Didier Jutras-Aswad

The rising prevalence of prescription opioid injection and its association with hepatitis C incidence among street-drug users

AIMS   To examine trends in prescription opioid (PO) injection and to assess its association with hepatitis C virus (HCV) seroconversion among injection drug users (IDUs). DESIGN   Prospective cohort study. SETTING   Montreal, Canada. PARTICIPANTS   HCV-negative IDUs at baseline, reporting injection in the past month. MEASUREMENTS   Semi-annual visits included HCV antibody testing and an interview-administered questionnaire assessing risk behaviours. HCV incidence rate was calculated using the person-time method. Time-updated Cox regression models were conducted to examine predictors of HCV incidence. FINDINGS   The proportion of IDUs reporting PO injection increased from 21% to 75% between 2004 and 2009 (P < 0.001). Of the 246 participants (81.6% male; mean age 34.5 years; mean follow-up time 23 months), 83 seroconverted to HCV [incidence rate: 17.9 per 100 person-years; 95% confidence interval (CI) 14.3, 22.1]. Compared to non-PO injectors, PO injectors were more likely to become infected [adjusted hazard ratio (AHR): 1.87; 95%CI:1.16, 3.03]. An effect modification was also found: PO injectors who did not inject heroin were more likely to become infected (AHR: 2.88; 95%CI: 1.52, 5.45) whereas no association was found for participants using both drugs (AHR: 1.19; 95% CI: 0.61, 2.30). Other independent predictors of HCV incidence were: cocaine injection, recent incarceration and >30 injections per month. CONCLUSIONS   Prescription opioid injectors who do not inject heroin are at greater risk for HCV seroconversion than are those injecting both heroin and prescription opioids. Important differences in age, behaviour and social context suggest a need for targeted outreach strategies to this population.

Neurobiological consequences of maternal cannabis on human fetal development and its neuropsychiatric outcome

Despite the high prevalence of marijuana use among pregnant women and adolescents, the impact of cannabis on the developing brain is still not well understood. However, growing evidence supports that the endocannabinoid system plays a major role in CNS patterning in structures relevant for mood, cognition, and reward, such as the mesocorticolimbic system. It is thus clear that exposure to cannabis during early ontogeny is not benign and potential compensatory mechanisms that might be expected to occur during neurodevelopment appear insufficient to eliminate vulnerability to neuropsychiatric disorders in certain individuals. Both human longitudinal cohort studies and animal models strongly emphasize the long-term influence of prenatal cannabinoid exposure on behavior and mental health. This review provides an overview of the endocannabinoid system and examines the neurobiological consequences of cannabis exposure in pregnancy and early life by addressing its impact on the development of neurotransmitters systems relevant to neuropsychiatric disorders and its association with these disorders later in life. It posits that studying in utero cannabis exposure in association with genetic mutations of neural systems that have strong relationships to endocannabinoid function, such as the dopamine, opioid, glutamate, and GABA, might help to identify individuals at risk. Such data could add to existing knowledge to guide public health platform in regard to the use of cannabis and its derivatives during pregnancy.

Sustained Drug Use Changes After Hepatitis C Screening and Counseling Among Recently Infected Persons Who Inject Drugs: A Longitudinal Study

BACKGROUND Notification of hepatitis C virus (HCV) positive status is known to have short-term impacts on subsequent alcohol, drug use and injection behaviors among persons who inject drugs (PWID). It remains to be established whether postscreening behavioral changes extend over time for PWID and whether screening test notification has behavioral impacts among HCV-negative PWID. This study sought to longitudinally assess substance use and injection behaviors after HCV status notification among HCV seroconverters and HCV-negative PWID. METHODS Initially HCV-seronegative PWID (n = 208) were followed prospectively between 2004 and 2011 in Montreal, Canada. Semiannual screening visits included blood sampling and an interview-administered questionnaire assessing substance use and injection behaviors. Multivariable generalized estimating equation analyses were conducted to assess substance use and behavior changes over time and compare changes between HCV seroconverters and HCV-seronegative participants while adjusting for baseline characteristics. RESULTS Of the 208 participants (83% male; mean age, 34.7 years, mean follow-up time, 39 months), 69 (33.2%) seroconverted to HCV. A linear decrease in syringe sharing behavior was observed over time after HCV and status notification, whereas a 10% decrease for each additional 3 months of follow-up was observed for injection cocaine and heroin use among HCV seroconverters but not among HCV-seronegative PWID (P < .05). No significant changes were observed in alcohol use. CONCLUSIONS Our results indicate that notification of HCV-positive status is associated with reduced injection drug use among seroconverters. Among PWID deemed seronegative after screening, there is no sustained trend for change in risk behavior.

