Benzodiazepine use, quality of life and psychiatric symptom burden in oral and injectable opioid agonist treatment: a cross-sectional study.

BACKGROUND: Use of benzodiazepines (BZD) in patients receiving opioid agonist treatment (OAT) is common and associated with a variety of negative health and social outcomes. This cross-sectional study investigates the impact of BZD use in OAT patients on their quality of life (QoL). METHODS: A convenience sample of patients receiving oral OAT or heroin-assisted treatment in two outpatient centres in Basel, Switzerland was investigated. Participants (n = 141) completed self-report questionnaires on psychiatric symptoms and psychological distress (The Symptom Checklist 27, SCL-27), depressive state (German version of the Center for Epidemiological Studies Depression Scale), quality of life (Lancashire Quality of Life Profile, LQOLP) and use of BZD and other drugs (self-report questionnaire). Substance use was assessed by urine toxicology testing. RESULTS: In bivariate analysis, total QoL scores were significantly lower for lifetime, current, and prolonged BZD users compared to participants without the respective use patterns. There was no significant relationship between BZD dose and QoL. In multivariable linear regression models controlling for psychiatric symptom load and depressive state, only lifetime use predicted lower QoL, whereas other BZD use patterns were not significantly associated. CONCLUSIONS: The association of lower QoL and BZD use in OAT patients is strongly confounded by co-occurring depressive state and psychiatric symptoms. Careful diagnosis and treatment of co-occurring mental disorders in OAT is paramount to improve QoL in this patient population and may also help reduce BZD use.

Orbitofrontal response to drug-related stimuli after heroin administration.

The compulsion to seek and use heroin is frequently driven by stress and craving during drug-cue exposure. Although previous neuroimaging studies have indicated that craving is mediated by increased prefrontal cortex activity, it remains unknown how heroin administration modulates the prefrontal cortex response. This study examines the acute effects of heroin on brain function in heroin-maintained patients. Using a crossover, double-blind, placebo-controlled design, 27 heroin-maintained patients performed functional magnetic resonance imaging 20 minutes after the administration of heroin or placebo (saline) while drug-related and neutral stimuli were presented. Images were processed and analysed with statistical parametric mapping. Plasma concentrations of heroin and its main metabolites were assessed using high-performance liquid chromatography. Region of interest analyses showed a drug-related cue-associated blood-oxygen-level-dependent activation in the orbitofrontal cortex (OFC) in heroin-dependent patients during both treatment conditions (heroin and placebo). This activation of the OFC was significantly higher after heroin than after placebo administration. These findings may indicate the importance of OFC activity for impulse control and decision-making after regular heroin administration and may emphasize the benefit of the heroin-assisted treatment in heroin dependence.

Altered prefrontal connectivity after acute heroin administration during cognitive control.

Neuroimaging studies have reported reduced activity in a broad network of brain regions during response inhibition in heroin-dependent patients. However, how heroin in an acute dose modulates the neural correlates of response inhibition and the underlying brain connectivity has not yet been investigated. In this double-blind placebo-controlled study, we used functional magnetic resonance imaging to examine whether acute heroin administration changed whole brain activity during response inhibition in 26 heroin-dependent patients. We then applied dynamic causal modelling to investigate the effect of an acute dose of heroin on the functional interactions between the dorsal anterior cingulate cortex (dACC) and the bilateral inferior frontal gyri (IFG). Heroin acutely reduced dACC activity, as well as the inhibition-induced modulation of connectivity from the dACC to the right IFG compared with placebo. Furthermore, dACC activity was positively related to false alarm rates after placebo but not heroin administration. These results suggest that acute heroin administration impairs cognitive control in dependent patients by reducing the activity in the dACC activity and the functional connectivity from the dACC to the right IFG.

Acute effects of heroin on negative emotional processing: relation of amygdala activity and stress-related responses.

