Microdosing with psychedelics has gained considerable media attention where it is portrayed as a performance enhancer, especially popular on the work floor. While reports are in general positive, ...scientific evidence about potential negative effects is lacking aside from the prevalence and motives for use. The present study addressed this gap by surveying psychedelic users about their experience with microdosing including their dosing schedule, motivation, and potential experienced negative effects.
An online questionnaire was launched on several websites and fora between March and July 2018. Respondents who had consented, were 18 years of age or older, and had experience with microdosing were included in the analyses.
In total, 1116 of the respondents were either currently microdosing (79.5%) or microdosed in the past (20.5%). Lysergic acid diethylamide (10 mcg) and psilocybin (0.5 g) were the most commonly used psychedelics with a microdosing frequency between 2 and 4 times per week. The majority of users, however, were oblivious about the consumed dose. Performance enhancement was the main motive to microdose (37%). The most reported negative effects were of psychological nature and occurred acutely while under the influence.
In line with media reports and anecdotes, the majority of our respondents microdosed to enhance performance. Negative effects occurred mostly acutely after substance consumption. However, the main reason to have stopped microdosing was that it was not effective. Future experimental placebo-controlled studies are needed to test whether performance enhancement can be quantified and to assess potential negative effects after longer term microdosing.
The use of psychedelic substances at sub-sensorium 'microdoses', has gained popular academic interest for reported positive effects on wellness and cognition. The present study describes microdosing ...practices, motivations and mental health among a sample of self-selected microdosers (n = 4050) and non-microdosers (n = 4653) via a mobile application. Psilocybin was the most commonly used microdose substances in our sample (85%) and we identified diverse microdose practices with regard to dosage, frequency, and the practice of stacking which involves combining psilocybin with non-psychedelic substances such as Lion's Mane mushrooms, chocolate, and niacin. Microdosers were generally similar to non-microdosing controls with regard to demographics, but were more likely to report a history of mental health concerns. Among individuals reporting mental health concerns, microdosers exhibited lower levels of depression, anxiety, and stress across gender. Health and wellness-related motives were the most prominent motives across microdosers in general, and were more prominent among females and among individuals who reported mental health concerns. Our results indicate health and wellness motives and perceived mental health benefits among microdosers, and highlight the need for further research into the mental health consequences of microdosing including studies with rigorous longitudinal designs.
Reducing the moment of inertia improves the sensitivity of a mechanically based torque sensor, the parallel of reducing the mass of a force sensor, yet the correspondingly small displacements can be ...difficult to measure. To resolve this, we incorporate cavity optomechanics, which involves co-localizing an optical and mechanical resonance. With the resulting enhanced readout, cavity-optomechanical torque sensors are now limited only by thermal noise. Further progress requires thermalizing such sensors to low temperatures, where sensitivity limitations are instead imposed by quantum noise. Here, by cooling a cavity-optomechanical torque sensor to 25 mK, we demonstrate a torque sensitivity of 2.9 yNm/. At just over a factor of ten above its quantum-limited sensitivity, such cryogenic optomechanical torque sensors will enable both static and dynamic measurements of integrated samples at the level of a few hundred spins.
Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce cognitive, antidepressant, ...anxiolytic, and antiaddictive effects suggested to arise from biological changes similar to conventional antidepressants or the rapid-acting substance ketamine. The proposed route is by inducing brain neuroplasticity. This review attempts to summarize the evidence that psychedelics induce neuroplasticity by focusing on psychedelics' cellular and molecular neuroplasticity effects after single and repeated administration. When behavioral parameters are encountered in the selected studies, the biological pathways will be linked to the behavioral effects. Additionally, knowledge gaps in the underlying biology of clinical outcomes of psychedelics are highlighted. The literature searched yielded 344 results. Title and abstract screening reduced the sample to 35; eight were included from other sources, and full-text screening resulted in the final selection of 16 preclinical and four clinical studies. Studies (
n
= 20) show that a single administration of a psychedelic produces rapid changes in plasticity mechanisms on a molecular, neuronal, synaptic, and dendritic level. The expression of plasticity-related genes and proteins, including Brain-Derived Neurotrophic Factor (BDNF), is changed after a single administration of psychedelics, resulting in changed neuroplasticity. The latter included more dendritic complexity, which outlasted the acute effects of the psychedelic. Repeated administration of a psychedelic directly stimulated neurogenesis and increased BDNF mRNA levels up to a month after treatment. Findings from the current review demonstrate that psychedelics induce molecular and cellular adaptations related to neuroplasticity and suggest those run parallel to the clinical effects of psychedelics, potentially underlying them. Future (pre)clinical research might focus on deciphering the specific cellular mechanism activated by different psychedelics and related to long-term clinical and biological effects to increase our understanding of the therapeutic potential of these compounds.
Background:
In the past few years, the issue of ‘microdosing’ psychedelics has been openly discussed in the public arena where claims have been made about their positive effect on mood state and ...cognitive processes such as concentration. However, there are very few scientific studies that have specifically addressed this issue, and there is no agreed scientific consensus on what microdosing is.
Aim:
This critique paper is designed to address questions that need to be answered by future scientific studies and to offer guidelines for these studies.
