamine injection among PWID increased four-fold from 2011 to 2019, with elevated risk of initiation in gay and bisexual men.

Stimulant use among unstably housed individuals is associated with increased risks of psychiatric co-morbidity, violence, HIV transmission, and overdose. Due to a lack of highly effective treatments, evidence-based policies targeting the prevention of stimulant use disorder are of critical importance. However, little empirical evidence exists on risks associated with initiating or returning to stimulant use among at-risk populations. In a longitudinal cohort of unstably housed women in San Francisco (2016-2019), self-reported data on stimulant use, housing status, and mental health were collected monthly for up to 6 months, and factors associated with initiating stimulants after a period of non-use were identified through logistic regression. Among 245 participants, 42 (17.1%) started using cocaine and 46 (18.8%) started using methamphetamine. In analyses adjusting for demographics and socio-structural exposures over the preceding month, experiencing street homelessness was associated with initiating cocaine use (AOR: 2.10; 95% CI: 1.04, 4.25) and sheltered homelessness with initiating methamphetamine use (AOR: 2.57; 95% CI: 1.37, 4.79). Other factors-including race, income, unmet subsistence needs, mental health, and treatment adherence-did not reach levels of significance, suggesting the paramount importance of policies directed toward improving access to permanent supportive housing to prevent stimulant use among unstably housed women.

Methamphetamine use is common among persons with opioid use disorder. This study evaluated associations between methamphetamine use and treatment with agonist medications for opioid use disorder (MOUD, specifically buprenorphine, and/or methadone) in U.S. rural communities.

The Rural Opioid Initiative (ROI) is a consortium spanning 10 states and 65 rural counties that included persons who reported past 30-day use of opioids and/or injection drug use between 1/2018 and 3/2020. Analyses were restricted to participants who had ever used opioids and had data on past 30-day methamphetamine use. Multivariable models examined the relationship between methamphetamine use and utilization of agonist MOUD.

Among 2899 participants, 2179 (75.2%) also reported recent methamphetamine use. Persons with methamphetamine use compared to those without were younger, more likely to have injected drugs, be unhoused, criminal justice involved, and less likely to have health insurance. Adjusted for age, sex, race, and study site, recent methamphetamine use was associated with lower relative odds of past 30-day methadone treatment (aOR=0.66; 95% CI: 0.45-0.99) and fewer methadone treatment days (aIRR=0.76; 0.57-0.99), but not past 30-day buprenorphine receipt (aOR=0.90; 0.67-1.20), buprenorphine treatment days in past 6 months: aIRR=0.88; 0.69-1.12) or perceived inability to access buprenorphine (aOR=1.12; 0.87-1.44) or methadone (aOR=1.06; 0.76-1.48).

Methamphetamine use is common among persons who use opioids in rural U.S. areas and negatively associated with current treatment and retention on methadone but not buprenorphine. Future studies should examine reasons for this disparity and reduce barriers to methadone for persons who use opioids and methamphetamine.

Methamphetamine use disorder (MethUD) disproportionately affects men who have sex exclusively with men or with men and women (collectively MSM/W), compared to men who have sex with women (MSW). This study is the first MethUD medication trial to compare treatment effect for these groups, hypothesizing that extended-release injectable naltrexone 380mg every 3 weeks plus oral extended-release bupropion 450mg daily would be less effective for MSM/W than MSW.

Data come from men (N = 246) in a multi-site, double-blind, randomized, placebo-controlled trial with sequential parallel comparison design. In Stage 1 (6-weeks), participants were randomized to active treatment or placebo. In Stage 2 (6-weeks), Stage 1 placebo non-responders were rerandomized. Treatment response was ≥3 methamphetamine-negative urine samples, out of four obtained at the end of Stages 1 and 2. Treatment effect was the active-versus-placebo between-group difference in the weighted average Stages 1 and 2 responses.

MSM/W (n = 151) were more likely than MSW (n = 95) to be Hispanic, college-educated, and living with HIV. Adjusting for demographics, among MSM/W, response rates were 13.95 % (active treatment) and 2.78 % (placebo) in Stage 1; 23.26 % (active treatment) and 4.26 % (placebo) in Stage 2. Among MSW, response rates were 7.69 % (active treatment) and 5.80 % (placebo) in Stage 1; 3.57 % (active treatment) and 0 % (placebo) in Stage 2. Treatment effect was significantly larger for MSM/W (h = 0.1479) than MSW (h = 0.0227) (p = 0.04).

Findings suggest efficacy of extended-release naltrexone plus bupropion for MSM/W, a population heavily burdened by MethUD. While a secondary outcome, this intriguing finding merits testing in prospective trials.

