Showing papers in "Journal of Psychopharmacology in 2018"
TL;DR: This article highlights the pharmacological mechanisms of classic psychedelics that it is believed render their effects exceptionally sensitive to context, and develops an evidence base for long-held assumptions about the critical importance of context in relation to psychedelic use that can help minimise harms and maximise potential benefits.
Abstract: Psychedelic drugs are making waves as modern trials support their therapeutic potential and various media continue to pique public interest. In this opinion piece, we draw attention to a long-recognised component of the psychedelic treatment model, namely ‘set’ and ‘setting’ – subsumed here under the umbrella term ‘context’. We highlight: (a) the pharmacological mechanisms of classic psychedelics (5-HT2A receptor agonism and associated plasticity) that we believe render their effects exceptionally sensitive to context, (b) a study design for testing assumptions regarding positive interactions between psychedelics and context, and (c) new findings from our group regarding contextual determinants of the quality of a psychedelic experience and how acute experience predicts subsequent long-term mental health outcomes. We hope that this article can: (a) inform on good practice in psychedelic research, (b) provide a roadmap for optimising treatment models, and (c) help tackle unhelpful stigma still surrounding these compounds, while developing an evidence base for long-held assumptions about the critical importance of context in relation to psychedelic use that can help minimise harms and maximise potential benefits.
286 citations
TL;DR: Both high-dose psilocybin groups showed large significant positive changes on longitudinal measures of interpersonal closeness, gratitude, life meaning/purpose, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping, and community observer ratings.
Abstract: Psilocybin can occasion mystical-type experiences with participant-attributed increases in well-being. However, little research has examined enduring changes in traits. This study administered psil...
235 citations
TL;DR: An expert review of the aetiology, assessment, and treatment of autism spectrum disorder, and recommendations for diagnosis, management and service provision was coordinated by the British Association for Psychopharmacology, and evidence graded.
Abstract: An expert review of the aetiology, assessment, and treatment of autism spectrum disorder, and recommendations for diagnosis, management and service provision was coordinated by the British Association for Psychopharmacology, and evidence graded. The aetiology of autism spectrum disorder involves genetic and environmental contributions, and implicates a number of brain systems, in particular the gamma-aminobutyric acid, serotonergic and glutamatergic systems. The presentation of autism spectrum disorder varies widely and co-occurring health problems (in particular epilepsy, sleep disorders, anxiety, depression, attention deficit/hyperactivity disorder and irritability) are common. We did not recommend the routine use of any pharmacological treatment for the core symptoms of autism spectrum disorder. In children, melatonin may be useful to treat sleep problems, dopamine blockers for irritability, and methylphenidate, atomoxetine and guanfacine for attention deficit/hyperactivity disorder. The evidence for use of medication in adults is limited and recommendations are largely based on extrapolations from studies in children and patients without autism spectrum disorder. We discuss the conditions for considering and evaluating a trial of medication treatment, when non-pharmacological interventions should be considered, and make recommendations on service delivery. Finally, we identify key gaps and limitations in the current evidence base and make recommendations for future research and the design of clinical trials.
179 citations
TL;DR: How excitotoxicity is involved in the pathogenesis of different neurological and psychiatric disorders and the promising strategies targeting the excitOToxic insult are discussed.
Abstract: Neurological and psychiatric disorders are leading contributors to the global disease burden, having a serious impact on the quality of life of both patients and their relatives. Although the molecular events underlying these heterogeneous diseases remain poorly understood, some studies have raised the idea of common mechanisms involved. In excitotoxicity, there is an excessive activation of glutamate receptors by excitatory amino acids, leading to neuronal damage. Thus, the excessive release of glutamate can lead to a dysregulation of Ca2+ homeostasis, triggering the production of free radicals and oxidative stress, mitochondrial dysfunction and eventually cell death. Although there is a consensus in considering excitotoxicity as a hallmark in most neurodegenerative diseases, increasing evidence points to the relevant role of this pathological mechanism in other illnesses affecting the central nervous system. Consequently, antagonists of glutamate receptors are used in current treatments or in clinical trials in both neurological and psychiatric disorders. However, drugs modulating other aspects of the excitotoxic mechanism could be more beneficial. This review discusses how excitotoxicity is involved in the pathogenesis of different neurological and psychiatric disorders and the promising strategies targeting the excitotoxic insult.
