Cocaine-positive Urine Research Articles

Abstract 263: Cocaine Use and Acute Ischemic Stroke: Determining TOAST Etiology & Infarct Locations

Introduction Cocaine‐induced vasospasm of small vessels has long been proposed as a mechanism for ischemic stroke (1). However, there are limited studies to date that have classified cocaine‐related ischemic strokes under a subtype of the Trial of ORG 10127 in Acute Stroke Treatment (TOAST) criteria. This study aims to describe cocaine‐related ischemic strokes by TOAST criteria, treatment, and clinical outcome. Methods A retrospective review was performed to identify patients with acute ischemic stroke and a positive cocaine urine toxicology screen at our stroke center from June 2020 – May 2022. Baseline demographics, urine toxicology, National Institute of Health Stroke Scale (NIHSS) scores, neuroimaging, TOAST criteria, location of stroke, home medications, comorbidities, medical management, and in‐patient outcomes were collected. Data analysis was conducted on IBM SPSS Version 28. Results A total of 74 patients were identified to have a positive cocaine status on admission with a diagnosis of new strokes. The mean age was found to be age 60.8 years old with a majority male population at 73.0% (54/74). Seventy‐eight percent (58/74) were found to be cocaine positive on admission with the remaining endorsing a history of cocaine use. The most common category under the TOAST criteria was large artery atherosclerosis 39.2% (29/74). Among the cocaine‐positive cohort, 10.8% (8/74) of patients received thrombolytics. Most patients had intracranial atherosclerotic disease (46/74, 62.2%) on imaging and in the area of the stroke (41/74, 55.4%). Overall mortality was low (72/74, 97.3%) and modified Rankin score (mRS) at discharge was less than 3 for 59.5% (44/74) of patients. Conclusion Our data suggests that although cocaine may contribute to small vessel disease, cocaine‐related ischemic strokes may have a higher association with large artery atherosclerosis. This study highlights the importance of future larger studies to investigate atherosclerosis as a contributor to cocaine‐induced ischemic strokes.

Impulsivity and Treatment Outcomes in Individuals with Cocaine Use Disorder: Examining the Gap between Interest and Adherence

Background: Impulsivity is implicated in the development and maintenance of Cocaine Use Disorder (CUD). Less work has examined impulsivity’s role on interest in initiating treatment, treatment adherence, or treatment response. No pharmacotherapies are approved for CUD, so efforts to understand and bolster the effects of psychotherapy are important in guiding and refining treatment. The present study examined the impact of impulsivity on interest in treatment, treatment initiation, treatment adherence, and treatment outcomes in individuals with CUD. Methods : Following the completion of a larger study on impulsivity and CUD participants were offered 14 sessions of (12 weeks) Cognitive Behavioral Relapse Prevention (CBT-RP). Before starting treatment, participants completed seven self-report and four behavioral measures of impulsivity. Sixty-eight healthy adults (36% female) with CUD (aged 49.4 ± 7.9) expressed an interest in treatment. Results: Greater scores on several self-report measures of impulsivity, and fewer difficulties with delayed gratification were associated with increased interest in treatment in both males and females. 55 participants attended at least 1 treatment session, while 13 participants did attend a single session. Individuals who attended at least one treatment session scored lower on measures of lack of perseverance and procrastination. Still, measures of impulsivity did not reliably predict session attendance nor the frequency of cocaine-positive urine samples throughout treatment. Males attended nearly twice as many treatment sessions as females despite nonsignificant associations between impulsivity in males and the number of sessions attended. Conclusions : Greater impulsivity in individuals with CUD was associated with expressing an interest in treatment, but not treatment adherence or response.

Association of prescribed oral stimulants on cocaine use among patients enrolled in opioid agonist treatment: A retrospective longitudinal cohort study.

