Bupropion for treatment of amphetamine-type stimulant use disorder: A systematic review and meta-analysis of placebo-controlled randomized clinical trials.

BACKGROUND: This meta-analysis (PROSPERO-ID: CRD42022362962), pooled effect estimates of outcomes, from placebo-controlled randomized clinical trials (RCTs) examining bupropion efficacy and safety for amphetamine-type stimulant use disorder (ATSUD) treatment. METHOD: Electronic databases were searched for records published to October 31st, 2022, including MEDLINE, CINAHL, PsycINFO, EBM Reviews, EMBASE, PubMed, Web of Science, trial registries. Inclusion criteria were RCTs comparing bupropion to placebo in ATSUD. Cochrane RoB2 tool and GRADE evidence certainty assessment were employed. Outcomes included amphetamine-type stimulant (ATS) use by urinalysis, retention in treatment, treatment adherence, ATS craving, addiction severity, depressive symptom severity, drop-out following adverse events (AEs), and serious AEs. Random-effect meta-analysis was conducted presenting standardized mean difference (SMD), risk ratio (RR), and risk difference (RD). RESULTS: Eight RCTs (total N=1239 participants) were included. Bupropion compared to placebo was associated with reduced ATS use (RR: 0.90; 95% CI: 0.84, 0.96), end-of-treatment ATS craving (SMD: -0.38; 95%CI: -0.63, -0.13), and adherence (RR: 0.91; 95%CI: 0.84, 0.99). Subgroup analysis showed greater reduction in ATS use with longer trial duration (12 weeks) (RR: 0.85; 95%CI: 0.78, 0.93) and greater reduction in end-of-treatment ATS craving in studies with mixed ATS use frequency (SMD: -0.46; 95%CI: -0.70, -0.22) and male-only samples (SMD: -1.26; 95%CI: -1.87, -0.65). CONCLUSION: Bupropion showed a significant modest reduction in ATS use and ATS craving (both rated as very low-quality evidence), larger in males (craving), and with longer treatment (ATS use). These results may inform future studies. More research is warranted on who might benefit from bupropion as ATSUD treatment.

Use of non-medical cannabis in epilepsy: A scoping review.

Objective: The use of medical cannabis among people with epilepsy (PWE) has been garnering increasing interest. In this scoping review, we aimed to summarize the literature on recreational/non-medical cannabis (NMC) use in PWE, focusing on the experience, habits, and beliefs of PWE regarding NMC. Methods: Four databases (OVID Medline, OVID Embase, Ovid APA PsycInfo, and Web of Science) were searched for studies describing NMC use in PWE. NMC was defined as cannabis products procured from sources other than by prescription. Studies that consisted in original research and that detailed the experience, habits, and/or beliefs of PWE regarding NMC use were included in the analysis. Data pertaining to study identification, demographics, NMC use, and epilepsy characteristics were extracted. Descriptive statistical analyses and reflexive thematic analyses were performed to map these data. Results: In total, 3,228 records were screened, and 66 were included for analysis: 45 had mainly adult samples, whereas 21 had mainly pediatric samples. Most studies were published after 2010, originated from the USA, and were cross-sectional. The median number of PWE using cannabis in these studies was 24.5 (1-37,945). No studies showcased elderly PWE, and most had predominantly Caucasian samples. The lifetime prevalence of NMC use in PWE was variable, ranging between 0.69 and 76.8%. Factors frequently associated with NMC use in PWE were male sex, younger adult age, and lower education status. Children with epilepsy took NMC primarily for seizure control, using high CBD/THC ratios, and only orally. Adults with epilepsy took NMC for various reasons including recreationally, using variable CBD/THC ratios, and predominantly through smoking. The majority of PWE across all studies perceived that NMC aided in seizure control. Other aspects pertaining to NMC use in PWE were rarely reported and often conflicting. Conclusion: The literature on NMC use in PWE is sparse and heterogeneous, with many salient knowledge gaps. Further research is necessary to better understanding the experience, habits, and beliefs of PWE pertaining to NMC.

