Use Of Addictive Drugs Research Articles

Role of Ghrelin in Drug Abuse and Reward-Relevant Behaviors: A Burgeoning Field and Gaps in the Literature

Ghrelin is a gut-brain hormone that regulates energy balance through food consumption. While ghrelin is well known for its role in hypothalamic activation and homeostatic feeding, more recent evidence suggests that ghrelin also is involved in hedonic feeding through the dopaminergic reward pathway. This paper investigated how ghrelin administration (intraperitoneal, intracerebroventricular, or directly into dopaminergic reward-relevant brain regions) activates the dopaminergic reward pathway and associated reward-relevant behavioral responses in rodents. A total of 19 empirical publications that examined one or more of these variables were included in this review. Overall, ghrelin administration increases dopamine levels in the nucleus accumbens, as well as reward-relevant behaviors such as food (both standard chow and palatable foods) and alcohol consumption. Ghrelin administration also increases operant responding for sucrose, and conditioned place preference. Following a review of the small body of literature examining the effects of ghrelin administration on the dopamine reward pathway, we present a model of the relationship between ghrelin and dopaminergic reward activation. Specifically, ghrelin acts on ghrelin receptors (GHS-R1A) in the ventral tegmental area (VTA) and lateral dorsal tegmental nucleus (LDTg) to stimulate the mesolimbic dopamine reward pathway, which results in increased rewarding behaviors in rodents. Results from this review suggest that selective antagonism of the ghrelin system may serve as potential treatment for addictive drug use. This review highlights gaps in the literature, including a lack of examination of sex- or age-related differences in the effects of ghrelin on dopamine reward processes. In light of vulnerability to drug abuse among female and adolescent populations, future studies should target these individual difference factors.

Glutamate transporter GLT‐1 mediates N‐acetylcysteine inhibition of cocaine reinstatement

Both pre-clinical and clinical studies indicate that N-acetylcysteine (NAC) may be useful in treating relapse to addictive drug use. Cocaine self-administration in rats reduces both cystine-glutamate exchange and glutamate transport via GLT-1 in the nucleus accumbens, and NAC treatment normalizes these two glial processes critical for maintaining glutamate homeostasis. However, it is not known if one or both of these actions by NAC is needed to inhibit relapse to cocaine seeking. To determine whether the restoration of GLT-1 and/or cystine-glutamate exchange is required for NAC to inhibit cue-induced reinstatement of cocaine seeking, we utilized the rat self-administration/extinction/reinstatement model of cocaine relapse. Rats were pre-treated in the nucleus accumbens with vivo-morpholino antisense oligomers targeting either GLT-1 or xCT (catalytic subunit of the cystine-glutamate exchanger) overlapping with daily NAC administration during extinction (100 mg/kg, i.p. for the last 5 days). Rats then underwent cue-induced reinstatement of active lever pressing in the absence of NAC, to determine if preventing NAC-induced restoration of one or the other protein was sufficient to block the capacity of chronic NAC to inhibit reinstatement. The vivo-morpholino suppression of xCT reduced cystine-glutamate exchange but did not affect NAC-induced reduction of reinstated cocaine seeking. In contrast, suppressing NAC-induced restoration of GLT-1 not only prevented NAC from inhibiting reinstatement, but augmented the capacity of cues to reinstate cocaine seeking. We hypothesized that the increased reinstatement after inhibiting NAC induction of GLT-1 resulted from increased extracellular glutamate, and show that augmented reinstatement is prevented by blocking mGluR5. Restoring GLT-1, not cystine-glutamate exchange, is a key mechanism whereby daily NAC reduces cue-induced cocaine reinstatement.

