Self-blinding citizen science to explore psychedelic microdosing.

Microdosing is the practice of regularly using low doses of psychedelic drugs. Anecdotal reports suggest that microdosing enhances well-being and cognition; however, such accounts are potentially biased by the placebo effect. This study used a 'self-blinding' citizen science initiative, where participants were given online instructions on how to incorporate placebo control into their microdosing routine without clinical supervision. The study was completed by 191 participants, making it the largest placebo-controlled trial on psychedelics to-date. All psychological outcomes improved significantly from baseline to after the 4 weeks long dose period for the microdose group; however, the placebo group also improved and no significant between-groups differences were observed. Acute (emotional state, drug intensity, mood, energy, and creativity) and post-acute (anxiety) scales showed small, but significant microdose vs. placebo differences; however, these results can be explained by participants breaking blind. The findings suggest that anecdotal benefits of microdosing can be explained by the placebo effect.

Psychedelic psychotherapy, therapy enhanced with psychedelic drugs such as LSD or psilocybin (the active ingredient of 'magic mushrooms'), has been suggested to improve psychological well-being. For this reason, trials on psychedelic therapy for the treatment of depression, addiction and other conditions are ongoing. Recently, 'microdosing' ­ a way of administering psychedelics that involves taking about 10% of a recreational dose two or three times per week ­ has gained popularity. Unlike taking large doses of psychedelics, microdosing does not induce hallucinations, but anecdotal reports suggest that it yields similar benefits as psychedelic therapy. A key feature of modern medicine are 'placebo control' studies that compare two groups of patients: one that takes a drug and another that takes inactive pills, known as placebos. Crucially, neither group knows whether they are taking drug or placebo. This control ensures that observed effects are due to the drug itself and not to unrelated psychological causes. For example, in trials of mood medicines, participants often expect to feel happier, which in itself improves their mood even when taking a placebo. This is known as the placebo effect. Restrictive drug policies make placebo-controlled studies on psychedelics difficult and expensive, in particular for microdosing, which involves taking psychedelics over a longer time period. To overcome this problem, Szigeti et al. developed a new citizen-science approach, where microdosers implemented their own placebo control based on online instructions. The advantages are the low cost and the ability to recruit participants globally. The experiment was completed by 191 microdosers, making it the largest placebo-controlled study on psychedelics to-date, for a fraction of the cost of an equivalent clinical study. The trial examined whether psychedelic microdosing can improve cognitive function and psychological well-being. The team found that microdosing significantly increased a number of psychological measures, such as well-being and life satisfaction. However, participants taking placebo also improved: there were no significant differences between the two groups. The findings confirmed positive anecdotes about microdosing improving people's moods, but at the same time show that taking empty capsules, knowing they might be microdoses, have the same benefits. This result suggests that the observed benefits are not caused by the microdose, but rather by psychological expectations. The study's innovative 'do-it-yourself' approach to placebo control may serve as a template for future citizen science studies on other popular phenomena where positive expectations and social factors could play a role, such as cannabidiol (CBD) oils, nootropics and nutrition.

Oxytocin reduces the link between neural and affective responses after social exclusion.

Being socially excluded triggers negative emotional and behavioral reactions. We examined the influence of oxytocin on the processing of social exclusion. To this end, intranasal oxytocin or placebo were administered in a double-blind trial to 90 females while neurophysiological and emotional reactions to exclusion in a Cyberball game were assessed. In the placebo group a positive correlation was found between self-reports of rejection and late positive potential (LPP) amplitude when being omitted in the game. This correlation was absent in the oxytocin group. No main effects of oxytocin on the self-reports of rejection or the LPP in exclusion trials were found. The hypothesis that oxytocin exacerbates feeling rejected after social exclusion via enhancing the salience of social cues could not be confirmed. However, our results show that the link between neural and affective reactions to social exclusion is eliminated by oxytocin. This mechanism might explain how oxytocin enacts its multiple influences on behavior.

A Behavioral Test Battery for the Repeated Assessment of Motor Skills, Mood, and Cognition in Mice.