121 citations
TL;DR: The findings highlight the value of qualitative research in the psychopharmacological investigation of psychedelics and describe perceived connections between drug- and non-drug factors, and provide suggestions for future research trial design and clinical applications.
Abstract: Background:Recent pilot trials suggest feasibility and potential efficacy of psychedelic-facilitated addiction treatment interventions. Fifteen participants completed a psilocybin-facilitated smoki...
118 citations
TL;DR: The findings of this pilot dose response trial support previous investigations of MDMA-assisted psychotherapy as an innovative, efficacious treatment for posttraumatic stress disorder.
Abstract: Background:Posttraumatic stress disorder often does not resolve after conventional psychotherapies or pharmacotherapies. Pilot studies have reported that 3,4-methylenedioxymethamphetamine (MDMA) combined with psychotherapy reduces posttraumatic stress disorder symptoms.Aims:This pilot dose response trial assessed efficacy and safety of MDMA-assisted psychotherapy across multiple therapy teams.Methods:Twenty-eight people with chronic posttraumatic stress disorder were randomized in a double-blind dose response comparison of two active doses (100 and 125 mg) with a low dose (40 mg) of MDMA administered during eight-hour psychotherapy sessions. Change in the Clinician-Administered PTSD Scale total scores one month after two sessions of MDMA served as the primary outcome. Active dose groups had one additional open-label session; the low dose group crossed over for three open-label active dose sessions. A 12-month follow-up assessment occurred after the final MDMA session.Results:In the intent-to-treat set, th...
107 citations
TL;DR: Psilocybin with psychological support might produce lasting changes in attitudes and beliefs, and the possibility of drug-induced changes in belief systems seems sufficiently intriguing and timely to deserve further investigation.
Abstract: Rationale:Previous research suggests that classical psychedelic compounds can induce lasting changes in personality traits, attitudes and beliefs in both healthy subjects and patient populations.Aim:Here we sought to investigate the effects of psilocybin on nature relatedness and libertarian–authoritarian political perspective in patients with treatment-resistant depression (TRD).Methods:This open-label pilot study with a mixed-model design studied the effects of psilocybin on measures of nature relatedness and libertarian–authoritarian political perspective in patients with moderate to severe TRD (n=7) versus age-matched non-treated healthy control subjects (n=7). Psilocybin was administered in two oral dosing sessions (10 mg and 25 mg) 1 week apart. Main outcome measures were collected 1 week and 7–12 months after the second dosing session. Nature relatedness and libertarian–authoritarian political perspective were assessed using the Nature Relatedness Scale (NR-6) and Political Perspective Questionnair...
94 citations
TL;DR: This algorithm-based approach for drug treatment of agitation/aggression in Alzheimer’s/mixed dementia has been implemented in several Canadian Hospital Inpatient Units and impact should be assessed in future research.
Abstract: Introduction:Behavioural and psychological symptoms of dementia (BPSD) include agitation and aggression in people with dementia. BPSD is common on inpatient psychogeriatric units and may prevent in...
77 citations
TL;DR: It is suggested that 5-MeO-DMT is used infrequently, predominantly for spiritual exploration, has low potential for addiction, and might have psychotherapeutic effects.
Abstract: Background/aim:5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a psychoactive compound found in several plants and in high concentrations in Bufo alvarius toad venom. Synthetic, toad, and plant-sou...
72 citations
TL;DR: This is the first demonstration that cannabidiol can reduce the motivation to seek and consume methamphetamine, and suggests that cannABidiol might be worth trialing as a novel pharmacotherapy for methamphetamine dependence.
Abstract: Background:Methamphetamine is an addictive stimulant that can cause many adverse physical, psychological and psychosocial effects. Preliminary evidence shows cannabidiol, a non-intoxicating constit...
56 citations
TL;DR: In this paper, the activation likelihood estimation meta-analysis framework was used to identify those brain regions that consistently demonstrate functional alterations among cannabis users versus non-users across neuroimaging studies.