The Co‐Use of Tobacco and Cannabis Among Adolescents Over a 30‐Year Period

This study explores the patterns of use and co-use of tobacco and cannabis among Ontario adolescents over 3 decades and if characteristics of co-users and single substance users have changed. Co-use trends for 1981-2011 were analyzed using the Centre for Addiction and Mental Health Ontario Student Drug Use and Health Survey, which includes 38,331 students in grades 7, 9, and 11. A co-user was defined as someone reporting daily tobacco and/or cannabis use in the past month. Trends over time (by gender and academic performance) were analyzed with logistic regression. The prevalence of tobacco-only use, cannabis-only use, and co-use fluctuated considerably. During 1981-1993, there were more tobacco-only users than co-users and cannabis-only users; since 1993 the prevalence of tobacco use has decreased dramatically. Co-use prevalence peaked at 12% (95% confidence interval: 9, 15) in 1999, when prevalence of overall use of both substances was highest. In 2011, 92% of tobacco users also used cannabis, up from 16% in 1991. In 2011 nearly all students who smoke tobacco daily also use cannabis. Non-regular use of either substance is highest now compared with the past 3 decades. Contemporary tobacco and cannabis co-users are significantly different than past users. Youth prevention programs should understand the changing context of cannabis and tobacco among youth.

An urgent precaution system to detect students at risk of substance abuse through classification algorithms

In recent years, the use of addictive drugs and substances has turned out to be a challenging social problem worldwide. The illicit use of these types of drugs and substances appears to be increasing among elementary and high school students. After becoming addicted to drugs, life becomes unbearable and gets even worse for their users. Scientific studies show that it becomes extremely difficult for an individual to break this habit after being a user. Hence, preventing teenagers from addiction becomes an important issue. This study focuses on an urgent precaution system that helps families and educators prevent teenagers from developing this type of addiction. The aim of this study is to detect a teenager's probability of being a drug abuser using classification algorithms in machine learning and data mining. The objective is not to test the classifiers theoretically on the benchmark datasets, but rather to use this study as a basis for advanced and detailed studies in this field in the future. This paper not only uses a special dataset but also focuses on psychometrics and statistics. The findings of this study show that if there is a computed high risk for a teenager, some precautions, if necessary, may be taken by educators and parents to keep the teenager away from those substances.

Prevalence and Awareness of Sexually Transmitted Infections among Inmates of a Drug Rehabilitation Center in Saudi Arabia: A Cross-Sectional Study

Background: Drug addicts constitute a high-risk group for the transmission of HIV and other Sexually Transmitted Infections (STIs). The aim of the study was to screen inmates at a drug rehabilitation center for the presence of commonly occurring STIs. We also aimed to correlate the prevalence of STIs with injecting and noninjecting drug use and awareness about the prevention of STIs. Methods: This cross-sectional study was conducted on a convenience sample of 115 inpatients at Al Amal Hospital for the Treatment of Addiction and Rehabilitation between September 1, 2011 and November 1, 2012. Demographic data, use of intravenous and other addictive drugs, and awareness about condom use for protection against STIs were documented. Blood samples were collected, and serum and DNA were extracted to test for HIV and Hepatitis B Virus (HBV) using enzyme-linked immunosorbent assay and for syphilis using polymerase chain reaction. The data were analyzed using the Statistical Package for the Social Sciences. Results: Of the total participants, 18 had one or more STIs, including syphilis (n=11), HIV (n=5), HBV (n=5) and combined HBV and syphilis (n=3). The prevalence of STIs was higher among injecting drug users than among noninjecting drug users. Compared to the group that did not have STIs, very few participants who were positive for STIs were aware that condoms provided protection against STIs. Conclusions: The prevalence of HIV, HBV and syphilis among male drug addicts in Saudi Arabia is very high. Healthcare providers should focus on raising awareness and providing treatment and counselling to this high-risk population.

