Showing papers in "Journal of Psychopharmacology in 2014"
TL;DR: An open-label pilot study administering moderate and high psilocybin doses within a structured 15-week smoking cessation treatment protocol demonstrated that 12 of 15 participants showed seven-day point prevalence abstinence at 6-month follow-up, substantially exceeds rates commonly reported for other behavioral and/or pharmacological therapies.
Abstract: Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, rigorous follow-up has not been conducted. To determine the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an open-label pilot study administering moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin within a structured 15-week smoking cessation treatment protocol. Participants were 15 psychiatrically healthy nicotine-dependent smokers (10 males; mean age of 51 years), with a mean of six previous lifetime quit attempts, and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake. Biomarkers assessing smoking status, and self-report measures of smoking behavior demonstrated that 12 of 15 participants (80%) showed seven-day point prevalence abstinence at 6-month follow-up. The observed smoking cessation rate substantially exceeds rates commonly reported for other behavioral and/or pharmacological therapies...
539 citations
University of Cape Town1, University of Southampton2, University of Manchester3, Imperial College London4, Karolinska Institutet5, University of Göttingen6, University of Groningen7, Centre for Addiction and Mental Health8, University of Hertfordshire9, National Institutes of Health10, North Bristol NHS Trust11, University of London12, Newcastle University13, Leiden University14, Dresden University of Technology15
TL;DR: This revision of the 2005 British Association for Psychopharmacology guidelines for the evidence-based pharmacological treatment of anxiety disorders provides an update on key steps in diagnosis and clinical management, including recognition, acute treatment, longer-term treatment, combination treatment, and further approaches for patients who have not responded to first-line interventions.
Abstract: This revision of the 2005 British Association for Psychopharmacology guidelines for the evidence-based pharmacological treatment of anxiety disorders provides an update on key steps in diagnosis and clinical management, including recognition, acute treatment, longer-term treatment, combination treatment, and further approaches for patients who have not responded to first-line interventions. A consensus meeting involving international experts in anxiety disorders reviewed the main subject areas and considered the strength of supporting evidence and its clinical implications. The guidelines are based on available evidence, were constructed after extensive feedback from participants, and are presented as recommendations to aid clinical decision-making in primary, secondary and tertiary medical care. They may also serve as a source of information for patients, their carers, and medicines management and formulary committees.
475 citations
TL;DR: It is concluded that ketamine challenge is useful for studying the positive, negative, and cognitive symptoms, dopaminergic and GABAergic dysfunction, age of onset, functional dysconnectivity, and abnormal cortical oscillations observed in acute schizophrenia.
Abstract: The observation that antagonists of the N-methyl-D-aspartate glutamate receptor (NMDAR), such as phencyclidine (PCP) and ketamine, transiently induce symptoms of acute schizophrenia had led to a paradigm shift from dopaminergic to glutamatergic dysfunction in pharmacological models of schizophrenia. The glutamate hypothesis can explain negative and cognitive symptoms of schizophrenia better than the dopamine hypothesis, and has the potential to explain dopamine dysfunction itself. The pharmacological and psychomimetic effects of ketamine, which is safer for human subjects than phencyclidine, are herein reviewed. Ketamine binds to a variety of receptors, but principally acts at the NMDAR, and convergent genetic and molecular evidence point to NMDAR hypofunction in schizophrenia. Furthermore, NMDAR hypofunction can explain connectional and oscillatory abnormalities in schizophrenia in terms of both weakened excitation of inhibitory -aminobutyric acidergic (GABAergic) interneurons that synchronize cortical networks and disinhibition of principal cells. Individuals with prenatal aberrations of NMDAR might experience the onset of schizophrenia towards the completion of synaptic pruning in adolescence, when network connectivity drops below a critical value. We conclude that ketamine challenge is useful for studying the positive, negative, and cognitive symptoms, dopaminergic and GABAergic dysfunction, age of onset, functional dysconnectivity, and abnormal cortical oscillations observed in acute schizophrenia.
243 citations
TL;DR: The findings point to a possible effect of CBD in improving quality of life measures in PD patients with no psychiatric comorbidities; however, studies with larger samples and specific objectives are required before definitive conclusions can be drawn.
Abstract: Introduction:Parkinson’s disease (PD) has a progressive course and is characterized by the degeneration of dopaminergic neurons. Although no neuroprotective treatments for PD have been found to dat...