Modulation of the Endocannabinoid System: Vulnerability Factor and New Treatment Target for Stimulant Addiction

Cannabis is one of the most widely used illicit substance among users of stimulants such as cocaine and amphetamines. Interestingly, increasing recent evidence points toward the involvement of the endocannabinoid system (ECBS) in the neurobiological processes related to stimulant addiction. This article presents an up-to-date review with deep insights into the pivotal role of the ECBS in the neurobiology of stimulant addiction and the effects of its modulation on addictive behaviors. This article aims to: (1) review the role of cannabis use and ECBS modulation in the neurobiological substrates of psychostimulant addiction and (2) evaluate the potential of cannabinoid-based pharmacological strategies to treat stimulant addiction. A growing number of studies support a critical role of the ECBS and its modulation by synthetic or natural cannabinoids in various neurobiological and behavioral aspects of stimulants addiction. Thus, cannabinoids modulate brain reward systems closely involved in stimulants addiction, and provide further evidence that the cannabinoid system could be explored as a potential drug discovery target for treating addiction across different classes of stimulants.

Cannabis-Dependence Risk Relates to Synergism between Neuroticism and Proenkephalin SNPs Associated with Amygdala Gene Expression: Case- Control Study

Background Many young people experiment with cannabis, yet only a subgroup progress to dependence suggesting individual differences that could relate to factors such as genetics and behavioral traits. Dopamine receptor D2 (DRD2) and proenkephalin (PENK) genes have been implicated in animal studies with cannabis exposure. Whether polymorphisms of these genes are associated with cannabis dependence and related behavioral traits is unknown. Methodology/Principal Findings Healthy young adults (18–27 years) with cannabis dependence and without a dependence diagnosis were studied (N = 50/group) in relation to a priori-determined single nucleotide polymorphisms (SNPs) of the DRD2 and PENK genes. Negative affect, Impulsive Risk Taking and Neuroticism-Anxiety temperamental traits, positive and negative reward-learning performance and stop-signal reaction times were examined. The findings replicated the known association between the rs6277 DRD2 SNP and decisions associated with negative reinforcement outcomes. Moreover, PENK variants (rs2576573 and rs2609997) significantly related to Neuroticism and cannabis dependence. Cigarette smoking is common in cannabis users, but it was not associated to PENK SNPs as also validated in another cohort (N = 247 smokers, N = 312 non-smokers). Neuroticism mediated (15.3%–19.5%) the genetic risk to cannabis dependence and interacted with risk SNPs, resulting in a 9-fold increase risk for cannabis dependence. Molecular characterization of the postmortem human brain in a different population revealed an association between PENK SNPs and PENK mRNA expression in the central amygdala nucleus emphasizing the functional relevance of the SNPs in a brain region strongly linked to negative affect. Conclusions/Significance Overall, the findings suggest an important role for Neuroticism as an endophenotype linking PENK polymorphisms to cannabis-dependence vulnerability synergistically amplifying the apparent genetic risk.

Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans.

