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This article reviews both human and nonhuman primate research dealing with the social psychobiologic effects of anabolic/androgenic steroids (AS). Descriptive research and anecdotal reports within the realm of sport suggest that AS may have a variety of psychological and behavioral effects including psychotic episodes and increased aggression. Recent investigations with a nonhuman primate model confirm that the effects of AS on psychological states and overt behavior can be quite varied, ranging from those that can be characterized as active (e.g., mania and aggression) to more passive states (e.g., depression and social withdrawal). There are also profound physiological effects of a biobehavioral origin that constitute a risk for cardiovascular disease. The most striking aspect of AS is that the effects of this drug are due to an interaction between its pharmacologic properties and the social milieu. [ABSTRACT FROM AUTHOR]

Treatment for drug-induced depression usually consists of cessation or reduction of the causative agent and psychopharmacologic management. In addition, psychotherapy can be useful as an adjunctive treatment. The author presents case material related to a young woman with an inborn physical illness, who became depressed during the course of interferon treatment for a medical complication, hepatitis virus infection. In addition to the cessation of interferon and pharmacologic management, supportive psychotherapy of a psychodynamic orientation was started in order to address the patient’s low self-esteem and anxiety about her future. During the course of psychotherapy, it was understood that the premature cessation of interferon was, to her, a narcissistic injury. It was also important to explore the meanings of her inborn illness and her guilty feelings. After reviewing various formulations of depression, the author discusses the case material from an integrative perspective, which describes vicious cycles of depression. [ABSTRACT FROM AUTHOR]

Objective: To perform a systematic review and meta-analysis of studies investigating predictors of medication adherence in children and adolescents with severe mental illness (SMI).Method: A systematic literature search was conducted in PubMed/MEDLINE, Web of Science, and PsycINFO from 1980 through October 1st, 2017, for original peer-reviewed articles that investigated predictors of adherence to psychopharmacologic treatment among children (≤18-years-old) with a primary psychotic disorder, bipolar disorder, depression, recent suicide attempt, or psychiatric hospitalization. Effect sizes (ESs) for individual predictors were extracted and combined using DerSimonian-Laird random-effects meta-analysis. Meta-regression and moderator analyses were conducted to investigate subgroups. This review complied with Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines.Results: A total of 28 studies (n = 180,870) met inclusion criteria; 65.9% (±20.9%) of children and adolescents with SMI were medication adherent. Adherence was associated with patient and family attitudes toward care, adherence to psychotherapy, and insight. Nonadherence was associated with illness severity, substance use, and attention-deficit/hyperactivity disorder. Heterogeneity was moderate-to-large for most ES estimates (I2 > 50%). Age, sex, underlying diagnosis, and study methodology emerged as significant moderators.Conclusion: Medication nonadherence among youth with SMI is highly prevalent. Children and adolescents with more severe illness and higher comorbidity burden are at greater risk for nonadherence. Positive interpersonal care processes and adherence to nonpharmacological treatment may be protective. These findings inform development of a risk profile for nonadherence among youth with SMI. Future prospective research is needed to address the shortcomings in the existing literature and inform interventions to improve adherence. [ABSTRACT FROM AUTHOR]

The aim of this study is looking for answers of is there relationship between alcohol and drug abuse with criminal activity and what are the effects, dimensions and types of this relationship. The data used in this study were taken from the unpublished PhD thesis of Şahinli (2016). The research was conducted between December 2014 and January 2015. Sample group of study was 346 prisoners, and population group was 4220 prisoners. Thus, this study was conducted with 97,5% confidence level. In the sample group, 274 (79,8%) of the prisoners were male while 70 (20,2%) were women. The prisoners' ages vary between 18 and 70 years and the average age were 35. Face to face method was used with prisoners who were in prisons of Ankara. Surveys were fulfilled to prisoners in their wards of prisons. In the study, five hypotheses were identified to examine the relationship between alcohol and drug use and criminal behavior. These hypotheses are based on the psychopharmacological model and the economic model which included in Goldstein's (1985) tripartite model. It is concluded that drugs are more related to crime in terms of economic model and using alcohol is more related to crime in terms of psychopharmacological model. According to another result of the study is alcohol is more related to violent behavior than to other drugs. [ABSTRACT FROM AUTHOR]

Abstract: The antidepressant‐like activity of ethanol seed extract of Aframomum melegueta (AM) in mice was evaluated in this study. The duration of immobility was measured 30 min after oral administration of AM (25–400 mg/kg) in forced swim test. In the unpredictable chronic mild stress (UCMS) paradigm, mice were treated with AM (25–100 mg/kg) 30 min before exposure to different stressors for 14 days. Thereafter, sucrose preference test, tail suspension test, and test for anxiety were done. The brain concentrations of malondialdehyde and glutathione were estimated spectrophotometrically. Brain histology and population of healthy neurons in cornu ammonis 3 of the hippocampus were also assessed. AM (25 and 50 mg/kg) significantly decreased the duration of immobility in forced swim test and prevented UCMS‐induced anhedonia and anxiety‐like behaviors, suggesting antidepressant potentials. The extract decreased malondialdehyde and increased glutathione concentrations in UCMS‐induced mice. Therefore, AM extract offers protection against UCMS‐induced damage to cornu ammonis 3 hippocampal neuronal cells indicating neuroprotection. Practical applications: The seed of Grains of Paradise (Aframomum melegueta) is used in traditional medicine for fatigue and impotence, which are prominent symptoms of major depression. It is also widely chewed for its presumed central nervous system stimulant and endurance promoting effects. The results of this study revealed valuable evidence concerning the possible use of Grains of Paradise as an affordable natural, alternative, and/or complementary therapy with antioxidative and neuroprotective potentials. Consumption of these seeds in the right quantity might provide health benefits as Grains of Paradise exhibited antidepressant‐like effect via inhibition of oxidative stress and neuroprotection. [ABSTRACT FROM AUTHOR]

A model of psychological intervention for common mental disorders in Primary Care is analized. Two clinical psychologists and four resident psychologists interviewed 566 users to treat mild to moderate anxiety/depression disorders, bereavement or nonorganic insomnia disorders. Standardized assessment leads to a stepped intervention: indication of no treatment, brief group or individual intervention in Primary Care Center (PCC) or referral to Mental Health. Socio-demographic and clinical variables describe the sample and allow comparison betwen groups. Of the 566 interviewees, the mean age was 37 years, 70% were women, 50% with psychopharmacological treatment and 10% on sick leave. The steps of intervention were: 19% were intervention indication of no treatment, 71% PCC intervention and 10% were referred to Mental Health. Adaptive, emotional and generalized anxiety disorders were predominant, with significant differences between centers depending on the location and clinical psychologist integration mode in PCC. Integrating the clinical psychologist in PCC improve access to psychological interventions and reduces mild to moderate mental disorders medication. Assessment prevents unnecessary treatment onset and increases the likelihood of appropriate treatment indications, which is cost-effective. [ABSTRACT FROM AUTHOR]