Cannabis Use and Health-Related "Harm to Others": Toward a Conceptual Framework and Evidence Base for Public Health.

Cannabis use has become increasingly common as more jurisdictions liberalize controls, including legalization and allowing nonmedical cannabis use among adults, to better protect public health and safety. Little attention has been given to possible health-related "harm to others," as are considered in other substance use domains. We propose a framework and review evidence on public health domains in which cannabis use may produce health-related harm to others, namely from (a) interpersonal violence, (b) motor vehicle crash-related injuries, (c) pregnancy-related outcomes, and (d) secondhand exposure. These domains are associated with moderate risks of adverse outcomes that, however, may involve substantial health harm to others, and therefore warrant consideration in guiding regulations and in evaluating the public health impacts of cannabis use and different policy options for its control.

Lower-Risk Cannabis Use Guidelines (LRCUG) for reducing health harms from non-medical cannabis use: A comprehensive evidence and recommendations update.

BACKGROUND: Cannabis use is common, especially among young people, and is associated with risks for various health harms. Some jurisdictions have recently moved to legalization/regulation pursuing public health goals. Evidence-based 'Lower Risk Cannabis Use Guidelines' (LRCUG) and recommendations were previously developed to reduce modifiable risk factors of cannabis-related adverse health outcomes; related evidence has evolved substantially since. We aimed to review new scientific evidence and to develop comprehensively up-to-date LRCUG, including their recommendations, on this evidence basis. METHODS: Targeted searches for literature (since 2016) on main risk factors for cannabis-related adverse health outcomes modifiable by the user-individual were conducted. Topical areas were informed by previous LRCUG content and expanded upon current evidence. Searches preferentially focused on systematic reviews, supplemented by key individual studies. The review results were evidence-graded, topically organized and narratively summarized; recommendations were developed through an iterative scientific expert consensus development process. RESULTS: A substantial body of modifiable risk factors for cannabis use-related health harms were identified with varying evidence quality. Twelve substantive recommendation clusters and three precautionary statements were developed. In general, current evidence suggests that individuals can substantially reduce their risk for adverse health outcomes if they delay the onset of cannabis use until after adolescence, avoid the use of high-potency (THC) cannabis products and high-frequency/-intensity of use, and refrain from smoking-routes for administration. While young people are particularly vulnerable to cannabis-related harms, other sub-groups (e.g., pregnant women, drivers, older adults, those with co-morbidities) are advised to exercise particular caution with use-related risks. Legal/regulated cannabis products should be used where possible. CONCLUSIONS: Cannabis use can result in adverse health outcomes, mostly among sub-groups with higher-risk use. Reducing the risk factors identified can help to reduce health harms from use. The LRCUG offer one targeted intervention component within a comprehensive public health approach for cannabis use. They require effective audience-tailoring and dissemination, regular updating as new evidence become available, and should be evaluated for their impact.

Exploring cannabidiol effects on inflammatory markers in individuals with cocaine use disorder: a randomized controlled trial.

Cocaine use disorder (CUD) is a major public health issue associated with physical, social, and psychological problems. Excessive and repeated cocaine use induces oxidative stress leading to a systemic inflammatory response. Cannabidiol (CBD) has gained substantial interest for its anti-inflammatory properties, safety, and tolerability profile. However, CBD anti-inflammatory properties have yet to be confirmed in humans. This exploratory study is based on a single-site randomized controlled trial that enrolled participants with CUD between 18 and 65 years, randomized (1:1) to daily receive either CBD (800 mg) or placebo for 92 days. The trial was divided into a 10-day detoxification (phase I) followed by a 12-week outpatient follow-up (phase II). Blood samples were collected from 48 participants at baseline, day 8, week 4, and week 12 and were analyzed to determine monocytes and lymphocytes phenotypes, and concentrations of various inflammatory markers such as cytokines. We used generalized estimating equations to detect group differences. Participants treated with CBD had lower levels of interleukin-6 (p = 0.017), vascular endothelial growth factor (p = 0.032), intermediate monocytes CD14+CD16+ (p = 0.024), and natural killer CD56negCD16hi (p = 0.000) compared with participants receiving placebo. CD25+CD4+T cells were higher in the CBD group (p = 0.007). No significant group difference was observed for B lymphocytes. This study suggests that CBD may exert anti-inflammatory effects in individuals with CUD.