An emerging public health threat of methamphetamine/opioid co-use is occurring in North America, including increases in overdoses related to concomitant methamphetamine/opioid use. This presents a potential risk to established treatments for opioid use disorder (i.e., medications for opioid use disorder [MOUD]). To date, few studies have examined the impact of methamphetamine use on MOUD-related outcomes, and no studies have synthesized data on MOUD retention.

A scoping review was undertaken to examine the impact of methamphetamine use on MOUD retention. All original published research articles were searched in Embase, MEDLINE, PsychINFO, CINAHL, Scopus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Cochrane Protocols, and Google scholar databases. Data were extracted into a standardized data extraction chart. Findings were presented narratively.

All eight included studies demonstrated an increased likelihood of treatment discontinuation or dropout among patients enrolled in MOUD who used methamphetamine. The frequency of methamphetamine use was also associated with MOUD dropout, in that those who used methamphetamine more often were more likely to discontinue MOUD. The definitions and measurements of MOUD retention varied considerably, as did the magnitude of effect size.

Results indicate that methamphetamine use has an undesirable impact on MOUD retention and results in an increased risk of treatment discontinuation or dropout. Strategies to identify concurrent methamphetamine use among individuals engaging in MOUD and educate them on the increased risk for dropout should be undertaken. Further research is needed to understand how MOUD retention among patients with concomitant opioid and methamphetamine use can be improved.

A transition in viewing mental disorders from conditions defined as a set of unique characteristics to one of the quantitative variations on a collection of dimensions allows overlap between disorders. The overlap can be utilized to extend to treatment approaches. Here, we consider the overlap between attention-deficit/hyperactivity disorder and substance use disorder to probe the suitability to use methylphenidate as a treatment for substance use disorder. Both disorders are characterized by maladaptive goal-directed behavior, impaired cognitive control, hyperactive phasic dopaminergic neurotransmission in the striatum, prefrontal hypoactivation, and reduced frontal cortex gray matter volume/density. In addition, methylphenidate has been shown to improve cognitive control and normalize associated brain activation in substance use disorder patients and clinical trials have found methylphenidate to improve clinical outcomes. Despite the theoretical basis and promising, but preliminary, outcomes, many questions remain unanswered. Most prominent is whether all patients who are addicted to different substances may equally profit from methylphenidate treatment.

Introduction: While substance use contributes to a substantial burden of disease, access to evidence-based harm reduction interventions remains limited or inaccessible. Preliminary research suggests that some individuals use cannabis to reduce the harms associated with their use of other substances, including opioids and stimulants. This study examines factors associated with the self-reported use of cannabis for harm reduction among people who use drugs (PWUD). Methods: We drew data from three prospective, community-recruited cohorts of PWUD in Vancouver, Canada, between June 2016 and May 2018. Multivariable generalized linear mixed-effects modeling was used to examine factors associated with the primary outcome of "use of cannabis for harm reduction," defined as self-reported use of cannabis to substitute for other substances, treat withdrawal, or come down off other drugs. Results: One thousand nine hundred thirty-six participants contributed 5706 observations. In adjusted analyses, daily methamphetamine use (adjusted odds ratio [AOR]=1.43, 95% confidence interval [CI]: 1.09-1.89), experiencing barriers to accessing addiction treatment (AOR=1.92, 95% CI: 1.21-3.03), and enrollment in addiction treatment modalities other than opioid agonist therapy (AOR=1.64, 95% CI: 1.17-2.29) were positively associated with using cannabis for harm reduction. Older age was negatively associated (AOR=0.97, 95% CI: 0.95-0.98). Among 1281 (66.2%) participants who use cannabis, daily cannabis use and obtaining cannabis from unregulated dispensaries were also independent correlates of using cannabis for harm reduction. Discussion and Conclusions: Individuals who were more likely to use cannabis for harm reduction reported difficulty accessing addiction treatment or used substances, such as methamphetamines, where effective treatments are limited. These findings highlight the need to better understand the potential harm-reducing impacts of cannabis among PWUD in these scenarios.

Australia has one of the highest rates in the world of the use of the crystalline form of methamphetamine, a highly addictive stimulant that is often associated with a chronic, relapsing dependency. Methamphetamine use is associated with both acquisitive and violent offending, which cause substantial personal and societal costs. Whilst the short-term euphoria and stimulation provide a positive reinforcement to methamphetamine use, the aversive states of withdrawing from methamphetamine and the associated craving, which may last up to five weeks into abstinence, underlie the negative reinforcement to continued methamphetamine use. Although many methamphetamine-dependent users experience high levels of psychological distress, it is likely that less than half engage with treatment or support services, and current intervention and treatment programmes have high discontinuation rates. Stigma and discrimination, even from paramedics and health clinicians, are prominent barriers to methamphetamine-dependent users accessing treatment in Australia.