The objective of this work is to analyze the scientific literature production on borderline personality disorder in Spain over the 2010-2015 period, making a comparative study of articles collected from scientific journals in the field of psychology from several perspectives: year of publication, type of journal (indexing), type of study, clinical sample and main topic. After the analysis of 80 articles obtained in WOS, Scopus, Psicodoc, Dialnet, and ISOC databases, it was found that most analysis units appear in type C and D publications in adult population and in theoretical studies, being the prevailing subject different psychotherapeutic strategies, especially Dialectic-Behavioral and Transference-Focused Therapy, although with increasing trends of new procedures applied to BPD population. The scarcity of publications on topics such as psychopharmacological and etiological studies, design of new measuring instruments, or differential diagnosis deserves special attention. [ABSTRACT FROM AUTHOR]

Rationale: Episodic foresight is a fundamental human capacity. It refers to the ability to simulate future situations and organise current actions accordingly. While there is some evidence that opiate users have a reduced capacity to imagine themselves in future situations, no study to date has assessed whether opiate users show deficits in the ability to take steps in the present in anticipation of future needs. Objective: In this study, we assessed whether this functional aspect of episodic foresight is impaired in chronic opiate users and the extent to which any deficits are associated with executive dysfunction. Methods and results: Participants were 33 long-term opiate users enrolled in an opiate substitution program and 34 controls. Relative to controls, the opiate users displayed significant impairment (medium effect size η = 0.08) in the two behavioural measures of episodic foresight used (items acquired and items used in the VW Foresight task). Furthermore, executive functioning was associated with foresight ability, although this was restricted to items acquired, and the associations were generally stronger for the control group. Conclusions: These data provide important evidence suggesting that the functional aspect of episodic foresight is disrupted in long-term opiate users. While these deficits appear to have some links to impaired executive control, additional work is needed to gain a more complete understanding of the underlying cognitive and neural mechanisms involved. This, in turn, will have important implications for tailoring interventions with opiate users to maximise the likelihood of successful independent functioning. [ABSTRACT FROM AUTHOR]

This manuscript reviews research exploring the relationship between prenatal, perinatal, and adolescent exposure to marijuana and aggressive behavior, including physical aggression. Areas of inquiry include animal research, as well as human research, on prenatal exposure and on marijuana use during adolescence. Potential psychosocial and psychopharmacological mechanisms are identified, as well as relevant confounds. The prenatal marijuana exposure literature provides minimal support for a direct relationship with aggressive behavior in childhood. The adolescent use literature suggests a marginal (at best) association between acute intoxication and aggressive behavior, and an association between chronic use and aggressive behavior heavily influenced by demographic variables, rather than direct, psychopharmacological mechanisms. Cannabis withdrawal symptoms also may include aggression and anger, but there is little evidence to suggest that these effects are large or specific to withdrawal from marijuana compared to other substances. This review will offer recommendations for clinical care and public policy, as well as important questions for future research. [ABSTRACT FROM AUTHOR]

Rationale: Anecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empirical support for these effects is limited, and no previous studies have assessed both acute effects of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as associations with cannabis dependence. Objectives: The objectives of this study were (1) to examine acute effects of cannabis with CBD (Cann + CBD) and without CBD (Cann-CBD) on effort-related decision-making and (2) to examine associations between cannabis dependence, effort-related decision-making and reward learning. Methods: In study 1, 17 participants each received three acute vaporized treatments, namely Cann-CBD (8 mg THC), Cann + CBD (8 mg THC + 10 mg CBD) and matched placebo, followed by a 50 % dose top-up 1.5 h later, and completed the Effort Expenditure for Rewards Task (EEfRT). In study 2, 20 cannabis-dependent participants were compared with 20 non-dependent, drug-using control participants on the EEfRT and the Probabilistic Reward Task (PRT) in a non-intoxicated state. Results: Cann-CBD reduced the likelihood of high-effort choices relative to placebo ( p = 0.042) and increased sensitivity to expected value compared to both placebo ( p = 0.014) and Cann + CBD ( p = 0.006). The cannabis-dependent and control groups did not differ on the EEfRT. However, the cannabis-dependent group exhibited a weaker response bias than the control group on the PRT ( p = 0.007). Conclusions: Cannabis acutely induced a transient amotivational state and CBD influenced the effects of THC on expected value. In contrast, cannabis dependence was associated with preserved motivation alongside impaired reward learning, although confounding factors, including depression, cannot be disregarded. This is the first well powered, fully controlled study to objectively demonstrate the acute amotivational effects of THC. [ABSTRACT FROM AUTHOR]

Rationale: Contextual fear memory depends on the hippocampus, but the role of unilateral hippocampus in this type of memory remains unclear. Objectives: Herein, pharmacological inactivation or excitotoxic lesions were used to study the role of unilateral hippocampus in the stages of contextual fear memory. Results: The pharmacological experiments revealed that compared with the control groups, unilateral hippocampal blockade did not impair 1-day recent memory following learning, whereas bilateral hippocampal blockade significantly impaired this memory. The lesion experiments showed that compared with the control groups, the formed contextual fear memory was retained for 7 days and that 30-day remote memory was markedly reduced in unilateral hippocampal lesion groups. Conclusions: These results indicate that an intact bilateral hippocampus is required for the formation of remote memory and that unilateral hippocampus is sufficient for recent contextual fear memory. [ABSTRACT FROM AUTHOR]

Modern psychopharmacological research in humans focuses on how specific psychoactive molecules modulate oscillatory brain activity. We present state-of-the-art EEG methods applied in a resting-state drug study. Thirty healthy male nonsmokers were randomly allocated either to a nicotine group (14 subjects, 7 mg transdermal nicotine) or a placebo group (16 subjects). EEG activity was recorded in eyes-open (EO) and eyes-closed (EC) conditions before and after drug administration. A source reconstruction (minimum norm algorithm) analysis was conducted within a frequency range of 8.5–18.4 Hz subdivided into three different frequency bands. During EO, nicotine reduced the power of oscillatory activity in the 12.5- to 18.4-Hz frequency band in the left middle frontal gyrus. In contrast, in the EC condition, nicotine reduced the power in the 8.5- to 10.4-Hz frequency band in the superior frontal gyri and in the 10.5- to 12.4-Hz and 12.5- to 18.4-Hz frequency bands in the supplementary motor areas. In summary, nicotine reduced the power of the 12.5- to 18.4-Hz band in the left middle frontal gyrus during EO, and it reduced power from 8.5 to 18.4 Hz in a brain area spanning from the superior frontal gyri to the supplementary motor areas during EC. In conclusion, the results suggest that nicotine counteracts the phenomenon of anteriorization of α activity, hence potentially increasing the level of vigilance. [ABSTRACT FROM AUTHOR]

Background: In view of the well-known increase in prescriptions of stimulants for children and adolescents over the last 20 years, it is important to study trends in the prevalence and incidence of the use of other psychotropic drugs by this age group as well, to enable an early response to potential problems in the current care situation. Methods: We used nationwide data from German statutory health insurance funds (Allgemeine Ortskrankenkasse [AOK], all insurees; Techniker Krankenkasse [TK], a 50% randomized sample) concerning all insurees aged 0-17 years (5.0 million people in 2012) to study trends in the prevalence and incidence of psychotropic medication use as well as initially prescribing medical specialties over the period 2004-2012, both for the overall group of psychotropic drugs and for selected subgroups of drugs. Results: From 2004 to 2012, the prevalence of psychotropic drug prescriptions (not including herbal and homeopathic substances) for children and adolescents rose from 19.6 to 27.1 per 1000 individuals. Marked rises were seen for stimulants (10.5 to 19.1 per 1000) and antipsychotic drugs (2.3 to 3.1 per 1000), while the prevalence of antidepressant prescriptions remained constant at about 2 per 1000. The rates of new prescriptions from 2006 to 2012 were generally constant or decreasing; for the overall group of (non-herbal, non-homeopathic) psychotropic drugs, the rate of new prescriptions fell from 9.9 to 8.7 per 1000. There was a trend toward the issuance of new prescriptions by medical specialists, rather than by family physicians and pediatricians. Conclusion: The observed increased prevalence of psychotropic drug use among children and adolescents appears to be due not to an increased rate of initial prescriptions for these drugs, but rather to a rise in the number of patients who, once having received such drugs, were given further prescriptions for them in the years that followed. [ABSTRACT FROM AUTHOR]