BACKGROUND: Negative emotional states and abnormal stress reactivity are central components in drug addiction. The brain stress system in the amygdala is thought to play a key role in the maintenance of drug dependence through negative reinforcement. Although acute heroin administration was found to reduce anxiety, craving, and stress hormone release, whether these effects are reflected in amygdala activity has not yet been investigated. METHODS: With a randomized, crossover, double-blind design, saline and heroin were administered to 22 heroin-dependent patients, whereas 17 healthy control subjects were included for the placebo administration only. We used functional magnetic resonance imaging to investigate blood oxygen level-dependent responses during fearful faces processing. Stress reactivity was measured by adrenocorticotropic hormone levels and by cortisol concentrations in serum and saliva 60 min after substance administration. Anxiety and craving levels were assessed with self-report ratings. RESULTS: Heroin administration acutely reduced the left amygdala response to fearful faces relative to the saline injection. Patients receiving saline showed a significantly higher left amygdala response to fearful faces than healthy control subjects, whose activity did not differ from patients receiving heroin. The left amygdala activity correlated significantly with scores on state-anxiety and levels of adrenocorticotropic hormone, serum cortisol, and saliva cortisol among all patients and control subjects. CONCLUSIONS: Our results show a direct relation between the acute heroin effects on stress-related emotions, stress reactivity, and left amygdala response to negative facial expressions. These findings provide new insights into the mechanisms underlying negative reinforcement in heroin addiction and the effects of regular heroin substitution.

Organic food processing: a framework for concept, starting definitions and evaluation.

In 2007 EU Regulation (EC) 834/2007 introduced principles and criteria for organic food processing. These regulations have been analysed and discussed in several scientific publications and research project reports. Recently, organic food quality was described by principles, aspects and criteria. These principles from organic agriculture were verified and adapted for organic food processing. Different levels for evaluation were suggested. In another document, underlying paradigms and consumer perception of organic food were reviewed against functional food, resulting in identifying integral product identity as the underlying paradigm and a holistic quality view connected to naturalness as consumers' perception of organic food quality. In a European study, the quality concept was applied to the organic food chain, resulting in a problem, namely that clear principles and related criteria were missing to evaluate processing methods. Therefore the goal of this paper is to describe and discuss the topic of organic food processing to make it operational. A conceptual background for organic food processing is given by verifying the underlying paradigms and principles of organic farming and organic food as well as on organic processing. The proposed definition connects organic processing to related systems such as minimal, sustainable and careful, gentle processing, and describes clear principles and related criteria. Based on food examples, such as milk with different heat treatments, the concept and definitions were verified. Organic processing can be defined by clear paradigms and principles and evaluated according criteria from a multidimensional approach. Further work has to be done on developing indicators and parameters for assessment of organic food quality.

Acute effects of heroin on emotions in heroin-dependent patients.

BACKGROUND: Euphoria has been described in heroin-dependent individuals after heroin administration. However, affective disturbances and disorders are common in heroin dependence. The present study examined the acute effects of heroin on emotions in heroin-dependent patients. METHODS: This randomized controlled crossover trial included 28 heroin-dependent patients (67.9% male, n = 19) in stable heroin-assisted treatment and 20 healthy controls. The patients were administered heroin or saline (placebo), the controls were administered saline. Data measuring mood, affects and heroin craving (BDI, AMRS, STAI, STAXI, and HCQ) were assessed before and 60 minutes after substance injection. RESULTS: Before substance injection, heroin-dependent patients showed significantly higher levels of anxiety and depression than healthy controls (p < .0001). Heroin administration-but not placebo administration-was associated with a significant decrease in all negative emotions, including craving, and a significant increase in emotional well-being (p < .0001), irrespective of perceived intoxication and sedation. After the experiment, the patients did not differ from healthy controls in their emotions, once they had received heroin. CONCLUSIONS: Heroin dampens craving, negative emotions, and increases positive emotions. These findings indicate that heroin regulates emotions and underscore the clinical benefit of opioid substitution treatment for heroin-dependent patients.

Association of frontal gray matter volume and cerebral perfusion in heroin addiction: a multimodal neuroimaging study.