Pharmacological and toxicological studies in neurodegeneration require comprehensive behavioral analysis in mice because motor dysfunctions and dysfunctions in mood and cognition are common and often shared symptoms in neurodegenerative diseases. Shown here is a behavioral test battery for motor, mood, and cognition, which can be repeatedly tested in a longitudinal study. This battery assesses the overall behavioral phenotype in mice by examining each domain of behavior with at least two independent well-accepted tests (i.e., open-field test and rotarod test for motor function, social interaction test, elevated plus maze test, and forced swim test for emotional function, and Morris water maze test and novel object recognition test for cognitive function). Therefore, this sensitive and comprehensive test battery is a powerful tool for the study of behavioral alternation in neurodegeneration.

The human body odor compound androstadienone increases neural conflict coupled to higher behavioral costs during an emotional Stroop task.

The androgen derivative androstadienone (AND) is a substance found in human sweat and thus may act as human chemosignal. With the current experiment, we aimed to explore in which way AND affects interference processing during an emotional Stroop task which used human faces as target and emotional words as distractor stimuli. This was complemented by functional magnetic resonance imaging (fMRI) to unravel the neural mechanism of AND-action. Based on previous accounts we expected AND to increase neural activation in areas commonly implicated in evaluation of emotional face processing and to change neural activation in brain regions linked to interference processing. For this aim, a total of 80 healthy individuals (oral contraceptive users, luteal women, men) were tested twice on two consecutive days with an emotional Stroop task using fMRI. Our results suggest that AND increases interference processing in brain areas that are heavily recruited during emotional conflict. At the same time, correlation analyses revealed that this neural interference processing was paralleled by higher behavioral costs (response times) with higher interference related brain activation under AND. Furthermore, AND elicited higher activation in regions implicated in emotional face processing including right fusiform gyrus, inferior frontal gyrus and dorsomedial cortex. In this connection, neural activation was not coupled to behavioral outcome. Furthermore, despite previous accounts of increased hypothalamic activation under AND, we were not able to replicate this finding and discuss possible reasons for this discrepancy. To conclude, AND increased interference processing in regions heavily recruited during emotional conflict which was coupled to higher costs in resolving emotional conflicts with stronger interference-related brain activation under AND. At the moment it remains unclear whether these effects are due to changes in conflict detection or resolution. However, evidence most consistently suggests that AND does not draw attention to the most potent socio-emotional information (human faces) but rather highlights representations of emotional words.

Impact of Erythropoiesis-Stimulating Agents on Behavioral Measures in Children Born Preterm.

OBJECTIVE: To evaluate the impact of erythropoiesis-stimulating agents (ESAs) administered during initial hospitalization and family demographic factors on behavior at 3.5-4 years of age. STUDY DESIGN: Children were enrolled who had previously participated in a randomized study of ESAs (n = 35) or placebo (n = 14) in infants born preterm with birth weights of 500-1250 g. A term healthy control group (n = 22) also was recruited. Behavior was evaluated by parent report with the Behavioral Assessment System of Children-2. Principal component analyses identified 2 demographic factors, a Socioeconomic Composite (SEC) and a Family Stress Composite. A multivariate general linear model evaluated the impact of study group and sex on the 4 composite scales of the Behavioral Assessment System of Children-2. Demographic factors were treated as covariates and interactions with study group (ESA, placebo, and term) were examined. RESULTS: The ESA group had significantly better scores than the placebo group on behavioral symptoms (P = .04) and externalizing scales (P = .04). An interaction was observed between study group and SEC (P = .001). A beneficial effect of ESAs was maximal in the children with lower SEC scores. CONCLUSIONS: The beneficial effects of ESAs on childhood behavior were maximal in children with lower SEC scores. ESAs seemed to ameliorate the adverse impact of lower SEC on behavioral domains seen in the placebo group. This effect was independent of the beneficial effect of ESAs on global cognition we reported previously. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01207778 and NCT00334737.

Is rivastigmine safe as pretreatment against nerve agents poisoning? A pharmacological, physiological and cognitive assessment in healthy young adult volunteers.