The objective of this study was to measure the association of prescribed oral stimulants with the consumption of cocaine among a population of patients receiving Opioid Agonist Therapy (OAT). The study was a retrospective clinical cohort study using the medical records of all patients receiving OAT who attended treatment clinics within the Canadian Addiction Treatment Centers (CATC) in Ontario from April 2014 to February 2021. Linear mixed-effects models were fit for the exposure of prescribed oral stimulants, and the outcome of a positive urinalysis drug screen for cocaine. Covariates for age, sex, and a random effect for patients were fitted to account for differences between and within patient observations over time. Among patients receiving OAT therapy n = 314 patients were prescribed oral stimulants and n = 11,879 patients were not prescribed oral stimulants among Ontario CATC clinics (n = 92, n = 145 physicians), the mean age at enrollment for patients receiving oral stimulants was 37.0, SD = 8.8, with 43.6% female patients and for patients not receiving oral stimulants mean age was 36.6, SD = 10.7, with 39.6% female patients. Linear mixed effects models showed no difference in cocaine-positive urine tests over time for fixed effects B = 0.001, however, when considering the Interclass correlation coefficient (ICC) between the fixed effects, we found that time since the prescription of an oral stimulant was associated with a decrease of ICC = -0.14 in cocaine positive urine tests. Increasing age at prescription ICC = -0.92, and being male ICC = -0.23 were associated with decreasing cocaine-positive urine. The use of oral stimulant prescriptions to treat cocaine use had no clinically significant benefit in a real-world setting. Patients who receive prescriptions for oral stimulants consume more cocaine before and after treatment compared to patients without an oral stimulant prescription. We also observed that cocaine use was reduced with increased time since treatment initiation.

Moderation of buprenorphine therapy for cocaine dependence efficacy by variation of the Prodynorphin gene.

The aim of this secondary analysis was to identify prodynorphin (PDYN) genetic markers moderating the therapeutic response to treatment of cocaine dependence with buprenorphine/naloxone (Suboxone®; BUP). Cocaine-dependent participants (N = 302) were randomly assigned to a platform of injectable, extended-release naltrexone (XR-NTX) and one of three daily medication arms: 4mg BUP (BUP4), 16mg BUP (BUP16), or placebo (PLB) for 8weeks (Parent Trial Registration: Protocol ID: NIDA-CTN-0048, Clinical Trials.gov ID: NCT01402492). DNA was obtained from 277 participants. Treatment response was determined from weeks 3 to 7 over each 1-week period by the number of cocaine-positive urines per total possible urines. In the cross-ancestry group, the PLB group had more cocaine-positive urines than the BUP16 group (P = 0.0021). The interactions of genetic variant × treatment were observed in the rs1022563 A-allele carrier group where the BUP16 group (N = 35) had fewer cocaine-positive urines (P = 0.0006) than did the PLB group (N = 26) and in the rs1997794 A-allele carrier group where the BUP16 group (N = 49) had fewer cocaine-positive urines (P = 0.0003) than did the PLB group (N = 58). No difference was observed in the rs1022563 GG or rs1997794 GG genotype groups between the BUP16 and PLB groups. In the African American-ancestry subgroup, only the rs1022563 A-allele carrier group was associated with treatment response. These results suggest that PDYN variants may identify patients who are best suited to treatment with XR-NTX plus buprenorphine for cocaine use disorder pharmacotherapy.

The Buprenorphine Analogue BU10119 Attenuates Drug-Primed and Stress-Induced Cocaine Reinstatement in Mice.

There are no Food and Drug Administration-approved medications for cocaine use disorder, including relapse. The μ-opioid receptor (MOPr) partial agonist buprenorphine alone or in combination with naltrexone has been shown to reduce cocaine-positive urine tests and cocaine seeking in rodents. However, there are concerns over the abuse liability of buprenorphine. Buprenorphine's partial agonist and antagonist activity at the nociception receptor (NOPr) and κ-opioid receptor (KOPr), respectively, may contribute to its ability to inhibit cocaine seeking. Thus, we hypothesized that a buprenorphine derivative that exhibits antagonist activity at MOPr and KOPr with enhanced agonist activity at the NOPr could provide a more effective treatment. Here we compare the pharmacology of buprenorphine and two analogs, BU10119 and BU12004, in assays for antinociception and for cocaine- and stress-primed reinstatement in the conditioned place preference paradigm. In vitro and in vivo assays showed that BU10119 acts as an antagonist at MOPr, KOPr, and δ-opioid receptor (DOPr) and a partial agonist at NOPr, whereas BU12004 showed MOPr partial agonist activity and DOPr, KOPr, and NOPr antagonism. BU10119 and buprenorphine but not BU12004 lessened cocaine-primed reinstatement. In contrast, BU10119, BU12004, and buprenorphine blocked stress-primed reinstatement. The selective NOPr agonist SCH221510 but not naloxone decreased cocaine-primed reinstatement. Together, these findings are consistent with the concept that NOPr agonism contributes to the ability of BU10119 and buprenorphine to attenuate reinstatement of cocaine-conditioned place preference in mice. The findings support the development of buprenorphine analogs lacking MOPr agonism with increased NOPr agonism for relapse prevention to cocaine addiction. SIGNIFICANCE STATEMENT: There are no Food and Drug Administration-approved medications for cocaine use disorder. Buprenorphine has shown promise as a treatment for cocaine relapse prevention; however, there are concerns over the abuse liability of buprenorphine. Here we show a buprenorphine analogue, BU10119, which lacks μ-opioid receptor agonism and inhibits cocaine-primed and stress-primed reinstatement in a conditioned place-preference paradigm. The results suggest the development of BU10119 for the management of relapse to cocaine seeking.