Prelimbic Cortex and Ventral Tegmental Area Modulate Synaptic Plasticity Differentially in Nucleus Accumbens During Cocaine-Reinstated Drug Seeking

Addictive drug use causes long-lasting changes in synaptic strength and dendritic spine morphology in the nucleus accumbens that might underlie the vulnerability to relapse. Although activity in mesocorticolimbic circuitry is required for reinstating cocaine seeking, its role in reinstatement-associated synaptic plasticity is not well characterized. Using rats extinguished from cocaine self-administration, we found potentiated synaptic strength (assessed as the AMPA/NMDA current amplitude ratio) and increased spine head diameter in medium spiny neurons in the accumbens core (NAcore). The basal changes in synaptic strength and morphology in cocaine-extinguished animals were further augmented during cocaine-induced reinstatement. Two NAcore afferents contributing to cocaine reinstatement are glutamatergic inputs from the prelimbic prefrontal cortex (PL) and dopamine from the ventral tegmental area (VTA). Pharmacological inhibition of either PL or VTA prevented cocaine-primed reinstatement. However, inhibiting the PL further potentiated AMPA/NMDA and spine head diameter, while inactivating the VTA or the combined systemic administration of dopamine D1 and D2 antagonists prevented the increase in AMPA/NMDA and spine diameter induced by cocaine priming. These data indicate that neuronal activity in the VTA and associated dopamine receptor stimulation is necessary for the synaptic potentiation in the NAcore during cocaine-induced reinstatement. Although activity in the PL was necessary for reinstatement, it inhibited synaptic potentiation initiated by an acute cocaine injection. Thus, although the PL and VTA differentially regulate the direction of synaptic plasticity induced by a cocaine-priming injection, coordinated synaptic potentiation by both NAcore afferents is necessary for cocaine-induced relapse.

Caudate nucleus‐dependent navigational strategies are associated with increased use of addictive drugs

This study aimed to investigate the relationship between navigational strategies and the use of abused substances in a sample of healthy young adults. Navigational strategies were assessed with the 4-on-8 virtual maze (4/8VM), a task previously shown to dissociate between hippocampal-dependent spatial navigational strategies and caudate nucleus-dependent stimulus-response navigational strategies. Spatial strategies involve learning the spatial relationships between the landmarks in an environment, while response learning strategies involve learning a rigid set of stimulus-response type associations, e.g., see the tree, turn left. We have shown that spatial learners have increased gray matter and fMRI activity in the hippocampus compared with response learners, while response learners have increased gray matter and fMRI activity in the caudate nucleus. We were interested in the prevalence of use of substances of abuse in spatial and response learners because of the evidence that people who score high on traits such as novelty seeking, sensation seeking, reward seeking, and impulsivity, are more cue-responsive and more likely to use substances of abuse. Since response learners show increased activity and gray matter in the caudate nucleus of the striatum, which is a brain area involved in addiction, we hypothesized that response learners would have a greater use of abused substances than spatial learners. Fifty-five young adults were tested on the 4/8VM and completed a time-line follow-back assessment of drug and alcohol use. We found that response learners had smoked a significantly greater number of cigarettes in their lifetime than spatial learners, were more likely to have used cannabis, and had double the lifetime alcohol consumption. We discuss the possible relationship between substance abuse and response strategies as well as the implications for the hippocampus, risks of neurological and psychiatric disorders, and healthy cognition. © 2013 The Authors. Hippocampus Published by Wiley Periodicals, Inc.

Addiction: Why is it a disorder of choice and decision?

The financial and social costs of addiction are staggeringly high; countless clinical reports and memoirs document the personal pain and chaos caused by addicted family members. In response, many addiction professionals and much of the public conclude that addiction is a disease. No one, the argument goes, would cause so much harm to themselves and others voluntarily. Yet research tells a different story. Clinical, historical, and biographical evidence reveals that economic conditions, legal sanctions, and the opinions of others, particularly family members and loved ones, influence the course of drug use in addicts. In contrast these same factors have little influence on the symptoms of the diseases addiction is said to be like, such as Alzheimer's, heart disease, and cancer. In support of these points, NIH epidemiological research shows that addiction has the highest remission rate of any psychiatric disorder, that most of those addicted to illegal drugs quit by age 30, and they typically quit without professional assistance. Of course, not all addicts quit by age 30, and dependence on legal drugs has a longer time course. However, analysis reveals that these are not qualitatively different outcomes, so that the choice framework fits both legal and illegal drugs and those who quit and those who don't quit. Nevertheless addiction is a disorder, which implies that its cost outweigh its benefits, which, in turn, appears to contradict choice accounts. However, research-based choice principles, such as hyperbolic discounting and melioration, predict semi-stable choice sequences that are optimal in the short run but suboptimal in the long run. That is, choice theory predicts a pattern of drug binging, remission, relapse, and eventual resolution. These finding do not make addiction any less of a problem, but they point to the most effective way to deal with addiction. The immediate implication is to reward abstinence and penalize drug use. Although this is a simplistic formula, it has been put to effective use in a wide range of settings.