Clonidine, an alpha agonist, formally prescribed in clinical medicine as antihypertensive medication, is currently being used more frequently to address a multitude of psychiatric entities. The long-acting formulation is approved by the Food and Drug Administration for use in treating the attention- deficit/hyperactivity disorder. In addition to this only legitimate indication, it has long been used successfully for opiate detoxification, post-traumatic stress disorder and de la Tourette syndrome. Moreover, clonidine helps in the treatment of neuroleptic-induced akathisia, stimulant-induced insomnia and clozapine-induced sialorrhea. It has been tried in treating menopausal syndrome and psychogenic polydipsia. Although the strength of evidence supporting the use of clonidine in such clinical scenarios is highly variable and oscillating, from strong to only flimsy, this overview is intended to shed some light on the clonidine portfolio as a potential and attractive addition to the psychopharmacologic armamentarium. [ABSTRACT FROM AUTHOR]

The effects of medication on neuropsychological performance have yet to be fully investigated, particularly in older patients. As such, the present case study was undertaken to examine the specific impact of benzodiazepine use on neuropsychological performance by providing a comparison of the test–retest data of an 81-year-old patient taking lorazepam. A comprehensive neuropsychological evaluation was conducted: (a) during the initial referral, while the patient had been taking high doses of lorazepam for approximately 3 years; and (b) 6 months after complete titration, which was 1 year after the initial evaluation. Normative scores derived from the 2 trials were compared via calculation of Reliable Change Indexes. Neuropsychological performance during both evaluations was indicative of dementia, including similar degrees of impairment in delayed memory, verbal fluency, and olfaction. However, scores obtained during the second evaluation were somewhat higher, with significant improvements observed in immediate memory, visuospatial/construction abilities, language function, abstract concept formation, and set shifting. Results of the current case study suggest that several neuropsychological domains may be particularly sensitive to chronic benzodiazepine use. Although the overall diagnostic picture in the present study remained unaltered, clinicians should be cognizant of such medication effects and the potential for these neuropsychological alterations to obscure differential diagnosis. [ABSTRACT FROM PUBLISHER]

BACKGROUND: Split treatment refers to the involvement of 2 mental health professionals in the care of a psychiatric patient--one providing psycho-therapy and the other psychopharmacologic management. Despite the widespread use of split treatment in outpatient psychiatric care, little data exist on its core features or cost-effectiveness compared with other models of treatment. METHODS: We reviewed published studies on split treatment, summarized the research data on split treatment, and created principles to guide its use in practice. RESULTS: Few data-based studies have examined the split treatment model. Both prescribing psychiatrists and psychotherapists have specific and unique concerns and sensitivities in the split model that are likely to affect the overall success of treatment. Among the concerns are respect for the other treating professional, staying within the appropriate boundaries of one's expertise, efficient communication with the co-treater, and parallel accessibility in emergency situations. CONCLUSIONS: Proper application of split care principles is likely to result in a better-coordinated and more effective approach to treatment of psychiatric patients. Recommendations for future research are offered. [ABSTRACT FROM AUTHOR]

Objectives: This concluding commentary offers a brief overview of progress to date in providing telemental health services to children, and then offers a critical vision for future research needed to provide the rigorous empirical foundation for telemental health to be considered a well-established format for the delivery of children's mental health services.Methods: We review how recent years have witnessed advances in the science and practice of children's telemental health, and the articles in this special series collectively offered a critical step forward in the establishment of a guiding literature to provide informed direction for child providers incorporating remote technologies to extend their practices.Results: Researchers must be cautious not to develop a "horse race" mentality and a misguided search for a decisive "winner" regarding the ultimate effectiveness of child telemental health versus traditional clinic-based treatments. Instead, research efforts are needed to examine key mediators and moderators of telemental health treatment response. The question should not be simply whether telemental health strategies are supported, but rather when, under what circumstances, and for whom telemental health formats may be most indicated. Barriers to the continued evolution of children's telemental health are discussed, and we consider issues of telemental health reimbursement and matters of cross-state professional jurisdiction.Conclusions: Continued efforts are needed in order to fully actualize the potential of children's telemental health to optimize the quality and transform the accessibility of mental health services for all children, regardless of income or geography. [ABSTRACT FROM AUTHOR]

Identification and analysis of synthetic cannabinoids (SCs) in biological specimens remains an ongoing challenge for forensic toxicologists. Analytical method development is both resource and time consuming, and falls behind the illicit production of newer SCs. Distinguishing optimal metabolic targets and specific SC use is further complicated by metabolic pathway convergence between different SCs. Gaining further insight into the prevalence and psychopharmacologic role of these drugs in forensic cases, particularly in individuals suspected of driving impaired, is important. The prevalence of SC metabolites (SCMs) in suspects of impaired driving in Washington, DC between June 2012 and August 2013 was studied. A total of 526 urine samples were screened for 12 SCMs by liquid chromatography tandem mass spectrometry in separate duplicate analyses. Nineteen cases (3.6%) confirmed positive for the following SCMs: UR-144 N-pentanoic acid (n = 17;89%), JWH-073 butanoic acid (n = 3;16%), JWH-018 pentanoic acid (n = 3;16%), AM-2201 4-hydroxypentyl (n = 3;16%) and 5-fluoro PB22 3-carboxyindole (n = 1;5%). This study made use of existing analytical methodology to provide insight into the prevalence of synthetic cannabinoid use in DUID cases. Understanding the range and extent of use in these cases can provide valuable information to the forensic community. [ABSTRACT FROM AUTHOR]

Psychotropic properties of CA-7043× and CA-7050×, new fluorinated derivatives of tetrahydrocarbasoles, were examined on outbred CD1 mice and transgenic 5×FAD mice with Alzheimer disease. Both agents exerted cognitive-stimulating and anxiolytic effects in a dose of 5 mg/kg. In the new cage test, they retarded extinction of orientation and exploratory behavior. CA-7043× produced an anxiolytic effect on CD1 mice assessed in the open-field test and exerted cognitive-stimulating action in the new location test. In the same tests, CA-7050× demonstrated the cognitive-stimulating and anxiolytic effects on transgenic 5×FAD mice. [ABSTRACT FROM AUTHOR]

