The present study describes microdosing practices, motivations and mental health among a sample of self-selected microdosers (n = 4,050) and
non-microdosers (n = 4,653) 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.
…Design and participants: We collected cross-sectional data between November 2019 and July 2020 from self-selected respondents
recruited via media related to psychedelic use such as podcasts and online psychedelic research conference presentations. Participants were directed to the
Microdose.me website. The website directed participants to install the Quantified Citizen (QC) application32 to
their Apple mobile device. The QC application was only available on Apple iOS devices at the time of study; as such, participants were limited to iPhone users. The
application hosted the study and participants completed questionnaires and assessments entirely within the application. To encourage participation, users were
explicitly not asked to submit any personally identifiable information and use of the application was designed to be completely anonymous. All participants
endorsed being 18 years of age or older and capable of responding to an English survey. Nonetheless, given the anonymous nature of the study design, these
inclusion criteria could not be verified beyond participant self-report. All participants provided informed consent prior to study initiation. Data are drawn from
the baseline and supplementary questionnaires from a longitudinal study of microdosing and mental health and consisted of a maximal total of 123 questions,
organized hierarchically such that many items were contingent on prior responses.
Josikinz recently posted a wonderful video on Youtube titled “Psychedelic Entities—broken down and described”. I really appreciate the use of high-quality psychedelic replication
art throughout the video in order to illustrate what they are talking about. I recommend watching the whole video; below an excerpt that discusses what happens
when you try to ask these entities questions (starting at 10:53):
…Personal Commentary: …a substantial potion of the people who encounter them will go as far as to assert that these experiences are not simply
fabrications of the mind, but rather beings from another world that exist independently of the human brain. This is a viewpoint that was originally popularized in
mainstream culture by the likes of Terence McKenna, who famously theorized that the machine elves he encountered under the influence of DMT were either
extraterrestrial in nature, interdimensional beings from a higher plane of existence, time-traveling humans from the future, or an ecology of souls that apparently
includes both our ancestors and those who are yet to be born. As far as I can tell, the most common reasonings behind this viewpoint are that the experience of
encountering these entities is often interpreted as feeling more realistic and well-defined than that of any sober experience the person has ever had. Alongside
this, there is often a sense that the encounter itself is so incomprehensibly complex and other-worldly that there is simply no possible way that the human brain
could generate such an experience on its own.
In regards to this particular notion, it is then sometimes asserted that consciousness must be an antenna of sorts that receives either all or some of its
subjective experiences from that of an unknown interdimensional source. Furthermore, the source of this received input is sometimes said to be adjustable depending
on the person’s brain state. With substances such as psychedelics simply “tuning” our consciousness into the analogous equivalent of a different radio station or
TV channel. This is an idea that was once again further popularized by Terence McKenna, who is famously quoted as saying: “I don’t believe that consciousness is
generated in the brain anymore than TV programs are made inside my TV. The box is too small.”
…In my personal opinion, if autonomous entities were truly something that exists beyond the human mind, I think there would likely be a single verifiable case
of them conveying information to a person that they did not already know or could not have come to the conclusion of within that moment. This would also likely be
testable to some degree, which has led myself and my close friends to casually experiment with asking DMT entities a variety of questions over the years [emphasis mine]. These questions have included math problems,
metaphysical questions, philosophical questions, and queries pertaining to the general nature of beings inhabiting their particular world. However, each attempt at
doing so has resulted in the entities simply ignoring the question, arrogantly scoffing at the absurdity of us asking them such a trivial thing, or replying with
vague ambiguous wording that the person’s own mind could have easily come up with. This has even been the case when the entities are presenting themselves as
vastly more complex, knowledgeable, and powerful than the humans that they are interacting with.
[commentary] 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
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
All psychological outcomes improved statistically-significantly from baseline to after the 4 weeks long dose period for the microdose group; however, the
placebo group also improved and no statistically-significant between-groups differences were observed. Acute (emotional state, drug intensity, mood, energy, and
creativity) and post-acute (anxiety) scales showed small, but statistically-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.