Structure and function are closely related in the healthy human brain. In patients with chronic heroin exposure, brain imaging studies have identified long-lasting changes in gray matter (GM) volume. More recently, we showed that acute application of heroin in dependent patients results in hypoperfusion of fronto-temporal areas compared with the placebo condition. However, the relationship between structural and cerebral blood flow (CBF) changes in heroin addiction has not yet been investigated. Moreover, it is not known whether there is any interaction between the chronic structural changes and the short and long-term effects on perfusion caused by heroin. Using a double-blind, within-subject design, heroin or placebo (saline) was administered to 14 heroin-dependent patients from a stable heroin-assisted treatment program, in order to observe acute short-term effects. Arterial spin labeling (ASL) was used to calculate perfusion quantification maps in both treatment conditions, while Voxel-Based Morphometry (VBM) was conducted to calculate regional GM density. VBM and ASL data were used to calculate homologous correlation fields by Biological Parametric Mapping (BPM) and a whole-brain Pearson r correlation. We correlated each perfusion condition (heroin and placebo) separately with a VBM sample that was identical for the two treatment conditions. It was assumed that heroin-associated perfusion is manifested in short-term effects, while placebo-associated perfusion is more related to long-term effects. In order to restrict our analyses to fronto-temporal regions, we used an explicit mask for our analyses. Correlation analyses revealed a significant positive correlation in frontal areas between GM and both perfusion conditions (heroin and placebo). Heroin-associated perfusion was also negatively correlated with GM in the inferior temporal gyrus on both hemispheres. These findings indicate that, in heroin-dependent patients, low GM volume is positively associated with low perfusion within frontal regions.

Treatment or "high": benzodiazepine use in patients on injectable heroin or oral opioids.

Benzodiazepine (BZD) use is widespread among opioid-maintained patients worldwide. We conducted a cross-sectional survey to investigate motives and patterns of BZD use and psychiatric comorbidity in a convenience sample of patients (n=193) maintained on oral opioid agonists or diacetylmorphine (DAM). Prolonged BZD use and high-risk behaviors like parenteral use were common. After principal component analysis, motives were divided into those related to negative affect regulation, positive affect regulation (i.e. reward-seeking) and somato-medical problems. Negative affect regulation and somato-medical motives were associated with prolonged use. Psychiatric comorbidity was associated with several self-therapeutic motives, most importantly to lose anxiety. Patients maintained on DAM were more likely to be ex-users of BZD and report high positive affect regulation. Therefore, patients maintained on different agonists may have deviating motives for BZD use, which could be of importance when addressing this issue. Treatment of psychiatric comorbidity, in particular anxiety, depressive and sleeping disorders, may be helpful in reducing BZD use, particularly in patients maintained on oral opioids.

Inferior frontal cortex modulation with an acute dose of heroin during cognitive control.

Impairments in inhibitory control and in stimulus-driven attention are hallmarks of drug addiction and are associated with decreased activation in the right inferior frontal gyrus (IFG). Although previous studies indicate that the response inhibition function is impaired in abstinent heroin dependents, and that this is mediated by reduced IFG activity, it remains completely unknown whether and how an acute dose of heroin modulates IFG activity during cognitive control in heroin-dependent patients. This study investigates the acute effects of heroin administration on IFG activity during response inhibition and stimulus-driven attention in heroin-dependent patients. Using a cross-over, double-blind, placebo-controlled design, saline and heroin were administered to 26 heroin-dependent patients from stable heroin-assisted treatment, while performing a Go/No-Go event-related functional magnetic resonance imaging task to assess right IFG activity during motor response inhibition, as well as during oddball-driven attention allocation. Relative to saline, heroin significantly reduced right IFG activity during both successful response inhibition and oddball-driven attention allocation, whereas it did not change right IFG activity during response inhibition after correction for the effect of attention allocation. These heroin-induced effects were not related to changes in drug craving, state anxiety, behavioral performance, or co-consumption of psychostimulant drugs. This study demonstrates that heroin administration acutely impairs stimulus-driven attention allocation, as indicated by reduced IFG activity in response to infrequently presented stimuli, and does not specifically modulate IFG activity during response inhibition.

Acute effects of intravenous heroin on the hypothalamic-pituitary-adrenal axis response: a controlled trial.