Rivastigmine, a reversible cholinesterase inhibitor, approved as a remedy in Alzheimer's disease, was suggested as pretreatment against nerve agents poisoning. We evaluated the pharmacokinetic, pharmacodynamic, physiologic, cognitive and emotional effects of repeated rivastigmine in young healthy male adults, in a double blind, placebo controlled crossover trial. Three groups completed 3 treatment periods: 0, 1.5 and 3mg twice a day, for a total of 5 intakes. Parameters monitored were: vital signs, ECG, laboratory tests, sialometry, visual accommodation, inspiratory peak flow, and cognitive function tests. Adverse reactions were mild. Peak blood levels and peak cholinesterase inhibition increased with repeated intakes, and high variability and non-linear pharmacokinetics were demonstrated. In addition, two cognitive functions were affected (perceptual speed and dynamic tracking). The complicated pharmacological profile and the high inter-personal variability limit the potential use of rivastigmine as pretreatment for war fighters and first responders.

[The assessment of the effects of cytoflavin and cardioxipin on the emotional status of rats with dyslipidemia].

OBJECTIVE: To compare the effects of cytoflavin and cardioxipin on the emotional status of rats with experimental disturbance of lipid metabolism using the uplifted cruciform labyrinth method. MATERIAL AND METHODS: The disturbance of lipid metabolism was induced by the introduction of exogenic cholesterol-in -oil emulsion in dosage 40 mg /kg of body mass during 20 days. Pharmacological treatment was performed in the 11th day. The drugs were injected intraperitoneally during 10 days: cytoflavin in dose 1,75 ml/ kg (175 mg/kg with succinic acid), cardioxipin in dose 52,5 mg/kg. RESULTS AND CONCLUSION: Cytoflavin and cardioxipin caused the positive changes in the parameters of emotional status of rats in conditions of experimental dyslipidemia.

Iron supplementation in infancy contributes to more adaptive behavior at 10 years of age.

Most studies of behavioral/developmental effects of iron deficiency anemia (IDA) or iron supplementation in infancy have found social-emotional differences. Differences could relate to behavioral inhibition or lack of positive affect and altered response to reward. To determine long-term behavioral effects, the study was a follow-up of a randomized controlled trial of behavioral/developmental effects of preventing IDA in infancy. Healthy Chilean infants free of IDA at age 6 mo were randomly assigned to iron supplementation or no added iron (formula with iron/powdered cow milk, vitamins with/without iron) from ages 6 to 12 mo. At age 10 y, 59% (666 of 1123) and 68% (366 of 534) of iron-supplemented and no-added-iron groups were assessed. Social-emotional outcomes included maternal-reported behavior problems, self-reported behavior, examiner ratings, and video coding of a social stress task and gamelike paradigms. Examiners rated the iron-supplemented group as more cooperative, confident, persistent after failure, coordinated, and direct and reality-oriented in speech and working harder after praise compared with the no-added-iron group. In a task designed to elicit positive affect, supplemented children spent more time laughing and smiling together with their mothers and started smiling more quickly. In the social stress task they smiled and laughed more and needed less prompting to complete the task. All P values were <0.05; effect sizes were 0.14-0.36. There were no differences in behaviors related to behavioral inhibition, such as anxiety/depression or social problems. In sum, iron supplementation in infancy was associated with more adaptive behavior at age 10 y, especially in affect and response to reward, which may improve performance at school and work, mental health, and personal relationships.

Oxytocin increases the influence of public service advertisements.

This paper presents a neurophysiologic model of effective public service advertisements (PSAs) and reports two experiments that test the model. In Experiment 1, we show that after watching 16 PSAs participants who received oxytocin, compared to those given a placebo, donated to 57% more causes, donated 56% more money, and reported 17% greater concern for those in the ads. In Experiment 2, we measured adrenocorticotropin hormone (ACTH) and oxytocin levels in blood before and after participants watched a PSA. As predicted by the model, donations occurred when participants had increases in both ACTH and oxytocin. Our results indicate that PSAs with social content that cause OT release will be more effective than those that do not. Our results also explain why some individuals do not respond to PSAs.

Writing out prescriptions: hyperrealism and the chemical regulation of mood.