…It is worth noting that the current study was designed to protect blinding integrity by including placebos for the microdose group as well, administering the
microdose capsules on different days of the week and by including the half-half group. The 3-arm design can be seen as a strength in this regard, adding ambiguity
and thus strengthening blinding. Illustrative of the integrity of the blind, we received several emails from participants in the PL group who were in disbelief
after opening their unused envelopes containing unused capsules after the conclusion of the study:
“I counted the number of cut blotters I had in the left overs: they are 8…so you must be right… Which is incredible […] Some days during the test were
really, really focused and colours more vivid. This sensation was really new to me”.
“I have just checked the remaining envelopes and it appears that I was indeed taking placebos throughout the trial. I’m quite astonished […] It seems I was
able to generate a powerful ‘altered consciousness’ experience based only the expectation around the possibility of a microdose”.
“An empty pill with strong belief/intentions makes nearly everything. You put spirituality into an empty pill here…wow!”
eLife digest: 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 2 or 3× 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 2021 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
The trial examined whether psychedelic microdosing can improve cognitive function and psychological well-being. The team found that microdosing
statistically-significantly increased a number of psychological measures, such as well-being and life satisfaction. However, participants taking placebo also
improved: there were no statistically-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.
Psychedelic microdosing describes the ingestion of near-threshold perceptible doses of classic psychedelic substances. Anecdotal reports and observational
studies suggest that microdosing may promote positive mood and well-being, but recent placebo-controlled studies failed to find compelling evidence for this.
The present study collected web-based mental health and related data using a prospective (before, during and after) design. Individuals planning a weekly
microdosing regimen completed surveys at strategic timepoints, spanning a core 4-week test period. 81 participants completed the primary study endpoint. Results
revealed increased self-reported psychological well-being, emotional stability and reductions in state anxiety and depressive symptoms at the four-week primary
endpoint, plus increases in psychological resilience, social connectedness, agreeableness, nature relatedness and aspects of psychological flexibility. However,
positive expectancy scores at baseline predicted subsequent improvements in well-being, suggestive of a substantial placebo response. This study highlights a role
for positive expectancy in predicting positive outcomes following psychedelic microdosing and cautions against zealous inferences on its putative therapeutic
…Due to the pragmatic challenges of doing so via an online observational study, the present study did not include a placebo control condition. We did, however,
employ a prospective, naturalistic design that included baseline sampling of expectations about possible outcomes from the impending microdosing. Well-being, state
anxiety and depressive symptom scores were measured weekly on five occasions (pre-dosing at baseline to week 4 of the microdosing regimen) in order to track
time-dependent changes. Neuroticism/emotional stability
was measured pre-dosing at baseline and post-dosing at week 4 only. It was predicted that well-being and emotional stability would be increased, and that
depression and anxiety scores would be decreased, at the key-endpoint (4 weeks) compared with baseline. Capitalising on the nature of the prospective design, we
also predicted that baseline positive expectations about microdosing would be related to any subsequent improvements in well-being, depressive symptoms and anxiety
scores. Finally, exploratory analyses were performed to assess pre-post changes in a range of secondary psychological outcomes of interest.
…Expectancy effect on main outcome change scores: One-tailed partial correlations using Pearson coefficient were employed in order to
investigate the effects of baseline expectations on endpoint change scores (endpoint—baseline) for the primary outcome variables (well-being, depressive symptoms
and anxiety), whilst controlling for the corresponding baseline scores. In line with our main hypothesis, expectations for well-being improvement were
statistically-significantly associated with change scores in well-being (r = 0.275 [d = −0.57], p = 0.007), depressive symptoms
(r = −0.263 [d = −0.54], p = 0.009) and anxiety (r = −0.220 [d = −0.45], p = 0.025). These results indicate
that baseline expectations were predictive of mental health change at the study endpoint.
Key Points: Question: Can long-term supplementation with vitamin D3 prevent depression in the general adult population?