Heroin dependence is associated with a stressful environment and with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. The present study examined the acute effects of intravenous heroin versus placebo on the HPA axis response in heroin-dependent patients. Twenty-eight heroin-dependent patients in heroin-assisted treatment and 20 age- and sex-matched healthy participants were included in a controlled trial in which patients were twice administered heroin or saline in a crossover design, and healthy controls were only administered saline. The HPA axis response was measured by adrenocorticotropic hormone (ACTH) levels and by cortisol levels in serum and saliva before and 20 and 60 minutes after substance administration. Craving, withdrawal, and anxiety levels were measured before and 60 minutes after substance application. Plasma concentrations of heroin and its main metabolites were assessed using high-performance liquid chromatography. Heroin administration reduces craving, withdrawal, and anxiety levels and leads to significant decreases in ACTH and cortisol concentrations (P < 0.01). After heroin administration, cortisol concentrations did not differ from healthy controls, and ACTH levels were significantly lower (P < 0.01). In contrast, when patients receive saline, all hormone levels were significantly higher in patients than in healthy controls (P < 0.01). Heroin-dependent patients showed a normalized HPA axis response compared to healthy controls when they receive their regular heroin dose. These findings indicate that regular opioid administration protects addicts from stress and underscore the clinical significance of heroin-assisted treatment for heroin-dependent patients.

The Effect of Steps to Promote Higher Levels of Farm Animal Welfare across the EU. Societal versus Animal Scientists' Perceptions of Animal Welfare.

Information about animal welfare standards and initiatives from eight European countries was collected, grouped, and compared to EU welfare standards to detect those aspects beyond minimum welfare levels demanded by EU welfare legislation. Literature was reviewed to determine the scientific relevance of standards and initiatives, and those aspects going beyond minimum EU standards. Standards and initiatives were assessed to determine their strengths and weaknesses regarding animal welfare. Attitudes of stakeholders in the improvement of animal welfare were determined through a Policy Delphi exercise. Social perception of animal welfare, economic implications of upraising welfare levels, and differences between countries were considered. Literature review revealed that on-farm space allowance, climate control, and environmental enrichment are relevant for all animal categories. Experts' assessment revealed that on-farm prevention of thermal stress, air quality, and races and passageways' design were not sufficiently included. Stakeholders considered that housing conditions are particularly relevant regarding animal welfare, and that animal-based and farm-level indicators are fundamental to monitor the progress of animal welfare. The most notable differences between what society offers and what farm animals are likely to need are related to transportation and space availability, with economic constraints being the most plausible explanation.

The European Market for Animal-Friendly Products in a Societal Context.

This article takes a future focus on the direction in which social forces develop the market for animal-friendly products in Europe. On the basis of qualitative data gathered in the context of the European EconWelfare project, the differences across eight European countries are studied. The findings suggest that, given international trade barriers that prevent an improvement of animal welfare through legislation, many stakeholders believe that the market is the most viable direction to improve farm animal welfare. Economic productivity of the chain remains, however, an issue that on a fundamental level conflicts with the objective to improve animal welfare. With the help of a deeper conceptual understanding of willingness to pay for animal welfare, the paper finds that the European market for animal-friendly products is still largely fragmented and that the differences between European countries are considerable. A more animal-friendly future that is achieved through the market will therefore need substantial policy attention from stakeholders in society.

Organic food quality: a framework for concept, definition and evaluation from the European perspective.

Consumers buy organic food because they believe in the high quality of the product. Furthermore, the EU legal regulatory framework for organic food and farming defines high quality of the products as an important goal of production. A major challenge is the need to define food quality concepts and methods for determination. A background is described which allows embedding of the quality definitions as well as evaluation methods into a conceptual framework connected to the vision and mission of organic agriculture and food production. Organic food quality is defined through specific aspects and criteria. For evaluation each criterion has to be described by indicators. The determination of indicators should be through parameters, where parameters are described by methods. Conversely, the conceptual framework is described according to underlying principles and starting definitions are given, but further work has do be done on the detailed scientific description of the indicators. Furthermore, parameters have to be defined for the evaluation of suitability of these indicators for organic food production.

The impact of diacetylmorphine on hypothalamic-pituitary-adrenal axis activity and heroin craving in heroin dependence.