Abstract: Lagging behind rapid changes to state laws, societal views, and medical practice is the scientific investigation of cannabis's impact on the human brain. While several brain imaging studies have contributed important insight into neurobiological alterations linked with cannabis use, our understanding remains limited. Here, we sought to delineate those brain regions that consistently demonstrate functional alterations among cannabis users versus non-users across neuroimaging studies using the activation likelihood estimation meta-analysis framework. In ancillary analyses, we characterized task-related brain networks that co-activate with cannabis-affected regions using data archived in a large neuroimaging repository, and then determined which psychological processes may be disrupted via functional decoding techniques. When considering convergent alterations among users, decreased activation was observed in the anterior cingulate cortex, which co-activated with frontal, parietal, and limbic areas and was linked with cognitive control processes. Similarly, decreased activation was observed in the dorsolateral prefrontal cortex, which co-activated with frontal and occipital areas and linked with attention-related processes. Conversely, increased activation among users was observed in the striatum, which co-activated with frontal, parietal, and other limbic areas and linked with reward processing. These meta-analytic outcomes indicate that cannabis use is linked with differential, region-specific effects across the brain.
TL;DR: Lifetime classic psychedelic use and psilocybin use per se with criminal behavior among over 480,000 United States adult respondents pooled from the last 13 available years of the National Survey on Drug Use and Health contribute to a compelling rationale for the initiation of clinical research with classic psychedelics, including p silocybin, in forensic settings.
Abstract: Criminal behavior exacts a large toll on society and is resistant to intervention. Some evidence suggests classic psychedelics may inhibit criminal behavior, but the extent of these effects has not been comprehensively explored. In this study, we tested the relationships of classic psychedelic use and psilocybin use per se with criminal behavior among over 480,000 United States adult respondents pooled from the last 13 available years of the National Survey on Drug Use and Health (2002 through 2014) while controlling for numerous covariates. Lifetime classic psychedelic use was associated with a reduced odds of past year larceny/theft (aOR = 0.73 (0.65–0.83)), past year assault (aOR = 0.88 (0.80–0.97)), past year arrest for a property crime (aOR = 0.78 (0.65–0.95)), and past year arrest for a violent crime (aOR = 0.82 (0.70–0.97)). In contrast, lifetime illicit use of other drugs was, by and large, associated with an increased odds of these outcomes. Lifetime classic psychedelic use, like lifetime illicit...
TL;DR: Intranasal ketamine, with the drug formulation and delivery device used, was not a useful treatment approach in this study and acute tolerability was poor, requiring prolonged treatment administration time in some individuals.
Abstract: Background:Ketamine research in depression has mostly used intravenous, weight-based approaches, which are difficult to translate clinically. Intranasal (IN) ketamine is a promising alternative but no controlled data has been published on the feasibility, safety and potential efficacy of repeated IN ketamine treatments.Methods:This randomised, double-blind, placebo-controlled pilot study compared a 4-week course of eight treatments of 100 mg ketamine or 4.5 mg midazolam. Each treatment was given as 10 separate IN sprays, self-administered 5 min apart. The study was stopped early due to poor tolerability after five treatment-resistant depressed participants were included. Feasibility, safety (acute and cumulative), cognitive and efficacy outcomes were assessed. Plasma ketamine and norketamine concentrations were assayed after the first treatment.Results:Significant acute cardiovascular, psychotomimetic and neurological side effects occurred at doses < 100 mg ketamine. No participants were able to self-admi...
TL;DR: In this article, the effect on anxiety ratings, safety and tolerability of 3 months of weekly ketamine in 20 patients with treatment-refractory DBS was evaluated in a maintenance treatment study.
Abstract: Objective:In this maintenance treatment study, we sought to evaluate the effect on anxiety ratings, safety and tolerability of 3 months of weekly ketamine in 20 patients with treatment-refractory D...
TL;DR: Changes in illicit opioid use predict self-reported anhedonia, suggesting a possible causal relationship whereby anhedania is likely to worsen with frequent drug use and diminish with prolonged abstinence, however, anhedonian does not appear to drive further drug use.
Abstract: Background:Anhedonia is a commonly reported symptom among substance-dependent populations that appears to diminish with sustained abstinence. However, previous research has not determined whether a...
TL;DR: Clinicians need to be vigilant for the occurrence of pneumonia in patients commencing antipsychotics, especially those with other risk factors for pneumonia including older age, chronic respiratory disease, cerebrovascular disease, dysphagia and smoking.