Findings: In this randomized clinical trial that included 18 353 adults aged 50 years or older without depression or clinically relevant
depressive symptoms at baseline, vitamin D3 supplementation compared with placebo did not result in statistically-significant differences in the
incidence and recurrence of depression or clinically relevant depressive symptoms (hazard ratio, 0.97) or for change in mood scores over a 5-year treatment
Meaning: These findings do not support the use of vitamin D3 in adults to prevent depression.
Importance: Low levels of 25-hydroxyvitamin D have been associated with higher risk for depression later in life, but there have been few
long-term, high-dose large-scale trials.
Objective: To test the effects of vitamin D3 supplementation on late-life depression risk and mood scores.
Design, Setting, and Participants: There were 18 353 men and women aged 50 years or older in the VITAL-DEP (Vitamin D and Omega-3Trial-Depression Endpoint Prevention) ancillary study to VITAL, a randomized clinical trial of cardiovascular disease and cancer prevention among 25 871 adults in the US. There were 16 657
at risk for incident depression (ie. no depression history) and 1696 at risk for recurrent depression (ie. depression history but no treatment for depression
within the past 2 years). Randomization occurred from November 2011 through March 2014; randomized treatment ended on December 31, 2017, and this was the
final date of follow-up.
Intervention: Randomized assignment in a 2 × 2 factorial design to vitamin D3 (2000 IU/d of cholecalciferol) and fish oil or
placebo; 9181 were randomized to vitamin D3 and 9172 were randomized to matching placebo.
Main Outcomes and Measures: The primary outcomes were the risk of depression or clinically relevant depressive symptoms (total of incident and
recurrent cases) and the mean difference in mood scores (8-item Patient Health Questionnaire depression scale [PHQ-8];
score range, 0 points [least symptoms] to 24 points [most symptoms]; the minimal clinically important difference for change in scores was 0.5 points).
Results: Among the 18 353 randomized participants (mean age, 67.5 [SD, 7.1] years; 49.2% women), the median treatment duration was 5.3 years
and 90.5% completed the trial (93.5% among those alive at the end of the trial). Risk of depression or clinically relevant depressive symptoms was not
statistically-significantly different between the vitamin D3 group (609 depression or clinically relevant depressive symptom events; 12.9/1000
person-years) and the placebo group (625 depression or clinically relevant depressive symptom events; 13.3/1000 person-years) (hazard ratio, 0.97 [95%
CI, 0.87 to 1.09]; p = 0.62); there were no statistically-significant differences between groups in depression
incidence or recurrence. No statistically-significant differences were observed between treatment groups for change in mood scores over time; mean change in
PHQ-8 score was not statistically-significantly different from zero (mean difference for change in mood scores, 0.01
points [95% CI, −0.04 to 0.05 points]).
Conclusions and Relevance: Among adults aged 50 years or older without clinically relevant depressive symptoms at baseline, treatment with
vitamin D3 compared with placebo did not result in a statistically-significant difference in the incidence and recurrence of depression or clinically
relevant depressive symptoms or for change in mood scores over a median follow-up of 5.3 years. These findings do not support the use of vitamin D3 in
adults to prevent depression.
Stimulants such as methylphenidate are increasingly
used for cognitive enhancement but precise mechanisms are unknown. We found that methylphenidate boosts willingness to expend cognitive effort by altering the
benefit-to-cost ratio of cognitive work. Willingness to expend effort was greater for participants with higher striatal dopamine synthesis capacity, whereas
methylphenidate and sulpiride, a selective D2 receptor antagonist, increased cognitive motivation more for participants with
lower synthesis capacity. A sequential sampling model informed by momentary gaze revealed that decisions to expend effort are related to amplification of
benefit-versus-cost information attended early in the decision process, whereas the effect of benefits is strengthened with higher synthesis capacity and by
methylphenidate. These findings demonstrate that methylphenidate boosts the perceived
benefits versus costs of cognitive effort by modulating striatal dopamine signaling.