BACKGROUND/AIM: Heroin dependence is a chronic relapsing disorder characterized by the compulsion to seek and use heroin. Stress and craving are seen as key factors for heroin use. Moreover, altered hypothalamic-pituitary-adrenal (HPA) axis function has been frequently reported. However, the acute effects of diacetylmorphine (DAM) on HPA axis activity and craving have not been investigated in a controlled study. The present randomized controlled study examined whether DAM administration differs from placebo (saline) administration with regard to HPA axis response and heroin craving. METHODS: In a crossover experiment, 28 DAM-maintained heroin-dependent patients were first injected with DAM and then saline, or the converse. Plasma adrenocorticotropic hormone (ACTH) and cortisol in saliva and serum were measured at baseline and 20 and 60 min after both injections. Heroin craving was measured at baseline and 60 min after both injections, by means of the Heroin Craving Questionnaire. RESULTS: Compared to saline, DAM administration induced a significant decrease in plasma ACTH (p < 0.01), serum cortisol (p < 0.0001) and saliva cortisol (p < 0.01), as well as in craving (p < 0.0001), over time. CONCLUSION: Since acute DAM administration suppresses the stress response, DAM-assisted treatment may be an effective alternative to methadone maintenance in stress-sensitive heroin-dependent patients.

Alpha-synuclein and heroin craving in opiate-dependent patients on injectable heroin maintenance.

Research suggests that alpha-synuclein (SNCA) and NACP-Rep1, a polymorphic complex microsatellite repeat ~10 kb upstream of the SNCA gene translational start, may be involved in substance-use behaviors and craving. This study was the first to examine the effects of diacetylmorphine (DAM) on peripheral SNCA protein expression along with craving in opiate-dependent patients and to compare their NACP-Rep1 allele lengths with those of healthy controls. Using an experimental design, opiate-dependent patients on injectable heroin maintenance were investigated at four time points, twice pre- and post-injection of DAM. SNCA protein levels of 30 DAM-maintained patients were measured using enzyme-linked immunosorbent assay. Participant-rated effects were assessed in 42 patients by Tiffany's Heroin Craving Questionnaire (HCQ), Gossop's Short Opiate Withdrawal Scale and Visual Analogs. NACP-Rep1 alleles of 42 patients and 101 controls were analyzed. One-way repeated-measures ANOVAs provided significant overall effects for SNCA protein content (P = 0.028), craving (P < 0.001), withdrawal symptomatology (P < 0.001) and mood (P < 0.001), indicating that DAM injections may not only reduce craving but also SNCA protein expression. However, there was no association between protein expression and craving. Relative to controls, patients had significantly longer NACP-Rep1 alleles (P < 0.001). NACP-Rep1 allele lengths correlated positively with HCQ total scores averaged across all time points (r = 0.420; P = 0.006) as well as with post-DAM HCQ total scores in the morning (r = 0.488, P = 0.001) and afternoon (r = 0.423, P = 0.005). The findings provide evidence of a contributory role of SNCA and NACP-Rep1 for opiate dependence.

Symptom complaints of patients prescribed either oral methadone or injectable heroin.

Many methadone patients and untreated heroin users have an ambivalent attitude toward methadone maintenance. This may be a result of the widespread belief that methadone produces various side effects not found with heroin. This study compared the symptom complaints of patients on oral methadone maintenance (MMT) with those of patients prescribed injectable heroin (IHT). A convenience sample of 117 (63 MMT, 54 IHT) patients was recruited from two maintenance clinics. With the use of a self-completion questionnaire, patients were interviewed about a range of symptoms they had experienced and which, in their view, were due to maintenance substance immediately after the last 10 opioid administrations, during the previous week and previous year. The complaints of the two groups overlapped considerably with only few significant differences; these appeared related to the route of administration. IHT patients reported a larger number of complications experienced immediately after administration than MMT patients (p = .007). From the patients' view, methadone does not produce many more or side effects very different from heroin and thus seems at least as tolerable as heroin for maintenance treatment.

Hypertension and hyperlipidaemia: garlic helps in mild cases.

Forty-seven non-hospitalised patients with mild hypertension took part in a randomised, placebo-controlled, double-blind trial conducted by 11 general practitioners. The patients who were admitted had diastolic blood pressures between 95 and 104 mmHg after a two-week acclimatization phase. The patients then took either a preparation of garlic powder (Kwai) or a placebo of identical appearance for 12 weeks. Blood pressure and plasma lipids were monitored during treatment after four, eight and 12 weeks. Significant differences between the placebo and the drug group were found during the course of therapy. For example, the supine diastolic blood pressure in the group having garlic treatment fell from 102 to 91 mmHg after eight weeks (p less than 0.05) and to 89 mmHg after 12 weeks (p less than 0.01). The serum cholesterol and triglycerides were also significantly reduced after eight and 12 weeks of treatment. In the placebo group, on the other hand, no significant changes occurred.