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The dopamine β-hydroxylase (DβH) enzyme transforms dopamine into noradrenaline. We hypothesized that individuals with low activity DBH genotypes (rs1611115 CT/TT) are more sensitive to the influence of cannabis and cocaine on cognitive impulse control and functional connectivity in the limbic ‘reward’ circuit because they experience a drug induced hyperdopaminergic state compared to individuals with high activity DBH genotypes (rs1611115 CC). Regular drug users ( N  = 122) received acute doses of cannabis (450 μg/kg THC), cocaine HCl 300 mg and placebo. Cognitive impulse control was assessed by means of the Matching Familiar Figures Test (MFFT). Resting state fMRI was measured in a subset of participants to determine functional connectivity between the nucleus accumbens (NAc) and (sub)cortical areas. The influence of cannabis and cocaine on impulsivity and functional connectivity significantly interacted with DBH genotype. Both drugs increased cognitive impulsivity in participants with CT/TT genotypes but not in CC participants. Both drugs also reduced functional connectivity between the NAc and the limbic lobe, prefrontal cortex, striatum and thalamus and primarily in individuals with CT/TT genotypes. Correlational analysis indicated a significant negative association between cognitive impulsivity and functional connectivity in subcortical areas of the brain. It is concluded that interference of cannabis and cocaine with cognitive impulse control and functional corticostriatal connectivity depends on DBH genotype. The present data provide a neural substrate and behavioral mechanism by which drug users can progress to drug seeking and may also offer a rationale for targeted pharmacotherapy in chronic drug users with high risk DBH genotypes.

Illicit drug use rates are high among Canadian youth, and are particularly pronounced in Northern Ontario. The availability and accessibility of effective substance use-related treatments and services are required to address this problem, especially among rural and remote Northern communities. In order to assess specific service and treatment needs, as well as barriers and deterrents to accessing and utilizing services and treatments for youth who use illicit drugs in Northern Ontario, we conducted the present study. This study utilized a mixed-methods design and incorporated a community-based participatory research approach. Questionnaires were administered in conjunction with audio-recorded semi-structured interviews and/or focus groups with youth (aged 14-25) who live in Northern Ontario and use illicit drugs. Interviews with 'key informants' who work with the youth in each community were also conducted. Between August and December 2017, the research team traveled to Northern Ontario communities and carried out data collection procedures. A total of 102 youth and 35 key informants from eleven different Northern Ontario communities were interviewed. The most commonly used drugs were prescription opioids, cocaine and crack-cocaine. Most participants experienced problems related to their drug use, and reported 'fair' mental and physical health status. Qualitative analyses highlighted an overall lack of services; barriers to accessing treatment and services included lack of motivation, stigmatization, long wait-lists and transportation/mobility issues. Articulated needs revolved around the necessity of harm reduction-based services, low-threshold programs, specialized programming, and peer-based counselling. Although each community varied in terms of drug use behaviors and available services, an overall need for youth-specific, low-threshold services was identified. Information gathered from this study can be used to help inform rural and remote communities towards improving treatment and service system performance and provision.

Rationale Partial dopamine receptor agonists have been proposed as candidate pharmacotherapies for cocaine dependence. Objective This 42-day, within-subject, human laboratory study assessed how maintenance on aripiprazole, a partial D 2 receptor agonist, influenced smoked cocaine self-administration, cardiovascular measures, subjective effects, and cocaine craving in nontreatment-seeking, cocaine-dependent volunteers. Methods In order to achieve steady-state concentrations, participants ( n  = 8 men) were administered placebo and aripiprazole (15 mg/day) capsules in counter-balanced order for 21 days. A smoked cocaine dose–response curve (0, 12, 25, 50 mg) was determined twice under placebo and aripiprazole maintenance. Sessions comprised a “sample” trial, when participants smoked the cocaine dose available that session, and five choice trials, when they responded on a progressive-ratio schedule of reinforcement to receive the cocaine dose or receive $5.00. Results Cocaine’s reinforcing, subjective, and cardiovascular effects were dose-dependent. Aripiprazole significantly increased cocaine (12, 25 mg) self-administration. Following a single administration of cocaine (25 mg), aripiprazole decreased ratings of how much participants would pay for that dose. Following repeated cocaine (50 mg) self-administration, aripiprazole decreased ratings of cocaine quality, craving, and good drug effect as compared to placebo. Conclusions These data suggest that aripiprazole may have increased self-administration to compensate for a blunted subjective cocaine effect. Overall, the findings do not suggest aripiprazole would be useful for treating cocaine dependence.

Evidence linking cocaine to the risk of pulmonary hypertension (PH) is limited and inconsistent. We examined whether cocaine use, in the absence of other known causes of PH, was associated with elevated systolic pulmonary artery pressure (sPAP) and increased probability of PH. We compared patients with documented cocaine use to a randomly selected age, sex, and race-matched control group without history of cocaine use. All participants had no known causes of PH and underwent echocardiography for noninvasive estimation of sPAP. We used routinely reported echocardiographic parameters and contemporary guidelines to grade the probability of PH. In 88 patients with documented cocaine use (mean age ± standard deviation 51.7 ± 9.5 years), 33% were women and 89% were of Black race. The commonest route of cocaine use was smoking (74%). Cocaine users compared with the control group had significantly higher sPAP (mean ± standard deviation, 30.1 ± 13.1 vs 22.0 ± 9.8 mm Hg, p <0.001) and greater likelihood of PH (25% vs 10%, p = 0.012). In multivariable analyses adjusted for potential confounders including left ventricular diastolic dysfunction, cocaine use conferred a fivefold greater odds of echocardiographic PH (p = 0.006). Additionally, a stepwise increase in the likelihood of PH was noted across cocaine users with negative or no drug screen on the day of echocardiography to cocaine users with a positive drug screen (multivariable p for trend = 0.008). In conclusion, cocaine use was associated with a higher sPAP and an increased likelihood of echocardiographic PH with a probable acute-on-chronic effect.