241 citations
TL;DR: The present guidelines summarise current literature, generating expert consensus recommendations for the treatment of ADHD in children and adults, and provide a review of recent research in the fields of neuroimaging, neuropsychology and genetics of ADHD.
Abstract: Attention deficit hyperactivity disorder (ADHD) is a common condition with a high societal burden. The present guidelines summarise current literature, generating expert consensus recommendations for the treatment of ADHD in children and adults. These guidelines also provide a review of recent research in the fields of neuroimaging, neuropsychology and genetics of ADHD. Novel discoveries in these areas have informed physiological models for the disease. Since the publication of the previous British Association for Psychopharmacology guidelines in 2008, new drugs have been licensed and further compounds are being investigated. The publication of randomised controlled trials of psychological interventions has contributed to the range of treatment options for ADHD. As the disorder has been diagnosed more frequently there has been greater focus on comorbid conditions and how they impact treatment. Services have continued to develop for the treatment of ADHD in adults and care agreements have been introduced to facilitate access to treatment.
235 citations
TL;DR: This small, open label naturalistic study shows that up to six low dose ketamine infusions can safely be given within an existing NHS clinical structure to patients who continue their antidepressants.
Abstract: Background:Ketamine has a rapid antidepressant effect in treatment-resistant depression (TRD). The effects on cognitive function of multiple ketamine infusions and of concurrent antidepressant medi...
139 citations
TL;DR: The NBOMe drugs have emerged recently, are frequently bought using the internet and have similar effects to other hallucinogenic drugs; however, they may pose larger risks, due to the limited knowledge about them, their relatively low price and availability via the internet.
Abstract: The NBOMe compounds are a novel series of hallucinogenic drugs that are potent agonists of the 5-HT2A receptor, have a short history of human consumption and are available to buy online, in most countries. In this study, we sought to investigate the patterns of use, characteristics of users and self-reported effects. A cross-sectional anonymous online survey exploring the patterns of drug use was conducted in 2012 (n = 22,289), including questions about the use of 25B-NBOMe, 25C-NBOMe, and 25I-NBOMe and comparison drugs. We found that 2.6% of respondents (n = 582) reported having ever tried one of the three NBOMe drugs and that at 2.0%, 25I-NBOMe was the most popular (n = 442). Almost all (93.5%) respondents whose last new drug tried was a NBOMe drug, tried it in 2012, and 81.2% of this group administered the drug orally or sublingually/buccally. Subjective effects were similar to comparison serotonergic hallucinogens, though higher ‘negative effects while high’ and greater ‘value for money’ were reported...
117 citations
TL;DR: In a subgroup analysis of patients with high/very high drinking risk levels at screening and at randomisation (the target population), there was a significant effect in favour of nalmefene on TAC at month 6, and on both HDD and Tac at month 13.
Abstract: This study evaluated the long-term efficacy and safety of nalmefene treatment in reducing alcohol consumption. We randomised (1:3) 675 alcohol-dependent patients ≥ 18 years of age to 52 weeks of as-needed treatment with placebo or nalmefene 18 mg/day: A total of 112 patients (68%) in the placebo group and 310 (62%) in the nalmefene group completed the study. At month 6, the co-primary outcome variables showed no statistically-significant differences between the treatment groups; but at month 13, nalmefene was more effective than placebo, both in the reduction of the number of heavy drinking days (HDDs) (- 1.6 days/month (95% CI - 2.9; - 0.3); p = 0.017) and the reduction of total alcohol consumption (TAC) (- 6.5 g/day last month (95% CI - 12.5; - 0.4); p = 0.036). In a subgroup analysis of patients with high/very high drinking risk levels at screening and at randomisation (the target population), there was a significant effect in favour of nalmefene on TAC at month 6, and on both HDD and TAC at month 13. Improvements in Clinical Global Impression and liver enzymes were greater with nalmefene, compared to placebo. Most adverse events were mild or moderate, and transient; adverse events, including those leading to dropout, were more common with nalmefene. This study provides evidence for the long-term safety and efficacy of nalmefene as-needed in alcohol-dependent patients whom continue to drink heavily, following a brief intervention.
112 citations
TL;DR: Effects on emotion recognition and emotional empathy were evident at a low dose of MDMA and likely contribute to the popularity of the drug.