Young adults' trajectories of Ecstasy use: A population based study

Young adults' Ecstasy use trajectories have important implications for individual and population-level consequences of Ecstasy use, but little relevant research has been conducted. This study prospectively examines Ecstasy trajectories in a population-based sample. Data are from the Natural History Study of Drug Use, a retrospective/prospective cohort study conducted in Australia. Population screening identified a probability sample of Ecstasy users aged 19–23years. Complete data for 30months of follow-up, comprising 4 time intervals, were available for 297 participants (88.4% of sample). Trajectories were derived using cluster analysis based on recent Ecstasy use at each interval. Trajectory predictors were examined using a generalized ordered logit model and included Ecstasy dependence (World Mental Health Composite International Diagnostic Instrument), psychological distress (Hospital Anxiety Depression Scale), aggression (Young Adult Self Report) and contextual factors (e.g. attendance at electronic/dance music events). Three Ecstasy trajectories were identified (low, intermediate and high use). At its peak, the high-use trajectory involved 1–2days Ecstasy use per week. Decreasing frequency of use was observed for intermediate and high-use trajectories from 12months, independently of market factors. Intermediate and high-use trajectory membership was predicted by past Ecstasy consumption (>70 pills) and attendance at electronic/dance music events. High-use trajectory members were unlikely to have used Ecstasy for more than 3years and tended to report consistently positive subjective effects at baseline. Given the social context and temporal course of Ecstasy use, Ecstasy trajectories might be better understood in terms of instrumental rather than addictive drug use patterns.

Behavioral characteristics and pharmacological manipulations of a nicotine-entrainable circadian oscillator

Chronic daily administration of nicotine and other drugs of abuse has been found to entrain pre- and post-drug circadian locomotor activity episodes that oscillate on a 24-h schedule and persist for several days after administration ceases. This drug-entrainable oscillator system could conceivably lead to circadian rhythms of drug seeking and drug use in human drug addicts. The present study (1) characterizes the ability of daily nicotine administration to entrain circadian wheel-running activity episodes in rats across a range of doses, lighting schedules, and food access; and (2) tests whether pre- and post-nicotine episodes can be altered through pharmacological manipulations. Adult female rats were housed in wheel boxes for 35–60 d, and both wheel-running and feeding-related behaviors were measured continuously. Following acclimation, nicotine or saline was administered for 16–24 d, and the rats were left undisturbed for several test days to observe the persistence of nicotine-entrained activity. The results showed that nicotine dose-dependently entrains wheel-running activity, and the highest dose of 1.0 mg/kg produces robust pre- and post-nicotine circadian activity episodes under constant, fixed, and variable light/dark schedules. In the pharmacological manipulation experiment, nicotine-entrained rats were administered one of seven pharmacological treatments (varenicline, mecamylamine, acamprosate, topiramate, naltrexone, SB-334867, or bupropion) in place of the nicotine injection for 2 d, and the rats were not disturbed for four subsequent days. Most of the treatment drugs significantly reduced post-nicotine activity episodes, but only three treatments affected pre-nicotine episodes: the μ- and κ-opioid receptor antagonist naltrexone, the orexin-1 receptor antagonist SB-334867, and the AMPA (2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid)/kainate antagonist topiramate. These results show that chronic daily nicotine administration is a robust zeitgeber that dose-dependently entrains a nonphotic oscillator system that includes opioid, orexin, and glutamate pathways.