Approach:
Owing to its proximity for a possible approval in clinical use and short-lasting pharmacokinetics, our focus is predominantly on psilocybin. Psilocybin is allegedly, next to lysergic acid diethylamide (LSD), one of the two most frequently used psychedelics to microdose. Where relevant and available, data for other psychedelic drugs are also mentioned.
Conclusion:
It is concluded that while most anecdotal reports focus on the positive experiences with microdosing, future research should also focus on potential risks of (multiple) administrations of a psychedelic in low doses. To that end, (pre)clinical studies including biological (e.g. heart rate, receptor turnover and occupancy) as well as cognitive (e.g. memory, attention) parameters have to be conducted and will shed light on the potential negative consequences microdosing could have.
Energy harvesting devices based on the triboelectric effect have attracted great attention because of their higher output performance compared to other nanogenerators, which have been utilized in ...various wearable applications. Based on the working mechanism, the triboelectric performance is mainly proportional to the surface charge density of the triboelectric materials. Various approaches, such as modification of the surface functional group and dielectric composition of the triboelectric materials, have been employed to enhance the surface charge density, leading to improvements in triboelectric performances. Notably, tuning the dielectric properties of triboelectric materials can significantly increase the surface charge density because the surface charge is proportional to the relative permittivity of the triboelectric material. The relative dielectric constant is modified by dielectric polarization, such as electronic, vibrational (or atomic), orientation (or dipolar), ionic, and interfacial polarization. Therefore, such polarization represents a critical factor toward improving the dielectric constant and consequent triboelectric performance. In this review, we summarize the recent insights on the improvement of triboelectric performance via enhanced dielectric polarization.
Sclerostin has traditionally been thought of as a local inhibitor of bone acquisition that antagonizes the profound osteoanabolic capacity of activated Wnt/β-catenin signaling, but serum sclerostin ...levels in humans exhibit a correlation with impairments in several metabolic parameters. These data, together with the increased production of sclerostin in mouse models of type 2 diabetes, suggest an endocrine function. To determine whether sclerostin contributes to the coordination of whole-body metabolism, we examined body composition, glucose homeostasis, and fatty acid metabolism in Sost−/− mice as well as mice that overproduce sclerostin as a result of adeno-associated virus expression from the liver. Here, we show that in addition to dramatic increases in bone volume, Sost−/− mice exhibit a reduction in adipose tissue accumulation in association with increased insulin sensitivity. Sclerostin overproduction results in the opposite metabolic phenotype due to adipocyte hypertrophy. Additionally, Sost−/− mice and those administered a sclerostin-neutralizing antibody are resistant to obesogenic diet-induced disturbances in metabolism. This effect appears to be the result of sclerostin’s effects on Wnt signaling and metabolism in white adipose tissue. Since adipocytes do not produce sclerostin, these findings suggest an unexplored endocrine function for sclerostin that facilitates communication between the skeleton and adipose tissue.
Graphene devices on standard SiO(2) substrates are highly disordered, exhibiting characteristics that are far inferior to the expected intrinsic properties of graphene. Although suspending the ...graphene above the substrate leads to a substantial improvement in device quality, this geometry imposes severe limitations on device architecture and functionality. There is a growing need, therefore, to identify dielectrics that allow a substrate-supported geometry while retaining the quality achieved with a suspended sample. Hexagonal boron nitride (h-BN) is an appealing substrate, because it has an atomically smooth surface that is relatively free of dangling bonds and charge traps. It also has a lattice constant similar to that of graphite, and has large optical phonon modes and a large electrical bandgap. Here we report the fabrication and characterization of high-quality exfoliated mono- and bilayer graphene devices on single-crystal h-BN substrates, by using a mechanical transfer process. Graphene devices on h-BN substrates have mobilities and carrier inhomogeneities that are almost an order of magnitude better than devices on SiO(2). These devices also show reduced roughness, intrinsic doping and chemical reactivity. The ability to assemble crystalline layered materials in a controlled way permits the fabrication of graphene devices on other promising dielectrics and allows for the realization of more complex graphene heterostructures.
While learning-based control techniques often outperform classical controller designs, safety requirements limit the acceptance of such methods in many applications. Recent developments address this ...issue through so-called predictive safety filters, which assess if a proposed learning-based control input can lead to constraint violations and modifies it if necessary to ensure safety for all future time steps. The theoretical guarantees of such predictive safety filters rely on the model assumptions and minor deviations can lead to failure of the filter putting the system at risk. This article introduces an auxiliary soft-constrained predictive control problem that is always feasible at each time step and asymptotically stabilizes the feasible set of the original predictive safety filter problem, thereby providing a recovery mechanism in safety-critical situations. This is achieved by a simple constraint tightening in combination with a terminal control barrier function. By extending discrete-time control barrier function theory, we establish that the proposed auxiliary problem provides a "predictive" control barrier function. The resulting algorithm is demonstrated using numerical examples.
This paper provides new insights on consumers payment choice by comparing cost of paying with cash to paying with cards. Our novel method accounts for how much change is received in the form of ...banknotes and metal coins, assuming that the weight and size of coins are inconvenient to carry. We use the regression discontinuity design approach to estimate the model using the 2013 Bank of Canada Method-of-Payments Survey and find a significant number of cash users who switch to paying with debit or credit cards at transaction values marginally above $5 and $10. We attribute this finding to the burden of receiving coins as change associated with the currency denomination structure. Our proposed methodology is general and can be applied to other countries and institutional details.
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