Prevalence, Characteristics, and Management of Chronic Noncancer Pain Among People Who Use Drugs: A Cross-Sectional Study.

INTRODUCTION: Most studies on chronic noncancer pain (CNCP) in people who use drugs (PWUD) are restricted to people attending substance use disorder treatment programs. This study assessed the prevalence of CNCP in a community-based sample of PWUD, identified factors associated with pain, and documented strategies used for pain relief. METHODS: This was a cross-sectional study nested in an ongoing cohort of PWUD in Montreal, Canada. Questionnaires were administered to PWUD seen between February 2017 and January 2018. CNCP was defined as pain lasting three or more months and not associated with cancer. RESULTS: A total of 417 PWUD were included (mean age = 44.6 ± 10.6 years, 84% men). The prevalence of CNCP was 44.8%, and the median pain duration (interquartile range) was 12 (5-18) years. The presence of CNCP was associated with older age (>45 years old; odds ratio [OR] = 1.8, 95% CI = 1.2-2.7), male sex (OR = 2.3, 95% CI = 1.2-4.2), poor health condition (OR = 1.9, 95% CI = 1.3-3.0), moderate to severe psychological distress (OR = 2.9, 95% CI = 1.8-4.7), and less frequent cocaine use (OR = 0.5, 95% CI = 0.3-0.9). Among CNCP participants, 20.3% used pain medication from other people, whereas 22.5% used alcohol, cannabis, or illicit drugs to relieve pain. Among those who asked for pain medication (N = 24), 29.2% faced a refusal from the doctor. CONCLUSIONS: CNCP was common among PWUD, and a good proportion of them used substances other than prescribed pain medication to relieve pain. Close collaboration of pain and addiction specialists as well as better pain assessment and access to nonpharmacological treatments could improve pain management in PWUD.

A systematic review of technology-based psychotherapeutic interventions for decreasing cannabis use in patients with psychosis.

Persistent use of cannabis in persons with psychosis is associated with poor symptomatic and functional outcomes and increased healthcare costs. Face-to-face psychological interventions (e.g., Cognitive Behavioral Therapy- [CBT], Motivation Enhancement Therapy- [MET]) are widely used in treating problematic cannabis use. We aimed to comprehensively review the efficacy of technology-based psychological interventions (TBPIs) in decreasing cannabis use, the design of TBPIs, and TBPI-related preferences in individuals with psychosis. For the systematic review, we searched six major databases from their inception to November 27, 2019. We included empirical articles of quantitative and qualitative methodologies related to TBPIs in individuals with psychosis and cannabis misuse and used narrative synthesis to report results. Only eight articles were found showing that technology-based motivational and psycho-education interventions and cognitive enhancement therapy were minimally efficient in achieving cannabis abstinence or decreasing frequency of use. Qualitative exploratory methods and participatory action research were used to elicit patient and clinician preferences and TBPIs were tailored accordingly to improve cannabis use related outcomes. Research on TBPIs in individuals with psychosis and cannabis misuse is in its early phases. A significant research effort is needed for the development of adapted interventions for CUD to capitalize on the potential of web-based applications.

"I love having benzos after my coke shot": The use of psychotropic medication among cocaine users in downtown Montreal.