Background: Numerous anecdotal reports suggest that repeated use of very low doses of lysergic acid diethylamide (LSD), known as microdosing, improves mood and cognitive function. These effects are consistent both with the known actions of
LSD on serotonin receptorsand with limited evidence that higher doses of LSD
(100–200 μg) positively bias emotion processing. Yet, the effects of such sub-threshold doses of LSD have not been
tested in a controlled laboratory setting. As a first step, we examined the effects of single very low doses of LSD (0–26 μg) on mood and behavior in healthy volunteers under double-blind conditions.
Methods: Healthy young adults (N = 20) attended 4 laboratory sessions during which they received 0 (placebo), 6.5, 13, or 26 μg of
LSD in randomized order at 1-week intervals. During expected peak drug effect, they completed mood questionnaires
and behavioral tasks assessing emotion processing and cognition. Cardiovascular measures and body temperature were also assessed.
Results: LSD produced dose-related subjective effects across the 3 doses (6.5, 13, and 26 μg).
At the highest dose, the drug also increased ratings of vigor and slightly decreased positivity ratings of images with positive emotional content. Other mood
measures, cognition, and physiological measures were unaffected.
Conclusions: Single microdoses of LSD produced orderly dose-related subjective effects in
healthy volunteers. These findings indicate that a threshold dose of 13 μg of LSD might be used safely in an
investigation of repeated administrations. It remains to be determined whether the drug improves mood or cognition in individuals with symptoms of depression.
Naturally occurring and psychedelic drug-occasioned experiences interpreted as personal encounters with God are well described but have not been systematically
compared. In this study, five groups of individuals participated in an online survey with detailed questions characterizing the subjective phenomena,
interpretation, and persisting changes attributed to their single most memorable God encounter experience (n = 809 Non-Drug, 1184 psilocybin, 1251
lysergic acid diethylamide (LSD), 435 ayahuasca, and 606 N,N-dimethyltryptamine (DMT)). Analyses of differences in experiences were adjusted statistically for demographic differences between groups. The
Non-Drug Group was most likely to choose “God” as the best descriptor of that which was encountered while the psychedelic groups were most likely to choose
“Ultimate Reality.” Although there were some other differences between non-drug and the combined psychedelic group, as well as between the four psychedelic groups,
the similarities among these groups were most striking. Most participants reported vivid memories of the encounter experience, which frequently involved
communication with something having the attributes of being conscious, benevolent, intelligent, sacred, eternal, and all-knowing. The encounter experience
fulfilled a priori criteria for being a complete mystical experience in approximately half of the participants. More than two-thirds of those who identified as
atheist before the experience no longer identified as atheist afterwards. These experiences were rated as among the most personally meaningful and spiritually
significant lifetime experiences, with moderate to strong persisting positive changes in life satisfaction, purpose, and meaning attributed to these experiences.
Among the four groups of psychedelic users, the psilocybin and LSD groups were most similar and the ayahuasca
group tended to have the highest rates of endorsing positive features and enduring consequences of the experience. Future exploration of predisposing factors and
phenomenological and neural correlates of such experiences may provide new insights into religious and spiritual beliefs that have been integral to shaping human
culture since time immemorial.
The phenomenon of ‘microdosing’, that is, regular ingestion of very small quantities of psychedelic substances, has seen a rapid explosion of popularity in
recent years. Individuals who microdose report minimal acute effects from these substances yet claim a range of long-term general health and wellbeing benefits.
There have been no published empirical studies of microdosing and the current legal and bureaucratic climate makes direct empirical investigation of the effects of
In Study One we conducted a systematic, observational investigation of individuals who microdose. We tracked the experiences of 98 microdosing participants, who
provided daily ratings of psychological functioning over a six week period. 63 of these additionally completed a battery of psychometric measures tapping mood,
attention, wellbeing, mystical experiences, personality, creativity, and sense of agency, at baseline and at completion of the study. Analyses of daily ratings
revealed a general increase in reported psychological functioning across all measures on dosing days but limited evidence of residual effects on following days.