Abstract: Objectives:The purpose of this study was to investigate the association of antipsychotic exposure to the incidence and mortality of pneumonia.Methods:The design of this study involved meta-analysis...
TL;DR: The findings suggest that neurocognitive function would not deteriorate after six ketamine infusions, while verbal learning and speed of processing improved over 13 days and 26 days of observation, respectively, but this change was mainly accounted for by improvements in severity of depressive symptoms over time.
Abstract: Background:Ketamine has proven to have rapid, robust antidepressant effects on treatment-resistant depression. However, whether repeated ketamine infusions would cause short-and long-term neurocogn...
TL;DR: Both anhedonia and depression severity related to decreased dmPFC RSFC with the precuneus, a part of the default mode network, but it is found that increased RSFC connectivity with the ACC/paracingulate gyrus related to anhedonian whereas increased RS FC with the frontal pole related to depression severity.
Abstract: Introduction: Given the heterogeneity within depression, in this study we aim to examine how RSFC in adolescents is related to anhedonia and depression severity on a continuum in line with the RDoC approach.
Methods: We examined how RSFC in the dorsal medial prefrontal cortex (dmPFC), nucleus accumbens (NAcc) and pregenual anterior cingulate cortex (pgACC) was related to anhedonia and depression severity in eighty six adolescents (13-21 yrs.).
Results: We found both anhedonia and depression severity related to decreased dmPFC RSFC with the precuneus, a part of the default mode network. However we also found that increased dmPFC connectivity with the ACC/paracingulate gyrus related to anhedonia whereas increased RSFC with the frontal pole related to depression severity.
Discussion: This work extends the view that the dmPFC is a potential therapeutic target for depression in two ways. 1. We report dmPFC connectivity in adolescents and 2. We show different dmPFC RSFC specific to anhedonia and depression severity, providing neural targets for intervention in young people at risk of depression.
TL;DR: Functional magnetic resonance spectroscopy (fMRS), which uses sequential scans for dynamic measurement of a range of brain metabolites in activated brain areas, has lately been applied to a variety of task or stimulus conditions, producing interesting insights into neurometabolite responses to neural activation.
Abstract: Abnormalities of the glutamate system are increasingly implicated in schizophrenia but their exact nature remains unknown. Proton magnetic resonance spectroscopy (1H-MRS), while fundamental in revealing glutamatergic alterations in schizophrenia, has, until recently, been significantly limited and thought to only provide static measures. Functional magnetic resonance spectroscopy (fMRS), which uses sequential scans for dynamic measurement of a range of brain metabolites in activated brain areas, has lately been applied to a variety of task or stimulus conditions, producing interesting insights into neurometabolite responses to neural activation. Here, we summarise the existing 1H-MRS studies of brain glutamate in schizophrenia. We then present a comprehensive review of research studies that have utilised fMRS, and lastly consider how fMRS methods might further the understanding of glutamatergic abnormalities in schizophrenia.
TL;DR: Investigation of the effect of seltorexant on sleep efficiency after single and multiple dose administration in subjects with insomnia disorder without psychiatric comorbidity resulted in a prolonged total sleep time, shorter latency to persistent sleep and wake after sleep onset.
Abstract: Background:Seltorexant is a potent and selective antagonist of the orexin-2 receptor that is being developed for the treatment of insomnia and major depressive disorder.Aims:The primary objective w...
TL;DR: There was no evidence of any benefits of cannabidiol on anxiety or persecutory ideation in healthy volunteers with high trait paranoia, and a larger sample will be required for a definitive study.
Abstract: Background:Previous studies have suggested that cannabidiol has anxiolytic and antipsychotic properties, raising hopes that cannabidiol will translate to the psychiatric clinic. Cannabidiol may be particularly useful for anxiety and paranoia in those at-risk of major mental illness.Methods:Immersion in a controlled 3D virtual-reality scenario was used to assay persecutory ideation and anxiety in a sample of non-clinical volunteers (n=32) pre-selected for high paranoid traits. Participants were randomised to receive oral cannabidiol (600 mg) or placebo 130 min prior to entering virtual-reality. Well-validated rating scales were used to assay persecutory thinking and anxiety. Salivary cortisol concentration, heart rate and blood pressure were measured over the course of the experimental session.Results:Immersion in the virtual-reality session elicited anxiety as indexed by the Beck’s anxiety inventory (p<0.005), and increased cortisol concentration (p=0.05), heart rate (p<0.05) and systolic blood pressure (...