BACKGROUND: Cocaine abuse is a major public health issue due to its role in the HIV and hepatitis C virus (HCV) epidemics in North America. A significant area of concern among people who use cocaine (PWUC), injected or smoked, is their frequent misuse of prescription drugs, particularly psychotropic medication (PM), such as tranquilizers, sedatives, stimulants, and antipsychotics. This paper aims to describe and understand practices of PM use among PWUC in downtown Montreal. METHOD: Ethnographic methods including participant observation and semi-structured interviews were used in an iterative manner. RESULTS: Two thirds of the 50 participants were male. They ranged in age from 20 to 60 and most were homeless. A significant proportion of them reported polydrug use patterns that included frequent concomitant opioid use (heroin and/or prescription opioids (PO)). Benzodiazepine-based tranquilizers and the atypical antipsychotic quetiapine were the most frequently used PM. Routes of PM administration were oral, nasal and, to a lesser degree, intravenous. Five main PM use practices were identified: 1) "downers" from cocaine high (benzodiazepines and quetiapine); 2) enhancers of heroin/PO effects (benzodiazepines); 3) reducers or suppressors of heroin/PO withdrawal symptoms (benzodiazepines); 4) enablers of a different type of "trip" (benzodiazepines); and 5) treatment for mental and physical problems (benzodiazepines and quetiapine). CONCLUSION: PM use practices showed several complementary functions that PM fulfill in a context of polydrug use. The soothing and stimulating effects of PM reinforce the patterns of drug use among participants, posing various risks including overdose, HIV/HCV transmission, PM dependence and accidents. The results highlight the need for clinicians to assess clients' substance use patterns when prescribing PM and to question PWUC about PM use. The findings also underline certain unmet service needs in relation to overdose, HIV/HCV and mental health prevention/treatment among cocaine users.

High hepatitis C incidence in relation to prescription opioid injection and poly-drug use: Assessing barriers to hepatitis C prevention.

BACKGROUND: Prescription opioid (PO) injection and poly-drug use have been associated with hepatitis C virus (HCV) infection among people who inject drugs (PWID). Poly-drug use is often a barrier to key HCV preventive programmes including opioid agonist treatment. The contribution of specific drug combinations to high HCV incidence in poly-drug users has not been assessed previously. Addressing this knowledge gap could enhance HCV treatment and prevention efforts. We examined the association between specific drugs and number of drugs used in addition to injected POs, and HCV seroconversion. METHODS: PWID participating in a cohort study in Montréal (HEPCO), HCV-seronegative at baseline and followed between 2004 and 2013, were included. Data were collected by interview-administered questionnaires. Blood samples were tested for HCV new infections at each 3-6 month follow-up visit. Time-varying Cox regression models were utilized. RESULTS: Of 356 participants (81.5% males; mean age: 34.7 years), 123 (34.6%) reported injected POs in the past month at baseline. In univariate analyses, recent use of the following drugs was associated with HCV seroconversion: injected POs, injected cocaine, injected heroin, non-injected tranquilisers, and smoked crack/cocaine. The relative excess risk of HCV seroconversion due to interaction (RER1HR) was the highest for co-use of injected POs with the following substances: injected cocaine (RER1HR=3.44), smoked crack/cocaine (RER1HR=1.27), and non-injected tranquilisers (RER1HR=0.8). In addition, a significant linear trend (p<0.001) towards higher risk was observed with increasing the number of these three drugs used in combination with injected POs. CONCLUSION: Specific drugs and number of drugs used in addition to injected POs play a modulating role in the risk of HCV primary infection. Poly-drug use among people who inject POs has to be addressed in order to improve harm reduction programmes and reduce HCV transmission in this high-risk population.

Reversing the Atypical Valuation of Drug and Nondrug Rewards in Smokers Using Multimodal Neuroimaging.