Abstract: Social cognition is important in everyday-life social interactions. The social cognitive effects of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and methylphenidate (both used for neuroenhancement and as party drugs) are largely unknown. We investigated the acute effects of MDMA (75 mg), methylphenidate (40 mg) and placebo using the Facial Emotion Recognition Task, Multifaceted Empathy Test, Movie for the Assessment of Social Cognition, Social Value Orientation Test and the Moral Judgment Task in a cross-over study in 30 healthy subjects. Additionally, subjective, autonomic, pharmacokinetic, endocrine and adverse drug effects were measured. MDMA enhanced emotional empathy for positive emotionally charged situations in the MET and tended to reduce the recognition of sad faces in the Facial Emotion Recognition Task. MDMA had no effects on cognitive empathy in the Multifaceted Empathy Test or social cognitive inferences in the Movie for the Assessment of Social Cognition. MDMA produced subjective 'empathogenic' effects, such as drug liking, closeness to others, openness and trust. In contrast, methylphenidate lacked such subjective effects and did not alter emotional processing, empathy or mental perspective-taking. MDMA but not methylphenidate increased the plasma levels of oxytocin and prolactin. None of the drugs influenced moral judgment. Effects on emotion recognition and emotional empathy were evident at a low dose of MDMA and likely contribute to the popularity of the drug.
110 citations
TL;DR: The preliminary data that obesity is associated with blunted dopamine release is provided and the positive correlation between dopamine release and food craving in obesity may seem contradictory with the latter finding but is presumably related to heterogeneity within the obese subjects.
Abstract: Introduction:The neurotransmitter dopamine is important in the regulation of food intake. It is hypothesised that obese people experience less reward from food due to lower striatal dopamine releas...
78 citations
TL;DR: Investigation of how modulation of the opioid system, via use of MOP (mu), DOP (delta) and KOP (kappa) agents, restores the balance of a dysregulated system in alcohol dependence should increase insight into this disease process and therefore guide better methods for understanding and treating alcohol dependence in the future.
Abstract: The role of the brain opioid system in alcohol dependence has been the subject of much research for over 25 years. This review explores the evidence: firstly describing the opioid receptors in terms of their individual subtypes, neuroanatomy, neurophysiology and ligands; secondly, summarising emerging data from specific neurochemical, behavioural and neuroimaging studies, explaining the characteristics of addiction with a focus on alcohol dependence and connecting the opioid system with alcohol dependence; and finally reviewing the known literature regarding opioid antagonists in clinical use for alcohol dependence. Further interrogation of how modulation of the opioid system, via use of MOP (mu), DOP (delta) and KOP (kappa) agents, restores the balance of a dysregulated system in alcohol dependence should increase our insight into this disease process and therefore guide better methods for understanding and treating alcohol dependence in the future.
TL;DR: Results indicate that vortioxetine can increase pyramidal cell output, which leads to enhanced synaptic plasticity in the hippocampus, which may provide a cellular correlate to the observed preclinical and clinical cognition-enhancing effects of vortoxetine.
Abstract: Vortioxetine, a novel antidepressant with multimodal action, is a serotonin (5-HT)3, 5-HT7 and 5-HT1D receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist and a 5-HT transporter (SERT) inhibitor Vortioxetine has been shown to improve cognitive performance in several preclinical rat models and in patients with major depressive disorder Here we investigated the mechanistic basis for these effects by studying the effect of vortioxetine on synaptic transmission, long-term potentiation (LTP), a cellular correlate of learning and memory, and theta oscillations in the rat hippocampus and frontal cortex Vortioxetine was found to prevent the 5-HT-induced increase in inhibitory post-synaptic potentials recorded from CA1 pyramidal cells, most likely by 5-HT3 receptor antagonism Vortioxetine also enhanced LTP in the CA1 region of the hippocampus Finally, vortioxetine increased fronto-cortical theta power during active wake in whole animal electroencephalographic recordings In comparison, the selective SERT inhibitor escitalopram showed no effect on any of these measures Taken together, our results indicate that vortioxetine can increase pyramidal cell output, which leads to enhanced synaptic plasticity in the hippocampus Given the central role of the hippocampus in cognition, these findings may provide a cellular correlate to the observed preclinical and clinical cognition-enhancing effects of vortioxetine
TL;DR: Overall, DMT seems to have a very desirable effect profile indicating a high abuse liability that maybe offset by a low urge to use more, suggesting its popularity may increase.