TL;DR: Silymarin significantly reversed the CUMS-induced changes in the hippocampus and cerebral cortex in mice, correlated to the alleviation of monoaminergic, neurogenesis, and attenuation of inflammatory cytokines system and oxidative stress by modulation of corticosterone response, restoration of antioxidant defense system in cerebral cortex and hippocampus.
Abstract: Silymarin, a plant-derived polyphenolic flavonoid of Silybum marianum, elicited significant antidepressant-like activity in an acute restraint stress model of depression. It improved monoamines, mainly 5-hydroxytryptamine (5-HT) levels in the cortex, dopamine (DA) and norepinephrine (NE) in the cerebellum in mice. The present study was undertaken to explore the antidepressant potential of silymarin in chronic unpredictable mild stress (CUMS) induced depressive-like behavior in mice, and to find out its probable mechanism(s) of action, mainly neurogenesis, neuroinflammation, and/or oxidative stress. The mice were subjected to CUMS for 28 days (4 weeks) and administered with silymarin (100 mg/kg and 200 mg/kg), or fluoxetine or vehicle from days 8 to 28 (3 weeks simultaneously). Animals were evaluated for behavioral changes, such as anhedonia by sucrose preference test, behavioral despair by forced swim test, and exploratory behaviors by an open field test. In addition, neurobiochemical alterations, mainly monoamines, 5-HT, NE, DA, neurotrophic factor BDNF, and cytokines, IL-6, TNF-α, oxidant-antioxidant parameters by determining the malondialdehyde formation (an index of lipid peroxidation process), superoxide dismutase (SOD) and catalase (CAT) activity in hippocampus and cerebral cortex along with serum corticosterone were investigated. Our findings reveal that mice subjected to CUMS exhibited lower sucrose preference, increase immobility time without affecting general locomotion of the animals, and reduce BDNF, 5-HT, NE, and DA level, increased serum corticosterone, IL-6 and TNF-α along with an oxidant-antioxidant imbalance in the hippocampus and cerebral cortex. Silymarin significantly reversed the CUMS-induced changes in the hippocampus and cerebral cortex in mice. Thus, the possible mechanism involved in the antidepressant-like activity of silymarin is correlated to the alleviation of monoaminergic, neurogenesis (enhancing 5-HT, NE, and BDNF levels), and attenuation of inflammatory cytokines system and oxidative stress by modulation of corticosterone response, restoration of antioxidant defense system in cerebral cortex and hippocampus.
TL;DR: High doses of psilocybin elicited subjective effects at least as strong as the lower doses and resulted in positive persisting subjective effects 30 days after, indicating that a complete mystical experience was not a prerequisite for positive outcomes.
Abstract: Aim The aim of the current study was to investigate the relationship between escalating higher doses of psilocybin and the potential psilocybin occasioned positive subjective effects. Methods Healthy participants ( n=12) were given three escalating doses of oral psilocybin (0.3 mg/kg; 0.45 mg/kg; 0.6 mg/kg) or (18.8-36.6 mg; 27.1-54.0 mg; 36.3-59.2 mg) a minimum of four weeks apart in a supervised setting. Blood and urine samples, vital signs, and electrocardiograms were obtained. Subjective effects were assessed using the Mystical Experience Questionnaire and Persisting Effects Questionnaire. Results There was a significant linear dose-related response in Mystical Experience Questionnaire total score and the transcendence of time and space subscale, but not in the rate of a complete mystical experience. There was also a significant difference between dose 3 compared to dose 1 on the transcendence of time and space subscale, while no dose-related differences were found for Mystical Experience Questionnaire total scores or rate of a mystical experience. Persisting Effects Questionnaire positive composite scores 30 days after completion of the last dose were significantly higher than negative composite scores. Persisting Effects Questionnaire results revealed a moderate increase in sense of well-being or life satisfaction on average that was associated with the maximum Mystical Experience Questionnaire total score. Pharmacokinetic measures were associated with dose but not with Mystical Experience Questionnaire total scores or rate of a mystical experience. Conclusions High doses of psilocybin elicited subjective effects at least as strong as the lower doses and resulted in positive persisting subjective effects 30 days after, indicating that a complete mystical experience was not a prerequisite for positive outcomes.
