Pharmacogenetics of Dopamine ß-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 ß-hydroxylase (DBH) (C-1021T, rs1611115), which reduces DßH's conversion of dopamine to NE. We hypothesize that doxazosin would be more effective in CUD patients who have these genetically lower DßH levels. This 12-week, double-blind, randomized, placebo-controlled trial included 76 CUD patients: 49 with higher DßH levels from the DBH CC genotype and 27 with lower DßH levels from T-allele carriers (CT or TT). Patients 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. 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 DßH and NE levels, as compared with no net reduction in the CC genotype group with normal DßH 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.

Acceptability of safe drug consumption spaces among people who inject drugs in rural West Virginia.

AIM: Safe consumption spaces (SCS) are indoor environments in which people can use drugs with trained personnel on site to provide overdose reversal and risk reduction services. SCS have been shown to reduce fatal overdoses, decrease public syringe disposal, and reduce public drug consumption. Existing SCS research in the USA has explored acceptability for the hypothetical use of SCS, but primarily among urban populations of people who inject drugs (PWID). Given the disproportionate impact of the opioid crisis in rural communities, this research examines hypothetical SCS acceptability among a rural sample of PWID in West Virginia. METHODS: Data were drawn from a 2018 cross-sectional survey of PWID (n = 373) who reported injection drug use in the previous 6 months and residence in Cabell County, West Virginia. Participants were asked about their hypothetical use of a SCS with responses dichotomized into two groups, likely and unlikely SCS users. Chi-square and t tests were conducted to identify differences between likely and unlikely SCS users across demographic, substance use, and health measures. RESULTS: Survey participants were 59.5% male, 83.4% non-Hispanic White, and 79.1% reported likely hypothetical SCS use. Hypothetical SCS users were significantly (p < .05) more likely to have recently (past 6 months) injected cocaine (38.3% vs. 25.7%), speedball (41.0% vs. 24.3%), and to report preferring drugs containing fentanyl (32.5% vs. 20.3%). Additionally, likely SCS users were significantly more likely to have recently experienced an overdose (46.8% vs. 32.4%), witnessed an overdose (78.3% vs. 60.8%), and received naloxone (51.2% vs. 37.8%). Likely SCS users were less likely to have borrowed a syringe from a friend (34.6% vs. 48.7%). CONCLUSIONS: Rural PWID engaging in high-risk behaviors perceive SCS as an acceptable harm reduction strategy. SCS may be a viable option to reduce overdose fatalities in rural communities.

Injecting-related health harms and overuse of acidifiers among people who inject heroin and crack cocaine in London: a mixed-methods study.

BACKGROUND: Venous access is a priority for people who inject drugs (PWID). Damage and scarring of peripheral veins can exacerbate health harms, such as skin and soft tissue infections (SSTI), and promote transitions to femoral and subcutaneous injecting. Brown heroin available in Europe requires acidification for injection preparation. In this paper, we present mixed-methods data to explore our hypothesis of a link between overly acidic injection solutions, venous damage and SSTI risk. METHODS: We present a structured survey (n = 455) and in-depth qualitative interview (n = 31) data generated with PWID in London for the Care & Prevent study. Participants provided life history data and detail on injecting environments and drug preparation practices, including the use of acidifiers. Bivariate and multivariate analyses were conducted using a logistic regression for binary outcomes to explore associations between outcomes and excessive acidifier use. Grounded theory principles informed inductive qualitative analysis. Mixed-methods triangulation was iterative with results comparison informing the direction and questions asked of further analyses. RESULTS: Of the 455 participants, most (92%) injected heroin and/or crack cocaine, with 84% using citric as their primary acid for drug preparation. Overuse of acidifier was common: of the 418 who provided an estimate, 36% (n = 150) used more than ½ a sachet, with 30% (n = 127) using a whole sachet or more. We found associations between acidifier overuse, femoral injecting and DVT, but not SSTI. Qualitative accounts highlight the role of poor heroin quality, crack cocaine use, information and manufacturing constraints in acidifier overuse. Painful injections and damage to peripheral veins were common and often attributed to the use of citric acid. CONCLUSIONS: To reduce injecting-related injury and associated consequences, it is crucial to understand the interplay of environmental and practice-based risks underpinning venous damage among PWID. Overuse of acidifier is a modifiable risk factor. In the absence of structural supports such as safe injecting facilities or the prescribing of pharmaceutical diamorphine, there is an urgent need to revisit injecting paraphernalia design and distribution in order to alleviate health harms and distress among the most marginalised.