Emotion recognition in individuals with cocaine use disorder: the role of abstinence length and the social brain network.

Emotion recognition is impaired in drug addiction. However, research examining the effects of cocaine use on emotion recognition yield mixed evidence with contradictory results potentially reflecting varying abstinence durations. Therefore, we investigated emotion recognition and its neural correlates in individuals with cocaine use disorder (CUD) parsed according to abstinence duration. Emotion recognition performance was compared between current cocaine users (CUD + , n = 28; cocaine-positive urine), short-term abstainers (CUD-ST, n = 23; abstinence < 6months), long-term abstainers (CUD-LT, n = 20; abstinence ≥ 6months), and controls (n = 45). A sample subset (n = 73) underwent structural magnetic resonance imaging to quantify regional gray matter volume (GMV) using voxel-based morphometry. CUD + demonstrated greater difficulty recognizing happiness than CUD-ST and controls, and sadness and fear compared to controls (p < 0.01). For fear, CUD-ST also performed worse than controls (p < 0.01), while no differences emerged between CUD-LT and controls. Whole-brain analysis revealed lower GMV in the bilateral cerebellum in CUD + compared to CUD-LT and controls; a similar pattern was observed in the amygdala (CUD + < CUD-LT) (pFWE < 0.01). Collapsed across all participants, poorer recognition for happiness was associated with lower right cerebellar GMV (pFWE < 0.05). Emotion recognition is impaired with current cocaine use, and selective deficits (in fear) may persist with up to 6months of abstinence. Lower cerebellar GMV may underlie deficits in positive emotion recognition. Interventions targeting emotional-social-cognitive deficits, especially among active users, may enhance treatment success for individuals with CUD.

Sleep time differs among people who co-use cocaine and cannabis compared to people who only use cocaine

ObjectivePeople who use cocaine experience numerous sleep problems and often use cannabis to mitigate these problems. However, co-using cocaine and cannabis may result in worse sleep outcomes when compared to using cocaine only. The current study examined group differences in subjective sleep outcomes among people who use cocaine and people who co-use cocaine and cannabis. MethodsParticipants were 82 individuals with cocaine use disorder who were enrolled in a randomized clinical trial for cocaine treatment. Sleep outcomes, assessed at baseline prior to treatment, were measured with the Saint Mary's Hospital Sleep Questionnaire and included total sleep time, perceived sleep quality, difficulty falling asleep, and daytime alertness. Analysis of covariance and Kruskal-Wallis tests were used to compare sleep outcomes between participants with urine samples that tested positive for both cocaine and cannabis at baseline, those who tested positive for cocaine only, and those who tested negative for all drugs. ResultsTotal reported sleep time was highest among those with a drug negative urine, followed by those with a cocaine positive urine and those who tested positive for cocaine and cannabis. There were no differences in perceived sleep quality, difficulty falling asleep, or daytime alertness between groups. ConclusionsPeople who co-use cocaine and cannabis may report reduced sleep time relative to those who only use cocaine. Co-use of cannabis may exacerbate sleep difficulties in people who use cocaine by decreasing total sleep time, although it is important to note that the groups each reported similar sleep quality. Implications for treatment and directions for future research are discussed.

Randomized trial of methadone treatment of arrestees: 24-month post-release outcomes

BackgroundWe report on the 24-month post-release outcomes of arrestees with opioid use disorder (OUD) enrolled in a randomized trial comparing three treatment approaches initiated in jail. MethodsAdults (N = 225) receiving medically supervised withdrawal from opioids in the Baltimore Detention Center within a few days of arrest were randomly assigned to: (1) interim methadone treatment plus patient navigation (IM + PN) started in the Detention Center; (2) IM; or (3) Enhanced Treatment-as-Usual (ETAU) consisting of detoxification with methadone and referral to treatment in the community. Participants in both methadone conditions could transfer to standard methadone treatment following release. Participants were interviewed at baseline, and 1, 3, 6, 12, and 24 months post-release. Urine was drug tested at follow-up and official arrest records were obtained. ResultsOn an intention-to-treat basis, there were no significant differences among the three conditions over the 24-month post-release period in terms of opioid- or cocaine-positive urine test results or self-reported opioid or cocaine use, meeting opioid or cocaine use disorder criteria, self-reported criminal behavior, or the number of official arrests. There were 9 fatal overdoses, none occurring during methadone treatment, and 109 hospitalizations unrelated to the study. ConclusionsGiven the high morbidity and mortality found in this population of arrestees and costs to society associated with their health care utilization and continued crime and arrests, research aimed at finding more effective interventions should be continued. Clinical trial registrationClinicalTrials.gov: NCT 02334215.

Use of Amphetamine-Type Stimulants Among Emergency Department Patients With Untreated Opioid Use Disorder

Concurrent use of amphetamine-type stimulants among individuals with opioid use disorder can exacerbate social and medical harms, including overdose risk. The study evaluated rates of amphetamine-type stimulant use among patients with untreated opioid use disorder presenting at emergency departments in Baltimore, MD; New York, NY; Cincinnati, OH; and Seattle, WA. Emergency department (ED) patients with untreated opioid use disorder (N=396) and enrolled between February 2017 and January 2019 in a multisite hybrid type III implementation science study were evaluated for concurrent amphetamine-type stimulant use. Individuals with urine tests positive for methamphetamine, amphetamine, or both were compared with amphetamine-type stimulant-negative patients. Overall, 38% of patients (150/396) were amphetamine-type stimulant positive; none reported receiving prescribed amphetamine or methamphetamine medications. Amphetamine-type stimulant-positive versus -negative patients were younger: mean age was 36 years (SD 10 years) versus 40 years (SD 12 years), 69% (104/150) versus 46% (114/246) were white, 65% (98/150) versus 54% (132/246) were unemployed, 67% (101/150) versus 49 (121/246) had unstable housing, 47% (71/150) versus 25% (61/245) reported an incarceration during 1 year before study admission, 60% (77/128) versus 45% (87/195) were hepatitis C positive, 79% (118/150) versus 47% (115/245) reported drug injection during 1 month before the study admission, and 42% (62/149) versus 29% (70/244) presented to the ED for an injury. Lower proportions of amphetamine-type stimulant-positive patients had cocaine-positive urine test results (33% [50/150] versus 52% [129/246]) and reported seeking treatment for substance use problems as a reason for their ED visit (10% [14/148] versus 19% [46/246]). All comparisons were statistically significant at P<.05 with the false discovery rate correction. Amphetamine-type stimulant use among ED patients with untreated opioid use disorder was associated with distinct sociodemographic, social, and health factors. Improved ED-based screening, intervention, and referral protocols for patients with opioid use disorder and amphetamine-type stimulant use are needed.

The predictive validity of the progress assessment, a clinician administered instrument for use in measurement-based care for substance use disorders

We tested the predictive validity of the Progress Assessment (PA), a brief counselor administered tool for use in measurement-based care for substance use disorders. The PA includes 5 items assessing relapse risk and 5 items assessing factors protective against relapse. Data were drawn from a completed study of continuing care for cocaine dependence (McKay et al., 2013) and includes 12 months of follow-up on158 participants (76% male) who received brief telephone or face-to-face sessions. Each session began with the administration of the PA, followed by cognitive-behavioral counseling tied to the results of the PA and anticipated risky situations. Outcome was assessed via urine toxicology every 3 months. As administered in an effectiveness trial, average PA risk and protective scales within each 3-month segment of the study predicted urine toxicology results at the end of that period, with higher risk scores and lower protective scores predicting greater rates of cocaine positive urine drug screens. PA scores did not predict dropout from continuing care participation. The 10-item PA shows promise as a pragmatic clinical tool for ongoing monitoring during continuing care for substance dependence.

A Positive Cocaine Urine Toxicology Test and the Effect on Intraoperative Hemodynamics Under General Anesthesia.

Cocaine has a short biological half-life, but inactive urine metabolites may be detectable for a week following use. It is unclear if patients who test positive for cocaine but have a normal electrocardiogram and vital signs have a greater percentage of hemodynamic events intraoperatively. A total of 328 patients with a history of cocaine use who were scheduled for elective noncardiac surgery under general anesthesia were enrolled. Patients were categorized into cocaine-positive versus cocaine-negative groups based on the results of their urine cocaine toxicology test. The primary aim of this study was to evaluate whether asymptomatic cocaine-positive patients had similar percentages of intraoperative hemodynamic events, defined as (1) a mean arterial blood pressure (MAP) of <65 or >105 mm Hg and (2) a heart rate (HR) of <50 or >100 beats per minute (bpm) compared to cocaine-negative patients. The study was powered to assess if the 2 groups had an equivalent mean percent of intraoperative hemodynamic events within specific limits using an equivalence test of means consisting of 2 one-sided tests. The cocaine-positive group had a blood pressure (BP) that was outside the set limits 19.4% (standard deviation [SD] 17.7%) of the time versus 23.1% (SD 17.7%) in the cocaine-negative group (95% confidence interval [CI], 0.5-7.0). The cocaine-positive group had a HR outside the set limits 9.6% (SD 16.2%) of the time versus 8.2% (SD 14.9%) in the cocaine-negative group (95% CI, 4.3-1.5). Adjusted for age, sex, body mass index (BMI), smoking status, and the presence of comorbid hypertension, renal disease, and psychiatric illness, the cocaine-positive and cocaine-negative patients were similar within a 7.5% margin of equivalence for MAP data (β coefficient = 2%, P = .003, CI, 2-6) and within a 5% margin of equivalence for HR data (β coefficient = 0.2%, P < .001, CI, 4-3). Asymptomatic cocaine-positive patients undergoing elective noncardiac surgery under general anesthesia have similar percentages of intraoperative hemodynamic events compared to cocaine-negative patients.

Doxazosin treatment in cocaine use disorder: pharmacogenetic response based on an alpha-1 adrenoreceptor subtype D genetic variant

ABSTRACTBackground: The α1 antagonist doxazosin reduces cocaine use in individuals with cocaine use disorder (CUD) through a functional polymorphism of the α1 adrenoreceptor. The regulatory role of the α1 adrenoreceptor subtype D (ADRA1D) gene polymorphism in CUD is uncharacterized.Objectives: To study how the genetic variant of ADRA1D gene (T1848A, rs2236554) may affect the treatment efficacy of doxazosin in reducing cocaine use.Methods: This 12-week pilot trial included 76 participants with CUD with ADRA1D (T1848A, rs2236554) AA (N = 40) or AT/TT genotype (N = 36). Participants were randomized to doxazosin (8 mg/day, N = 47) or placebo (N = 29), and followed with thrice weekly urine toxicology and once weekly cognitive behavioral psychotherapy.Results: The AA and the AT/TT groups had comparable baseline rates of cocaine positive urines at weeks 1–2 (~ 76%). In the placebo group, an increase of cocaine positive urines in the AT/TT group was found as compared to the AA group (24% vs. 9%). In the doxazosin group, a greater decrease in cocaine positive urines was found in the AT/TT group relative to the AA group. The difference between the doxazosin and placebo groups in cocaine negative urines became evident at weeks 5–6 and peaked at weeks 9–10 (~35% difference). The AT/TT group demonstrated a significant medication and time by medication effect (p < .001), whereas the AA group did not.Conclusion: The T-allele carriers showed a greater reduction of cocaine use after treatment with doxazosin in participants with the ADRA1D gene polymorphism (T1848A), suggesting that this SNP may serve as a pharmacogenetic marker in pharmacotherapy of CUD.

Accelerated Intermittent Theta-Burst Stimulation as a Treatment for Cocaine Use Disorder: A Proof-of-Concept Study.

There are no effective treatments for cocaine use disorder (CUD), a chronic, relapsing brain disease characterized by dysregulated circuits related to cue reactivity, reward processing, response inhibition, and executive control. Transcranial magnetic stimulation (TMS) has the potential to modulate circuits and networks implicated in neuropsychiatric disorders, including addiction. Although acute applications of TMS have reduced craving in urine-negative cocaine users, the tolerability and safety of administering accelerated TMS to cocaine-positive individuals is unknown. As such, we performed a proof-of-concept study employing an intermittent theta-burst stimulation (iTBS) protocol in an actively cocaine-using sample. Although our main goal was to assess the tolerability and safety of administering three iTBS sessions daily, we also hypothesized that iTBS would reduce cocaine use in this non-treatment seeking cohort. We recruited 19 individuals with CUD to receive three open-label iTBS sessions per day, with approximately a 60-min interval between sessions, for 10 days over a 2-week period (30 total iTBS sessions). iTBS was delivered to left dorsolateral prefrontal cortex (dlPFC) with neuronavigation guidance. Compliance and safety were assessed throughout the trial. Cocaine use behavior was assessed before, during, and after the intervention and at 1- and 4-week follow-up visits. Of the 335 iTBS sessions applied, 73% were performed on participants with cocaine-positive urine tests. Nine of the 14 participants who initiated treatment received at least 26 of 30 iTBS sessions and returned for the 4-week follow-up visit. These individuals reduced their weekly cocaine consumption by 78% in amount of dollars spent and 70% in days of use relative to pre-iTBS cocaine use patterns. Similarly, individuals reduced their weekly consumption of nicotine, alcohol, and THC, suggesting iTBS modulated a common circuit across drugs of abuse. iTBS was well-tolerated, despite the expected occasional headaches. A single participant developed a transient neurological event of uncertain etiology on iTBS day 9 and cocaine-induced psychosis 2 weeks after discontinuation. It thus appears that accelerated iTBS to left dlPFC administered in active, chronic cocaine users is both feasible and tolerable in actively using cocaine participants with preliminary indications of efficacy in reducing both the amount and frequency of cocaine (and other off target drug) use. The neural underpinnings of these behavioral changes could help in the future development of effective treatment of CUD.

573 Safety of Esophagogastroduodenoscopy in Patients With Active Cocaine Use: A Pilot Study

INTRODUCTION: The timing of when to perform endoscopy in patients with a positive cocaine urine drug screen (UDS+C) varies across institutions and is based on expert opinions and personal experience. There are no clear published guidelines or reported studies in the English literature examining the safety of endoscopy in active users of cocaine. This study aimed to describe the incidence of adverse events of esophagogastroduodenoscopy (EGD) in patients with active cocaine use in a single inner-city tertiary hospital in Chicago. METHODS: We examined consecutive records of patients who underwent an EGD at the John H. Stroger, Jr. Hospital of Cook County from October 2016 to October 2018 and identified those who had a UDS + C within 4 days. We examined the demographics and outcomes of these patients including pre- and post-procedure hemodynamics. Paired T-tests were used to analyze the periprocedural hemodynamics. RESULTS: A total of 2122 patients were identified during the study period of which 129 patients had a positive urine drug screen and 50 had a UDS + C. From these patients, we identified 20 who had a UDS + C within 4 days of an EGD. These active users were predominately male (n=16) and African-American (n = 14). The majority underwent urgent procedures (n=16) in an inpatient setting (n = 19). The average time since a UDS + C was 2.3 days (SD ± 1.26). 8 patients were ASA class II and 12 were ASA class III. 14 patients underwent monitored anesthesia care (MAC) sedation and 6 underwent general anesthesia. 12 patients had abnormal electrocardiograms. The most frequent comorbidity was concurrent drug or alcohol abuse (n = 14) followed by hypertension (n = 7). There were no adverse endoscopic or anesthesia events, but 3 patients had transient procedural events (1 with oxygen desaturation and 2 with hypotension). Pre- and post-procedure hemodynamics were within normal ranges and blood pressure showed a statistically but not clinically significant decrease from a mean of 136/79 mmHg to 129/77 mmHg (P &lt; 0.05). CONCLUSION: No major adverse events occurred in the active cocaine users undergoing EGD in our retrospective single center study. The decrease in blood pressure in our study was statistically but not clinically significant. Our study suggests that EGD with anesthesia support appears to be safe in patients with active cocaine use. More studies with larger sample sizes are needed to confirm these findings and further guide the safety and timing of endoscopy in cocaine users.

Pharmacogenetic role of dopamine transporter (SLC6A3) variation on response to disulfiram treatment for cocaine addiction.

Disulfiram has been beneficial in treating cocaine addiction in several studies. Patients with two SLC6A3 (DAT1) rs28363170 10-repeat alleles who have with genetically high dopamine transporter (DAT) levels may benefit from increased dopamine levels resulting from disulfiram treatment. After stabilization for 2 weeks on methadone, 70 cocaine and opioid codependent patients were randomized into disulfiram and placebo groups for 12 weeks of treatment. We genotyped the SLC6A3 (DAT1) 40 bp 3'-untranslated region variable number tandem repeat variant and evaluated its role in moderating disulfiram efficacy for cocaine dependence. Among the 10,10-repeat genotype group, cocaine-positive urines dropped from 78% to 48% and from 80% to 75% among the 9-repeat carrier group in the disulfiram group (P = 0.0001, with an effect size of 0.09). No difference was observed in cocaine-positive urines in the placebo group between the 10,10-repeat genotype and the 9-allele carrier patients. We found that patients with genetically higher DAT levels had better treatment outcomes with disulfiram pharmacotherapy of cocaine dependence than those with lower DAT levels. (Am J Addict 2019;28:311-317).

Injection opioid use as a predictor of treatment outcomes among methadone-maintained opioid-dependent patients

BackgroundInjection opioid use is associated with more severe health and psychosocial consequences relative to non-injection use, but few studies have examined whether injection use is associated with methadone maintenance treatment outcomes. The present study examined differential MMT outcomes among opioid injectors and non-injectors. MethodsData were extracted from the clinic charts of opioid-dependent MMT patients (N = 290; n = 115 injectors) enrolled in a university-affiliated, urban MMT clinic. Injection status was examined as a predictor of short- (3-month opioid, cocaine, benzodiazepine and cannabis urine drug screens) and long- (days retained in treatment) term MMT outcomes. ResultsBivariate analyses revealed injection users were less likely to be African American and to have completed high school, were more likely to have started heroin use before age 21, to report having hepatitis C, to report a baseline cocaine use disorder, and had higher methadone doses at 3-months into treatment. Injection status significantly predicted a greater proportion of cocaine-positive urine drug screens in the first 3 months of treatment, but did not significantly predict opioid, benzodiazepine or cannabis drug screens, or length of treatment retention. ConclusionThis is one of a handful of studies to examine injection status as a predictor of MMT outcomes. Injection status is associated with cocaine use early in treatment, which has implications for the focus of treatment.

195 Screening Electrocardiograms in Cocaine-Positive Chest-Pain-Free Psychiatric Patients Requiring Medical Clearance

Current practice at our large, public, urban academic emergency department (ED) is to obtain a screening electrocardiogram (ECG) as part of the medical clearance process on all patients who require transfer to an inpatient psychiatric facility and test positive for cocaine on a urine toxicology screen regardless of the presence or absence of chest pain. The purpose of this retrospective quality improvement study is to examine the utility and impact of a screening ECG for patients with urine toxicology screening positive for cocaine who are chest-pain-free and require medical clearance prior to transfer to an inpatient psychiatric facility. An institutional review board-approved, retrospective chart review between January 2014 - December 2015 was performed of all ED patients (1) over 18 years of age, (2) without chest pain documented in the medical record, (3) who required medical clearance in the ED prior to transfer to an inpatient psychiatric facility, (4) who tested positive for cocaine on a screening urine toxicology test, and (5) for whom a screening ECG was obtained. All ECGs were interpreted by an attending physician. Abnormal ECGs were defined as: nonspecific ST changes, T wave inversions, sinus tachycardia, ST elevation, or ST depression. All abnormal ECGs were compared to prior ECGs if available, and if no change noted then these were categorized as normal. Primary outcome was disposition of the patient to an inpatient psychiatric facility versus inpatient medical admission. Secondary outcomes were rates of a subsequent cardiac workup, including inpatient medical admission, cardiac enzymes, stress testing, cardiology consultation, and cardiac catheterization. During the study period, 1968 ED patients tested positive for cocaine on a urine toxicology screen and 853 met inclusion criteria. ECGs were normal in 809 (95%, 95% CI [93%, 96%]) patients, and abnormal in 44 (5%, 95% CI [4%, 7%]) patients. Of the 44 patients with abnormal ECGs, 4 were admitted for a cardiac workup. Two patients had positive troponins in the ED. Two patients had cardiology consultations and 3 had further cardiac stress testing performed, all of which were negative or non-diagnostic. No cardiac catheterizations were performed on any patients. Based on the results of our study, the majority of ED patients with recent cocaine use but without chest pain have a normal ECG. Of the minority of patients with an abnormal ECG, there were no cases of acute myocardial ischemia or infarction identified in the absence of chest pain. Therefore, a screening ECG in patients without chest pain simply because of a cocaine-positive urine toxicology test does not appear to identify any cases of myocardial ischemia or infarction and may, in fact, lead to over-testing, increased admission, misuse of resources, and increased cost. Limitations of this study include its retrospective, chart review design. Additionally, there is the possibility of a patient not being forthcoming regarding the presence or absence of chest pain and being categorized incorrectly.

β-Blocker treatment and prognosis in acute coronary syndrome associated with cocaine consumption: The RUTI-Cocaine Study

BackgroundThe use of β-blocker therapy in the setting of acute coronary syndrome (ACS) associated with cocaine consumption (ACS-ACC) is discouraged due to the risk of coronary vasoconstriction. We examined the prognostic value of β-blocker therapy in a contemporary ACS cohort. Methods and resultsProspective, single-center study conducted between January 2001 and December 2014 that examined cocaine use among young (≤50-year-old) consecutive patients admitted with an ACS. During the study period, 1002 patients were admitted; of these, 57 (5.7%) had a positive cocaine urine test We collected data on clinical characteristics and major adverse cardiovascular events (MACE) during follow-up. Among ACS-ACC patients, 33 (57.9%) received β-blocker therapy during hospital admission and after discharge. During a median follow-up of 4.0 (IQR: 2.4–6.5) years after the index event, 2 (6.1%) patients treated with β-blocker therapy died and 6 (18.2%) experienced hospital re-admission for myocardial infarction (MI); in contrast, there were 5 (20.8%) deaths and 5 (20.8%) readmissions due to MI in patients without β-blocker therapy. Lower rates of MACE were observed in patients treated with β-blocker therapy (30.3%) than those without β-blocker therapy (41.7%). The 90-day survival was higher in patients treated with β-blocker therapy (87.5% vs. 100%; Log rank test p = 0.035). ConclusionsIn patients with ACS-ACC, β-blocker treatment was associated with a significantly better clinical outcome, with lower rates of death and MI. Our findings support the evidence for long-term β-blocker administration in high-risk patients and highlight the need for large prospective multicenter studies of β-blocker treatment in ACS-ACC.

Reprint of The effect of N-acetylcysteine and working memory training on cocaine use, craving and inhibition in regular cocaine users: correspondence of lab assessments and Ecological Momentary Assessment

IntroductionEffective treatment for cocaine use disorder should dampen hypersensitive cue-induced motivational processes and/or strengthen executive control. Using a randomized, double-blind, placebo-controlled intervention, the primary aim of this study was to investigate the effect of N-Acetylcysteine (NAC) and working memory (WM)-training to reduce cocaine use and craving and to improve inhibition assessed in the laboratory and during Ecological Momentary Assessment (EMA). The second aim was to examine correspondence between laboratory and EMA data. MethodsTwenty-four of 38 cocaine-using men completed a 25-day intervention with 2400mg/day NAC or placebo and WM-training as well as two lab-visits assessing cocaine use, craving and inhibition (Stop Signal task). Additionally, cocaine use, craving and cognition (Stroop task) were assessed using EMA during treatment, with 26 participants completing 819 assessments. ResultsCocaine problems according to the Drug Use Disorder Identification Test (DUDIT) decreased more after NAC than after placebo, and the proportion of cocaine-positive urines at lab-visit 2 was lower in the NAC group. No NAC effects were found on craving. For cocaine use and craving, results from the lab data were generally similar to EMA results. NAC also showed some effects on cognitive control: improved inhibition assessed with the Stop Signal task in the lab, and decreased classic Stroop performance during EMA. There were no significant effects of number of completed WM-training sessions. ConclusionsOverall this study revealed mixed findings regarding the treatment of cocaine use disorders with NAC and WM-training. The effect of NAC on inhibition should be further investigated.

Pharmacogenetics of Dopamine β-Hydroxylase in cocaine dependence therapy with doxazosin.

The α1 -adrenergic antagonist, doxazosin, has improved cocaine use disorder (CUD) presumably by blocking norepinephrine (NE) stimulation and reward from cocaine-induced NE increases. If the NE levels for release were lower, then doxazosin might more readily block this NE stimulation and be more effective. The NE available for release can be lower through a genetic polymorphism in dopamine β-hydroxylase (DBH) (C-1021T, rs1611115), which reduces DβH's conversion of dopamine to NE. We hypothesize that doxazosin would be more effective in CUD patients who have these genetically lower DβH levels. This 12-week, double-blind, randomized, placebo-controlled trial included 76 CUD patients: 49 with higher DβH levels from the DBH CC genotype and 27 with lower DβH levels from T-allele carriers (CT or TT). Patients were randomized to doxazosin (8mg/day, N=47) or placebo (N=29) and followed with thrice weekly urine toxicology and once weekly cognitive behavioral psychotherapy. Cocaine use was reduced at a higher rate among patients in the doxazosin than in the placebo arm. We found significantly lower cocaine use rates among patients carrying the T-allele (CT/TT) than the CC genotype. The percentage of cocaine positive urines was reduced by 41 percent from baseline in the CT/TT group with low DβH and NE levels, as compared with no net reduction in the CC genotype group with normal DβH and NE levels. The DBH polymorphism appears play an important role in CUD patients' response to doxazosin treatment, supporting a pharmacogenetic association and potential application for personalized medicine.