The category of panic disorder was significantly indebted to early psychopharmacological experiments (in the late 1950s and early 1960s) by the psychiatrist Donald Klein, in collaboration with Max Fink. Klein's technique of "psychopharmacological dissection" underpinned his transformation of clinical accounts of anxiety and was central in effecting the shift from agoraphobic anxiety (with its spatial imaginary of city squares and streets) to panic. This technique disaggregated the previously unitary affect of anxiety-as advanced in psychoanalytic accounts-into two physiological and phenomenological kinds. "Psychopharmacological dissection" depended on particular modes of clinical observation to assess drug action and to interpret patient behavior. The "intimate geographies" out of which panic disorder emerged comprised both the socio-spatial dynamics of observation on the psychiatric ward and Klein's use of John Bowlby's model of separation anxiety- as it played out between the dyad of infant and mother-to interpret his adult patients' affectively disordered behavior. This essay, in offering a historical geography of mid-twentieth-century anxiety and panic, emphasizes the importance of socio-spatial setting in understanding how clinical and scientific experimentation opens up new ways in which affects can be expressed, shaped, observed, and understood. [ABSTRACT FROM AUTHOR]

Emerging evidence indicates that treatment context profoundly affects psychopharmacological interventions. We review the evidence for the interaction between drug application and the context in which the drug is given both in human and animal research. We found evidence for this interaction in the placebo response in clinical trials, in our evolving knowledge of pharmacological and environmental effects on neural plasticity, and in animal studies analyzing environmental influences on psychotropic drug effects. Experimental placebo research has revealed neurobiological trajectories of mechanisms such as patients’ treatment expectations and prior treatment experiences. Animal research confirmed that “enriched environments” support positive drug effects, while unfavorable environments (low sensory stimulation, low rates of social contacts) can even reverse the intended treatment outcome. Finally we provide recommendations for context conditions under which psychotropic drugs should be applied. Drug action should be steered by positive expectations, physical activity, and helpful social and physical environmental stimulation. Future drug trials should focus on fully controlling and optimizing such drug × environment interactions to improve trial sensitivity and treatment outcome. [ABSTRACT FROM AUTHOR]

Pharmacological neuroenhancement (PN) describes the use of psychoactive drugs for the purpose of enhancing cognition (e. g., fatigue, concentration, memory etc.) by healthy subjects without medical need. Drugs used for this purpose can be divided into freely available, over the- counter drugs (e. g., methylxanthines such as caffeine), prescription drugs (e. g., antidementia drugs, methylphenidate) and illicit drugs (e. g., illicit amphetamines). Clinical studies have shown that the aforementioned substances only have limited pro-cognitive effects and have considerable safety risks and side effects. The German judicial perspective shows legal differences between substances (drugs, food, food supplements, fortified food) that can be bought in a supermarket, drugs that can be bought in a pharmacy as over-the-counter- (OTC-) drugs, drugs with or without the need for a prescription and illicit drugs. Supermarket drugs and fortified food can be sold freely and follow the general rules of civil and penal law; regarding acquisition, parents are responsible for their children. OTC drugs require special information about therapy. Regarding prescription drugs, there are legal problems caused by an off-label use and the non-medical purposes of PN drugs. Furthermore, prescription stimulants for PN are governed by the specialized law for narcotics, and their use might be punished. Beyond the general lack of rules for regulation for PN drug use there are specific needs for prevention (e. g., control of the black market, etc.). Possible future policy will depend, among others, on the probability with which effective PN drugs with an acceptable risk-benefit ratio will be available, on individual and societal implications, and on public opinion towards PN. While 4 different general policy scenarios can be identified, it is important to advance a broad societal debate on PN to collect relevant empirical data and to address enhancement-related conceptual issues. [ABSTRACT FROM AUTHOR]

Objective: Although direct-to-consumer (DTC) marketing of pharmacologic interventions is effective and common, similar approaches have yet to be evaluated in the promotion of psychological treatments (PTs). This is the first randomized controlled trial evaluating the potential of DTC marketing of PTs. Method: Participants (N = 344; 75.0% female, mean age = 18.6 years, 48.5% non-Hispanic White) were randomly assigned to consume one of four extended commercial campaigns embedded within unrelated programming across 3 weeks. The four campaign conditions were a PT campaign, a PT informing about medication side effects campaign, a medication campaign, and a neutral campaign. Attitudes about and intention to seek psychological treatment were assessed prior to campaign exposure (Tl), 1 week following the final week of campaign exposure (T2), and at a 3-month follow-up evaluation (T3). Results: The percentage of participants who newly intended psychological treatment at T2 or T3 differed by condition, with those assigned to the PT campaign slightly more likely to have intended to receive psychological treatment at T2 or T3 than those in other conditions. Baseline reports of emotional symptoms moderated the effect of condition on attitudes toward PT and perceived likelihood of seeking treatment in the future. Conclusions: Findings support the preliminary utility of DTC marketing of psychological treatments. Increasing consumer knowledge of PTs may be a worthwhile complement to current dissemination and implementation efforts aimed at promoting the uptake of PTs in mental health care. [ABSTRACT FROM AUTHOR]

The article presents a study on the long-term psychopharmacological treatment of children first diagnosed with attention-deficit/hyperactivity disorder (ADHD) as preschoolers. Topics covered include the reassessment of the children who paricipated in the Preschool ADHD Treatment Study (PATS) 3 and 6 years after completion of the study, the medications taken by the children including stimulant monotherapy, atomoxetine and antipsychotics, and the categories of psychiatric medications used.

With increasing life expectancies in most Western populations, the number of people experiencing age-associated cognitive impairment is increasing. Research is needed to identify factors that may help the elderly maintain or even improve cognitive function in the face of advancing age. This review evaluates whether dietary supplementation with natural pharmaceuticals can be used as a means to improve cognitive function or limit cognitive decline. The evidence surrounding popular supplements such as Ginkgo biloba, fish oils, Bacopa monnieri, polyphenol extracts, and vitamins is reviewed briefly. Potential mechanisms of action are also highlighted. This review also discusses challenges surrounding cognitive testing in psychopharmacological research, highlighting discrepancies between the domains of human cognition as described by contemporary models and as measured in clinical trials. [ABSTRACT FROM PUBLISHER]

Effective psychopharmacological medication with good tolerability represents the cornerstone of treatment for severe mental illness; however, the 1-year adherence rates are only approximately 50 %. The term adherence emphasizes the collaborative responsibility of the clinician and the patient for a positive treatment outcome. Reasons for non-adherence are manifold and include patient-specific factors, such as self-stigmatization, lack of social and familial support, cognitive impairment and substance use besides insufficient effectiveness and the occurrence of side effects of the psychotropic drugs. To enhance adherence, both clinician and patient have to fully understand all the reasons for and against adherence to medication before a collaborative decision is made on future long-term treatment. A positive attitude towards medication critically depends on whether patients feel that the medication supports the attainment of the individual goals. [ABSTRACT FROM AUTHOR]