Addiction: choice or compulsion?

Normative thinking about addiction has traditionally been divided between, on the one hand, a medical model which sees addiction as a disease characterized by compulsive and relapsing drug use over which the addict has little or no control and, on the other, a moral model which sees addiction as a choice characterized by voluntary behavior under the control of the addict. Proponents of the former appeal to evidence showing that regular consumption of drugs causes persistent changes in the brain structures and functions known to be involved in the motivation of behavior. On this evidence, it is often concluded that becoming addicted involves a transition from voluntary, chosen drug use to non-voluntary compulsive drug use. Against this view, proponents of the moral model provide ample evidence that addictive drug use involves voluntary chosen behavior. In this article we argue that although they are right about something, both views are mistaken. We present a third model that neither rules out the view of addictive drug use as compulsive, nor that it involves voluntary chosen behavior.

Addiction and choice: theory and new data.

Addiction’s biological basis has been the focus of much research. The findings have persuaded experts and the public that drug use in addicts is compulsive. But the word “compulsive” identifies patterns of behavior, and all behavior has a biological basis, including voluntary actions. Thus, the question is not whether addiction has a biology, which it must, but whether it is sensible to say that addicts use drugs compulsively. The relevant research shows most of those who meet the American Psychiatric Association’s criteria for addiction quit using illegal drugs by about age 30, that they usually quit without professional help, and that the correlates of quitting include legal concerns, economic pressures, and the desire for respect, particularly from family members. That is, the correlates of quitting are the correlates of choice not compulsion. However, addiction is, by definition, a disorder, and thereby not beneficial in the long run. This is precisely the pattern of choices predicted by quantitative choice principles, such as the matching law, melioration, and hyperbolic discounting. Although the brain disease model of addiction is perceived by many as received knowledge it is not supported by research or logic. In contrast, well established, quantitative choice principles predict both the possibility and the details of addiction.

Nur transcription factors in stress and addiction

The Nur transcription factors Nur77 (NGFI-B, NR4A1), Nurr1 (NR4A2), and Nor-1 (NR4A3) are a sub-family of orphan members of the nuclear receptor superfamily. These transcription factors are products of immediate early genes, whose expression is rapidly and transiently induced in the central nervous system by several types of stimuli. Nur factors are present throughout the hypothalamus-pituitary-adrenal (HPA) axis where are prominently induced in response to stress. Drugs of abuse and stress also induce the expression of Nur factors in nuclei of the motivation/reward circuit of the brain, indicating their participation in the process of drug addiction and in non-hypothalamic responses to stress. Repeated use of addictive drugs and chronic stress induce long-lasting dysregulation of the brain motivation/reward circuit due to reprogramming of gene expression and enduring alterations in neuronal function. Here, we review the data supporting that Nur transcription factors are key players in the molecular basis of the dysregulation of neuronal circuits involved in chronic stress and addiction.

Choice to view cocaine images predicts concurrent and prospective drug use in cocaine addiction

BackgroundIdentifying variables that predict drug use in treatment-seeking drug addicted individuals is a crucial research and therapeutic goal. This study tested the hypothesis that choice to view cocaine images is associated with concurrent and prospective drug use in cocaine addiction. MethodsTo establish choice-concurrent drug use associations, 71 cocaine addicted subjects (43 current users and 28 treatment seekers) provided data on (A) choice to view cocaine images and affectively pleasant, unpleasant, and neutral images [collected under explicit contingencies (when choice was made between two fully visible side-by-side images) and under more probabilistic contingencies (when choice was made between pictures hidden under flipped-over cards)]; and (B) past-month cocaine and other drug use. To establish choice-prospective drug use associations, 20 of these treatment-seeking subjects were followed over the next 6 months. ResultsBaseline cocaine-related picture choice as measured by both tasks positively correlated with subjects’ concurrent cocaine and other drug use as driven by the actively-using subjects. In a subsequent multiple regression analysis, choice to view cocaine images as compared with affectively pleasant images (under probabilistic contingencies) was the only predictor that continued to be significantly associated with drug use. Importantly, this same baseline cocaine>pleasant probabilistic choice also predicted the number of days drugs were used (cocaine, alcohol, and marijuana) over the next 6 months. ConclusionsSimulated cocaine choice – especially when probabilistic and when compared with other positive reinforcers – may provide a valid laboratory marker of current and future drug use in cocaine addiction.