Using contemporary literary sources, we explore the powerful ideological framework that normalises prescription dependency as part of everyday life, focusing upon the treatment of mood disorders. Through a literary critical methodology, we read novels by American hyperrealists such as Bret Easton Ellis, David Foster Wallace and Rick Moody as symptomatic of prescription culture. Though we argue that these writers brilliantly understand the dangers of mood medication, they do not escape its logic, rather, 'writing it out' as they write against it. Indeed, we propose that their novels bear ironic similarities to medical texts such as the British National Formulary, usually seen as a neutral handbook for physicians' guidance in prescribing. We explicate their method as that of deconstruction, which, in contrast to more obvious critiques of chemical treatment, such as therapy, neither analyses nor cures. Though this method underplays the possibility of pragmatic and political resistance exemplified by alternative formularies such as the long-established feminist health manual Our Bodies, Ourselves, we argue that its very ambiguity uniquely exposes the complex determinisms associated with prescribed medication. We thus propose the value of drawing on deconstructive literature to better understand 'health' interventions such as prescription drugs for the regulation of mood.

Disability associated with alcohol abuse and dependence.

BACKGROUND: Alcohol use disorders (AUD), i.e., alcohol dependence and abuse, are major contributors to burden of disease. A large part of this burden is because of disability. However, there is still controversy about the best disability weighting for AUD. The objective of this study was to provide an overview of alcohol-related disabilities. METHODS: Systematic literature review and expert interviews. RESULTS: There is heterogeneity in experts' descriptions of disabilities related to AUD. The major core attributes of disability related to AUD are changes of emotional state, social relationships, memory and thinking. The most important supplementary attributes are anxiety, impairments of speech and hearing. CONCLUSIONS: This review identified the main patterns of disability associated with AUD. However, there was considerable variability, and data on less prominent patterns were fragmented. Further and systematic research is required for increasing the knowledge on disability related to AUD and for application of interventions for reducing the associated burden.

Quality of life and cholinesterase inhibitors: a qualitative study of patients with Alzheimer's disease and their carers.

OBJECTIVES: Cholinesterase inhibitors' (ChEIs) impact on cognitive functioning in Alzheimer's disease has been extensively researched. The effect of ChEIs on improving day-to-day living and quality of life in conjunction with level of functioning for patients or their carers has not been investigated. METHOD: Five spouse dyads (patient and carer) and one additional carer were interviewed about their perceptions of ChEIs in relation to their influence on daily life for both parties. Interviews were transcribed and thematic analysis conducted. RESULTS: Themes identified were forgetfulness, differences in long-term versus short-term memory, independence/dependence, negative emotion, no appreciable benefit, sense of hopelessness, carer as motivator, stabilization of the patient, and never regain what has been lost. CONCLUSIONS: This study suggests that ChEI medication does not enhance life for the patient or their primary caregiver. Further qualitative and quantitative research is required into the impact of ChEIs upon both the patient and their caregivers.

Emotional expression during attention-deficit/hyperactivity disorders treatment: initial assessment of treatment effects.

OBJECTIVE: The purpose of this research was to provide an initial examination of the effects of atomoxetine and stimulants on emotional expression using a newly developed scale for assessing emotional expression in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: The parent-rated Expression and Emotion Scale for Children (EESC) was collected during two studies. During a cross-sectional validation study, the EESC was completed to assess the child's current treatment and retrospectively for previous medication. In a randomized, placebo-controlled trial of atomoxetine, the EESC was collected at baseline and endpoint. RESULTS: In the validation study, no statistically significant differences in EESC scores were found between groups taking atomoxetine (n = 74) and stimulants (n = 105). Patients who switched from a stimulant to atomoxetine (n = 40) had greater improvement in emotional expression than those switched to another stimulant (n = 21) (p = 0.008). In the clinical trial, no difference in rates of worsening of emotional expression were observed (atomoxetine 8.8%, placebo 12.3%; p = 0.440). CONCLUSION: No treatment differences in emotional expression were observed based on current medications. However, stimulant patients needing to switch medications may have greater improvements in emotional expression by switching to atomoxetine.

Misuse of "study drugs:" prevalence, consequences, and implications for policy.

BACKGROUND: Non-medical/illegal use of prescription stimulants popularly have been referred to as "study drugs". This paper discusses the current prevalence and consequences of misuse of these drugs and implications of this information for drug policy. RESULTS: Study drugs are being misused annually by approximately 4% of older teens and emerging adults. Yet, there are numerous consequences of misuse of prescription stimulants including addiction, negative reactions to high dosages, and medical complications. Policy implications include continuing to limit access to study drugs, finding more safe prescription drug alternatives, interdiction, and public education. CONCLUSION: Much more work is needed on prescription stimulant misuse assessment, identifying the extent of the social and economic costs of misuse, monitoring and reducing access, and developing prevention and cessation education efforts.