Abstract: This paper presents original research on prevalence, user characteristics and effect profile of N,N-dimethyltryptamine (DMT), a potent hallucinogenic which acts primarily through the serotonergic system. Data were obtained from the Global Drug Survey (an anonymous online survey of people, many of whom have used drugs) conducted between November and December 2012 with 22,289 responses. Lifetime prevalence of DMT use was 8.9% (n=1980) and past year prevalence use was 5.0% (n=1123). We explored the effect profile of DMT in 472 participants who identified DMT as the last new drug they had tried for the first time and compared it with ratings provided by other respondents on psilocybin (magic mushrooms), LSD and ketamine. DMT was most often smoked and offered a strong, intense, short-lived psychedelic high with relatively few negative effects or "come down". It had a larger proportion of new users compared with the other substances (24%), suggesting its popularity may increase. Overall, DMT seems to have a very desirable effect profile indicating a high abuse liability that maybe offset by a low urge to use more.
King's College London1, Poznan University of Medical Sciences2, University of Zagreb3, University of Bonn4, Aarhus University Hospital5, Heidelberg University6, Université libre de Bruxelles7, University of Alberta8, University of Cambridge9, Wellcome Trust Centre for Human Genetics10, Dalhousie University11
TL;DR: While there is a significant relationship between the CYP450 genotype and serum concentrations of escitalopram and nortriptyline, the genotypes are not predictive of differences in treatment response for either drug.
Abstract: AIMS:
Antidepressant response varies between patients, possibly due to differences in the rate cytochrome P450 enzymes metabolise antidepressants into inactive compounds. Drug metabolism rates are influenced by common variants in the genes encoding these enzymes. However, it remains unclear whether treatment outcomes can be predicted by either CYP450 genotype or antidepressant serum concentration.
METHODS:
In GENDEP (a pharmacogenetic study of depressed individuals treated with either escitalopram or nortriptyline), serum concentrations of antidepressants and their primary metabolite were measured after eight weeks treatment and variants in CYP2D6 and CYP2C19 were genotyped.
RESULTS:
Amongst patients taking escitalopram (n=223), the genotype CYP2C19 was significantly associated with escitalopram serum concentrations and desmethylescitalopram:escitalopram ratio. For those taking nortriptyline (n=161), the CYP2D6 genotype was significantly associated with nortriptyline and 10-hydroxynortriptyline serum concentrations and 10-hydroxynortriptyline:nortrip-tyline ratio. CYP450 genotypes conferring greater enzyme activity were linked to lower drug serum concentrations and higher metabolite:drug ratios. Nonetheless, no significant association was found between either CYP450 genotype or antidepressant serum concentration and treatment response.
CONCLUSIONS:
While there is a significant relationship between the CYP450 genotype and serum concentrations of escitalopram and nortriptyline, the genotypes are not predictive of differences in treatment response for either drug. Furthermore, differences in antidepressant serum concentrations are not associated with variability in treatment response.
TL;DR: It is found that hallucinogen use predicted a reduced likelihood of supervision failure and may promote alcohol and other drug abstinence and prosocial behavior in a population with high rates of recidivism.
Abstract: Hallucinogen-based interventions may benefit substance use populations, but contemporary data informing the impact of hallucinogens on addictive behavior are scarce. Given that many individuals in the criminal justice system engage in problematic patterns of substance use, hallucinogen treatments also may benefit criminal justice populations. However, the relationship between hallucinogen use and criminal recidivism is unknown. In this longitudinal study, we examined the relationship between naturalistic hallucinogen use and recidivism among individuals under community corrections supervision with a history of substance involvement (n=25,622). We found that hallucinogen use predicted a reduced likelihood of supervision failure (e.g. noncompliance with legal requirements including alcohol and other drug use) while controlling for an array of potential confounding factors (odds ratio (OR)=0.60 (0.46, 0.79)). Our results suggest that hallucinogens may promote alcohol and other drug abstinence and prosocial behavior in a population with high rates of recidivism.
TL;DR: A new approach to reduce alcohol use and harms that would have major public health and social impacts is put forward, based on the assumption that heavy drinking is key.