Objective This pilot study compared the pharmacologic treatment history and clinical outcomes observed in pediatric outpatients with psychiatric disorders exposed to drugs of abuse in utero to those of an age-matched, sex-matched and psychiatric disorder-matched, non-drug-exposed group. Methods In this matched cohort study, medical records of children treated at an academic, child and adolescent psychiatry outpatient clinic were reviewed. Children with caregiver-reported history of prenatal drug exposure were compared with a non-drug-exposed control group being cared for by the same providers. Patients were rated with the Clinical Global Impressions-Severity scale (CGI-S) throughout treatment. The changes in pre-treatment and post-treatment CGI-S scores and the total number of medication trials were determined between groups. Results The drug-exposed group ( n = 30) had a higher total number of lifetime medication trials compared with the non-drug-exposed group ( n = 28) and were taking significantly more total medications, at their final assessment. Unlike the non-drug-exposed group, the drug-exposed group demonstrated a lack of clinical improvement. Conclusions These results suggest that in utero drug-exposed children may be more treatment-refractory to or experience greater side effects from the pharmacologic treatment of psychiatric disorders than controls, although we cannot determine if early environment or drugs exposure drives these findings. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Interest in the therapeutic potential of psychedelic substances has recently resumed. During an early phase of human psychedelic research, their therapeutic application in different pathologies had been suggested, and the first evidence for efficacy was provided. The range of recent clinical applications of psychedelics spans from cluster headaches and obsessive-compulsive disorder to addiction and the treatment of fear and anxiety in patients suffering from terminal illness, indicating potentially different therapeutic mechanisms. A variety of approaches in psychotherapy emphasize subjective experiences, such as so-called peak experiences or afterglow phenomena, as differentially mediating therapeutic action. This review aims to re-evaluate earlier and recent concepts of how psychedelic substances may exert beneficial effects. After a short outline of neurophenomenological aspects, we discuss different approaches to how psychedelics are used in psychotherapy. Finally, we summarize evidence for the relationship between subjective experiences and therapeutic success. While the distinction between pharmacological and psychological action obviously cannot be clear-cut, they do appear to contribute differently from each other when their effects are compared with regard to pathologies. [ABSTRACT FROM PUBLISHER]

The opioid receptor antagonist naltrexone is successfully used in the treatment of opioid and alcohol dependence. However, questions have been raised about possible anhedonic side effects, because the opioid system is directly involved in hedonic responses to natural rewarding activities, possibly due to its indirect effects on the striatal dopamine transporter (DAT). In order to test this hypothesis, 30 rats were randomized to either a 10-day treatment with 3 mg/kg short-acting naltrexone or vehicle. No significant differences between the groups were found in striatal DAT availability, cumulative food intake (for 48 or 72 h), body weight gain and abdominal fatpad weight. Thus, the results of this study suggest that (sub)chronic treatment with short-acting naltrexone does not induce possible anhedonic effects. However, it cannot be ruled out the anhedonic effect of naltrexone is only short-lived and thus not detected in the current study. Therefore, future studies are needed to study possible acute anhedonic effects at several time points shortly after short-acting naltrexone administration and to directly compare the possible anhedonic effects of long-acting with those of short-acting opioid antagonists. [ABSTRACT FROM PUBLISHER]

A recent large population study of 130,000 adults in the United States failed to find evidence for a link between psychedelic use (lysergic acid diethylamide, psilocybin or mescaline) and mental health problems. Using a new data set consisting of 135,095 randomly selected United States adults, including 19,299 psychedelic users, we examine the associations between psychedelic use and mental health. After adjusting for sociodemographics, other drug use and childhood depression, we found no significant associations between lifetime use of psychedelics and increased likelihood of past year serious psychological distress, mental health treatment, suicidal thoughts, suicidal plans and suicide attempt, depression and anxiety. We failed to find evidence that psychedelic use is an independent risk factor for mental health problems. Psychedelics are not known to harm the brain or other body organs or to cause addiction or compulsive use; serious adverse events involving psychedelics are extremely rare. Overall, it is difficult to see how prohibition of psychedelics can be justified as a public health measure. [ABSTRACT FROM PUBLISHER]

Panic attacks, a major feature of panic disorder, can be modelled in rats by exposing animals to stimuli that induce escape reactions, such as the elevated T-maze or the activation of the dorsolateral periaqueductal grey. Since the cannabinoid CB1 receptor modulates various types of aversive responses, this study tested the hypothesis that enhancement of endocannabinoid signalling in the dorsolateral periaqueductal grey inhibits panic-like reactions in rats. Local injection of the CB1 agonist, arachidonoyl 2-Chloroethylamide (0.005–0.5 pmol), attenuated the escape response from the open arm of the elevated T-maze, a panicolytic effect. The anandamide hydrolysis inhibitor, URB597 (0.3–3 nmol), did not induce consistent results. In the test of dorsolateral periaqueductal grey stimulation with d,l-homocysteic acid, arachidonoyl 2-Chloroethylamide, at the lowest dose, attenuated the escape reaction. The highest dose of URB597 also inhibited this response, contrary to the result obtained in the elevated T-maze. This effect was reversed by the CB1 antagonist, AM251 (100 pmol). The present results confirm the anti-aversive property of direct CB1 receptor activation in the dorsolateral periaqueductal grey. The effect of the anandamide hydrolysis inhibitor, however, could be detected only in a model employing direct stimulation of this structure. Altogether, these results suggest that anandamide signalling is recruited only under certain types of aversive stimuli. [ABSTRACT FROM PUBLISHER]

Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions. Participants’ responses to psilocybin were qualitatively similar to those described in other populations. Abstinence did not increase significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p < 0.05). Gains were largely maintained at follow-up to 36 weeks. The intensity of effects in the first psilocybin session (at week 4) strongly predicted change in drinking during weeks 5–8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5. There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled trials with larger samples to investigate efficacy and mechanisms.TRIAL REGISTRATION: NCT02061293 [ABSTRACT FROM PUBLISHER]

Serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitors (SSRI) are the first-line recommended drug treatments for post-traumatic stress disorder (PTSD); but despite their benefits, much residual pathology remains and no new drugs have yet emerged with a clearly demonstrated benefit for treating the disorder. A case is made that tricyclic drugs deserve a closer look, based on their ability to affect several of the main neurotransmitters that are relevant to PTSD. Their promising efficacy, which was shown 30 years ago, had not been followed up, until a recent trial of desipramine found advantages over a SSRI in PTSD with comorbid alcohol dependence. Opportunities exist for studying newer and purportedly safer tricyclic formulations, as well as further the work with older, established compounds. A reappraisal of their risk:benefit ratio seems in order, when treating PTSD. [ABSTRACT FROM PUBLISHER]

Background Affective disorders are associated with an increased risk of cardiovascular disease, which, at least partly, appears to be independent of psychopharmacological treatments used to manage these disorders. Reduced heart rate variability (SDNN) and a low Omega-3 Index have been shown to be associated with increased risk for death after myocardial infarction. Therefore, we set out to investigate heart rate variability and the Omega-3 Index in euthymic patients with bipolar disorders. Methods We assessed heart rate variability (SDNN) and the Omega-3 Index in 90 euthymic, mostly medicated patients with bipolar disorders (Bipolar-I, Bipolar-II) on stable psychotropic medication, free of significant medical comorbidity and in 62 healthy controls. Heart rate variability was measured from electrocardiography under a standardized 30 minutes resting state condition. Age, sex, BMI, smoking, alcohol consumption and caffeine consumption as potential confounders were also assessed. Results Heart rate variability (SDNN) was significantly lower in patients with bipolar disorders compared to healthy controls (35.4 msec versus 60.7 msec; P < 0.0001), whereas the Omega-3 Index did not differ significantly between the groups (5.2% versus 5.3%). In a linear regression model, only group membership (patients with bipolar disorders versus healthy controls) and age significantly predicted heart rate variability (SDNN). Conclusion Heart rate variability (SDNN) may provide a useful tool to study the impact of interventions aimed at reducing the increased risk of cardiovascular disease in euthymic patients with bipolar disorders. The difference in SDNN between cases and controls cannot be explained by a difference in the Omega-3 Index. [ABSTRACT FROM AUTHOR]