Prefrontal dysfunction is a hallmark in drug addiction, yet interventions exploring modulation of prefrontal cortex function in drug addiction have not been fully investigated with regard to physiological alterations. We tested the hypothesis that non-invasive prefrontal stimulation would change neural activity in crack-cocaine addiction, investigating the effects of transcranial Direct Current Stimulation (tDCS) of Dorsolateral Prefrontal Cortex (DLPFC) induced cortical excitability modulation on the visual P3 Event Related Potentials (ERP) component under neutral and drug cue exposition in crack-cocaine addicts. Thirteen crack-cocaine users were randomly distributed to receive five applications (once a day, every other day) of bilateral (left cathodal/right anodal) tDCS (20 min, 2 mA, 35 cm2) or sham tDCS over the DLPFC. Brain activity was measured under crack-related or neutral visual-cued ERPs. There were significant differences in P3-related parameters when comparing group of stimulation (active vs. sham tDCS) and number of sessions (single vs. repetitive tDCS). After a single session of tDCS, P3 current intensity in the left DLPFC increased during neutral cues and decreased during crack-related cues. This effect was opposite to what was observed in the sham-tDCS group. In contrast, repetitive tDCS increased current density not only in the DLPFC, but also in a wider array of prefrontal areas, including presumably the frontopolar cortex (FPC) orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC), when subjects were visualizing crack-related cues. Thus, single and repetitive application of tDCS can impact cognitive processing of neutral and especially crack-related visual cues in prefrontal areas, which may be of importance for treatment of crack-cocaine addiction.

Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and (18)FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2-5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic inhibition may help identify potential benefits of this medication in cocaine addiction.

Prescription drug abuse and illicit drug use are common in chronic pain patients. Adherence monitoring with screening tests, and urine drug testing, periodic monitoring with prescription monitoring programs, has become a common practice in recent years. Random drug testing for appropriate use of opioids and use of illicit drugs is often used in pain management practices. Thus, it is expected that random urine drug testing will deter use of illicit drugs, and also improve compliance. To study the prevalence of illicit drug use in patients receiving opioids for chronic pain management and to compare the results of illicit drug use with the results from a previous study. A prospective, consecutive study. Interventional pain management practice setting in the United States. A total of 500 consecutive patients on opioids, considered to be receiving stable doses of opioids supplemental to their interventional techniques, were studied by random drug testing. Testing was performed by rapid drug screen. Results were considered positive if one or more of the monitored illicit drugs including cocaine, marijuana (THC), methamphetamine or amphetamines were present. Illicit drug use was evident in 80 patients, or 16%, with marijuana in 11%, cocaine in 5%, and methamphetamine and/or amphetamines in 2%. When compared with previous data, the overall illicit drug use was significantly less. Illicit drug use in elderly patients was absent. The prevalence of illicit drug abuse in patients with chronic pain receiving opioids continues to be a common occurence. This study showed significant reductions in overall illicit drug use with adherence monitoring combined with random urine drug testing.

We did a global review to synthesise data on the prevalence, harms, and interventions for stimulant use, focusing specifically on the use of cocaine and amphetamines. Modelling estimated the effect of cocaine and amphetamine use on mortality, suicidality, and blood borne virus incidence. The estimated global prevalence of cocaine use was 0·4% and amphetamine use was 0·7%, with dependence affecting 16% of people who used cocaine and 11% of those who used amphetamine. Stimulant use was associated with elevated mortality, increased incidence of HIV and hepatitis C infection, poor mental health (suicidality, psychosis, depression, and violence), and increased risk of cardiovascular events. No effective pharmacotherapies are available that reduce stimulant use, and the available psychosocial interventions (except for contingency management) had a weak overall effect. Generic approaches can address mental health and blood borne virus infection risk if better tailored to mitigate the harms associated with stimulant use. Substantial and sustained investment is needed to develop more effective interventions to reduce stimulant use.

This is a secondary analysis of data from a randomized trial of dually-focused interventions for nonadherent HIV patients with cocaine use disorders (Ingersoll et al. in Drug Alcohol Depend 116(1–3):177–187, 2011 ). We examined the relationships among baseline demographic, psychological, psychiatric, and behavioral characteristics and 6-months post-study ART adherence, log viral load (VL), ASI Drug Composite Score, and days using cocaine. We used the SAS GLMSELECT procedure to build multivariate models of each post-study outcome. Post-study ART adherence was related to 2 psychological variables; while logVL was related to 2 drug-related behaviors. ASI Drug Composite score was related to 2 psychiatric disorders, 1 demographic, and 1 psychological variable; in contrast, days using cocaine related to 1 behavioral and 3 psychological variables. Analyses show clear, robust relationships among behavioral, psychological and psychiatric diagnosis factors with post-study ART adherence and cocaine use outcomes. Future ART adherence interventions for cocaine users should consider tailoring to these patient characteristics.

Cocaine addiction is a major public health problem that is particularly difficult to treat. Without medically proven pharmacological treatments, interventions to change the maladaptive behavior of addicted individuals mainly rely on psychosocial approaches. Here we report on impairment in cocaine-addicted patients to act purposefully toward a given goal and on the influence of extended training on their behavior. When patients were rewarded for their behavior, prolonged training improved their response rate toward the goal but simultaneously rendered them insensitive to the consequences of their actions. By contrast, overtraining of avoidance behavior had no effect on patient performance. Our findings illustrate the ineffectiveness of punitive approaches and highlight the potential for interventions that focus on improving goal-directed behavior and implementing more desirable habits to replace habitual drug-taking.