BACKGROUND: Chronic substance use can disrupt the reward function of the anterior cingulate cortex (ACC), biasing the ACC to favor goal-directed behaviors that converge on drug use. Here we used multimodal neuroimaging methods to ask whether modulating reward-related signaling in the ACC can reverse the atypical valuation of nondrug and drug rewards in abstinent smokers. METHODS: We first recorded functional magnetic resonance imaging data from 20 moderately dependent cigarette smokers (mean age = 25 years; no history of neuropsychiatric disorders), following an overnight period of abstinence, to identify regions of the left dorsal lateral prefrontal cortex associated with the anticipation of drug-related rewards (cigarette puff). Next, we recorded the reward positivity-an electrophysiological signal believed to index sensitivity of the ACC to rewards-while participants engaged in two feedback tasks to gain either monetary or cigarette rewards. Lastly, guided by functional magnetic resonance imaging data, a robotic arm positioned a repetitive transcranial magnetic stimulation coil over a subject-specific dorsal lateral prefrontal cortex target, and 50 repetitive transcranial magnetic stimulation pulses were delivered at 10 Hz (excitatory stimulation) immediately before each block of 10 trials of the money condition and at 1 Hz (inhibitory stimulation) before each block of 10 trials of the cigarette condition. RESULTS: Our findings show that abstained smokers exhibited a heightened reward positivity to cigarette rewards relative to monetary rewards, and by applying excitatory or inhibitory repetitive transcranial magnetic stimulation to a subject-specific frontal-cingulate reward pathway, this pattern of results was reversed. CONCLUSIONS: By modulating how the brain links value to drug and nondrug rewards, novel brain-based treatments may finally be on the horizon.

Examining the link between cocaine binging and individual, social and behavioral factors among street-based cocaine users.

AIMS: To estimate the prevalence of cocaine binging and examine associated factors, to characterize binge episodes and to study the relationship between cocaine binging and HIV and HCV risk behaviors among street-based cocaine users. METHODS: A prospective cohort study was conducted in Montréal, Canada. Interviewer-administered questionnaire were carried out at 3-month intervals. Cocaine binging was defined as using large quantities of cocaine, without stopping, over a limited period of time, until resources run out or until being physically incapable of consuming. Generalized Estimation Equations (GEE) analyses were used. Covariates considered included demographic, behavioral, mental health and social risk factors. FINDINGS: In total, 605 participants were recruited. Prevalence of cocaine binging over the month prior to recruitment was 24.5%. Correlates of cocaine binging were older age (AOR 1.46), homelessness (AOR 1.44), criminal/marginal income strategies (AOR 1.61), high psychological distress (AOR 1.31), high cocaine dependence (AOR 3.71), drug overdoses (AOR 1.56) and smoking as the main route of cocaine administration (AOR 1.38). Additional GEE analyses showed that cocaine binging was significantly associated with the sharing of drug paraphernalia (AOR 1.35) and sexual relations under the influence of cocaine (AOR 1.21). CONCLUSION: Cocaine binging is frequent among street-based cocaine users and is associated with markers of vulnerability. It is also associated with increased odds of both sexual and drug use risk behaviors. Interventions need to be tailored in order to help cocaine bingers develop personal strategies that could prevent binging. Harm reduction programs should help cocaine bingers adequately assess their drug equipment needs.

Licit and illicit substance use among people who inject drugs and the association with subsequent suicidal attempt.

AIM: To estimate associations between recent licit and illicit substance use and subsequent suicide attempt among people who inject drugs (PWID). DESIGN: Secondary analysis of longitudinal data from a prospective cohort study of PWID followed bi-annually between 2004 and 2011. SETTING: Montréal, Canada. PARTICIPANTS: Seven hundred and ninety-seven PWID who reported injection drug use in the previous 6 months, contributing to a total of 4460 study visits. The median number of visits per participant was five (interquartile range: 3-8). MEASUREMENTS: An interviewer-administered questionnaire eliciting information on socio-demographic factors, detailed information on substance use patterns and related behaviours, mental health markers and suicide attempt. The primary exposure variables examined were past-month use of alcohol [heavy (≥ 60 drinks); moderate (one to 59 drinks); none], sedative-hypnotics, cannabis, cocaine, amphetamine and opioids [regular (≥ 4 days); occasional (1-3 days); none]. The outcome was a binary measure of suicide attempt assessed in reference to the previous 6 months. FINDINGS: In multivariate analyses, a positive association was found among licit substances between heavy alcohol consumption [adjusted odds ratio (AOR) = 2.05; 95% confidence interval (CI) = 1.12-3.75], regular use of sedative-hypnotics (AOR = 1.89; 95% CI = 1.21-2.95) and subsequent attempted suicide. Among illicit substances, occasional use of cannabis (AOR = 1.84; 95% CI = 1.09-3.13) had a positive association with subsequent suicide attempt. No statistically significant association was found for the remaining substances. CONCLUSION: Among people who inject drugs, use of alcohol, sedative-hypnotics and cannabis, but not cocaine, amphetamine or opioids, appears to be associated with an increased likelihood of later attempted suicide.