Objective TNF system (TNF and its soluble receptors sTNFR1 and 2) has been investigated as a potential molecular target in bipolar disorder. The aim of the study was to compare plasma levels of these receptors in unmedicated bipolar depressed patients compared with healthy controls, and to evaluate the effects of a 6-week lithium treatment on sTNFR1 and sTNFR2 levels. Methods The study enrolled 29 patients with unmedicated bipolar disorder in a major depressive episode and 27 matched controls. Patients had blood collected at baseline and after 6 weeks of lithium treatment. The concentration of sTNFRs was measured by ELISA. Results sTNFR1 and sTNFR2 levels were significantly increased in bipolar depression in comparison with healthy subjects. Lithium treatment did not significantly change sTNFR1 and sTNFR2 levels from baseline to endpoint. There was no correlation between improvement in depressive symptoms and the change in sTNFR1 or sTNFR1 levels. Conclusion These results reinforce the involvement of an activated immune response system in the pathophysiology of bipolar disorder, with no impact of lithium treatment on the related biomarkers. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background Oxidative stress-induced damage may be involved in tardive dyskinesia (TD) development. Superoxide dismutase (SOD), the key antioxidant enzyme, was found abnormal in TD. Objective We examined the role of oxidative stress in relation to TD and TD subtypes in schizophrenia using manganese SOD (MnSOD) as the biomarker. Methods We recruited 152 male chronic patients with ( n = 76) and without TD ( n = 76) meeting Diagnostic and Statistical Manual of Mental Disorders-IV criteria for schizophrenia and 75 male control subjects. We examined the MnSOD activity for all subjects. Positive and Negative Syndrome Scale and the Abnormal Involuntary Movement Scale (AIMS) were assessed in the patients. Results Manganese SOD activity was lower in patients with TD than non-TD ( p < 0.05). In the patients with TD, orofacial and total scores of AIMS were positively associated with MnSOD levels (both p < 0.05). Multiple regression analysis further confirmed that MnSOD was an independent contributor to both the orofacial and the total scores of AIMS (both p < 0.05). Conclusions Oxidative stress reflected by compromised oxidative defense may play a role in the development and severity of TD. There may be an etiologic relationship between increased SOD level and dyskinetic movements associated with TD. In particular, MnSOD activity may have a specific role in orofacial TD. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective The study evaluated relationships between frontal lobe function in patients with schizophrenia and both their social adjustment and medication, using 22-channel near-infrared spectroscopy (NIRS). Methods One hundred ninety-nine stable patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision schizophrenia, whose medication had not been changed within the preceding 3 months and who were able to visit our clinics for NIRS, were the study subjects. As a comparator, 144 healthy volunteers who underwent a physical examination and the Mini-International Neuropsychiatric Interview also received NIRS. Results The main outcomes evaluated were frontal lobe oxyhemoglobin concentration (OxHb) measured by NIRS, current medication, social adjustment, and scores on the Brief Psychiatric Rating Scale. The OxHb in schizophrenic patients (0.878 ± 1.1801 mMmm; n = 199) was significantly lower than that in the healthy volunteers (2.085 ± 1.7480 mM mm: n = 100) ( p < 0.001). NIRS-measured OxHb values reflected disease severity and degree of social adjustment in schizophrenic patients. Conclusions Patients with higher OxHb values were socially better adjusted than those with lower OxHb values. Patients treated with atypical antipsychotic monotherapy showed lower treatment resistance and better social adjustment than those treated with combination therapy. © 2014 The Authors. Human Psychopharmacology: Clinical and Experimental published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective Few studies have compared simultaneously different antidepressants in long-term treatment of major depressive disorder (MDD). Long-term prevention of recurrences should be the main goal of MDD treatment. The purpose of this study was to compare antidepressants of different pharmacological classes in terms of retention in treatment (no discontinuation for recurrences, hospitalizations, side effects). Methods One hundred and fifty outpatients with an MDD diagnosis, treated with antidepressants in mono-therapy, were included. Follow-up period was set at 24 months, and information have been obtained from charts, interviews with patients and their relatives, and from the Lombardy regional register. A survival analysis (Kaplan-Meier) was performed, considering recurrences, hospitalizations, or discontinuation due to side effects as 'death' events. Results In our sample, 48.7% of the patients presented a recurrence within the first 2 years of treatment. Bupropion appears less effective in long-term treatment of MDD than the other compared antidepressants, with exception of fluoxetine ( p = 0.09), amitriptyline ( p = 0.13), fluvoxamine ( p = 0.83), venlafaxine ( p = 0.5), and trazodone ( p = 0.58). Fluvoxamine appears to be less effective than citalopram ( p = 0.036), paroxetine ( p = 0.037), clomipramine ( p = 0.05), sertraline ( p = 0.011), and duloxetine ( p = 0.024). Conclusions Bupropion and fluvoxamine appear less effective in long-term treatment of MDD. These results should be confirmed by randomized placebo-controlled prospective studies with larger samples. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective To determine the past-year prevalence rates and correlates of simultaneous co-ingestion of prescription stimulants and other substances among US high school seniors. Methods Nationally representative probability samples of US high school seniors were surveyed as a part of the Monitoring the Future study. The sample consisted of five cohorts including a total of 12 431 high school seniors (modal age: 18 years) and represented a population that was 53% female. Results Among past-year nonmedical users of prescription stimulants ( n = 835), the estimated prevalence of any past-year simultaneous co-ingestion of prescription stimulants and other substances was 64.4%. The substances most commonly co-ingested with prescription stimulants included marijuana (51.1%) and alcohol (48.4%). Nonmedical users who co-ingested prescription stimulants with other substances were more likely to report non-oral routes of administration, recreational motives and greater subjective high when using prescription stimulants than nonmedical users who did not co-ingest prescription stimulants with other substances. Conclusions The majority of past-year nonmedical users of prescription stimulants reported simultaneous co-ingestion of prescription stimulants and other substances. The findings indicate that co-ingestion of prescription stimulants and other substances is a pervasive behavior among US adolescents who engage in nonmedical use of prescription stimulants and should be carefully considered in future clinical practice and research. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Rationale: The cAMP-dependent protein kinase A (PKA) signaling transduction pathway has been shown to play an important role in the modulation of several ethanol-induced behaviors. Different studies have demonstrated intracellular calcium (Ca)-dependent activation of the PKA cascade after ethanol administration. Thus, the cAMP cascade mediator Ca-dependent calmodulin (CaM) has been strongly implicated in the central effects of ethanol. Objectives: In this study, we assessed the role of the CaM inhibitor W7 on ethanol-induced stimulation, ethanol intake, and ethanol-induced activation of PKA. Methods: Swiss mice were pretreated with W7 (0-10 mg/kg) 30 min before ethanol (0-3.75 g/kg) administration. Immediately, animals were placed during 20 min in an open-field chamber. Ethanol (10 %, v/ v) intake in 2 h was assessed using a limited access paradigm. Experiments with caffeine (0-15 mg/kg), cocaine (0-4 mg/kg), and saccharine (0.1 %, w/ v) were designed to compare their results to those obtained with ethanol. Western blot was assayed 45 min after ethanol administration. Results: Results showed that pretreatment with W7, reduced selectively in a dose-dependent fashion ethanol-induced locomotor stimulation and ethanol intake. The ethanol-induced activation of PKA was also prevented by W7 administration. Conclusions: These results demonstrate that CaM inhibition resulted in a selective reduction of ethanol-stimulating effects and ethanol intake. The PKA activation induced by ethanol was blocked after the CaM blockade with W7. These results provide further evidence of the key role of cellular Ca-dependent pathways on the central effects of ethanol. [ABSTRACT FROM AUTHOR]