King's College London1, South London and Maudsley NHS Foundation Trust2, Imperial College London3, University of Barcelona4, Sussex Partnership NHS Foundation Trust5, Hannover Medical School6, Newcastle University7, St George's, University of London8, Central and North West London NHS Foundation Trust9, Oxleas NHS Foundation Trust10, University of Nottingham11
TL;DR: The variety of options available for the management of acute disturbance goes beyond the standard choices of lorazepam, haloperidol and promethazine and includes oral-inhaled loxapine, buccal midazolam, as well as a number of oral antipsychotics in addition to parenteral options.
Abstract: The British Association for Psychopharmacology and the National Association of Psychiatric Intensive Care and Low Secure Units developed this joint evidence-based consensus guideline for the clinical management of acute disturbance. It includes recommendations for clinical practice and an algorithm to guide treatment by healthcare professionals with various options outlined according to their route of administration and category of evidence. Fundamental overarching principles are included and highlight the importance of treating the underlying disorder. There is a focus on three key interventions: de-escalation, pharmacological interventions pre-rapid tranquillisation and rapid tranquillisation (intramuscular and intravenous). Most of the evidence reviewed relates to emergency psychiatric care or acute psychiatric adult inpatient care, although we also sought evidence relevant to other common clinical settings including the general acute hospital and forensic psychiatry. We conclude that the variety of options available for the management of acute disturbance goes beyond the standard choices of lorazepam, haloperidol and promethazine and includes oral-inhaled loxapine, buccal midazolam, as well as a number of oral antipsychotics in addition to parenteral options of intramuscular aripiprazole, intramuscular droperidol and intramuscular olanzapine. Intravenous options, for settings where resuscitation equipment and trained staff are available to manage medical emergencies, are also included.
TL;DR: A retrospective analysis of single-substance exposures of LSD or psilocybin-containing mushrooms reported to United States poison centers from 1 January 2000 to 31 December 2016 finds that LSD and PcM use occurs primarily in adolescents and young adults, who experience mild to moderate adverse effects.
Abstract: Background:Lysergic acid diethylamide (LSD) and psilocybin are serotonergic hallucinogens that are used primarily for recreational abuse Small studies evaluated the efficacy of LSD and psilocybin
TL;DR: A systematic review of 70 studies, including over 3000 patients with psychotic disorders or at increased risk of psychotic disorder, is undertaken in order to delineate potential neurobiological and neurochemical mechanisms that may underlie the effects of cannabis in psychotic disorders and suggest avenues for future research.
Abstract: A substantial body of credible evidence has accumulated that suggest that cannabis use is an important potentially preventable risk factor for the development of psychotic illness and its worse prognosis following the onset of psychosis. Here we summarize the relevant evidence to argue that the time has come to investigate the neurobiological effects of cannabis in patients with psychotic disorders. In the first section we summarize evidence from longitudinal studies that controlled for a range of potential confounders of the association of cannabis use with increased risk of developing psychotic disorders, increased risk of hospitalization, frequent and longer hospital stays, and failure of treatment with medications for psychosis in those with established illness. Although some evidence has emerged that cannabis-using and non-using patients with psychotic disorders may have distinct patterns of neurocognitive and neurodevelopmental impairments, the biological underpinnings of the effects of cannabis remain to be fully elucidated. In the second and third sections we undertake a systematic review of 70 studies, including over 3000 patients with psychotic disorders or at increased risk of psychotic disorder, in order to delineate potential neurobiological and neurochemical mechanisms that may underlie the effects of cannabis in psychotic disorders and suggest avenues for future research.
TL;DR: Results revealed that male psychedelic users reported better emotion regulation when compared to males with no history of psychedelic use, which mediated the relationship between psychedelic use and lower perpetration of intimate partner violence.