Analyses of pre and post study measures revealed reductions in reported levels of depression and stress; lower levels of distractibility; increased absorption; and
To better understand these findings, in Study Two we investigated pre-existing beliefs and expectations about the effects of microdosing in a sample of 263
naïve and experienced microdosers, so as to gauge expectancy bias. All participants believed that microdosing would have large and wide-ranging benefits in
contrast to the limited outcomes reported by actual microdosers. Notably, the effects believed most likely to change were unrelated to the
observed pattern of reported outcomes.
The current results suggest that dose controlled empirical research on the impacts of microdosing on mental health and attentional capabilities are needed.
Recently popular sub-perceptual doses of psychedelic substances such as truffles, referred to as microdosing, allegedly have multiple beneficial effects
including creativity and problem solving performance, potentially through targeting serotonergic 5-HT2A receptors and promoting cognitive flexibility,
crucial to creative thinking. Nevertheless, enhancing effects of microdosing remain anecdotal, and in the absence of quantitative research on microdosing
psychedelics it is impossible to draw definitive conclusions on that matter. Here, our main aim was to quantitatively explore the cognitive-enhancing potential of
microdosing psychedelics in healthy adults.
Methods: During a microdosing event organized by the Dutch Psychedelic Society, we examined the effects of psychedelic truffles (which were
later analyzed to quantify active psychedelic alkaloids) on two creativity-related problem-solving tasks: the Picture Concept Task assessing convergent thinking,
and the Alternative Uses Task assessing divergent thinking. A short version of the Ravens Progressive Matrices task assessed potential changes in fluid
intelligence. We tested once before taking a microdose and once while the effects were manifested.
Results: We found that both convergent and divergent thinking performance was improved after a non-blinded microdose, whereas fluid
intelligence was unaffected.
Conclusion: While this study provides quantitative support for the cognitive enhancing properties of microdosing psychedelics, future research
has to confirm these preliminary findings in more rigorous placebo-controlled study designs. Based on these preliminary results we speculate that psychedelics
might affect cognitive meta-control policies by optimizing the balance between cognitive persistence and flexibility. We hope this study will motivate future
microdosing studies with more controlled designs to test this hypothesis.
Introduction: User surveys indicate that expectations of higher drug purity are a key reason for cryptomarket use. In 2014–2015, Spain’s NGO Energy Control conducted a 1-year pilot project to provide a testing service to cryptomarket drug users using the Transnational European Drug Information (TEDI) guidelines.
In this paper, we present content and purity data from the trial.
Methods: 219 samples were analyzed by gas chromatography associated with mass spectrometry (GC/MS). Users were asked to report
what substance they allegedly purchased.
Results: 40 different advertised substances were reported, although 77.6% were common recreational drugs (cocaine, MDMA, amphetamines, LSD, ketamine, cannabis). In 200 samples (91.3%), the main result of analysis matched the advertised substance. Where the
advertised compound was detected, purity levels (m ± SD) were: cocaine 71.6 ± 19.4%; MDMA (crystal) 88.3 ±
1.4%; MDMA (pills) 133.3 ± 38.4 mg; Amphetamine (speed) 51.3 ± 33.9%; LSD 123.6 ± 40.5 μg; Cannabisresin THC: 16.5 ± 7.5% CBD: 3.4 ± 1.5%; Ketamine 71.3 ± 38.4%. 39.8% of cocaine samples contained the adulterant levamisole (11.6 ± 8%). No adulterants were found in MDMAand LSD samples.
Discussion: The largest collection of test results from drug samples delivered from cryptomarkets are reported in this study. Most substances
contained the advertised ingredient and most samples were of high purity. The representativeness of these results is unknown.
[Keywords: cryptomarkets, drug markets, purity, adulterants, drug checking, drug trend monitoring]
Predisposition to respond to placebo treatment may be in part a stable heritable trait.
Candidate placebo response pathways may interact with drugs to modify outcomes in both the placebo and drug treatment arms of clinical trials.
Genomic analysis of randomized placebo and no-treatment controlled trials are needed to fully realize the potential of the placebome.