Socio-cultural (gender) and biological (sex)-based differences contribute to psychostimulant susceptibility, potentially affecting treatment responsiveness among women with methamphetamine use disorder (MUD). The aims were to measure (i) how women with MUD independently and compared with men respond to treatment versus placebo and (ii) among women, how the hormonal method of contraception (HMC) affects treatment responsiveness.

This was a secondary analysis of ADAPT-2, a randomized, double-blind, placebo-controlled, multicenter, two-stage sequential parallel comparison design trial.

United States.

This study comprised 126 women (403 total participants); average age = 40.1 years (standard deviation = 9.6) with moderate to severe MUD.

Interventions were combination intramuscular naltrexone (380 mg/3 weeks) and oral bupropion (450 mg daily) versus placebo.

Treatment response was measured using a minimum of three of four negative methamphetamine urine drug tests during the last 2 weeks of each stage; treatment effect was the difference between weighted treatment responses of each stage.

At baseline, women used methamphetamine intravenously fewer days than men [15.4 versus 23.1% days, P = 0.050, difference = -7.7, 95% confidence interval (CI) = -15.0 to -0.3] and more women than men had anxiety (59.5 versus 47.6%, P = 0.027, difference = 11.9%, 95% CI = 1.5 to 22.3%). Of 113 (89.7%) women capable of pregnancy, 31 (27.4%) used HMC. In Stage 1 29% and Stage 2 5.6% of women on treatment had a response compared with 3.2% and 0% on placebo, respectively. A treatment effect was found independently for females and males (P < 0.001); with no between-gender treatment effect (0.144 females versus 0.100 males; P = 0.363, difference = 0.044, 95% CI = -0.050 to 0.137). Treatment effect did not differ by HMC use (0.156 HMC versus 0.128 none; P = 0.769, difference = 0.028, 95% CI -0.157 to 0.212).

Women with methamphetamine use disorder receiving combined intramuscular naltrexone and oral bupropion treatment achieve greater treatment response than placebo. Treatment effect does not differ by HMC.

Aggressive behavior of drug addicts threatens human security and social stability, and Methamphetamine (MA) addicts show especially aggressive behavior. Researches showed that the decreased activity of dorsolateral prefrontal cortex (DLPFC) is closely related to violence and aggression, and continuous transcranial direct current stimulation (tDCS) on DLPFC can increase the activity of this position. So, the purpose of this study was to investigate the effect of tDCS on DLPFC for the aggressive behavior of MA addicts. Ninety MA addicts were recruited and randomly divided into anodal tDCS group, cathode tDCS group and sham tDCS group (current intensity was set as 2 mA, 2 mA and 0 mA, respectively). The tDCS intervention was conducted twice a day for five consecutive days. Taylor Aggression Paradigm (TAP) was used to measure the proactive aggressiveness and reactive aggressiveness of MA addicts at different time points (Pretest, Day 1, and Day 5). At the same time, we also recruited 30 healthy adult males as healthy controls, and measured their aggressiveness through TAP for comparative analysis. The results showed that the aggressiveness of MA addicts was significantly higher than that of healthy controls. The aggressiveness of MA addicts was effectively reduced by the anode intervention of tDCS on the left DLPFC, especially when they were subjected to high-intensity provocation, the 2-way interaction between time and tDCS group was statistically significant (F_4,164 = 2.939, P = 0.022, η_p² = 0.067). This study can provide a reference for how to correct the aggressive behavior of MA addicts.

The client population eligible for treatment services supported by State Opioid Response (SOR) grant funding, administered by the Substance Abuse and Mental Health Services Administration (SAMHSA), was expanded to include individuals with a stimulant use disorder (stimUD) in 2020. Due to a significant need to improve services for individuals with stimUD in Montana, the Behavioral Health and Developmental Disabilities Division (BHDD) of the Montana Department of Public Health and Human Services used the grant opportunity to work with experts in the field of stimUD to pilot contingency management (CM) and the Treatment for Individuals who Use Stimulants (TRUST) treatment model. The CM protocol included twice weekly visits for twelve weeks, using an escalating schedule of gift card incentives contingent upon stimulant-negative urine samples. TRUST is a multi-component treatment program, incorporating exercise, group therapy, and individual therapy with content guided by cognitive behavioral therapy (CBT) and clinical research associate (CRA) materials. In addition to SOR dollars, BHDD used additional funding for CM reinforcers provided by state tax dollars to meet research-supported target incentive totals.