Cannabidiol as an Intervention for Addictive Behaviors: A Systematic Review of the Evidence.

Drug addiction is a chronically relapsing disorder characterized by the compulsive desire to use drugs and a loss of control over consumption. Cannabidiol (CBD), the second most abundant component of cannabis, is thought to modulate various neuronal circuits involved in drug addiction. The goal of this systematic review is to summarize the available preclinical and clinical data on the impact of CBD on addictive behaviors. MEDLINE and PubMed were searched for English and French language articles published before 2015. In all, 14 studies were found, 9 of which were conducted on animals and the remaining 5 on humans. A limited number of preclinical studies suggest that CBD may have therapeutic properties on opioid, cocaine, and psychostimulant addiction, and some preliminary data suggest that it may be beneficial in cannabis and tobacco addiction in humans. Further studies are clearly necessary to fully evaluate the potential of CBD as an intervention for addictive disorders.

Cigarette smoking may modify the association between cannabis use and adiposity in males.

INTRODUCTION: The few population-based studies that investigate the association between cannabis use and adiposity are inconclusive possibly because nicotine moderates the effect of cannabis on adiposity. The objective was to test the hypotheses that the association between cannabis use and adiposity in young men and women is modified by cigarette smoking. METHODS: Data were drawn from the Nicotine Dependence in Teens (NDIT) study, a 13-year prospective cohort investigation of the natural course of nicotine dependence. A total of 271 males and 319 females aged 12-13years at cohort inception provided data on past-year cannabis use and number of cigarettes smoked per day in the past three months, at age 20years. Outcomes included change in body mass index (BMI) and in waist circumference (WC) from ages 17 to 24years. The hypothesis was tested in multiple linear regression models that included interaction terms for cannabis use and cigarette smoking and controlled for physical activity, sedentary behavior, alcohol use, and level of the outcome at baseline. RESULTS: The association between cannabis use and change in adiposity was U-shaped in male non-smokers and in females, and an inverted U-shape in male smokers. In males, the interaction between cannabis use and cigarette smoking was significant in both the models for change in BMI (p=0.004; n=271) and change in WC (p=0.04; n=250). In females, the interaction between cannabis use and cigarette smoking was not significant. CONCLUSION: Smoking cigarettes appears to modify the association between cannabis use and adiposity in young men.

[Craving as a core symptom in substance use disorders: epidemiology, neurobiological substrates and clinical relevance]. / Le craving comme symptôme central de la toxicomanie : de ses fondements neurobiologiques à sa pertinence clinique.

OBJECTIVE: Observed by physicians and often reported by patients, craving is a core symptom of addiction, although not well defined nor understood completely. In the last several years, functional imaging as well as the measurement of different biological substrates of addiction have greatly evolved, allowing for a better understanding of the underlying neurobiological pathways of craving. Furthermore, with the development of the DSM-V and its inclusion as a diagnostic criterion for substance use disorders, craving has gained a whole new level of interest. Hence, the general objective of this article is to examine findings of studies that have led to a better understanding of craving and its implications. First, we address the definition of craving and its epidemiology in individuals with substance use disorders. We then summarize the results of the research conducted on the neurobiological substrates of craving. Finally, we present the role of craving in the cycle of addiction and its potential as a therapeutic target for pharmacological and non-pharmacological interventions. METHODS: Narrative review of the literature. RESULTS: The definition of craving has greatly evolved throughout the years, and it is commonly described as an abnormal desire or need to take a drug. While its conscious aspect is well known, whereas it is expressed subjectively, it is growingly also defined as an unconscious phenomenon illustrated by a physiologic activation that is not perfectly correlated with subjective measures. Available data on craving have also demonstrated the presence of this symptom in all three phases of the addiction cycle, including early and prolonged abstinence, long after the acute physical withdrawal syndrome. Three factors have been identified as potent craving inducers: the drug itself, drug related cues and stress. PET scan studies and fMRI studies confirmed the implication of dopaminergic pathways in craving, and have more recently shed light on the contribution of other neurotransmission systems, such as GABA, norepinephrine as well as the endocannabinoid and opioid systems, but their roles are not yet fully understood. Furthermore, craving-related activations of specific areas of the brain involved in learned habits and behavior as well as memory have been demonstrated by various studies; in contrast, regions associated with regulation and control of emotion have been demonstrated to be hypoactive during craving episodes. Finally, several studies have demonstrated that craving is a valid predictive indicator of relapse, making it an interesting target for pharmacological and non-pharmacological treatment. Several anti-craving medications have been shown to decrease craving, including varenicline for tobacco and naltrexone for alcohol dependence. Studies examining the efficacy of other anti-craving medications for other substances are growing in numbers. CONCLUSIONS: Available data on craving support its role as a core symptom of addiction and allow for a better understanding of the underlying neurobiological substrates. Studies tend to show that it is a valid indicator of relapse during early and prolonged abstinence. Further research is needed to truly understand the complexity of the neurobiological substrates involved in craving as well as to develop new anti-craving interventions to facilitate long-term abstinence in individuals with substance use disorders.