Rationale: Effective functioning of the neurotransmitter serotonin is important for optimal cognitive and emotional function. Dietary supplements able to increase availability to the brain of the precursor amino acid, tryptophan (TRP), and thereby enhance serotonin synthesis, can have measurable impact on these psychological processes. Objectives: This study involves a randomised controlled trial of a TRP-rich egg-white protein hydrolysate (DSM Nutritional Products Ltd., Switzerland) on plasma amino acids, cognition, mood and emotional processing in older women. Methods: Following a baseline test day without treatment, 60 healthy women aged 45-65 years received drinks containing either 2 or 4 g of TRP-rich protein hydrolysate product or 3.11 g casein hydrolysate as a control. One hour later, they undertook a 2-h battery of cognitive and emotional tests. Results: The TRP-rich protein hydrolysate produced the expected dose-dependent increase in the ratio of plasma TRP to competing large neutral amino acids. TRP-rich protein hydrolysate (2 g only) prevented both the decline in wellbeing and increase in fatigue seen over the test session in the control group. This treatment dose resulted in a significant shift in emotional processing towards positive words and reduced negative bias in assessing negative facial expressions. Effects on cognition were small and not statistically reliable and are not reported here. However, there was no evidence for any adverse effects. Conclusions: Consumption of a low dose of TRP-rich protein hydrolysate may have beneficial effects on emotional function that could promote feelings of wellbeing, possibly conferring resistance to deterioration in mood in healthy subjects or depressive episodes. [ABSTRACT FROM AUTHOR]

Rationale: An increase in the potency of the cannabis cigarettes has been observed over the past three decades. Objectives: In this study, we aimed to establish the impact of Δ9-tetrahydrocannabinol (THC) on the rating of subjective effects (intensity and duration of the effects), up to 23 % THC potency (69 mg THC) among recreational users. Methods: Recreational users ( N = 24) smoked cannabis cigarettes with four doses of THC (placebo 29, 49 and 69 mg of THC) on four separate test days in a randomized, double-blind, placebo-controlled, crossover study. The participants filled in three different questionnaires measuring subjective effects during the exposure up to 8 h post-smoking. The 'high' feeling, heart rate, blood pressure and THC serum concentrations were also regularly recorded during these 8 h. Results: THC significantly increased the high feeling, dizziness, dry-mouthed feeling, palpitations, impaired memory and concentration, and 'down', 'sedated' and 'anxious' feelings. In addition, THC significantly decreased alertness, contentment and calmness. A cubic relationship was observed between 'feeling the drug' and 'wanting more'. The THC-induced decrease in 'feeling stimulated' and increase in anxiety lasted up to 8 h post-smoking. Sedation at 8 h post-smoking was increased by a factor of 5.7 with the highest THC dose, compared to the placebo. Conclusions: This study shows a strong effect of cannabis containing high percentages of THC on the rating of subjective effects. Regular users and forensic toxicologists should be aware that the THC-induced increase in 'feeling sedated' continues longer with a 69 mg THC dose than with a 29 mg THC dose. [ABSTRACT FROM AUTHOR]

Rationale: Opioid antagonism reduces the consumption of palatable foods in humans but the neural substrates implicated in these effects are less well understood. Objectives: The aim of the present study was to examine the effects of the opioid antagonist, naltrexone, on neural response to rewarding and aversive sight and taste stimuli. Methods: We used functional magnetic resonance imaging (fMRI) to examine the neural responses to the sight and taste of pleasant (chocolate) and aversive (mouldy strawberry) stimuli in 20 healthy volunteers who received a single oral dose of naltrexone (50 mg) and placebo in a double-blind, repeated-measures cross-over, design. Results: Relative to placebo, naltrexone decreased reward activation to chocolate in the dorsal anterior cingulate cortex and caudate, and increased aversive-related activation to unpleasant strawberry in the amygdala and anterior insula. Conclusions: These findings suggest that modulation of key brain areas involved in reward processing, cognitive control and habit formation such as the dorsal anterior cingulate cortex (dACC) and caudate might underlie reduction in food intake with opioid antagonism. Furthermore we show for the first time that naltrexone can increase activations related to aversive food stimuli. These results support further investigation of opioid treatments in obesity. [ABSTRACT FROM AUTHOR]

Rationale: Adverse early life experiences are risk factors for drug abuse and addiction. Changes in brain opioid systems have been demonstrated in response to neonatal visceral pain (NVP), but the impact of these changes on abuse-related effects of morphine are unknown. The NVP procedure used models chronic visceral hyperalgesia persisting across development. Objectives: Intravenous self-administration, drug discrimination, and locomotor activity were used to compare the abuse-related effects of morphine in NVP and control rats. Methods: Rats self-administered 0.3 mg/kg/inj morphine under an FR1 schedule, and dose-effect functions for morphine were then established. Separate rats were trained to discriminate 3.2 mg/kg morphine from saline under an FR20 schedule, and morphine dose-effect functions were then determined in the absence and presence of 0.1 mg/kg naltrexone. A third group of rats was tested with a range of morphine doses in an assay of locomotor activity, then injected daily with 10 mg/kg morphine to assess locomotor sensitization. Results: NVP rats self-administered more morphine than controls at reinforcing doses. Discriminative stimulus effects of morphine were similar between groups, but in the presence of naltrexone, the ED for morphine was more than 12× greater in control rats than in NVP animals. Morphine did not stimulate locomotor activity at any tested dose in NVP rats, although significant effects were observed in controls. Finally, significant locomotor sensitization was observed only in NVP rats. Conclusions: NVP-induced changes in brain opioid systems have persistent pharmacological consequences into adulthood and may increase sensitivity to abuse-related effects of opioids across development. [ABSTRACT FROM AUTHOR]