What Is the Link between Eating, Reproducing, & Addiction?

We are wired with the drive to stay alive – with a system that makes it pleasurable for us to eat, to seek shelter, and to reproduce. The problem is that addictive substances can subvert these same processes that were intended to keep us alive and to ensure species survival. This column is the first in a series that will explore the neuroscientific bases of addiction. As a basis for understanding addiction, this article focuses on the brain’s reward system, also known as the pleasure center or motivation system, which is the foundation for life-maintaining but also addictive behaviors. Subsequent articles will explore the influence of genetics, learning, risk and protective factors, stress, and specific neurotransmitters, such as glutamate.As we know, the “reward system” includes key areas or centers, connecting tracts, and several key neurotransmitters. The main areas are the ventral tegmental area (VTA) located in the mid-brain just above the hippocampus and in front of the substantia nigra; the nucleus accumbens (NAc) in the striatum just below the front end of the corpus callosum; and the prefrontal cortex, located just behind the forehead and just in front of the motor areas of the cortex. Some of the other areas involved include the locus coeruleus, the amygdala, the hippocampus, and the insula. The main nerve bundles or tracts that connect these areas are the mesolimbic, mesocortical, and mesostriatal pathways. The main neurotransmitters include dopamine, endogenous opioids, endocannabinoids, serotonin, and glutamate, although it is likely that other neurotransmitters as well as neuropeptides are also involved (Figure 1).The power of the reward system has been revealed in experiments in which experimental animals were found to vigorously continue self-stimulation when electrodes were placed in various locations within the reward-system structures (Olds & Milner, 1954). Esch and Stefano (2004) reviewed the important role of this system both in maintaining health and in addiction. More recently, brain-imaging techniques such as positron emission tomography (PET) scanning have helped us appreciate how addiction itself modifies the function of the brain’s reward system. In research by Volkow and colleagues (2009, 2011), cocaine use in nonaddicted persons resulted in a significant increase in dopamine release in the vicinity of the nucleus accumbens. Both the speed of drug administration, which is a function of the route of administration, and the amount of dopamine subsequently released, were directly related to the “high” experienced by the drug recipient. In cocaine-addicted individuals, however, this response was altered so that the dopamine released in response to cocaine intake was markedly diminished. Instead, there was a marked increase in dopamine in response to conditioning cues – such as seeing a video of another person buying or smoking cocaine. When the stimulus for dopamine release occurred in response to these conditioned cues, the addicted person experienced “craving” for the drug. There was a direct relationship between addiction severity and dopamine release during the viewing of these videos (Volkow et al., 2011).Another recent finding related to addiction is the modulating influence of a variety of stress-related neuropeptides, particularly a corticotropin-releasing factor that has been shown to increase dopamine release in the nucleus accumbens during the development of addictive behaviors (Sinha, 2008). Neuropeptides are brain signaling molecules of fewer than 40 amino acids that can modulate neuronal function in ways that are similar, but not identical, to the actions of neurotransmitters (Burbach, 2011; Logrip et al., 2011). The use of addictive drugs and the associated stress are known to activate the hypothalamic–pituitary–adrenal (HPA) axis, an action that probably has a role in addiction but may have an even greater effect during drug abstinence in addicted persons. Research has shown that the increases in corticotropin-releasing factor that occur during withdrawal are related to the signs and symptoms associated with withdrawal, particularly the anxiety that may contribute to relapse (Shalev et al., 2009; Logrip et al., 2011).Given that we all have brain reward systems, why is it that some of us when exposed to potentially addictive substances develop addictions and others do not? The next column in this series will discuss the relationship between genetics and addiction. Exploring this relationship contributes another piece to understanding the complex puzzle of addiction.This project was funded by the National Institute on Drug Abuse, National Institutes of Health, Award Number R25DA028796. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Addiction neuroethics: the promises and perils of neuroscience research on addiction