[Treatment oriented to subjective well- being rather than symptom amelioration "at all costs"--paradigm change in treatment with antipsychotics]. / Befindlichkeitsorientierte Therapie mit Antipsychotika. Auch die Gefühle Ihrer Patienten zählen.

Modern antipsychotics differ from the classical drugs mainly in their improved efficacy in combating affective, negative and cognitive symptoms and by a modified side effect profile. The variability range of such substances enable a more differentiated approach to treatment to be adopted. Patients treated with typical antipsychotics report a more pronounced improvement in subjective well-being. In view of the increasing numbers of atypical antipsychotics, the involvement of the patients in the selection of the most appropriate drug is a must. Apart from symptom amelioration - the formerly predominant goal of treatment - greater emphasis is now placed on the well-being of the individual patient on antipsychotic therapy. With this approach, the physician-patient relationship, compliance and the long-term prognosis can all be appreciably improved.

A clinical laboratory model for direct assessment of medication-induced antihyperalgesia and subjective effects: initial validation study.

Analgesic medications are often tested in clinical laboratory studies by observing their ability to reduce the pain produced by noxious stimuli presented to healthy skin. These medications may then be used clinically to reduce disease-related hyperalgesia. This article describes a clinical laboratory model useful for testing a medication's ability to reduce hyperalgesia in humans. Results demonstrate that ultraviolet (UV) light induces hyperalgesia, commonly prescribed analgesic medications reduce UV-induced hyperalgesia, and this UV-induced hyperalgesia model can be used to assess the time course of a medication's antihyperalgesia effects. Coupled with participant-rated measures of drug liking and mood, this model may prove useful for predicting the clinical efficacy and side-effect profile of novel analgesic medications in cost-efficient and statistically powerful laboratory studies.

[An assessment of the individual sensitivity of Wistar rats to the development of morphine dependence]. / Otsenka individual'noi chuvstvitel'nosti krys linii Vistar k formirovaniiu zavisimosti k morfinu.

A search was made for behavioral and physiological indicators which could serve predictors of the individual sensitivity of Wistar rats to the development of physical morphine dependence. Animals with high sensitivity to the development of dependence initially demonstrated intensive ambulation and low motor rearing in the "open field" and had low nociception. Stable animals exhibited high ambulation and motor rearing with insignificant grooming activity as compared to other rats. It has been revealed that rats sensitive to the development of dependence demonstrate higher anxiety in the Vogel test as compared to the stable ones. The findings obtained allowed one to derive a number of equations to predict Wistar rats' individual sensitivity to the development of physical morphine dependence.

Exposure of humans to a volatile organic mixture. I. Behavioral assessment.

Exposure to a low-level mixture of volatile organic compounds, typical of those found in new buildings, has been reported to impair neurobehavioral function in persons who have experienced sick building syndrome (SBS). Sixty-six healthy young males who had no history of chemical sensitivity were exposed for 2.75 h to a complex mixture of volatile organic compounds at 0 and 25 mg/m3. Even though subjects reported more fatigue and more mental confusion following exposure to volatile organic compounds than to clean air, performance on 13 neurobehavioral tests was not affected. Practice or learning effects were observed if administration of many behavioral tests were repeated. Further studies are needed to clarify the relationship of exposure to volatile organic chemicals, neurobehavioral performance, and subject characteristics, e.g., age, gender, and chemical sensitivity.

Typology of mood assessment curves by means of cluster analysis of computerized mathematical descriptions of time-series mood data collected from depressive inpatients treated with antidepressants.

A recently developed method for the computerized description of mood curves was applied to self-evaluation mood data of a large sample of 136 depressive inpatients. The values of the mathematical parameters from this description were analysed by cluster analysis to determine different types of mood courses of patients undergoing therapy with antidepressants. In general, the most unfavorable type of mood course was overrepresented in the group of neurotic depressive patients, the most favorable one in the group of endogenous depressive patients. But in this latter diagnostic group, a remarkable proportion of patients with the unfavorable mood course was observed, indicating the well-known phenomenon of non-response to antidepressants. The results can be interpreted as a validation of the new method of computerized description of mood curves. This method might lead to interesting possibilities in drug treatment evaluation.