Abstract: Alcohol use is one of the top five causes of disease and disability in almost all countries in Europe, and in the eastern part of Europe it is the number one cause. In the UK, alcohol is now the leading cause of death in men between the ages of 16–54 years, accounting for over 20% of the total. Europeans above 15 years of age in the EU on average consume alcohol at a level which is twice as high as the world average. Alcohol should therefore be a public health priority, but it is not. This paper puts forward a new approach to reduce alcohol use and harms that would have major public health and social impacts. Our approach comprises individual behaviour and policy elements. It is based on the assumption that heavy drinking is key. It is simple, so it would be easy to introduce, and because it lacks stigmatising issues such as the diagnosis of addiction and dependence, it should not be contentious.
TL;DR: In conclusion, galantamine augmentation was shown to be a relatively effective and safe augmentative strategy for alleviating some of the autism-related symptoms.
Abstract: The role of cholinergic abnormalities in autism was recently evidenced and there is a growing interest in cholinergic modulation, emerging for targeting autistic symptoms. Galantamine is an acetylcholinesterase inhibitor and an allosteric potentiator of nicotinic receptors. This study aimed to evaluate the possible effects of galantamine as an augmentative therapy to risperidone, in autistic children. In this randomized, double-blind, placebo-controlled, parallel-group study, 40 outpatients aged 4-12 years whom had a diagnosis of autism (DSM IV-TR) and a score of 12 or higher on the Aberrant Behavior Checklist-Community (ABC-C) Irritability subscale were equally randomized to receive either galantamine (up to 24 mg/day) or placebo, in addition to risperidone (up to 2 mg/day), for 10 weeks. We rated participants by ABC-C and a side effects checklist, at baseline and at weeks 5 and 10. By the study endpoint, the galantamine-treated patients showed significantly greater improvement in the Irritability (P = 0.017) and Lethargy/Social Withdrawal (P = 0.005) subscales than the placebo group. The difference between the two groups in the frequency of side effects was not significant. In conclusion, galantamine augmentation was shown to be a relatively effective and safe augmentative strategy for alleviating some of the autism-related symptoms.
TL;DR: Using minimum 6-week clinical trial criteria, atomoxetine may demonstrate similar efficacy to methylphenidate comparing reduction in core ADHD symptoms in meta-analysis, although the diversity of the data makes interpretation complex.
Abstract: Background:Clinicians obtain critical prescribing knowledge from clinical papers and review articles. This is the first published systematic review of clinical atomoxetine data covering 2009–2011.Objective:We aim to update clinicians on current clinical atomoxetine data with specific reference to time of onset of efficacy and maximal efficacy. These data may allow critical analysis of comparative efficacy between atomoxetine and stimulant medications.Methods:A formal systematic review of atomoxetine data from January 2009–June 2011 was conducted. The search term used was “atomoxetine” in the English language. The search yielded 747 citations from which 106 are clinical data. This paper includes clinical efficacy and safety data and excludes quality-of-life and review papers.Results:Atomoxetine has an onset of action within 4 weeks (possibly within 1 week in subsequent responders) but requires at least 12 weeks for full response to be demonstrated. Treatment-naive cohorts (6–12 weeks) report effect sizes o...
TL;DR: A retrospective analysis of data from 75 previous alcohol, cannabis, cocaine and crack users suggests that ibogaine can be a safe and effective treatment for dependence on stimulant and other non-opiate drugs.
Abstract: Ibogaine is an alkaloid purported to be an effective drug dependence treatment. However, its efficacy has been hard to evaluate, partly because it is illegal in some countries. In such places, treatments are conducted in underground settings where fatalities have occurred. In Brazil ibogaine is unregulated and a combined approach of psychotherapy and ibogaine is being practiced to treat addiction. To evaluate the safety and efficacy of ibogaine, we conducted a retrospective analysis of data from 75 previous alcohol, cannabis, cocaine and crack users (72% poly-drug users). We observed no serious adverse reactions or fatalities, and found 61% of participants abstinent. Participants treated with ibogaine only once reported abstinence for a median of 5.5 months and those treated multiple times for a median of 8.4 months. This increase was statistically significant (p < 0.001), and both single or multiple treatments led to longer abstinence periods than before the first ibogaine session (p < 0.001). These results suggest that the use of ibogaine supervised by a physician and accompanied by psychotherapy can facilitate prolonged periods of abstinence, without the occurrence of fatalities or complications. These results suggest that ibogaine can be a safe and effective treatment for dependence on stimulant and other non-opiate drugs.