Objectives:Cannabidiol (CBD) is hypothesized as a potential treatment for opioid addiction, with safety studies an important first step for medication development. We determined CBD safety and pharmacokinetics when administered concomitantly with a high-potency opioid in healthy subjects. Methods:This double-blind, placebo-controlled cross-over study of CBD, coadministered with intravenous fentanyl, was conducted at the Clinical Research Center in Mount Sinai Hospital, a tertiary care medical center in New York City. Participants were healthy volunteers aged 21 to 65 years with prior opioid exposure, regardless of the route. Blood samples were obtained before and after 400 or 800 mg of CBD pretreatment, followed by a single 0.5 (session 1) or 1.0 &mgr;g/kg (session 2) of intravenous fentanyl dose. The primary outcome was the Systematic Assessment for Treatment Emergent Events (SAFTEE) to assess safety and adverse effects. CBD peak plasma concentrations, time to reach peak plasma concentrations (tmax), and area under the curve (AUC) were measured. Results:SAFTEE data were similar between groups without respiratory depression or cardiovascular complications during any test session. After low-dose CBD, tmax occurred at 3 and 1.5 hours in sessions 1 and 2, respectively. After high-dose CBD, tmax occurred at 3 and 4 hours in sessions 1 and 2, respectively. There were no significant differences in plasma CBD or cortisol (AUC P = NS) between sessions. Conclusions:Cannabidiol does not exacerbate adverse effects associated with intravenous fentanyl administration. Coadministration of CBD and opioids was safe and well tolerated. These data provide the foundation for future studies examining CBD as a potential treatment for opioid abuse.

Psychological distress increases needle sharing among cocaine users: Results from the COSMO study

Objective: Cocaine use and mental health disorders have both been separately identified as risk factors for blood borne virus infection. However, the contribution of specific underlying aspects of mental health to risks is not well documented. The aim of this study was to examine the association between psychological distress and risk behaviors for HIV and Hepatitis C infection among cocaine users. Methods: Individuals who either smoked or injected cocaine were recruited in community-based and addiction treatment programs located in downtown Montreal. Participants were asked to complete an interviewer-administered questionnaire assessing psychological distress based on the Kessler scale (K10). Three-month risk behaviors outcomes included drug injection material sharing (needle, dilution water, cooker, filters, backloading, frontloading or wash), and smoking equipment sharing. Socio-demographic data, severity of cocaine dependence and other substances use information were also collected. Statistical analyses were conducted using logistic regression. Results: Severe psychological distress was reported by 202 (34.3%) out of 589 participants (86.2% male; 76.6% ≥ 30y.o.). The prevalence of sharing was: 14.8% for needles, 24.9% for other injection equipment (378 injectors) and 68.3% for smoking material (508 smokers). Multivariate analysis showed that injectors with severe psychological distress were more likely to report needle sharing (Adjusted Odds Ratio (AOR): 2.1, 95% CI: 1.1-3.8). No significant association was found between K10 score and sharing of other paraphernalia. Conclusion: Severe psychological distress increases the risk of needle sharing, a major risk factor for HIV and HCV infection, but not sharing of other paraphernalia. These results suggest differential psychological mechanisms according to sharing practices. They also support the importance of screening for psychological distress in order to implement adequate preventive interventions aimed at cocaine users.

Associations of substance use patterns with attempted suicide among persons who inject drugs: Can distinct use patterns play a role?

BACKGROUND While the elevated risk of suicide attempt among persons who inject drugs (PWID) is well documented, whether use of different substances is associated with varying degrees of risk remains unclear. We sought to examine the associations between substance use patterns and attempted suicide in a prospective cohort of PWID in Montreal, Canada. METHODS Between 2004 and 2011, participants completed an interviewer-administered questionnaire eliciting information on socio-demographics, substance use patterns, related behaviors, and mental health markers. Generalized estimating equations were used to model the relationship between self-reported use of six common substances (cocaine, amphetamine, opioids, sedative-hypnotics, cannabis and alcohol), associated patterns of use (chronic, occasional and none), and a recent (past six-month) suicide attempt. RESULTS At baseline, of 1240 participants (median age: 39.1, 83.7% male), 71 (5.7%) reported a recent suicide attempt. Among 5621 observations collected during follow-up, 221 attempts were reported by 143 (11.5%) participants. In multivariate analyses adjusting for socio-demographics and psychosocial stressors, among primary drugs of abuse, chronic [adjusted odds ratio (AOR): 1.97] and occasional (AOR: 1.92) cocaine use, and chronic amphetamine use (AOR: 1.96) were independently associated with attempted suicide. Among co-used substances, chronic sedative-hypnotic use was independently associated with an attempt (AOR: 2.29). No statistically significant association was found for the remaining substances. CONCLUSION Among PWID at high risk of attempted suicide, stimulant users appear to constitute a particularly vulnerable sub-group. While the mechanisms underlying these associations remain to be elucidated, findings suggest that stimulant-using PWID should constitute a prime focus of suicide prevention efforts.