Placebos are indispensable controls in randomized clinical trials (RCTs), and placebo responses
statistically-significantly contribute to routine clinical outcomes. Recent neurophysiological studies reveal neurotransmitter pathways that mediate placebo
effects. Evidence that genetic variations in these pathways can modify placebo effects raises the possibility of using genetic screening to identify placebo
responders and thereby increase RCT efficacy and improve therapeutic care. Furthermore, the possibility of
interaction between placebo and drug molecular pathways warrants consideration in RCT design. The study of genomic
effects on placebo response, ‘the placebome’, is in its infancy. Here, we review evidence from placebo studies and RCTs
to identify putative genes in the placebome, examine evidence for placebo-drug interactions, and discuss implications for RCTs and clinical care.
Why does performing certain tasks cause the aversive experience of mental effort and concomitant deterioration in task performance? One explanation posits a
physical resource that is depleted over time. We propose an alternative explanation that centers on mental representations of the costs and benefits associated
with task performance. Specifically, certain computational mechanisms, especially those associated with executive function, can be deployed for only a limited number of simultaneous tasks at any given moment.
Consequently, the deployment of these computational mechanisms carries an opportunity cost – that is, the next-best use to which these systems might be
put. We argue that the phenomenology of effort can be understood as the felt output of these cost/benefit computations. In turn, the subjective experience of
effort motivates reduced deployment of these computational mechanisms in the service of the present task. These opportunity cost representations, then, together
with other cost/benefit calculations, determine effort expended and, everything else equal, result in performance reductions. In making our case for this
position, we review alternative explanations for both the phenomenology of effort associated with these tasks and for performance reductions over time. Likewise,
we review the broad range of relevant empirical results from across sub-disciplines, especially psychology and neuroscience. We hope that our proposal will help to
build links among the diverse fields that have been addressing similar questions from different perspectives, and we emphasize ways in which alternative models
might be empirically distinguished.
Why does performing certain tasks cause the aversive experience of mental effort and concomitant deterioration in task performance? One explanation posits a
physical resource that is depleted over time. We propose an alternative explanation that centers on mental representations of the costs and benefits associated
with task performance. Specifically, certain computational mechanisms, especially those associated with executive function,
can be deployed for only a limited number of simultaneous tasks at any given moment. Consequently, the deployment of these computational mechanisms carries an
opportunity cost—that is, the next-best use to which these systems might be put. We argue that the phenomenology of effort can be understood as the felt output of
these cost/benefit computations. In turn, the subjective experience of effort motivates reduced deployment of these computational mechanisms in the service of
the present task. These opportunity cost representations, then, together with other cost/benefit calculations, determine effort expended and, everything else
equal, result in performance reductions. In making our case for this position, we review alternative explanations for both the phenomenology of effort associated
with these tasks and for performance reductions over time. Likewise, we review the broad range of relevant empirical results from across sub-disciplines,
especially psychology and neuroscience. We hope that our proposal will help to build links among the diverse fields that have been addressing similar questions
from different perspectives, and we emphasize ways in which alternative models might be empirically distinguished.
The classical serotonergic psychedelics LSD, psilocybin,mescaline are not known to cause brain damage and are regarded as non-addictive. Clinical studies do not suggest
that psychedelics cause long-term mental health problems. Psychedelics have been used in the Americas for thousands of years. Over 30 million people currently
living in the US have used LSD, psilocybin, ormescaline.
To evaluate the association between the lifetime use of psychedelics and current mental health in the adult population.
Data drawn from years 2001 to 2004 of the National Survey on Drug Use and Health consisted of 130,152 respondents, randomly selected to be representative of the
adult population in the United States. Standardized screening measures for past year mental health included serious psychological distress (K6 scale), mental
health treatment (inpatient, outpatient, medication, needed but did not receive), symptoms of eight psychiatric disorders (panic disorder, major depressive
episode, mania, social phobia, general anxiety disorder, agoraphobia, post-traumatic stress disorder, and non-affective psychosis), and seven specific symptoms of non-affective psychosis.
