Brain mGlu5 Is Linked to Cognition and Cigarette Smoking but Does Not Differ From Control in Early Abstinence From Chronic Methamphetamine Use.

BACKGROUND: The group-I metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in methamphetamine exposure in animals and in human cognition. Because people with methamphetamine use disorder (MUD) exhibit cognitive deficits, we evaluated mGlu5 in people with MUD and controls and tested its association with cognitive performance. METHODS: Positron emission tomography was performed to measure the total VT of [18F]FPEB, a radiotracer for mGlu5, in brains of participants with MUD (abstinent from methamphetamine for at least 2 weeks, N = 14) and a control group (N = 14). Drug use history questionnaires and tests of verbal learning, spatial working memory, and executive function were administered. Associations of VT with methamphetamine use, tobacco use, and cognitive performance were tested. RESULTS: MUD participants did not differ from controls in global or regional VT, and measures of methamphetamine use were not correlated with VT. VT was significantly higher globally in nonsmoking vs smoking participants (main effect, P = .0041). MUD participants showed nonsignificant weakness on the Rey Auditory Verbal Learning Task and the Stroop test vs controls (P = .08 and P = .13, respectively) with moderate to large effect sizes, and significantly underperformed controls on the Spatial Capacity Delayed Response Test (P = .015). Across groups, Rey Auditory Verbal Learning Task performance correlated with VT in the dorsolateral prefrontal cortex and superior frontal gyrus. CONCLUSION: Abstinent MUD patients show no evidence of mGlu5 downregulation in brain, but association of VT in dorsolateral prefrontal cortex with verbal learning suggests that medications that target mGlu5 may improve cognitive performance.

Efficacy and Safety of Modafinil for Treatment of Amphetamine-Type Stimulant Use Disorder: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials: Efficacité et innocuité du modafinil pour le traitement des troubles liés à l'usage de stimulants de type amphétamine : revue systématique et méta-analyse d'essais randomisés contrôlés par placebo.

INTRODUCTION: Amphetamine-type stimulants (ATSs) are related to significant harm worldwide, with limited effective pharmacological treatments for ATS use disorder (ATSUD). Modafinil has been explored as a potential treatment for ATSUD. This systematic review and meta-analysis (PROSPERO ID: CRD42023388487) aimed to evaluate the efficacy and safety of modafinil for the treatment of ATSUD. METHODS: A comprehensive search of major indexing sources and trial registries, from inception to search date, was conducted on February 15, 2023, and updated on October 31, 2023. Eligible studies were randomized placebo-controlled trials (RCTs) of modafinil in individuals meeting the criteria for the Diagnostic and Statistical Manual of Mental Disorders, fourth and fifth editions, diagnoses of ATSUD. Eligible studies were assessed for risk of bias, using the Cochrane Risk of Bias tool. The primary outcome included the effect of modafinil on ATS use. Secondary outcomes included retention in treatment, ATS craving, treatment discontinuation due to adverse events (AEs), and serious AEs. Subgroup analysis by modafinil dose was conducted where appropriate. Risk ratio (RR) or Peto's odds ratio (OR) was calculated for the meta-analysis of dichotomous variables and standardized mean difference (SMD) was calculated for the random-effect meta-analysis of continuous variables. RESULTS: Five RCTs (N = 451 participants) were included. Modafinil did not significantly impact ATS use (RR = 0.99; 95% CI, 0.97 to 1.02; p = 0.655), retention in treatment (RR = 1.02; 95% CI, 0.91 to 1.14; p = 0.799), ATS craving (SMD = -0.36; 95% CI, -1.19 to 0.47; p = 0.398), or treatment discontinuation due to AEs (Peto's OR = 0.48; 95% CI, 0.20 to 1.14; p = 0.100). These results were consistent across subgroup analyses. More episodes of serious AEs were reported in the modafinil group than in the placebo group, at higher doses (Peto's OR = 4.80; 95% CI, 1.18 to 19.56, p = 0.029). CONCLUSION: There is currently no evidence suggesting that modafinil has a statistically significant effect on efficacy outcomes in populations with ATSUD. Continued research into effective treatments and harm reduction strategies for ATSUD is essential.

Implementing Heart Plus: Design and Early Results of a Novel Comanagement Clinic for Patients With Stimulant-associated Cardiomyopathy.

We describe the methodology, design, and early results of a novel multidisciplinary co management clinic model with Addiction Medicine and Cardiology providers using contingency management to engage patients with stimulant-associated cardiomyopathy (SA-CMP). Stimulant use, including methamphetamine and cocaine, is increasing in prevalence nationally and is associated with cardiovascular complications. People with SA-CMP have higher rates of mortality and acute care use (eg, emergency department visits, hospital admissions) and lower rates of outpatient care engagement than individuals with non-SA-CMP. This population also has disproportionately elevated rates of mental health and other medical comorbidities, challenges with social determinants of health, including housing and food insecurity, and representation from communities of color. This multidisciplinary comanagement care delivery model, called Heart Plus, was developed and funded as a quality improvement project. It led to a 5-fold increase in outpatient care engagement with a concomitant 53% decrease in acute care use. All participants reported a decrease in stimulant use. With increased clinical stability, patients were able to better engage with outpatient resources for social determinants of health, such as case management, social work, and housing and food service programs. Patients were also empowered to take control over their health while knowing that health care providers cared about their well-being.

The fourth wave of the overdose crisis: Examining the prominent role of psychomotor stimulants with and without fentanyl.

The current overdose and broader public health crisis involving illicit drug use is often referred to as the "opioid" or "fentanyl" crisis. Clearly there is extensive data on the profound damage done by opioids over the past 20 years and specifically by fentanyl in the past 5 years. However, there is an extensive array of data that suggests there is more to the current crisis than opioids/fentanyl. Much recent evidence indicates that methamphetamine and cocaine are playing a substantial and increasing role in the illicit drug crisis in the US-the 4th wave. This paper reviews data that illustrate the role of psychomotor stimulants in fatal overdoses, nonfatal overdoses, and emergency department visits. Despite the major detrimental role that stimulants are having on the public health in the US in 2023, there is virtually no evidence-based treatment available in practice for people with stimulant use disorder (StimUD). Although there are no medications with FDA-approval for the treatment of StimUD, there is a behavioral treatment, contingency management (CM), with over 3 decades of robust research supporting its efficacy for individuals with StimUD. Despite the overwhelming evidence supporting CM, it is not being widely used in routine treatment outside the VA healthcare system. This paper reviews some of the (a) evidence for CM, (b) CM protocol design elements that require consideration, (c) current obstacles to the widespread implementation of CM, and (d) strategies for addressing these obstacles. Overcoming these obstacles is a priority to allow routine use of CM as a treatment for StimUD.

The urgent need for contingency management among Tribal communities in the United States: Considerations for implementation, policy, and sovereignty.

In two randomized controlled trials, culturally adapted contingency management (i.e., incentives provided for substance-negative urine samples) was associated with reduced alcohol and drug use among geographically diverse American Indian and Alaska Native (AI/AN) adults. In response to interest in contingency management from other Tribal and AI/AN communities, our research team in collaboration with AI/AN behavioral health experts, translated the research into practice with new AI/AN community partners. Tenets of community-based participatory research were applied to develop, pilot, and refine contingency management training and implementation tools, and identify implementation challenges. In partnership with the AI/AN communities, four members of the university team developed tools and identified implementation and policy strategies to increase the successful uptake of contingency management in each location. Through our collaborative work, we identified policy barriers including inadequate federal funding of contingency management incentives and a need for further clarity regarding federal anti-kickback regulations. Adoption of contingency management is feasible and can strengthen Tribal communities' capacity to deliver evidence-based substance use disorder treatments to AI/AN people. Unfortunately, non-evidence-based limits to the use of federal funding for contingency management incentives discriminate against AI/AN communities. We recommend specific federal policy reforms, as well as other practical solutions for Tribal communities interested in contingency management.

Starting the Discussion: A Call to Enhance Care for People With Stimulant Use Disorder.

Stimulant use disorder (StUD) significantly contributes to substance-related morbidity and mortality in the United States. Overshadowed by the country's focus on opioid-related overdose deaths, stimulant and stimulant/opioid overdose deaths have increased dramatically over the last decade. Many individuals who use stimulants illicitly or have StUD have multiple, intersecting stigmatized characteristics which exacerbate existing barriers and create new obstacles to attaining addiction treatment. Illicit stimulant use, StUD, and stimulant-related overdose disproportionately impact minoritized racial and gender, and sexuality diverse groups. Historically, people who use illicit stimulants and those with StUD have been highly stigmatized, criminalized, and overly ignored by health care providers, policymakers, and the public compared to people who use other drugs and alcohol. As a result, most people needing treatment for StUD do not receive it. This is partly due to the lack of evidence-based treatment for StUD, which has resulted in few programs specializing in the care of people with StUD. The lack of available treatment is compounded by high rates of StUD in marginalized groups already reluctant to engage with the health care system. As health care professionals, we can improve outcomes for people with StUD by changing how we talk about, document, and respond to illicit stimulant use, related characteristics, behaviors, and social and structural determinants of health. To do this, we must seek to understand the lived realities of people with StUD and illicit stimulant use and use this knowledge to amend existing models of care.

Experiences of violence among people with stimulant use disorder in psychiatric inpatient settings: A qualitative study.

OBJECTIVE: To describe the perspectives of those with lived experience of stimulant use disorder on methamphetamine-related violence in psychiatric inpatient settings. METHOD: Eight adult psychiatric inpatients with stimulant use disorder were recruited. Semi-structured interviews were recorded, transcribed and analysed using thematic analysis. RESULTS: Participants reported that traumatic experiences predisposed those using methamphetamine to violent behaviour. Participants were fearful of psychiatric hospitalisation because of loss of autonomy and stigma. Methamphetamine use was associated with mercurial intense emotions. Participants believed these factors led to violence during psychiatric admissions. CONCLUSIONS: People with stimulant use disorder have a sophisticated understanding of the complex causal pathways from methamphetamine use to violent behaviour. Their lived experience can make an important contribution to service development.

Study protocol of a randomized controlled trial comparing two linkage models for HIV prevention and treatment in justice-involved persons.

BACKGROUND: Persons involved in the justice system are at high risk for HIV and drug overdose upon release to the community. This manuscript describes a randomized controlled trial of two evidence-based linkage interventions for provision of HIV prevention and treatment and substance use disorder (SUD) services in four high risk communities to assess which is more effective at addressing these needs upon reentry to the community from the justice system. METHODS: This is a 5-year hybrid type 1 effectiveness-implementation randomized controlled trial that compares two models (Patient Navigation [PN] or Mobile Health Unit [MHU] service delivery) of linking justice-involved individuals to the continuum of community-based HIV and SUD prevention and treatment service cascades of care. A total of 864 justice-involved individuals in four US communities with pre-arrest histories of opioid and/or stimulant use who are living with or at-risk of HIV will be randomized to receive either: (a) PN, wherein patient navigators will link study participants to community-based service providers; or (b) services delivered via an MHU, wherein study participants will be provided integrated HIV prevention/ treatment services and SUD services. The six-month post-release intervention will focus on access to pre-exposure prophylaxis (PrEP) for those without HIV and antiretroviral treatment (ART) for people living with HIV (PLH). Secondary outcomes will examine the continuum of PrEP and HIV care, including: HIV viral load, PrEP/ ART adherence; HIV risk behaviors; HCV testing and linkage to treatment; and sexually transmitted infection incidence and treatment. Additionally, opioid and other substance use disorder diagnoses, prescription, receipt, and retention on medication for opioid use disorder; opioid and stimulant use; and overdose will also be assessed. Primary implementation outcomes include feasibility, acceptability, sustainability, and costs required to implement and sustain the approaches as well as to scale-up in additional communities. DISCUSSION: Results from this project will help inform future methods of delivery of prevention, testing, and treatment of HIV, HCV, substance use disorders (particularly for opioids and stimulants), and sexually transmitted infections for justice-involved individuals in the community. TRIAL REGISTRATION: Clincialtrials.gov NCT05286879 March 18, 2022.

The Hypothesis of Subliminal Cue Reactivity in Addiction Revisited: An fMRI Study.

INTRODUCTION: Exposure to conditioned cues is a common trigger of relapse in addiction. It has been suggested that such cues can activate motivationally relevant neurocircuitry in individuals with substance use disorders even without being consciously perceived. We aimed to see if this could be replicated in a sample with severe amphetamine use disorder and a control group of healthy subjects. METHODS: We used fMRI to test the hypothesis that individuals with amphetamine use disorder, but not healthy controls, exhibit a specific neural reactivity to subliminally presented pictures related to amphetamine use. Twenty-four amphetamine users and 25 healthy controls were recruited and left data of sufficient quality to be included in the final analysis. All subjects were exposed to drug-related and neutral pictures of short duration (13.3 ms), followed by a backward visual mask image. The contrast of interest was drug versus neutral subliminal pictures. RESULTS: There were no statistically significant differences in BOLD signal between the drug and neutral cues, neither in the limbic regions of primary interest nor in exploratory whole-brain analyses. The same results were found both in amphetamine users and controls. DISCUSSION/CONCLUSION: We found no evidence of neural reactivity to subliminally presented drug cues in this sample of subjects with severe amphetamine dependence. These results are discussed in relation to the earlier literature, and the evidence for subliminal drug cue reactivity in substance use disorders is questioned.

A systematic review of the effect of ovarian sex hormones on stimulant use in females.

Stimulant use disorder is associated with significant global health burden. Despite evidence for sex differences in the development and maintenance of stimulant use disorder, few studies have focused on mechanisms underpinning distinct trajectories in females versus males, including the effect of the ovarian sex hormones estrogen and progesterone. This review aimed to identify and synthesise the existing preclinical and clinical literature on the effect of ovarian sex hormones on stimulant consumption in females. A systematic search of peer-reviewed literature identified 1593 articles, screened using the following inclusion criteria: (1) adult female humans or animals, (2) using stimulant drugs, (3) ovarian sex hormones were administered exogenously OR were measured in a validated manner and (4) with stimulant consumption as an outcome measure. A total of 50 studies (3 clinical and 47 preclinical) met inclusion criteria. High-estrogen (low progesterone) phases of the menstrual/estrus cycle were associated with increased stimulant use in preclinical studies, while there were no clinical studies examining estrogen and stimulant consumption. Consistent preclinical evidence supported progesterone use reducing stimulant consumption, which was also identified in one clinical study. The review was limited by inconsistent data reporting across studies and different protocols across preclinical laboratory paradigms. Importantly, almost all studies examined cocaine use, with impact on methamphetamine use a significant gap in the existing evidence. Given the safety and tolerability profile of progesterone, further research is urgently needed to address this gap, to explore the potential therapeutic utility of progesterone as a treatment for stimulant use disorder.

Cocaine reward is reduced by decreased expression of receptor-type protein tyrosine phosphatase D (PTPRD) and by a novel PTPRD antagonist.

Receptor-type protein tyrosine phosphatase D (PTPRD) is a neuronal cell-adhesion molecule/synaptic specifier that has been implicated in addiction vulnerability and stimulant reward by human genomewide association and mouse cocaine-conditioned place-preference data. However, there have been no reports of effects of reduced expression on cocaine self-administration. There have been no reports of PTPRD targeting by any small molecule. There are no data about behavioral effects of any PTPRD ligand. We now report (i) robust effects of heterozygous PTPRD KO on cocaine self-administration (These data substantially extend prior conditioned place-preference data and add to the rationale for PTPRD as a target for addiction therapeutics.); (ii) identification of 7-butoxy illudalic acid analog (7-BIA) as a small molecule that targets PTPRD and inhibits its phosphatase with some specificity; (iii) lack of toxicity when 7-BIA is administered to mice acutely or with repeated dosing; (iv) reduced cocaine-conditioned place preference when 7-BIA is administered before conditioning sessions; and (v) reductions in well-established cocaine self-administration when 7-BIA is administered before a session (in WT, not PTPRD heterozygous KOs). These results add to support for PTPRD as a target for medications to combat cocaine use disorders. 7-BIA provides a lead compound for addiction therapeutics.

Use of sustained release dextroamphetamine for the treatment of stimulant use disorder in the setting of injectable opioid agonist treatment in Canada: a case report.

BACKGROUND: For people with opioid use disorder who are not responding to oral opioid agonist treatment, evidence supports the effectiveness of injectable opioid agonist treatment with injectable hydromorphone (an opioid analgesic) and diacetylmorphine (pharmaceutical grade heroin). While this treatment is effective at reducing illicit opioid use, concurrent cocaine use is prevalent. Dextroamphetamine (a central nervous system stimulant) has been found to be a safe and effective treatment for cocaine dependence among people receiving injectable opioid agonist treatment in Europe. We present the first report of dextroamphetamine prescribing offered for the treatment of stimulant use disorder among a patient receiving iOAT outside of a clinical trial. This case report can be used to inform clinical practice in the treatment of cocaine use disorder, an area where interventions are currently lacking. CASE PRESENTATION: Dextroamphetamine was prescribed to a 51-year-old male who was diagnosed with concurrent opioid and stimulant use disorder in an injectable opioid agonist treatment clinic in Vancouver, Canada. He reported smoking crack cocaine daily for more than two decades and was experiencing health consequences associated with this use. He presented to his routine physician visit with the goal of reducing his cocaine use and was prescribed dextroamphetamine for the treatment of stimulant use disorder. After 4-weeks the patient was tolerating the medication with no observed adverse events and was achieving his therapeutic goal of reducing his cocaine use. CONCLUSIONS: Dextroamphetamine can be prescribed to support patients with stimulant use disorder to reduce or stop their use of cocaine. The case demonstrated that when dextroamphetamine was prescribed, a significant reduction in cocaine use was experienced among a patient that had been regularly using cocaine on a daily basis for many years. Daily contact with care for the opioid medication promoted adherence to the stimulant medication and allowed for monitoring of dose and tolerance. Settings where patients are in regular contact with care such as oral and injectable opioid agonist treatment clinics serve as a suitable location to integrate dextroamphetamine prescribing for patients that use illicit stimulants to reduce use and associated harms.

Interoceptive attention in opioid and stimulant use disorder.

Blunted anterior insula activation during interoceptive perturbations has been associated with stimulant (cocaine and amphetamine) use disorder (SUD) and is related to risk for and prognosis of SUD. However, little is known whether these interoceptive alterations extend to opioid use disorder (OUD). This exploratory study used the same experimental probe during functional magnetic resonance imaging (fMRI) to test the hypothesis that SUD and OUD exhibit interoceptive discrepancies characterized by subjective ratings and activation within the insula. Recently, abstinent individuals diagnosed with current SUD (n = 40) or current OUD (n = 20) were compared with healthy individuals (CTL; n = 30) on brain and self-report responses during an interoceptive attention task known to elicit insula activation. Participants selectively attended to interoceptive (heartbeat and stomach) and exteroceptive signals during blood-oxygen-level-dependent fMRI recording. Groups and conditions were compared on (a) activation within probabilistic cytoarchitectonic segmentations of the insula and (b) self-reported stimulus intensity. First, SUD showed amplified ratings of heart-related sensations but attenuation of dorsal dysgranular insula activity relative to CTL. Amplified ratings were linked to drug use recency, while attenuation was normalized with greater past-year stimulant use. Second, SUD and OUD showed attenuation of dorsal dysgranular insula activity during attention to stomach sensations relative to CTL. Taken together, these results are consistent with altered neural processing of interoceptive signals in drug addiction, particularly as a function of SUD. Future studies will need to determine whether interoceptive metrics help to explain substance use disorder pathophysiology and are useful for predicting outcomes.

Opioid, cocaine, and amphetamine use disorders are associated with higher30-day inpatient readmission rates in the United States.

Background: Patients with substance use disorders (SUDs) are more likely to experience serious health problems, high healthcare utilization, and premature death. However, little is known about the contribution of SUDs to medical 30-day readmission risk. We examined the association between SUDs and 30-day all cause readmission among non-pregnant adult in-patients in the US. Methods: We conducted a retrospective study using 2010-2014 data from the Nationwide Readmissions Database. Our primary focus was on opioid use compared to stimulant use (cocaine and amphetamine) identified by ICD-9-CM diagnosis codes in index hospitalizations. Multivariable logistic regression models were used to estimate adjusted odds ratios and 95% CI representing the association between substance use and 30-day readmission, overall and stratified by the principal reason for the index hospitalization. Results: Nearly 118 million index hospitalizations were included in the study, 4% were associated with opioid or stimulant use disorder. Readmission rates for users (19.5%) were higher than for nonusers (15.7%), with slight variation by the type of substance used: cocaine (21.8%), opioid (19.0%), and amphetamine (17.5%). After adjusting for key demographic, socioeconomic, clinical, and health system characteristics, SUDs and stimulant use disorders increased the odds of 30-day all-cause readmission by 20%. Conclusions: Reducing the frequency of inpatient readmission is an important goal for improving the quality of care and ensuring proper transition to residential/outpatient care among patients with SUDs. Differences between groups may suggest directions for further investigation into the distinct needs and challenges of hospitalized opioid- and other drug-exposed patients.

Managing attention deficit hyperactivity disorder in adults using illicit psychostimulants: A systematic review.

CONTEXT: Attention deficit hyperactivity disorder and stimulant use disorder commonly co-exist, and appropriate treatments have not been well established. OBJECTIVE: To provide guidance for treatment of co-existing attention deficit hyperactivity disorder and stimulant use disorder. DATA SOURCES: A systematic review of published English articles using MEDLINE, EMBASE, CINAHL, PsycINFO and Cochrane, utilising consistent search terms. STUDY SELECTION: Randomised controlled trials, comparing any treatment arm with a control group, for participants meeting Diagnostic and Statistical Manual of Mental Disorders or equivalent criteria for both attention deficit hyperactivity disorder and stimulant use disorder. RESULTS: Eight trials were identified for inclusion in this review. Four of eight studies showed improvement in attention deficit hyperactivity disorder outcome measures compared with placebo. Two of six studies that reported substance use outcomes showed improvement in treatment arms compared with placebo. Studies to show effect tended to be those with the highest treatment dosage. CONCLUSION: Evidence for the efficacy of treatment of patients with comorbid stimulant use disorder and attention deficit hyperactivity disorder is limited. Promising outcomes need replication in further studies utilising higher treatment dosage.

Racial and ethnic differences in treatment outcomes among adults with stimulant use disorders after a dosed exercise intervention.

The current study examined differences in substance abuse treatment outcomes among racial and ethnic groups enrolled in the Stimulant Reduction Intervention using Dosed Exercise (STRIDE) trial, a multisite randomized clinical trial implemented through the National Institute on Drug Abuse's (NIDA's) Clinical Trials Network (CTN). STRIDE aimed to test vigorous exercise as a novel approach to the treatment of stimulant abuse compared to a health education intervention. A hurdle model with a complier average causal effects (CACE) adjustment was used to provide an unbiased estimate of the exercise effect had all participants been adherent to exercise. Among 214 exercise-adherent participants, we found significantly lower probability of use for Blacks (z = -2.45, p = .014) and significantly lower number of days of use for Whites compared to Hispanics (z = -54.87, p = <.001) and for Whites compared to Blacks (z = -28.54, p = <.001), which suggests that vigorous, regular exercise might improve treatment outcomes given adequate levels of adherence.

Study protocol: a dose-escalating, phase-2 study of oral lisdexamfetamine in adults with methamphetamine dependence.

BACKGROUND: The treatment of methamphetamine dependence is a continuing global health problem. Agonist type pharmacotherapies have been used successfully to treat opioid and nicotine dependence and are being studied for the treatment of methamphetamine dependence. One potential candidate is lisdexamfetamine, a pro-drug for dexamphetamine, which has a longer lasting therapeutic action with a lowered abuse potential. The purpose of this study is to determine the safety of lisdexamfetamine in this population at doses higher than those currently approved for attention deficit hyperactivity disorder or binge eating disorder. METHODS/DESIGN: This is a phase 2 dose escalation study of lisdexamfetamine for the treatment of methamphetamine dependence. Twenty individuals seeking treatment for methamphetamine dependence will be recruited at two Australian drug and alcohol services. All participants will undergo a single-blinded ascending-descending dose regime of 100 to 250 mg lisdexamfetamine, dispensed daily on site, over an 8-week period. Participants will be offered counselling as standard care. For the primary objectives the outcome variables will be adverse events monitoring, drug tolerability and regimen completion. Secondary outcomes will be changes in methamphetamine use, craving, withdrawal, severity of dependence, risk behaviour and other substance use. Medication acceptability, potential for non-prescription use, adherence and changes in neurocognition will also be measured. DISCUSSION: Determining the safety of lisdexamfetamine will enable further research to develop pharmacotherapies for the treatment of methamphetamine dependence. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12615000391572 Registered 28th April 2015.

California's Recovery Incentives Program: Implementation strategies.

INTRODUCTION: Due to the increasing role of psychostimulants in the US drug poisoning crisis, there is an increasing need to effectively implement evidence-based treatment for individuals with stimulant use disorder (StimUD). Contingency management is a behavioral strategy with robust evidence of support for the treatment of StimUD. In 2023, California initiated a large-scale effort to implement CM as a treatment for individuals with a stimulant use disorder (cocaine, methamphetamine, amphetamine) called the Recovery Incentives Program: California's Contingency Management Benefit. METHODS: The Recovery Incentives Program is being systematically implemented using the Becker et al. Science to Service Lab (SSL) implementation approach with several augmentations for this project. The SSL features three core components: didactic training, performance feedback, and external facilitation. We have augmented this approach with a readiness assessment process for sites prior to CM service launch, and an ongoing fidelity monitoring and feedback component post-launch. RESULTS: The present paper is a preliminary report describing the use of this augmented SSL strategy for CM implementation in a large-scale implementation effort. Data are presented to describe the implementation activities during the first ten months of the Recovery Incentives Program. CONCLUSION: The California Recovery Incentives Program has been systematically implemented and appears to be receiving a positive response from treatment program staff and enrolled members. Future papers and evaluation reports will continue to document member response to the Program and report on the ongoing training and implementation process.

Prescription psychostimulants for the treatment of amphetamine-type stimulant use disorder: A systematic review and meta-analysis of randomized placebo-controlled trials.

BACKGROUND AND AIMS: There is currently no standard of care for pharmacological treatment of amphetamine-type stimulant (ATS) use disorder (ATSUD). This systematic review with meta-analysis (PROSPERO CRD42022354492) aimed to pool results from randomized placebo-controlled trials (RCTs) to evaluate efficacy and safety of prescription psychostimulants (PPs) for ATSUD. METHODS: Major indexing sources and trial registries were searched to include records published before 29 August 2022. Eligible studies were RCTs evaluating efficacy and safety of PPs for ATSUD. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. Risk ratio (RR) and risk difference were calculated for random-effect meta-analysis of dichotomous variables. Mean difference and standardized mean difference (SMD) were calculated for random-effect meta-analysis of continuous variables. RESULTS: Ten RCTs (n = 561 participants) were included in the meta-analysis. Trials studied methylphenidate (n = 7), with daily doses of 54-180 mg, and dextroamphetamine (n = 3), with daily doses of 60-110 mg, for 2-24 weeks. PPs significantly decreased end-point craving [SMD  -0.29; 95% confidence interval (CI) = -0.55, -0.03], while such a decrease did not reach statistical significance for ATS use, as evaluated by urine analysis (UA) (RR = 0.93; 95% CI = 0.85-1.01). No effect was observed for self-reported ATS use, retention in treatment, dropout following adverse events, early-stage craving, withdrawal and depressive symptoms. In a sensitivity analysis, treatment was associated with a significant reduction in UA positive for ATS (RR = 0.89; 95% CI = 0.79-0.99) after removing studies with a high risk of bias. In subgroup analyses, methylphenidate and high doses of PPs were negatively associated with ATS use by UA, while higher doses of PPs and treatment duration (≥ 20 weeks) were positively associated with longer retention. CONCLUSIONS: Among individuals with amphetamine-type stimulant use disorder, treatment with prescription psychostimulants may decrease ATS use and craving. While effect size is limited, it may increase with a higher dosage of medications.

Stimulant Drugs and Stimulant Use Disorder.

The authors aim to summarize several key points of stimulant drugs and stimulant use disorder, including their indications, short-term and long-term adverse effects, current treatment strategies, and association with opioid medications. The global prevalence of stimulant use has seen annual increase in the last decade. Multiple studies have shown that stimulant use and stimulant use disorder are associated with a range of individual and public health issues. Stimulant misuse has led to a significant increase of overdose deaths in the United States.