Addiction neuroethics: the promises and perils of neuroscience research on addiction

Methadone-drugs interactions: possible causes of methadone-related deaths

Background Methadone is an effective analgesic and it is widely used to suppress withdrawal symptoms from other opiates. Its consumption is usually associated with concomitant drug use in heroin addicts, and this combination is a possible risk factor for lethal outcome. The aim of this study was to analyze characteristics of methadone-related deaths (MRDs), and to evaluate the concomitant use of the drugs that can contribute to methadone toxicity.

War on Black Men: Arguments for the Legalization of Drugs

The leadership of the black community is concerned with welfare, with equality, with unemployment, with discrimination, with racism, with the pay gap, and with dozens of other such traditional issues. Oh, yes, they are also apprehensive about the use of addictive drugs. But, as we speak, young male members of this community are being incarcerated at frightful rates, and, even worse, are killing each other to boot. One would think that this latter issue would occupy the interest of black leaders front and center. After all, there are few worse problems than being jailed or killed. The present paper is dedicated to making the case that the black leadership has its priorities all wrong; that if they were to exercise true leadership, they would see the jailing and murder of young black men as perhaps the greatest threat to their community; and, if so, they would fervently support the legalization of all drugs.

Case Comment: Canada (Attorney General) v PHS Community Services Society

In September of this year, the Supreme Court of Canada released its decision in Canada (Attorney General) v PHS Community Services Society (“PHS Community Services Society”).[1] PHS Community Services Society is undoubtedly a landmark decision. Most importantly, the Court ordered the continued operation of Insite, North America’s only supervised injection site, and a health program that has proven to be overwhelmingly effective in addressing addiction drug use in Vancouver’s Downtown East Side (the “DTES”). But the decision is also critically important as part of the Supreme Court’s body of constitutional jurisprudence. In this case comment, I review the Court’s decision, and discuss three important issues raised by the Court’s analysis: (a) the availability of ministerial discretion as an “antidote” for an otherwise unconstitutional law; (b) what insight the decision may provide with respect to the relationship between the Court and Parliament; and (c) PHS Community Services Society’s utility as a precedent for future supervised injection sites. [1] Canada (Attorney General) v PHS Community Services Society, 2011 SCC 44, [2011] SCJ no 44 (QL) [PHS (SCC)].

Environmental enrichment blocks ethanol‐induced locomotor sensitization and decreases BDNF levels in the prefrontal cortex in mice

The use of addictive drugs can lead to long-term neuroplastic changes in the brain, including behavioral sensitization, a phenomenon related to addiction. Environmental enrichment (EE) is a strategy used to study the effect of environment on the response to several manipulations, including treatment with addictive drugs. Brain-derived neurotrophic factor (BDNF) has been associated with behaviors related to ethanol addiction. The aim of the present study was to evaluate the effects of EE on ethanol-induced behavioral sensitization and BDNF expression. Mice were exposed to EE and then repeatedly treated with a low dose (1.8 g/kg) of ethanol. Another group of mice was first subjected to repeated ethanol treatment according to the behavioral sensitization protocol and then exposed to EE. Environmental enrichment prevented the development of ethanol-induced behavioral sensitization and blocked behavioral sensitization in sensitized mice. Both repeated ethanol and EE decreased BDNF levels in the prefrontal cortex but not in the hippocampus. However, BDNF levels were lower in ethanol-treated mice exposed to EE. These findings suggest that EE can act on the mechanisms implicated in behavioral sensitization, a model for drug-induced neuroplasticity and relapse. Additionally, EE alters BDNF levels, which regulate addiction-related behaviors.