Pharmacokinetics of Sustained-Release Oral Dexamphetamine Sulfate in Cocaine and Heroin-Dependent Patients.

INTRODUCTION: Research has shown that sustained-release (SR) dexamphetamine is a promising agonist treatment for cocaine dependence. However, little is known about the pharmacokinetics (PKs) of SR oral dexamphetamine. This study examined the PKs of a new SR dexamphetamine formulation in cocaine plus heroin-dependent patients currently in heroin-assisted treatment. METHODS: The study was designed as an open-label PK study in 2 cohorts: n = 5 with once daily 60 mg and n = 7 with once daily 30 mg SR oral dexamphetamine. Five days of blood plasma dexamphetamine concentrations measured with liquid chromatography-mass spectrometry with PK parameter estimates using noncompartmental analysis. RESULTS: Twelve cocaine-dependent plus heroin-dependent patients in heroin-assisted treatment were included. The initial cohort 1 dose of 60 mg once daily was adjusted to 30 mg after mild to moderate adverse events. After oral administration, tmax values (coefficient of variation %) were 6.0 (17.0%) and 6.3 (16.3%) hours and t1/2 were 11 (24.6%) and 12 (25.4%) hours for 60 mg and 30 mg SR dexamphetamine, respectively. At steady state, CSSmax values were reached at 100 (27.5%) ng/mL and 58.4 (14.4%) ng/mL, whereas CSSmin values were 39.5 (38.9%) ng/mL and 21.8 (19.8%) ng/mL for 60 mg and 30 mg, respectively. CONCLUSIONS: The investigated SR formulation of dexamphetamine showed favorable slow-release characteristics in cocaine and heroin-dependent patients. A dose-proportional steady-state concentration was achieved within 3 days. These findings support the suitability of the SR formulation in the treatment of cocaine dependence.

Sustained-release dexamfetamine in the treatment of chronic cocaine-dependent patients on heroin-assisted treatment: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Heroin-assisted treatment is effective for methadone treatment-refractory heroin-dependent patients, but continued comorbid cocaine dependence remains problematic. Sustained-release dexamfetamine is a promising agonist pharmacotherapy for cocaine dependence and we aimed to assess its acceptance, efficacy, and safety. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, patients who were treatment-refractory, as indicated by at least two earlier failed treatments aimed at reducing or abstaining from cocaine use, and who regularly (≥8 days/month) used crack-cocaine were enrolled from four heroin-assisted treatment centres in the Netherlands. Eligible patients were randomly assigned (1:1) to receive either 12 weeks of daily, supervised prescription of 60 mg/day oral sustained-release dexamfetamine or placebo in addition to co-prescribed methadone and diacetylmorphine. Randomisation was done by the collaborating pharmacist, using a computer-generated random number sequence with stratification by treatment centre in blocks of four per stratum. Randomisation was masked to patients, staff, and researchers throughout the study. The primary outcome was the number of self-reported days of cocaine use during study treatment, assessed every 4 weeks. Primary and safety analyses were done in the intention-to-treat population. The study was registered with the European Union Drug Regulating Authorities Clinical Trials (EUdraCT 2013-004024-11) and with The Netherlands Trial Register (NTR2576). FINDINGS: Between Aug 8, 2014, and Feb 27, 2015, 111 patients were assessed for eligibility, of whom 73 were enrolled and randomised; 38 patients were assigned to the sustained-release dexamfetamine group and 35 to the placebo group. Sustained-release dexamfetamine treatment resulted in significantly fewer days of cocaine use than placebo treatment (mean 44·9 days [SD 29·4] vs 60·6 days [24·3], respectively [95% CI of difference 3·1-28·4]; p=0·031; Cohen's standardised effect size d=0·58). One or more adverse events were reported by 28 (74%) patients in the dexamfetamine group and by 16 (46%) patients in the placebo group. Most adverse events were transient and well-tolerated. INTERPRETATION: Sustained-release dexamfetamine is a well accepted, effective, and safe agonist pharmacotherapy for comorbid treatment-refractory cocaine dependence in heroin-dependent patients in heroin-assisted treatment. Future research should aim to replicate these findings in chronic cocaine-dependent and other stimulant-dependent patients in more routine treatment settings, including strategies to optimise treatment adherence like medication management interventions and contingency management. FUNDING: Netherlands Organisation for Health Research and Development.