Abstract: Background:Recent evidence suggests that psychedelic use predicts reduced perpetration of intimate partner violence among men involved in the criminal justice system. However, the extent to which this association generalizes to community samples has not been examined, and potential mechanisms underlying this association have not been directly explored.Aims:The present study examined the association between lifetime psychedelic use and intimate partner violence among a community sample of men and women. The study also tested the extent to which the associations were mediated by improved emotion regulation.Methods:We surveyed 1266 community members aged 16–70 (mean age=22.78, standard deviation=7.71) using an online questionnaire that queried substance use, emotional regulation, and intimate partner violence. Respondents were coded as psychedelic users if they reported one or more instance of using lysergic acid diethylamide and/or psilocybin mushrooms in their lifetime.Results/outcomes:Males reporting any ...
TL;DR: It is shown that partial dopamine agonists at high doses are effective in treating acute mania and major depressive disorder, which is resistant to classical antidepressants, low doses of partial dopamine receptor agonists as adjunct therapy may represent a relatively safe and effective alternative.
Abstract: The objective of this meta-analysis is to assess the efficacy and safety of partial and complete dopamine agonists in the treatment of acute mood disorder episodes. Randomized, double-blind and placebo-controlled trials of dopamine agonists in the treatment of acute mood disorder episodes were identified in the MEDLINE and PsycINFO databases and included in the meta-analysis. In monotherapy of mania, improved remission rates were found for cariprazine (odds ratio (OR): 2.08, P < 0.01) and for high-dose aripiprazole (OR: 3.00; P = 0.05), but not for low-dose aripiprazole. In bipolar depression, no improvement of remission and response rates was found for aripiprazole in monotherapy, whereas improved response rate (OR: 10.27, P < 0.01) was found for pramipexole only as an add-on to another mood stabilizer. In major depressive disorder, relatively similar improvements of remission rates were found for high-dose (OR: 1.96, p < 0.01) and low-dose aripiprazole (OR: 1.68, P = 0.01), as well as brexpiprazole (OR: 1.52, P = 0.05) as an add-on to antidepressant medication. Our meta-analysis shows that partial dopamine agonists at high doses are effective in treating acute mania. In major depressive disorder, which is resistant to classical antidepressants, low doses of partial dopamine agonists as adjunct therapy may represent a relatively safe and effective alternative.
TL;DR: Alternative explanations are presented to explain how stress and near death can produce altered states of consciousness without invoking the intermediacy of N,N-dimethyltryptamine.
Abstract: The pineal gland has a romantic history, from pharaonic Egypt, where it was equated with the eye of Horus, through various religious traditions, where it was considered the seat of the soul, the third eye, etc. Recent incarnations of these notions have suggested that N,N-dimethyltryptamine is secreted by the pineal gland at birth, during dreaming, and at near death to produce out of body experiences. Scientific evidence, however, is not consistent with these ideas. The adult pineal gland weighs less than 0.2 g, and its principal function is to produce about 30 µg per day of melatonin, a hormone that regulates circadian rhythm through very high affinity interactions with melatonin receptors. It is clear that very minute concentrations of N,N-dimethyltryptamine have been detected in the brain, but they are not sufficient to produce psychoactive effects. Alternative explanations are presented to explain how stress and near death can produce altered states of consciousness without invoking the intermediacy of N,N-dimethyltryptamine.
TL;DR: Recent research suggests that different biological mechanisms may underlie sex differences in responsiveness to stress, which could improve treatment outcomes for women.
Abstract: There is increasing recognition that women have a higher prevalence of certain psychiatric illnesses, and a differential treatment response and course of illness compared to men. Additionally, clinicians deal with a number of disorders like premenstrual syndrome, premenstrual dysphoric disorder, and postpartum depression, which affect women specifically and for which treatment and biological pathways are still unclear. In this article we highlight recent research which suggests that different biological mechanisms may underlie sex differences in responsiveness to stress. Sex differences are evident at the receptor level; where the corticotropin-releasing factor receptor shows differential coupling to adaptor proteins in males and females. The neuropeptide oxytocin also shows sex-specific effects in a range of social behaviors. It may act as a biomarker in post-traumatic stress disorder where sex differences are evident. Studies in women using hormonal contraception show that some of these oxytocin-mediated effects are likely influenced by sex hormones. In female rats rapid changes in circulating progesterone levels are associated with exaggerated behavioral responses to mild stress and blunted responses to benzodiazepines that could be prevented by acute treatment with low-dose fluoxetine. Perceived barriers in research on women have hindered progress. The development of a sex-specific psychopharmacology as a basis for translating this type of research into clinical practice is vital to improve treatment outcomes for women.