Rationale: Modulation of the endocannabinoid system has been found to interfere with opiate withdrawal. The potential of activation and blockade of the endocannabinoid system to prevent the aversive-affective state of naloxone-precipitated morphine withdrawal (MWD) was investigated in a one-trial conditioned place aversion (CPA) paradigm. Objective: CPA provides a sensitive measure of the motivational effects of acute MWD. The potential of the fatty acid amide hydrolase (FAAH) inhibitors, URB597 and PF-3845, the CB antagonist/inverse agonist, AM251, and the neutral CB antagonists, AM4113 and AM6527 (oral), to interfere with establishment of a MWD-induced CPA was investigated. As well, the potential of AM251 and AM4113 to interfere with reinstatement of a previously established MWD-induced CPA was investigated. Materials and methods: Using a one-trial place conditioning paradigm, rats were administered naloxone (1 mg/kg, subcutaneous (sc)) 24 h after receiving a high dose of morphine (20 mg/kg, sc) and were placed on the conditioning floor. To determine the effect of each pretreatment drug on the establishment of the MWD-induced CPA, URB597 (0.3 mg/kg, intraperitoneally (ip)), PF-3845 (10 mg/kg, ip), AM251 (1 or 2.5 mg/kg, ip), AM4113 (1 or 2.5 mg/kg, ip), and AM6527 (5 mg/kg, oral) were administered prior to conditioning. Results: AM251 (2.5, but not 1 mg/k), AM4113, and AM6527, but not URB597 or PF-3845, interfered with the establishment of the MWD-induced CPA. AM251 and AM4113 did not prevent reinstatement of the CPA. Conclusions: Neutral antagonism of the CB receptor reduces the aversive affective properties of morphine withdrawal. [ABSTRACT FROM AUTHOR]

Rationale: Recent case reports describe recreational use of quetiapine and drug-seeking behaviour to obtain quetiapine, an atypical antipsychotic. Objective: We examined the hypothesis that quetiapine (10, 20 or 40 mg/kg) alone or co-administered with (+)-amphetamine (0.25, 0.5, 0.75 or 2.0 mg/kg) will affect reward and/or decrease anxiety in rats, as measured by conditioned place preference (CPP) and elevated plus maze (EPM) test, respectively. Results: Quetiapine (20 mg/kg) produced greater open arm time and entries in the EPM test compared to 10 and 40 mg/kg, and quetiapine (10 mg/kg) significantly increased open arm entries and time when co-administered with (+)-amphetamine (0.5 mg/kg) compared to (+)-amphetamine (0.5 mg/kg) alone, suggesting decreased anxiety. Quetiapine (10, 20 or 40 mg/kg) produced no CPP when administered alone; the lowest dose of quetiapine (10 mg/kg) reduced CPP produced by a low dose of (+)-amphetamine (0.25 mg/kg), but had no significant effect on CPP produced by a higher dose (0.5 mg/kg). Discussion: The quetiapine-induced anxiolytic effect in the EPM might explain why humans are misusing quetiapine and combining it with (+)-amphetamine. It is possible that humans experience an anxiolytic effect of the combined drugs and relatively unaltered rewarding effects of (+)-amphetamine. The results shed some light on the question of why humans are abusing and misusing quetiapine, despite its dopamine (DA) D receptor antagonism; it will be the task of future studies to identify the pharmacological mechanism mediating this behaviour. [ABSTRACT FROM AUTHOR]

Rationale: Previous studies have shown the beneficial effects of enriched environment (EE) in rescuing behavioral deficits such as pre-pulse inhibition and locomotor hyperactivity associated with N-methyl-D-aspartate (NMDA) receptor blockade; however, cognitive deficits remain unresponsive. Objectives: We designed experiments to determine the consequences of raising rat pups in an EE on several behavioral aberrations, mainly cognitive deficits, observed in rats postnatally exposed to MK-801 (NMDA receptor antagonist). Methods: Male Wistar rats were injected with MK-801 (1 mg/kg) from postnatal day (P) 6-10. Rat pups were housed in an EE from birth up to the time of behavioral experiments at P28-34. The effects of EE in correcting MK-801-associated behaviors were assessed by rotarod, wire grip, open filed, and Morris water maze tests. Results: We found that EE not only has beneficial effects on cognitive performance of normal rats but also prevents spatial learning and memory deficits in Morris water maze induced by MK-801. Postnatal MK-801 treatment also led to motor deficits both in wire grip and accelerating rotarod tests. These deficits were not observed in MK-801-treated rats raised in EE. In the open field test, EE prevented increase in 'frequency of grooming' and decrease in 'time spent in the center' associated with MK-801. Conclusions: Our results suggest that exposure to an EE would be strongly beneficial in correcting deficits, notably cognitive, associated with MK-801. Given that the postnatal MK-801 treatment represents an animal model of schizophrenia, we propose timely environmental interventions might be an effective strategy in the protection against schizophrenia. [ABSTRACT FROM AUTHOR]

Rationale: The aberrant regulation of serotonin (5-HT) and dopamine (DA) in the brain has been implicated in neuropsychiatric disorders associated with marked impairments in empathy, such as schizophrenia and autism. Many psychiatric drugs bind to both types of receptors, and the anterior cingulate cortex (ACC) is known to be centrally involved with empathy. However, the relationship between the 5-HT/DA system in the ACC and empathic behavior is not yet well known. Objectives: We investigated the role of 5-HT/DA in empathy-like behavior and in the regulation of ACC neural activity. Methods: An observational fear learning task was conducted following microinjections of 5-HT, DA, 5-HT and DA, methysergide (5-HT receptor antagonist), SCH-23390 (DA D receptor antagonist), or haloperidol (DA D receptor antagonist) into the mouse ACC. The ACC neural activity influenced by 5-HT and DA was electrophysiologically characterized in vitro and in vivo. Results: The microinjection of haloperidol, but not methysergide or SCH-23390, decreased the fear response of observing mice. The administration of 5-HT and 5-HT and DA together, but not DA alone, reduced the freezing response of observing mice. 5-HT enhanced delta-band activity and reduced alpha- and gamma-band activities in the ACC, whereas DA reduced only alpha-band activity. Based on entropy, reduced complexity of ACC neural activity was observed with 5-HT treatment. Conclusions: The current results demonstrated that DA D receptors in the ACC are required for observational fear learning, whereas increased 5-HT levels disrupt observational fear and alter the regularity of ACC neural oscillations. [ABSTRACT FROM AUTHOR]

Rationale: Although newer interview methods such as Structured Interview Guide for the Montgomery-Asberg Depression Rating Scale (SIGMA; MADRS) with audiotaping and Rater Applied Performance Scale (RAPS) appraisal have been introduced to improve reliability of ratings in antidepressant clinical trials, there is limited evidence that these methods actually improve trial outcome. Objective: The objective of this study uis to evaluate outcome in four similarly designed trials of two recently approved antidepressants: two trials randomly used taped SIGMA interviews with RAPS appraisal and two trials used traditional semi-structured MADRS interviews. Methods: We reviewed data from patients who were screened ( N = 243) and randomized ( N = 148), evaluating the magnitude of change with placebo and antidepressants on mean total MADRS score. Results: Depressed patients assigned to placebo in trials using taped SIGMA interviews with RAPS appraisal had a significantly larger MADRS change score ( M = −11.5 ± 12.7) compared to patients assigned to placebo in trials using traditional semi-structured interviews (−5.4 ± 8.9; F( df = 1.57) = 5.58, p = 0.022). The error variance was also significantly larger in the placebo arm of trials using SIGMA interviews ( F = 5.43, p = 0.023). Depressed patients assigned to antidepressants had similar outcome in all of the four trials. Conclusion: The recently suggested modifications in obtaining clinical data in antidepressant trials such as taped SIGMA interviews with RAPS rating appraisals may in fact result in a higher magnitude of placebo response and a lower magnitude of antidepressant-placebo differences compared to the traditional methods of collecting clinical data. These results were unexpected and indicate the necessity to test new methods prospectively, no matter how intuitively sensible they seem, prior to their implementation. [ABSTRACT FROM AUTHOR]