We calculated weighted odds ratios by multivariate logistic regression controlling for a range of sociodemographic variables, use of illicit drugs, risk taking
behavior, and exposure to traumatic events.
21,967 respondents (13.4% weighted) reported lifetime psychedelic use. There were no statistically-significant associations between lifetime use of any
psychedelics, lifetime use of specific psychedelics (LSD, psilocybin, mescaline,
peyote), or past year use of LSD and increased rate of any of the mental health outcomes. Rather, in several cases
psychedelic use was associated with lower rate of mental health problems.
We did not find use of psychedelics to be an independent risk factor for mental health problems.
Transcranial laser stimulation improved cognitive and emotional functions in humans.
Randomized, placebo-controlled blind trials using attention, memory and mood tests.
Reaction time in a psychomotor vigilance task was statistically-significantly improved.
Memory retrieval latency and correct match-to-sample trials improved statistically-significantly.
Laser effects also led to 2 weeks of sustained positive emotional states.
This is the first controlled study demonstrating the beneficial effects of transcranial laser stimulation on cognitive and emotional functions in humans.
Photobiomodulation with red to near-infrared light is a novel
intervention shown to regulate neuronal function in cell cultures, animal models, and clinical conditions.
Reaction time in a sustained-attention psychomotor vigilance task (PVT) was statistically-significantly improved in
the treated (n = 20) vs. placebo control (n = 20) groups, especially in high novelty-seeking subjects. Performance in a delayed
match-to-sample (DMS) memory task showed also astatistically-significant improvement in treated vs. control groups as measured by memory retrieval latency and number of
correct trials. The Positive and Negative
Affect Schedule (PANAS-X), which tracks self-reported positive and negative affective (emotional) states over time, was administered immediately before
treatment and 2 weeks after treatment. The PANAS showed that while participants generally reported more positive
affective states than negative, overall affect improved statistically-significantly in the treated group due to more sustained positive emotional states as
compared to the placebo control group.
These data imply that transcranial laser stimulation could be used as a non-invasive and efficacious approach to increase brain functions such as those related
to cognitive and emotional dimensions. Transcranial infrared laser stimulation has also been proven to be safe and successful at improving neurological outcome in
humans in controlled clinical trials of stroke. This
innovative approach could lead to the development of non-invasive, performance-enhancing interventions in healthy humans and in those in need of neuropsychological
Background. Increasing concern is evident about contamination of foodstuffs and natural health products. Methods. Common off-the-shelf varieties of black,
green, white, and oolong teas sold in tea bags were used for analysis in this study. Toxic element testing was performed on 30 different teas by analyzing (1) tea
leaves, (2) tea steeped for 3–4 minutes, and (3) tea steeped for 15–17 minutes. Results were compared to existing preferred endpoints. Results. All brewed teas
contained lead with 73% of teas brewed for 3 minutes and 83% brewed for 15 minutes having lead levels considered unsafe for consumption during pregnancy and
lactation. Aluminum levels were above recommended guidelines in 20% of brewed teas. No mercury was found at detectable levels in any brewed tea samples. Teas
contained several beneficial elements such as magnesium, calcium, potassium, and phosphorus. Of trace minerals, only manganese levels were found to be excessive in
some black teas. Conclusions. Toxic contamination by heavy metals was found in most of the teas sampled. Some tea samples are considered unsafe. There are no
existing guidelines for routine testing or reporting of toxicant levels in “naturally” occurring products. Public health warnings or industry regulation might be
indicated to protect consumer safety.
Persistent forms of nondual awareness, enlightenment, mystical experience, and so forth (Persistent Non-Symbolic Experience) have been reported since antiquity.
Though sporadic research has been performed on them, the research reported here represents the initial report from the first larger scale cognitive psychology
study of this population.
Method: Assessment of the subjective experience of fifty adult participants reporting persistent non-symbolic experience was undertaken using
6–12 hour semi-structured interviews and evaluated using thematic analysis. