Perspectives of substance use disorder counselors on the benefits and drawbacks of medications for opioid use disorder.

Background: Medications for opioid use disorder (MOUD) are among the best tools we have to combat the opioid epidemic. Yet, use of MOUD among people with opioid use disorder (OUD) remains low. Interventions to increase MOUD access in the United States have largely focused on improving organizational capacity and addressing funding barriers, yet stigma toward MOUD may inhibit uptake even where MOUD is readily available. Substance use disorder (SUD) treatment counselors likely have considerable influence on a client's choice to initiate and adhere to MOUD, but beliefs that counselors convey about MOUD in interaction with clients are understudied. The current study explores what advantages and disadvantages that SUD treatment counselors communicate about buprenorphine, methadone, and naltrexone. Methods: From June to December 2021, we surveyed counselors from publicly-funded SUD treatment agencies under a municipality-wide mandate to offer MOUD to all clients with OUD. Counselors were asked to describe, in a free-response format, the most important advantages and disadvantages to communicate to their clients about taking buprenorphine, methadone, and naltrexone. Counselor responses were coded for one or more advantage and disadvantage. Results: A total of 271 SUD counselors from 29 agencies completed the survey, generating 1,995 advantages and disadvantages across three types of MOUD. The most frequently reported advantage across all three types of MOUD was their ability to reduce cravings and illicit drug use. The most frequently reported disadvantage related to the potential for some types of MOUD to develop long-term medication dependence. Conclusions: As the availability and variety of MOUD treatment options continue to expand, it is important that SUD counselors are equipped with evidence-based recommendations for OUD care. We identified misalignments with the MOUD-prescribing evidence base and stigmatizing language toward MOUD within counselors' responses, highlighting the potential to refine training materials for MOUD and mitigate stigmatizing beliefs.

Nonopioid Substance Use among Patients Who Recently Initiated Office-based Buprenorphine Treatment.

OBJECTIVES: Medications for opioid use disorder (MOUDs) like buprenorphine are a first-line treatment for individuals who have opioid use disorder (OUD); however, these medications are not designed to impact the use of other classes of drugs. This descriptive study provides up-to-date information about nonopioid substance use among patients who recently initiated office-based buprenorphine treatment for OUD using data from 2 ongoing clinical trials. METHODS: The study sample was composed of 257 patients from 6 federally qualified health centers in the mid-Atlantic region who recently (i.e., within the past 28 days) initiated office-based buprenorphine treatment between July 2020 and May 2022. After the screening and informed consent processes, participants completed a urine drug screen and psychosocial interview as a part of the study baseline assessment. Descriptive analyses were performed on urine drug screen results to identify the prevalence and types of substances detected. RESULTS: More than half of participants provided urine specimens that were positive for nonopioid substances, with marijuana (37%, n = 95), cocaine (22%, n = 56), and benzodiazepines (11%, n = 28) detected with the highest frequencies. CONCLUSIONS: A significant number of participants used nonopioid substances after initiating buprenorphine treatment, suggesting that some patients receiving MOUDs could potentially benefit from adjunctive psychosocial treatment and supports to address their nonopioid substance use.

Not in my treatment center: Leadership's perception of barriers to MOUD adoption.

INTRODUCTION: Despite their well-established effectiveness, medications for opioid use disorder (MOUD) are widely underutilized across the United States. In the context of a large publicly funded behavioral health system, we examined the relationship between a range of implementation barriers and a substance use disorder treatment agency's level of adoption of MOUD. METHODS: We surveyed leadership of publicly funded substance use disorder treatment centers in Philadelphia about the significance of barriers to implementing MOUD related to their workforce, organization, funding, regulations, and beliefs about MOUD's efficacy and safety. We queried leaders on the percentage of their patients with opioid use disorder who receive MOUD and examined associations between implementation barriers and MOUD adoption. RESULTS: Ratings of regulatory, organizational, or funding barriers of respondents who led high MOUD adopting agencies (N = 20) were indistinguishable from those who led agencies that were low adopting of MOUD (N = 23). In contrast, agency leaders who denied MOUD-belief or workforce barriers were significantly more likely to lead high-MOUD-adopting organizations. CONCLUSIONS: These findings suggest that leadership beliefs about MOUD may be a key factor of the organizational decision to adopt and should be a target of implementation efforts to increase direct provision of these medications.

Clinical Trial Design Challenges and Opportunities for Emerging Treatments for Opioid Use Disorder: A Review.

Importance: Novel treatments for opioid use disorder (OUD) are needed to address both the ongoing opioid epidemic and long-standing barriers to existing OUD treatments that target the endogenous µ-opioid receptor (MOR) system. The goal of this review is to highlight unique clinical trial design considerations for the study of emerging treatments for OUD that address targets beyond the MOR system. In November 2019, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the US Food and Drug Administration sponsored a meeting to discuss the current evidence regarding potential treatments for OUD, including cannabinoids, psychedelics, sedative-hypnotics, and immunotherapeutics, such as vaccines. Observations: Consensus recommendations are presented regarding the most critical elements of trial design for the evaluation of novel OUD treatments, such as: (1) stage of treatment that will be targeted (eg, seeking treatment, early abstinence/detoxification, long-term recovery); (2) role of treatment (adjunctive with or independent of existing OUD treatments); (3) primary outcomes informed by patient preferences that assess opioid use (including changes in patterns of use), treatment retention, and/or global functioning and quality of life; and (4) adverse events, including the potential for opioid-related relapse or overdose, especially if the patient is not simultaneously taking maintenance MOR agonist or antagonist medications. Conclusions and Relevance: Applying the recommendations provided here as well as considering input from people with lived experience in the design phase will accelerate the development, translation, and uptake of effective and safe therapeutics for individuals struggling with OUD.

Cross-ancestry meta-analysis of opioid use disorder uncovers novel loci with predominant effects in brain regions associated with addiction.

Despite an estimated heritability of ~50%, genome-wide association studies of opioid use disorder (OUD) have revealed few genome-wide significant loci. We conducted a cross-ancestry meta-analysis of OUD in the Million Veteran Program (N = 425,944). In addition to known exonic variants in OPRM1 and FURIN, we identified intronic variants in RABEPK, FBXW4, NCAM1 and KCNN1. A meta-analysis including other datasets identified a locus in TSNARE1. In total, we identified 14 loci for OUD, 12 of which are novel. Significant genetic correlations were identified for 127 traits, including psychiatric disorders and other substance use-related traits. The only significantly enriched cell-type group was CNS, with gene expression enrichment in brain regions previously associated with substance use disorders. These findings increase our understanding of the biological basis of OUD and provide further evidence that it is a brain disease, which may help to reduce stigma and inform efforts to address the opioid epidemic.

Deep Brain Stimulation Compared With Contingency Management for the Treatment of Cocaine Use Disorders: A Threshold and Cost-Effectiveness Analysis.

OBJECTIVES: Cocaine is the second most frequently used illicit drug worldwide (after cannabis), and cocaine use disorder (CUD)-related deaths increased globally by 80% from 1990 to 2013. There is yet to be a regulatory-approved treatment. Emerging preclinical evidence indicates that deep brain stimulation (DBS) of the nucleus accumbens may be a therapeutic option. Prior to expanding the costly investigation of DBS for treatment of CUD, it is important to ensure societal cost-effectiveness. AIMS: We conducted a threshold and cost-effectiveness analysis to determine the success rate at which DBS would be equivalent to contingency management (CM), recently identified as the most efficacious therapy for treatments of CUDs. MATERIALS AND METHODS: Quality of life, efficacy, and safety parameters for CM were obtained from previous literature. Costs were calculated from a societal perspective. Our model predicted the utility benefit based on quality-adjusted life-years (QALYs) and incremental-cost-effectiveness ratio resulting from two treatments on a one-, two-, and five-year timeline. RESULTS: On a one-year timeline, DBS would need to impart a success rate (ie, cocaine free) of 70% for it to yield the same utility benefit (0.492 QALYs per year) as CM. At no success rate would DBS be more cost-effective (incremental-cost-effectiveness ratio <$50,000) than CM during the first year. Nevertheless, as DBS costs are front loaded, DBS would need to achieve success rates of 74% and 51% for its cost-effectiveness to exceed that of CM over a two- and five-year period, respectively. CONCLUSIONS: We find DBS would not be cost-effective in the short term (one year) but may be cost-effective in longer timelines. Since DBS holds promise to potentially be a cost-effective treatment for CUDs, future randomized controlled trials should be performed to assess its efficacy.

Varenicline for the Treatment of Cocaine Dependence.

OBJECTIVES: Varenicline is a partial agonist at the α2ß4 and α6ß2 nAChR receptors and a full agonist at α7 receptors. Both α7 and α6ß2 receptors are implicated in the neural reward circuitry activated by cocaine use. A preliminary clinical trial suggested that varenicline treatment reduced cocaine use. This trial was intended to replicate and extend the findings of the previous trial. METHODS: This was a 12-week, double-blind, placebo-controlled clinical trial involving 156 subjects with DSM IV cocaine dependence. Subjects received up to 2 mg of varenicline or identical placebo daily along with weekly relapse prevention psychotherapy. The primary outcome measure was cocaine use measured by thrice-weekly urine drug screens. Additional outcome measures included end of study cocaine abstinence, cocaine craving, cocaine withdrawal symptom severity, cigarette use, and global improvement measure by the Clinical Global Improvement Scale. RESULTS: End of study cocaine abstinence, measured by urine drug screens during the last 3 weeks of the trial, was not different between groups (8% in the varenicline treated subjects and versus 9% in placebo-treated subjects). Generalized estimating equations analysis of urine drug screen results showed no significant difference between groups in cocaine abstinence over the 12 weeks of the trial. There were no significant differences between the 2 groups in cocaine craving or cocaine withdrawal symptom severity. Varenicline was well-tolerated. There were no medication-associated serious adverse events. CONCLUSIONS: Varenicline plus cognitive-behavioral therapy does not seem to be an efficacious treatment for cocaine dependence.

Analysis of genetic and clinical factors associated with buprenorphine response.

BACKGROUND: Buprenorphine, approved for treating opioid use disorder (OUD), is not equally efficacious for all patients. Candidate gene studies have shown limited success in identifying genetic moderators of buprenorphine treatment response. METHODS: We studied 1616 European-ancestry individuals enrolled in the Million Veteran Program, of whom 1609 had an ICD-9/10 code consistent with OUD, a 180-day buprenorphine treatment exposure, and genome-wide genotype data. We conducted a genome-wide association study (GWAS) of buprenorphine treatment response [defined as having no opioid-positive urine drug screens (UDS) following the first prescription]. We also examined correlates of buprenorphine treatment response in multivariable analyses. RESULTS: Although no variants reached genome-wide significance, 6 loci were nominally significant (p < 1 × 10-5), four of which were located near previously characterized genes: rs756770 (ADAMTSL2), rs11782370 (SLC25A37), rs7205113 (CRISPLD2), and rs13169373 (LINC01947). A higher maximum daily buprenorphine dosage (aOR = 0.98; 95 %CI: 0.97, 0.995), greater number of UDS (aOR = 0.97; 95 %CI: 0.96, 0.99), and history of hepatitis C (HCV) infection (aOR = 0.71; 95 %CI: 0.57, 0.88) were associated with a reduced odds of buprenorphine response. Older age (aOR: 1.01; 95 %CI: 1.000, 1.02) was associated with increased odds of buprenorphine response. CONCLUSIONS: This study had limited statistical power to detect genetic variants associated with a complex human phenotype like buprenorphine treatment response. Meta-analysis of multiple data sets is needed to ensure adequate statistical power for a GWAS of buprenorphine treatment response. The most robust phenotypic predictor of buprenorphine treatment response was intravenous drug use, a proxy for which was HCV infection.

Comparison of Treatments for Cocaine Use Disorder Among Adults: A Systematic Review and Meta-analysis.

Importance: In the US and the United Kingdom, cocaine use is the second leading cause of illicit drug overdose death. Psychosocial treatments for cocaine use disorder are limited, and no pharmacotherapy is approved for use in the US or Europe. Objective: To compare treatments for active cocaine use among adults. Data Sources: PubMed and the Cochrane Database of Systematic Reviews were searched for clinical trials published between December 31, 1995, and December 31, 2017. Study Selection: This meta-analysis was registered on Covidence.org (study 8731) on December 31, 2015. Clinical trials were included if they (1) had the term cocaine in the article title; (2) were published between December 31, 1995, and December 31, 2017; (3) were written in English; (4) enrolled outpatients 18 years or older with active cocaine use at baseline; and (5) reported treatment group size, treatment duration, retention rates, and urinalysis results for the presence of cocaine metabolites. A study was excluded if (1) more than 25% of participants were not active cocaine users or more than 80% of participants had negative test results for the presence of cocaine metabolites at baseline and (2) it reported only pooled urinalysis results indicating the presence of multiple substances and did not report the specific proportion of positive test results for cocaine metabolites. Multiple reviewers reached criteria consensus. Of 831 records screened, 157 studies (18.9%) met selection criteria and were included in the analysis. Data Extraction and Synthesis: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. Search results were imported from PubMed XML into Covidence.org then Microsoft Excel. Data extraction was completed in 2 iterations to ensure fidelity. Analyses included a multilevel random-effects model, a multilevel mixed-effects meta-regression model, and sensitivity analyses. Treatments were clustered into 11 categories (psychotherapy, contingency management programs, placebo, opioids, psychostimulants, anticonvulsants, dopamine agonists, antidepressants, antipsychotics, miscellaneous medications, and other therapies). Missing data were imputed using multiple imputation by chained equations. The significance threshold for all analyses was P = .05. Data were analyzed using the metafor and mice packages in R software, version 3.3.2 (R Foundation for Statistical Computing). Data were analyzed from January 1, 2018, to February 28, 2021. Main Outcomes and Measures: The primary outcome was the intention-to-treat logarithm of the odds ratio (OR) of having a negative urinalysis result for the presence of cocaine metabolites at the end of each treatment period compared with baseline. The hypothesis, which was formulated after data collection, was that no treatment category would have a significant association with objective reductions in cocaine use. Results: A total of 157 studies comprising 402 treatment groups and 15 842 participants were included. Excluding other therapies, the largest treatment groups across all studies were psychotherapy (mean [SD] number of participants, 40.04 [36.88]) and contingency management programs (mean [SD] number of participants, 37.51 [25.51]). Only contingency management programs were significantly associated with an increased likelihood of having a negative test result for the presence of cocaine (OR, 2.13; 95% CI, 1.62-2.80), and this association remained significant in all sensitivity analyses. Conclusions and Relevance: In this meta-analysis, contingency management programs were associated with reductions in cocaine use among adults. Research efforts and policies that align with this treatment modality may benefit those who actively use cocaine and attenuate societal burdens.

Sustained brain response to repeated drug cues is associated with poor drug-use outcomes.

A threefold increase in fatal cocaine overdoses during the past decade highlights the critical lack of medications for cocaine use disorders. The brain response to drug cues can predict future drug use; however, results have been mixed. We present preliminary evidence that a sustained response to repeated cocaine cues within a single task is a significant predictor of drug-use outcomes. Seventy-three cocaine inpatients were administered a passive-viewing fMRI task, featuring 500 ms novel evocative (cocaine, sexual, aversive) and neutral comparator cues in the first half (Half1), which were then repeated in the second half (Half2). After the baseline scan, patients received eight outpatient treatment weeks with twice-weekly drug screens. Drug-use outcome groups were empirically defined based on cocaine-positive or missing urines averaged across the outpatient phase: GOOD (<40%), POOR (>85%), and Intermediate (INT, between 40% and 85%) outcomes. Differences of response to initial (Half1) and repeated (Half2) cues in a priori (cue-reactive) regions were tested between outcome groups (3 [Group] × 2 [Halves] ANOVA). An interaction was found in the brain response to drug (but not sex or aversive) cues, with a significant difference between the GOOD and POOR outcome groups in Half2, driven by a significant decrease in brain response by the GOOD outcome group and a sustained brain response by the POOR outcome group, to repeated cocaine cues. The brain response to repeated drug cues may be a useful predictor of future drug use, encouraging future intervention studies to restore a "healthy" (decreasing) response to the repeated presentation of drug cues.

Collaborative care in the treatment of opioid use disorder and mental health conditions in primary care: A clinical study protocol.

BACKGROUND: People with opioid use disorder (OUD) often have a co-occurring psychiatric disorder, which elevates the risk of morbidity and mortality. Promising evidence supports the use of collaborative care for treating people with OUD in primary care. Whether collaborative care interventions that treat both OUD and psychiatric disorders will result in better outcomes is presently unknown. METHODS: The Whole Health Study is a 3-arm randomized controlled trial designed to test collaborative care treatment for OUD and the psychiatric disorders that commonly accompany OUD. Approximately 1200 primary care patients aged ≥18 years with OUD and depression, anxiety, or PTSD will be randomized to one of three conditions: (1) Augmented Usual Care, which consists of a primary care physician (PCP) waivered to prescribe buprenorphine and an addiction psychiatrist to consult on medication-assisted treatment; (2) Collaborative Care, which consists of a waivered PCP, a mental health care manager trained in psychosocial treatments for OUD and psychiatric disorders, and an addiction psychiatrist who provides consultation for OUD and mental health; or (3) Collaborative Care Plus, which consists of all the elements of the Collaborative Care arm plus a Certified Recovery Specialist to help with treatment engagement and retention. Primary outcomes are six-month rates of opioid use and six-month rates of remission of co-occurring psychiatric disorders. DISCUSSION: The Whole Health Study will investigate whether collaborative care models that address OUD and co-occurring depression, anxiety, or PTSD will result in better patient outcomes. The results will inform clinical care delivery during the current opioid crisis. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov registration: NCT04245423.

Prospective randomized pharmacogenetic study of topiramate for treating alcohol use disorder.

In a prior study, topiramate reduced heavy drinking among individuals who sought to reduce their drinking, with the effect moderated by a single nucleotide polymorphism (SNP; rs2832407) in GRIK1, which encodes the kainate GluK1 receptor subunit (Kranzler et al. 2014). The present study sought to replicate prospectively the effect of topiramate and rs2832407 in patients with DSM-5 alcohol use disorder (AUD) who sought to reduce or stop their drinking. We stratified the randomization on genotype (rs2832407*C-allele homozygotes vs. A-allele carriers) and assigned 170 European-American participants (71.2% male) to receive 12 weeks of treatment with topiramate (N = 85), at a maximal daily dosage of 200 mg, or matching placebo (N = 85). At each of nine treatment visits participants received brief counseling to reduce drinking and increase abstinent days. We hypothesized that topiramate-treated patients with the rs2832407*CC genotype would reduce heavy drinking days (HDDs) more than the other three groups. The rate of treatment completion was 91.8% in both groups. The mean number of HDDs per week in the placebo group was 1.67 (95% CI = (1.29, 2.16), p = 0.0001) times greater than in the topiramate group, which was confirmed by the topiramate group's significantly greater reduction in the concentration of the liver enzyme γ-glutamyltransferase and lower alcohol-related problems score. There was no significant difference in topiramate's effect on HDDs between genotype groups. Although consistent with other studies showing a reduction in heavy drinking with topiramate treatment, the prior finding of a moderating effect of rs2832407 genotype was not replicated in this prospective trial.

The relationship between insomnia and the intensity of drinking in treatment-seeking individuals with alcohol dependence.

BACKGROUND: Although insomnia is highly prevalent in alcohol use disorders(AUD), its associations with the severity of alcohol use, pre-existing psychiatric comorbidities and psychosocial problems are understudied. The present study evaluates the interplay between these factors using a structural equation model (SEM). METHODS: We assessed baseline cross-sectional data on patients with AUD (N = 123) recruited to a placebo-controlled medication trial. Severity of alcohol use was measured by the Brief Michigan Alcoholism Screening Test (B-MAST). Insomnia Severity Index was used to assess insomnia symptoms. The Hamilton scales for Depression and Anxiety, Short Index of Problems and Timeline Follow Back evaluated psychiatric symptoms, psychosocial consequences of drinking and level of alcohol consumption respectively. We used logistic regression to evaluate the association between insomnia and severity of alcohol use while controlling for covariates. We constructed a SEM with observed variables to delineate the effect of psychiatric symptoms, psychosocial factors and current alcohol use on the pathway between alcohol use severity and insomnia. RESULTS: The sample was predominately male(83.9 %), Black(54.6 %) and employed(60.0 %). About 45 % of the participants reported moderate-severe insomnia.The association between insomnia and B-MAST attenuated after adjustment for demographics, psychiatric symptoms and psychosocial problems(OR[95 % CI] = 1.17(0.99-1.47). SEM findings demonstrated that B-MAST and insomnia were linked to psychiatric symptoms (95 % Asymptotic-Confidence Interval (ACI): 0.015-0.159, p < 0.05) but not to psychosocial problems or current alcohol use. CONCLUSION: Among treatment-seeking patients with AUD, psychiatric burden mediated the relationship between severity of alcohol use and insomnia. Clinicians should screen for underlying psychiatric disorders among treatment-seeking patients with AUD complaining of insomnia.

Executive Summary of the Focused Update of the ASAM National Practice Guideline for the Treatment of Opioid Use Disorder.

: A Focused Update of the ASAM National Practice Guideline for the Treatment of Opioid Use Disorder is published in the current issue of the Journal of Addiction Medicine. The focused update included a search of Medline's PubMed database from January 1, 2014 to September 27, 2018, as well as a search of the grey literature (archives of the Clinical Guideline Clearinghouse, and key agency and society websites) for new practice guidelines and relevant systematic reviews addressing the use of medications and psychosocial treatments in the treatment of opioid use disorder, including within special populations. The search identified 11 practice guidelines and 35 systematic reviews that informed the subsequent RAND/UCLA Appropriateness Method (RAM) process employed to facilitate the focused update by a National Guideline Committee of addiction experts. New and updated recommendations were included if they were considered: (a) clinically meaningful and applicable to a broad range of clinicians treating addiction involving opioid use; and (b) urgently needed to ensure the Practice Guideline reflects the current state of the science for the existing recommendations, aligns with other relevant practice guidelines, and reflects newly approved medications and formulations.

Clinical Trials for Stimulant Use Disorders: Addressing Heterogeneities That May Undermine Treatment Outcomes.

In recent years, use of cocaine and amphetamines and deaths associated with stimulants have been on the rise, and there are still no FDA-approved medications for stimulant use disorders. One contributing factor may involve heterogeneity. At the neurobiological level, dual dopamine dysfunction may be undermining medication efficacy, suggesting a need for combination pharmacotherapies. At the population level, individual variability is expressed in a number of ways and, if left unaddressed, may interfere with medication efficacy. This chapter reviews studies investigating medications to address dopamine dysfunction, and it also identifies several prominent heterogeneities associated with stimulant (and other substance) use disorders. The chapter has implications for improving interventions to treat stimulant use disorders, and the theme of individual heterogeneity may have broader application across substance use disorders.

Craving and opioid use disorder: A scoping review.

INTRODUCTION: The subjective experience of drug craving is a prominent and common clinical phenomenon for many individuals diagnosed with opioid use disorder (OUD), and could be a valuable clinical endpoint in medication development studies. The purpose of this scoping review is to provide an overview and critical analysis of opioid craving assessments located in the published literature examining OUD. METHOD: Studies were identified through a search of PubMed, Embase, and PsychInfo databases and included for review if opioid craving was the focus and participants were diagnosed with or in treatment for OUD. RESULTS: Fifteen opioid craving assessment instruments were identified across the 87 studies included for review. The most common were the Visual Analog Scale (VAS, 41 studies), Desires for Drug Questionnaire (DDQ, 12 studies), Heroin Craving Questionnaire (HCQ, 10 studies), and Obsessive-Compulsive Drug Use Scale (OCDUS, 10 studies). Craving assessments varied considerably in their format, content, time frame, and underlying subscales, and only 6 of 15 had been psychometrically evaluated. DISCUSSION: This review identified a variety of opioid craving assessments, but few had been evaluated for their psychometric properties making it difficult to ascertain whether craving is being assessed optimally in studies of OUD. Thus, the development of a reliable and valid opioid craving assessment would be worthwhile and could be guided by recently published Food and Drug Administration Clinical Outcome Assessment (COA) guidelines. Importantly, a COA focused on opioid craving could be a valuable addition to research studies designed to evaluate novel treatments for OUD.

The treatment of cocaine use disorder.

Cocaine use continues to be a serious worldwide public health problem. Cocaine abuse is associated with substantial morbidity and mortality. Cocaine overdose deaths are increasing in the United States and, in certain populations, outnumber heroin and opiate overdose deaths. Psychosocial treatments remain the treatments of choice for cocaine use disorder (CUD), with standard approaches including contingency management and cognitive behavioral therapy. However, the effect sizes of these treatments are not large, and they are not effective for most patients. Consequently, investigators have sought to develop pharmacological agents to augment the efficacy of psychosocial treatments. Despite these efforts, no medications have yet been proven to be safe and effective for the treatment of CUD. The most promising pharmacological strategies for CUD treatment thus far include the use of dopamine agonists, such as long-acting amphetamine and modafinil or glutamatergic and GABAergic agents such as topiramate. Combination drugs may be especially promising.