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.

A case of hypomania during nicotine cessation treatment with bupropion.

Antidepressants can increase the spontaneous risk of hypomania or mania when used for treatment in affective disorders. When prescribed as an antidepressant, bupropion is generally considered to have a lower relative risk of inducing mood shifts. We describe the case of a 67-year-old man known for dysthymic disorder in remission on quetiapine and venlafaxine who experienced a first lifetime episode of hypomania with the introduction of bupropion SR for smoking cessation. To the best of our knowledge, this is the first case report of bupropion-induced mood shift when used specifically for nicotine cessation in a nonbipolar patient. This case highlights the need for clinicians who prescribe bupropion for smoking cessation to perform regular and systematic mood follow-ups during treatment. These follow-ups could even be more important when bupropion is selected to quit smoking in a patient already taking an antidepressant.

Treating the "unhealthy alcohol user" on medical wards: beyond withdrawal.

BACKGROUND: Alcohol use disorders (AUDs) are common among patients admitted to general hospitals. Unfortunately, AUDs often go undetected and untreated. Psychiatrists are frequently called upon to assist in the management of cases involving alcohol withdrawal. However, there is a dearth of knowledge regarding potential therapeutic approaches to AUDs beyond the acute withdrawal stage. OBJECTIVE: This article presents an overview of the epidemiology, clinical characteristics, and treatment of AUDs on medical wards, with a specific focus on the post alcohol-withdrawal phase. METHOD: This article is based on a survey of the published literature on AUDs and their treatment in the medical ward using the PubMed database. RESULTS: Various screening tools are available to facilitate the detection of AUDs. Among non-medically ill patients, brief psychological interventions have proven to be effective in primary care and emergency room settings, while pharmacotherapy has been shown to reduce the risk of relapse. Existing data on the implementation of these interventions in the general hospital setting remain scarce. CONCLUSION: Current evidence suggests the need for additional research in this area with a view toward clarifying AUD treatment guidelines for medically ill inpatients. The hospital stay could provide a valuable opportunity to initiate interventions for AUDs with medically ill patients, leading to significant changes in alcohol use behaviors and better health-related outcomes.

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.

Cannabis use correlates of syringe sharing among injection drug users.

This study examines whether the relation between acute cannabis use and syringe sharing during single injection days is similar among regular and nonregular users, participating in a cohort study of injection drug users in Montréal, Canada. 236 (36.6%) subjects were classified as regular cannabis users (RCUs), 227 (35.2%) as nonregular cannabis users (NRCUs), and 181 (28.1%) were abstinent. Cannabis use during a single injection day was associated with a fivefold increased risk of sharing (OR 4.92; 1.83-13.22) in NRCUs compared to RCUs. Our results indicate that cannabis use history should be considered when evaluating its potential effect on risk-taking behaviors.