TL;DR: Bupropion treatment at the EU-approved dose of ≤300 mg/day may offer advantages over SSRIs in the resolution of sleepiness and fatigue in remitted MDD patients.
Abstract: Unlike selective serotonin reuptake inhibitors (SSRIs), bupropion may be classified as a dual noradrenaline and dopamine reuptake inhibitor, a difference with potential implications for the treatment of residual sleepiness and fatigue in major depressive disorder (MDD). Post-hoc analysis of subjects with remitted MDD was performed on data pooled from six double-blind, randomized trials comparing the European Union (EU)-approved dose of ≤300 mg/day bupropion with SSRIs (sertraline, paroxetine or escitalopram) for the resolution of sleepiness and fatigue. Hypersomnia score was defined as the sum of scores of the Hamilton Depression Rating Scale (HDRS) items 22, 23, and 24; fatigue score as HDRS item 13 score; and remission as HDRS-17≤7. Similar proportions of bupropion- and SSRI-treated subjects achieved remission at study endpoint (169/343, 49.3% vs 324/656, 49.4%; last observation carried forward (LOCF), p=0.45). Fewer bupropion-treated remitters had residual symptoms of sleepiness (32/169, 18.9% vs 104/324, 32.1%; p<0.01) and fatigue (33/169, 19.5% vs 98/324, 30.2%; p<0.05). Bupropion-treated remitters also showed greater improvement (mean change from baseline) in sleepiness (p<0.05) and fatigue scores (p<0.01) at endpoint: benefits were evident from week 2 for sleepiness (p<0.01) and week 4 for fatigue (p<0.01). Bupropion treatment at the EU-approved dose of ≤300 mg/day may offer advantages over SSRIs in the resolution of sleepiness and fatigue in remitted MDD patients.
TL;DR: The results provide the first demonstration that selective MAO-A inhibition with pirlindole is able to revert the behavioural effects of stress exposure while promoting hippocampal adult neurogenesis and rescuing the stress-induced dendritic atrophy of granule neurons.
Abstract: There is accumulating evidence that adult neurogenesis and dendritic plasticity in the hippocampus are neuroplastic phenomena, highly sensitive to the effects of chronic stress and treatment with most classes of antidepressant drugs, being involved in the onset and recovery from depression. However, the effects of antidepressants that act through the selective inhibition of monoamine oxidase subtype A (MAO-A) in these phenomena are still largely unknown. In the present study, adult neurogenesis and neuronal morphology were examined in the hippocampus of rats exposed to chronic mild stress (CMS) and treated with the selective reversible MAO-A inhibitor (RIMA) drug, pirlindole and the selective serotonin reuptake inhibitor (SSRI), fluoxetine. The results provide the first demonstration that selective MAO-A inhibition with pirlindole is able to revert the behavioural effects of stress exposure while promoting hippocampal adult neurogenesis and rescuing the stress-induced dendritic atrophy of granule neurons.
TL;DR: The finding of elevated risk-taking among marijuana users is consistent with previous research that substance users may have impaired risk processing and suggests that risk- taking is not always associated with executive dysfunction, implying the involvement of distinct neural subsystems.
Abstract: OBJECTIVE: Adolescents who engage in regular marijuana use may have a higher propensity to take unsafe risks despite the possible negative consequences. We compared adolescents with a history of regular marijuana use to non-using teens on a behavioral measure of risk-taking. Given the involvement of the pre-frontal cortex in both risk-taking and executive functioning, we also examined whether risk-taking was associated with measures of executive functioning. METHOD: Fifty-eight demographically similar community youth (ages 17-20; 29% female), including 24 marijuana users and 34 non-using controls, completed the computerized Balloon Analog Risk Task (BART; Lejuez et al., 2002) and measures of substance use and executive function. Primary BART outcome measures included total number of popped balloons and average adjusted pumps (mean pumps excluding popped balloons). RESULTS: Marijuana users had more popped balloons than controls (pCONCLUSIONS: Our finding of elevated risk-taking among marijuana users is consistent with previous research that substance users may have impaired risk processing. Further, our results suggest that risk-taking is not always associated with executive dysfunction, implying the involvement of distinct neural subsystems. Language: en
TL;DR: Chronic cannabis use can cause cognitive, perceptual and personality alterations, which are associated with regional brain changes and possible changes in connectivity between functi... as mentioned in this paper, which can cause Cognitive, perceptual, and personality alteration.
Abstract: Chronic cannabis use can cause cognitive, perceptual and personality alterations, which are believed to be associated with regional brain changes and possible changes in connectivity between functi...
TL;DR: The neurochemical and behavioural profiles of lisdexamfetamine, methylphenidate and modafinil were compared by dual-probe microdialysis in the prefrontal cortex (PFC) and striatum of conscious rats with simultaneous locomotor activity measurement, showing larger and more sustained effects on catecholaminergic neurotransmission.
Abstract: Lisdexamfetamine dimesylate is a novel prodrug approved in North America, Europe and Brazil for treating attention deficit hyperactivity disorder (ADHD). It undergoes rate-limited hydrolysis by red blood cells to yield d-amphetamine. Following our previous work comparing lisdexamfetamine with d-amphetamine, the neurochemical and behavioural profiles of lisdexamfetamine, methylphenidate and modafinil were compared by dual-probe microdialysis in the prefrontal cortex (PFC) and striatum of conscious rats with simultaneous locomotor activity measurement. We employed pharmacologically equivalent doses of all compounds and those that spanned the therapeutically relevant and psychostimulant range. Lisdexamfetamine (0.5, 1.5, 4.5 mg/kg d-amphetamine base, per os (po)), methylphenidate (3, 10, 30 mg/kg base, po) and modafinil (100, 300, 600 mg/kg base, po) increased efflux of dopamine and noradrenaline in PFC, and dopamine in striatum. Only lisdexamfetamine increased 5-hydroxytryptamine (5-HT) efflux in PFC and striatum. Lisdexamfetamine had larger and more sustained effects on catecholaminergic neurotransmission than methylphenidate or modafinil. Linear correlations were observed between striatal dopamine efflux and locomotor activity for lisdexamfetamine and methylphenidate, but not modafinil. Regression slopes revealed greater increases in extracellular dopamine could be elicited without producing locomotor activation by lisdexamfetamine than methylphenidate. These results are consistent with clinical findings showing that lisdexamfetamine is an effective ADHD medication with prolonged duration of action and good separation between its therapeutic actions and stimulant side-effects.
TL;DR: It is concluded that the effect of LSD in this model can be considered antidepressant-like, and discussed in terms of a re-balance of hippocampal 5-HT2/5-HT1A signalling.
Abstract: A re-balance of postsynaptic serotonin (5-HT) receptor signalling, with an increase in 5-HT1A and a decrease in 5-HT2A signalling, is a final common pathway multiple antidepressants share. Given that the 5-HT1A/2A agonist lysergic acid diethylamide (LSD), when repeatedly applied, selectively downregulates 5-HT2A, but not 5-HT1A receptors, one might expect LSD to similarly re-balance the postsynaptic 5-HT signalling. Challenging this idea, we use an animal model of depression specifically responding to repeated antidepressant treatment (olfactory bulbectomy), and test the antidepressant-like properties of repeated LSD treatment (0.13 mg/kg/d, 11 d). In line with former findings, we observe that bulbectomised rats show marked deficits in active avoidance learning. These deficits, similarly as we earlier noted with imipramine, are largely reversed by repeated LSD administration. Additionally, bulbectomised rats exhibit distinct anomalies of monoamine receptor signalling in hippocampus and/or frontal cortex; ...
McMaster University1, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico2, Queen Elizabeth II Hospital3, Albert Einstein College of Medicine4, Stellenbosch University5, University of Pisa6, University of Barcelona7, Universidad Autónoma de la Ciudad de México8, University of Florence9, University of Cape Town10, Sheba Medical Center11
TL;DR: Results from this international cross-sectional study indicate that current OCD treatment is in line with evidence-based treatment guidelines, and no significant differences in OCD symptom severity were found between monotherapy and augmentation or between different therapeutic agents.
Abstract: Objective:It is unknown what next-step strategies are being used in clinical practice for patients with obsessive–compulsive disorder (OCD) who do not respond to first-line treatment. As part of a cross-sectional study of OCD, treatment and symptom information was collected.Method:Consecutive OCD out-patients in nine international centers were evaluated by self-report measures and clinical/structured interviews. OCD symptom severity was evaluated by the Yale Brown Obsessive Compulsive Scale (YBOCS) and Clinical Global Impression–Severity Scale (CGI-S). Clinical response to current treatment was evaluated by the CGI-Improvement Scale (CGI-I ≤ 2).Results:In total, 361 participants reported taking medication; 77.6% were taking a selective serotonin reuptake inhibitor; 50% reported use of at least one augmentation strategy. Antipsychotics were most often prescribed as augmenters (30.3%), followed by benzodiazepines (24.9%) and antidepressants (21.9%). No differences in OCD symptom severity were found between ...
TL;DR: This is the first study showing that the behavioural response to CO2 that characterises panic disorder patients is likely due to increased neural sensitivity to CO1 at brainstem level, and patients show increased brainstem activation in response to hypercapnia.
Abstract: Background:The biological basis of uncued panic attacks is not yet understood. An important theory concerning the nature and cause of panic disorder is the ‘suffocation false alarm theory’. This al...
TL;DR: It is concluded that deficits in empathy and ToM may play an important role in the impairments in social cognition and peer relationship in children with ADHD, especially children a hyperactive component.
Abstract: Impairments in ‘theory of mind’ (ToM) were linked to social cognition and reciprocal relationships deficits in children with attention deficit/hyperactivity disorder (ADHD). Twenty-four children wi...
TL;DR: A retrospective review of patients treated with clarithromycin for hypersomnia found that the drug may be useful in the treatment of hypersomnia associated with enhancement of GABA-A receptor function, and responders were significantly younger than non-responders.
Abstract: The macrolide antibiotic clarithromycin can enhance central nervous system excitability, possibly by antagonism of GABA-A receptors. Enhancement of GABA signaling has recently been demonstrated in a significant proportion of patients with central nervous system hypersomnias, so we sought to determine whether clarithromycin might provide symptomatic benefit in these patients. We performed a retrospective review of all patients treated with clarithromycin for hypersomnia, in whom cerebrospinal fluid enhanced GABA-A receptor activity in vitro in excess of controls, excluding those with hypocretin deficiency or definite cataplexy. Subjective reports of benefit and objective measures of psychomotor vigilance were collected to assess clarithromycin's effects. Clinical and demographic characteristics were compared in responders and non-responders. In total, 53 patients (38 women, mean age 35.2 (SD 12.8 years)) were prescribed clarithromycin. Of these, 34 (64%) reported improvement in daytime sleepiness, while 10 (19%) did not tolerate its side effects, and nine (17%) found it tolerable but without symptomatic benefit. In those who reported subjective benefit, objective corroboration of improved vigilance was evident on the psychomotor vigilance task. Twenty patients (38%) elected to continue clarithromycin therapy. Clarithromycin responders were significantly younger than non-responders. Clarithromycin may be useful in the treatment of hypersomnia associated with enhancement of GABA-A receptor function. Further evaluation of this novel therapy is needed.
TL;DR: Oleanolic acid potentiated the hypnotic effect of barbiturate and demonstrated an anxiolytic effect in both the light–dark box and elevated plus maze and monoamine oxidase activity remained unaltered by o Leanolic acid, chronic administration of oleanolic Acid augmented hippocampal BDNF level.
Abstract: Our study sought to evaluate the anxiolytic and antidepressant activities of oleanolic acid as well as the neural mechanisms involved. Animal models such as barbiturate sleep-induction, light–dark box, elevated plus maze, forced swimming test, tail suspension test and open field test were conducted. Male Albino Swiss mice were treated orally with vehicle 10 mL/kg, fluoxetine 20 mg/kg, imipramine 15 mg/kg, diazepam 1 mg/kg or oleanolic acid 5–40 mg/kg. Pretreatment (intraperitoneal) of animals with pentylenetetrazole (PTZ) 20 mg/kg, 1-(2-methoxyphenyl)-4-[4- (2-phthalimido) butyl]piperazine hydrobromide (NAN-190) 0.5 mg/kg, p-chlorophenylalanine methyl ester (PCPA) 100 mg/kg or α-methyl-p-tyrosine (AMPT) 100 mg/kg, WAY100635 (WAY) 0.3 mg/kg, prazosin (PRAZ) 1 mg/kg, yohimbine 2 mg/kg as well as monoamine oxidase assay and hippocampal brain-derived neurotrophic factor (BDNF) quantification were carried out. Oleanolic acid potentiated the hypnotic effect of barbiturate and demonstrated an anxiolytic effect i...