Prefrontal gray matter volume recovery in treatment-seeking cocaine-addicted individuals: a longitudinal study.

Deficits in prefrontal cortical (PFC) function have been consistently reported in individuals with cocaine use disorders (iCUD), and have separately been shown to improve with longer-term abstinence. However, it is less clear whether the PFC structural integrity possibly underlying these deficits is also modulated by sustained reduction in drug use in iCUD. Here, T1-weighted magnetic resonance imaging scans were acquired, and performance on a neuropsychological test battery was assessed, in 19 initially abstinent treatment-seeking iCUD, first at baseline and then after six months of significantly reduced or no drug use (follow-up). A comparison cohort of 12 healthy controls was also scanned twice with a similar inter-scan interval. The iCUD showed increased gray matter volume in the left inferior frontal gyrus and bilaterally in the ventromedial prefrontal cortex at follow-up compared to baseline; healthy controls, as expected, showed no changes over this same time period. The iCUD also showed improved decision making and cognitive flexibility, with the latter correlated significantly with the gray matter volume increases in the inferior frontal gyrus. Given its association with improved cognitive function, the longitudinal recovery in cortical gray matter volume, particularly in regions where structure and function are adversely affected by chronic drug use, reflects a quantifiable positive impact of significantly reduced drug use on cortical structural integrity.

Moderators of response to sertraline versus placebo among recently abstinent, cocaine dependent patients: A retrospective analysis of two clinical trials.

BACKGROUND AND OBJECTIVES: Moderators of treatment response to serotonin reuptake inhibitor sertraline (SRT) for cocaine dependence were assessed in two randomized, double blind, placebo-controlled clinical trials. METHODS: Generalized estimating equation modeling was performed on data from cocaine-dependent volunteers randomized to receive SRT or placebo (N = 126) who completed >2-week drug-free residential portions of the 12-week trials, in which subsequent outpatient treatment (weeks 3-12) included weekly cognitive behavioral therapy and thrice-weekly supervised urine toxicology. PRIMARY OUTCOME MEASURE: Relapse (2 consecutive cocaine-positive or missing urines) following residential stay. Potential moderators included treatment, sex, age, race, depression measures, baseline cocaine urine result, and alcohol dependence diagnosis (ADDx). RESULTS: Odds ratios (OR) for relapse showed placebo-treated participants were significantly more likely to relapse than SRT participants. Regardless of treatment condition, participants more likely to relapse were male, and those with lower Hamilton depression ratings, or baseline cocaine-negative urines. Older subjects or those with current ADDx had higher relapse risk than those without ADDx; however, treating older or ADDx participants with SRT reduced cocaine relapse more than placebo. DISCUSSION AND CONCLUSIONS: Women or those with more severe cocaine use or depressive symptoms may have fewer cocaine relapses regardless of medication treatment. SRT at 200 mg reduced cocaine relapse more than placebo, especially in older participants or in those with comorbid ADDx. SCIENTIFIC SIGNIFICANCE: SRT may be efficacious to support relapse prevention among cocaine-dependent patients in the context of brief residential followed by outpatient treatment, especially in older participants or those with comorbid alcohol/cocaine dependence. (Am J Addict 2017;26:807-814).

The female crack users: Higher rates of social vulnerability in Brazil.

Female crack users who sought treatment are a hard to find part of the population. We studied sociodemographic and behavioral characteristics of crack users undergoing treatment in psychosocial care centers for alcohol and other drugs in six Brazilian cities. We carried out a cross-sectional study of 816 crack users and collected data with the Addiction Severity Index. Women were more likely to be in vulnerable situations: had worst levels of education, were not receiving money enough to their basic needs; more likely to be HIV positive (10.1%), to report sexual abuse (34%), and to be separated from their children (20%).

Caring for crack users: strategies and work practices in the territory. / O cuidado ao usuário de crack: estratégias e práticas de trabalho no território.

OBJECTIVE: To know the care strategies for crack users in Brazil from the perspective of the Centre of Psychosocial Care for Alcohol and Other Drugs (CAPS AD). METHOD: This is a qualitative descriptive study. Data were collected by means of interviews conducted with eight professionals of a CAPS AD in the metropolitan region of Porto Alegre, between February and March 2013. Data were subjected to thematic analysis. RESULTS: The analysed data revealed the use of care strategies, such as itinerant teams, home visits, and the extended clinic, and that the work territory should essentially be the home of the professional. CONCLUSION: Care in the territory is considered an innovation in the field of mental healthcare because it enables care that focuses on social, cultural, and historical context of users.

Emotion regulation strategies in individuals with cocaine use disorder maintained on methadone.

BACKGROUND AND OBJECTIVES: Cognitive reappraisal (CR) and emotional suppression (ES), two emotion regulation strategies, are disrupted in other substance use disorders but have not been studied in cocaine dependence. METHODS: Methadone-maintained individuals with cocaine dependence (N = 72) completed assessment of CR, ES, cocaine use, and psychiatric symptoms. RESULTS: CR scores were associated with lower depression scores (r = -.29, p = .01), but not with cocaine abstinence during 8 weeks of treatment (r = .12, p = .29). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: CR appeared relevant to cocaine-dependent individuals' depression, but was not associated with abstinence or treatment outcome. (Am J Addict 2016;25:529-532).

Effects of a Single Lyric Analysis Intervention on Withdrawal and Craving With Inpatients on a Detoxification Unit: A Cluster-Randomized Effectiveness Study.

BACKGROUND: For patients hospitalized on inpatient detoxification units, reducing negative symptoms such as withdrawal and craving is a key treatment area. Although lyric analysis is a commonly utilized music therapy intervention for clients in substance abuse rehabilitation, there is a lack of randomized controlled music therapy studies systematically investigating how lyric analysis interventions can affect patients on a detoxification unit. OBJECTIVE: The purpose of this cluster-randomized effectiveness study was to measure the effects of single-session group lyric analysis interventions on withdrawal and craving with patients on a detoxification unit. A secondary purpose of this study was to determine if relationships existed between treatment effects and participants' familiarity with the song. METHODS: Participants (N = 144) were cluster-randomized to experimental (posttest only) or wait-list control (pretest only) conditions to provide treatment to all participants in an inclusive single-session design. RESULTS: Although participants in the experimental condition had lower withdrawal and craving means than participants in the control condition, these differences were not significant. Familiarity of the song in the lyric analysis was not related to withdrawal or craving. CONCLUSION: Group-based lyric analysis interventions may be effective for temporarily relieving withdrawal and craving in patients on a detoxification unit. Familiarity of the song did not affect results. Implications for clinical practice, suggestions for future research, and limitations are provided.

Similar and Different? Subjective Effects of Methylphenidate and Cocaine in Opioid-Maintained Patients.

Methylphenidate (MPH) is commonly prescribed for attention deficit hyperactivity disorder (ADHD). Recreational nonmedical use has been described and also occurs in patients on opioid maintenance treatment (OMT). MPH has been proposed for use as replacement therapy in cocaine dependence, although evidence for efficacy is inconclusive. We conducted a cross-sectional interview study on patterns of MPH use in a sample of 20 MPH-using patients on OMT with a history of cocaine use. We assessed symptoms of depression, ADHD during childhood, and retrospective subjective-effects profiles of MPH and cocaine. Risky patterns of MPH use were common, in particular illicit acquisition, use of high doses, and parenteral administration. Sixty percent of patients reported having used MPH as a substitute for cocaine. Correspondingly, the subjective-effect profiles of MPH and cocaine showed striking parallels, with overall effects of MPH being rated more positively than those of cocaine. Proportions of patients with elevated scores for depression or childhood ADHD were large, highlighting the importance of treating dual disorders in this population. Clinical studies on MPH substitution in cocaine-dependent patients on opioid maintenance treatment could benefit from consideration of the patterns of application of MPH in this population. Results are preliminary due to small sample size.

Self-reported cravings for heroin and cocaine during maintenance treatment with slow-release oral morphine compared with methadone: a randomized, crossover clinical trial.

OBJECTIVE: Craving, an urge or increased desire to take a drug, is part of a cluster of behavioral, cognitive, and physiological phenomena that can develop after substance use. Self-reported cravings for heroin and cocaine are compared in opioid dependent patients while receiving maintenance treatment with slow-release oral morphine (SROM) or methadone. METHODS: Data from a 22-week open-label, randomized, crossover trial (per protocol sample n = 157) were examined by analysis of variance (ANOVA). Cravings for heroin and cocaine during the past 7 days were assessed at baseline and thrice during each 11-week treatment period using a Visual Analog Scale (heroin, VAS-H; cocaine, VAS-C), German versions of the brief Heroin Craving Questionnaire (HCQ), and the brief Cocaine Craving Questionnaire (CCQ). RESULTS: Mean (SD) heroin craving scores under methadone were 3.3 (2.4) (VAS-H) and 2.9 (1.4) (HCQ). Heroin craving scores under SROM were significantly lower, at 2.5 (2.2) (VAS-H) and 2.6 (1.2) (HCQ) (ANOVA: VAS-H P < 0.0001, HCQ P = 0.010). Cocaine craving scores were not significantly different (methadone: 1.6 (2.0) (VAS-C) and 2.1 (1.2) (CCQ) vs SROM: 1.4 (1.9) (VAS-C) and 2.1 (1.2) (CCQ); ANOVA: VAS-C P = 0.175, CCQ P = 0.536). No significant carry-over effects were detected. CONCLUSIONS: This study demonstrates that SROM is clinically more effective than methadone in reducing general craving for heroin during opioid maintenance treatment while not affecting cocaine craving.

No evidence for reduction of opioid-withdrawal symptoms by cannabis smoking during a methadone dose taper.

BACKGROUND AND OBJECTIVES: To support medication development with cannabinoids, smoked cannabis has been said to alleviate symptoms of opioid withdrawal. We evaluated that hypothesis. METHODS: We analyzed data from the methadone-taper phase of a clinical trial we had conducted. Participants were 116 outpatient heroin and cocaine users (of whom 46 were also cannabis users) who stayed for the 10-week taper. Main outcome measures were weekly urine screens for cannabinoids, plus every-two-week assessments of opioid-withdrawal symptoms. RESULTS: Opioid-withdrawal scores did not differ overall between users and nonusers of cannabis. In a lagged analysis in the 46 users, there was a slight (not statistically significant) indication that weeks of higher opiate-withdrawal symptoms preceded weeks of cannabis use (effect-size r = .20, 95% CI -.10 to .46, p = .52). Even if this finding is taken to suggest self-medication with cannabis, a lagged analysis in the other temporal direction showed no indication that cannabis use predicted lower opiate-withdrawal symptoms the next week (effect-size r = .01, 95% CI -.28 to .30, p = .69). These findings persisted in sensitivity analyses controlling for each of 17 potential confounds. DISCUSSION AND CONCLUSION: With our findings, the clinical evidence for smoked cannabis as a reducer of opioid-withdrawal symptoms moves slightly further from "inconclusive" or "mixed" and closer to negative, at least in the context of a methadone dose taper like the one used here. SCIENTIFIC SIGNIFICANCE: This finding may remove one rationale for medication development using cannabinoids to treat opioid withdrawal, but leaves other rationales intact.

Prevalence of traumatic brain injury in cocaine-dependent research volunteers.

BACKGROUND: There is a high prevalence of traumatic brain injury (TBI) among those with substance dependence. However, TBI often remains undiagnosed in these individuals, due to lack of routine screening in substance use treatment settings or due to overlap in some of the cognitive sequelae (eg impulsivity, disinhibition) of TBI and cocaine dependence. METHODS: The prevalence of self-reported mild to moderate TBI in a group of cocaine-dependent (n = 95) and a group of healthy volunteers (n = 75) enrolled at the same facility was assessed. Additionally, the relationship between TBI and clinically relevant correlates, including impulsivity, cocaine use history, and treatment outcome in the cocaine-dependent group was also examined. RESULTS: A higher proportion of individuals with cocaine dependence (29.5%) reported having suffered a TBI in their lifetime compared to controls (8%) on a Closed Head Injury scale. Among cocaine users, the average age of sustaining TBI was significantly lower than the age of initiating cocaine use. Presence of TBI was not associated with higher impulsivity on the Barratt Impulsiveness Scale-11 or self-reported years of cocaine use. No differences were noted on treatment outcome for cocaine dependence as measured by treatment effectiveness scores (TES) between cocaine users with TBI and their non-TBI counterparts. CONCLUSIONS: These results are the first to highlight the high prevalence of TBI among individuals with cocaine dependence. This study underscores the possible role of TBI history as a risk factor for onset of cocaine use, however, more research is needed to determine the impact of co-morbid TBI as a complicating factor in the substance abuse treatment setting.

Prompted to treatment by the criminal justice system: Relationships with treatment retention and outcome among cocaine users.

BACKGROUND AND OBJECTIVES: A substantial portion of individuals entering treatment for substance use have been referred by the criminal justice system, yet there are conflicting reports regarding treatment engagement and outcome differences compared to those not referred. This study examined baseline characteristic and treatment outcome differences among cocaine-dependent individuals participating in cocaine treatment randomized trials. METHODS: This secondary analysis pooled samples across five completed randomized controlled trials, resulting in 434 participants. Of these, 67 (15%) were prompted to treatment by the criminal justice system. RESULTS: This subsample of criminal justice prompted (CJP) individuals did not differ from those not prompted by the criminal justice system in terms of gender, race/ethnicity, marital status, or age. However, the CJP group reported more years of regular cocaine use, more severe employment and legal problems, as well as less readiness to change prior to treatment. Treatment outcomes did not differ significantly from those without a criminal justice prompt, and on some measures the outcomes for CJP group were better (e.g., percentage of days cocaine abstinent, number of therapy sessions attended). DISCUSSION AND CONCLUSIONS: These findings suggest that being prompted to treatment by the criminal justice system may not lead to poorer treatment engagement or substance use outcomes for individuals participating in randomized controlled treatment trials. SCIENTIFIC SIGNIFICANCE: Despite some baseline indicators of poorer treatment prognosis, individuals who have been prompted to treatment by the criminal justice system have similar treatment outcomes as those presenting to treatment voluntarily.

D-cycloserine combined with cue exposure therapy fails to attenuate subjective and physiological craving in cocaine dependence.

BACKGROUND: Based on preclinical studies showing that the partial N-methyl-D-aspartate (NMDA) agonist D-cycloserine (DCS) facilitates extinction of cocaine self-administration and cocaine-induced conditioned place preference, we evaluated whether 50 mg of DCS would reduce craving to cocaine cues when combined with cue exposure (CE) in cocaine dependent humans. METHODS: In this double-blind placebo-controlled pilot study, 47 cocaine dependent participants were randomized to DCS or placebo (PBO), plus CE. Participants received DCS or PBO 30 minutes prior to two CE sessions, conducted one day apart. Craving and heart rate was assessed prior to CE sessions, during CE trials, and after CE trials. These measures were assessed again at a 1-week follow-up (session 3) after the second CE session. RESULTS: DCS failed to significantly attenuate cocaine cue reactivity based on subjective craving and physiological reactivity (heart rate) compared to PBO. The CE protocol, consisting of repeated exposure to drug cues combined with skills training, resulted in extinction to cocaine cues as suggested by decreased craving within and between sessions in both treatment conditions. All participants exhibited elevated heart rate with repeated exposures, demonstrating a potentiation in heart rate between sessions. CONCLUSIONS: 50 mg of DCS may not be effective for extinguishing reactivity to drug cues for individuals with cocaine dependence. SCIENTIFIC SIGNIFICANCE: Future studies examining the effect of DCS on facilitating extinction to drug cues should examine variations in cue exposure length, number of CE presentations, and timing of DCS dose administration prior to cue exposures, which may differentially impact drug cue reactivity.

Factors associated with willingness to participate in a pharmacologic addiction treatment clinical trial among people who use drugs.

BACKGROUND AND OBJECTIVES: Although new medications are needed to address the harms of drug addiction, rates of willingness to participate in addiction treatment trials among people who use drugs (PWUD), have not been well characterized. METHODS: One thousand twenty PWUD enrolled in two community-recruited cohorts in Vancouver, Canada, were asked whether they would be willing to participate in a pharmacologic addiction treatment trial. Logistic regression was used to identify factors independently associated with a willingness to participate. RESULTS: Among the 1,020 PWUD surveyed between June 1, 2013 and November 30, 2013, 58.3% indicated a willingness to participate. In multivariate analysis, factors independently associated with a willingness to participate in a pharmacologic addiction treatment trial included: daily heroin injection (Adjusted Odds Ratio [AOR] = 1.75; 95% Confidence Interval [CI]: 1.13 - 2.72); daily crack smoking (AOR = 1.81; 95% CI: 1.23 - 2.66); sex work involvement (AOR = 2.22; 95% CI: 1.21 - 4.06); HIV seropositivity (AOR = 1.49; 95% CI: 1.15 - 1.94); and methadone maintenance therapy participation (AOR = 1.77; 95% CI: 1.37-2.30). DISCUSSION AND CONCLUSIONS: High rates of willingness to participate in a pharmacologic addiction treatment trial were observed in this setting. Importantly, high-risk drug and sexual activities were positively associated with a willingness to participate, which may suggest a desire for new treatment interventions among PWUD engaged in high-risk behavior. SCIENTIFIC SIGNIFICANCE: These results highlight the viability of studies seeking to enroll representative samples of PWUD engaged in high-risk drug use.

[Contributions of ludic care in nursing to chemical detoxification due to the use of crack cocaine]. / Contribuições do cuidado lúdico em enfermagem na desintoxicação química devido ao uso de crack.

OBJECTIVE: to understand the contributions of ludic care in nursing by stimulating the acceptance of chemical detoxification from crack on the perception of people in the detoxification process. METHODS: an exploratory, descriptive study with a qualitative approach, performed with five people hospitalized for chemical detoxification from crack, from March to July 2013 in a chemical detox unit of a midsize hospital in the central region of Rio Grande do Sul. Data was collected using a semi-structured interview and was subjected to content analysis. RESULTS: Two categories emerged: Ludic care in nursing as a stimulus to the acceptance of chemical detoxification; Ludic care in nursing in the promotion for healthy living after chemical detoxification. CONCLUSION: ludic care in nursing proved to enhance the acceptance of chemical detoxification from crack in the reality investigated.

Vaccines against stimulants: cocaine and MA.

While the worldwide prevalence of cocaine use remains significant, medications, or small molecule approaches, to treat drug addictions have met with limited success. Anti-addiction vaccines, on the other hand, have demonstrated great potential for treating drug abuse using a distinctly different mechanism of eliciting an antibody response that blocks the pharmacological effects of drugs. We provide a review of vaccine-based approaches to treating stimulant addictions; specifically and cocaine addictions. This selective review article focuses on the one cocaine vaccine that has been into clinical trials and presents new data related to pre-clinical development of a methamphetamine (MA) vaccine. We also review the mechanism of action for vaccine induced antibodies to abused drugs, which involves kinetic slowing of brain entry as well as simple blocking properties. We present pre-clinical innovations for MA vaccines including hapten design, linkage to carrier proteins and new adjuvants beyond alum. We provide some new information on hapten structures and linkers and variations in protein carriers. We consider a carrier, outer membrance polysaccharide coat protein (OMPC), that provides some self-adjuvant through lipopolysaccharide components and provide new results with a monophosopholipid adjuvant for the more standard carrier proteins with cocaine and MA. The review then covers the clinical trials with the cocaine vaccine TA-CD. The clinical prospects for advances in this field over the next few years include a multi-site cocaine vaccine clinical trial to be reported in 2013 and phase 1 clinical trials of a MA vaccine in 2014.