Intentional cannabis use to reduce crack cocaine use in a Canadian setting: A longitudinal analysis.

BACKGROUND No effective pharmacotherapies exist for the treatment of crack cocaine use disorders. Emerging data suggests that cannabinoids may play a role in reducing cocaine-related craving symptoms. This study investigated the intentional use of cannabis to reduce crack use among people who use illicit drugs (PWUD). METHODS Data were drawn from three prospective cohorts of PWUD in Vancouver, Canada. Using data from participants reporting intentional cannabis use to control crack use, we used generalized linear mixed-effects modeling to estimate the independent effect of three pre-defined intentional cannabis use periods (i.e., before, during and after first reported intentional use to reduce crack use) on frequency of crack use. RESULTS Between 2012 and 2015, 122 participants reported using cannabis to reduce crack use, contributing a total of 620 observations. In adjusted analyses, compared to before periods, after periods were associated with reduced frequency of crack use (Adjusted Odds Ratio [AOR]=1.89, 95% Confidence Interval [CI]: 1.02-3.45), but not the intentional use periods (AOR=0.85, 95% CI: 0.51-1.41). Frequency of cannabis use in after periods was higher than in before periods (AOR=4.72, 95% CI: 2.47-8.99), and showed a tendency to lower frequency than in intentional cannabis use periods (AOR=0.56, 95% CI: 0.32-1.01). CONCLUSIONS A period of intentional cannabis use to reduce crack use was associated with decreased frequency of crack use in subsequent periods among PWUD. Further clinical research to assess the potential of cannabinoids for the treatment of crack use disorders is warranted.

Visits to primary care physicians among persons who inject drugs at high risk of hepatitis C virus infection: room for improvement

The role of primary care physicians (PCP) in hepatitis C virus (HCV) prevention is increasingly emphasized. Yet, little is known about the patterns of contacts with PCP among persons who inject drugs (PWID). We sought to assess the 6‐month prevalence of PCP visiting among PWID at risk of HCV infection and to explore the associated factors. Baseline data were collected from HCV‐seronegative PWID recruited in HEPCO, an observational Hepatitis Cohort study (2004–2011) in Montreal, Canada. An interviewer‐administered questionnaire elicited information on socio‐demographic factors, drug use patterns and healthcare services utilization. Blood samples were tested for HCV antibodies. Using the Gelberg‐Andersen Behavioral Model, hierarchical logistic regression analyses were conducted to identify predisposing, need and enabling factors associated with PCP visiting. Of the 349 participants (mean age = 34; 80.8% male), 32.1% reported visiting a PCP. In the multivariate model, among predisposing factors, male gender [adjusted odds ratio (AOR) = 0.45 (0.25–0.83)], chronic homelessness [AOR = 0.08 (0.01–0.67)], cocaine injection [AOR = 0.46 (0.28–0.76)] and reporting greater illegal or semi‐legal income [AOR = 0.48 (0.27–0.85)] were negatively associated with PCP visits. Markers of need were not associated with the outcome. Among enabling factors, contact with street nurses [AOR = 3.86 (1.49–9.90)] and food banks [AOR = 2.01 (1.20–3.37)] was positively associated with PCP visiting. Only one third of participating PWID reported a recent visit to a PCP. While a host of predisposing factors seems to hamper timely contacts with PCP among high‐risk PWID, community‐based support services may play an important role in initiating dialogue with primary healthcare services in this population.