In this pilot project, TRUST/CM was implemented by four state-approved treatment providers and three Federally Qualified Health Centers (FQHCs), all of which had little prior experience with CM as a component of their treatment programs for stimUD. This article examines the processes of training staff, the experiences among staff with initial implementation of the treatment model, and the client characteristics of initial pilot treatment cohorts. Data for this study include primary qualitative data collected from providers, as well as client characteristics collected on the SAMHSA Government Performance and Results Act (GPRA) data collection form.

Seven sites were trained in TRUST/CM, and these sites enrolled a total of 70 patients in the program. Qualitative data collected through interviews with site staff revealed the following themes: the value of intensive technical assistance being integrated in the program, concerns about staff retention and loss of expertise, adjustments of target client populations, and the importance of creative strategies for the provision of evidence-informed incentive totals.

TRUST/CM was implemented throughout Montana, including rural and urban communities. Qualitative and quantitative data support that providers viewed the CM component as beneficial for treatment retention and improved outcomes for people with stimUD. These implementation study results provide insight into challenges and solutions for providers who are considering the implementation of CM within either a state-approved substance use treatment clinic or FQHC.

Methadone maintenance therapy (MMT) has been a pillar of opioid addiction treatment. Opioid treatment programs (OTPs) have been faced with an escalating threat of stimulant use and related overdose deaths among patients. We know little about how providers currently address stimulant use while maintaining treatment for opioid use disorder.

We conducted 5 focus groups with 36 providers (n = 11 prescribers; 25 behavioral health staff), and collected an additional 46 surveys (n = 7 prescribers; 12 administrators; 27 behavioral health staff). Questions focused on perceptions of patient stimulant use and interventions. We applied inductive analysis to identify themes relevant to identification of stimulant use, use trends, intervention approaches, and perceived needs to improve care.

Providers indicated a trend of rising stimulant use among patients, especially those experiencing homelessness or comorbid health conditions. They reported a range of approaches to patient screening and intervention, including medication and harm reduction, improving treatment engagement, increasing level of care, and providing incentives. Providers expressed less agreement as to which of these interventions were effective, and though providers saw stimulant use as a common and severe problem, they reported little problem recognition and interest in treatment from their patients. A particular concern of providers was the prevalence and danger of synthetic opioids, such as fentanyl. They sought more research and resources to identify effective interventions and medications to address these issues. Also notable was an interest in contingency management (CM) and use of reinforcements/rewards to encourage stimulant use reduction.

Providers face challenges in treating patients who use both opioids and stimulants. Although methadone is available to treat opioid use, no such "silver bullet" exists for stimulant use disorder. The rise in stimulant and synthetic opioid (e.g., fentanyl) combination products is presenting an extraordinary challenge for providers whose patients are at unprecedented risk for overdose. Providing OTPs with more resources to address polysubstance use is critical. Existing research indicates strong support for CM in OTPs, but providers reported regulatory and financial barriers to implementation. Further research should develop effective interventions that are accessible to providers in OTPs.

People recently released from prison engage with emergency healthcare at greater rates than the general population. While retention in opioid agonist treatment (OAT) is associated with substantial reductions in the risk of opioid-related mortality postrelease, it is unknown how OAT affects contact with emergency healthcare. In a cohort of men who injected drugs regularly prior to imprisonment, we described rates of contact with ambulance services and EDs, and their associations with use of OAT, in the 3 months after release from prison.

Self-report data from a prospective observational cohort of men who regularly injected drugs before a period of sentenced imprisonment, recruited between September 2014 and May 2016, were linked to state-wide ambulance and ED records over a 3-month postrelease period in Victoria, Australia. We used generalised linear models to estimate associations between OAT use (none/interrupted/retained) and contact with ambulance and EDs postrelease, adjusted for other covariates.

Among 265 participants, we observed 77 ambulance contacts and 123 ED contacts over a median of 98 days of observation (IQR 87-125 days). Participants who were retained in OAT between prison release and scheduled 3-month postrelease follow-up interviews had lower rates of contact with ambulance (adjusted incidence rate ratio (AIRR) 0.33, 95% CI 0.14 to 0.76) and ED (AIRR 0.43, 95% CI 0.22 to 0.83), compared with participants with no OAT use postrelease. Participants with interrupted OAT use did not differ from those with no OAT use in rates of contact with ambulance or ED.

We found lower rates of contact with emergency healthcare after release among people retained in OAT, but not among people reporting interrupted OAT use, underscoring the benefits of postrelease OAT retention. Strategies to improve accessibility and support OAT retention after leaving prison are important for men who inject drugs.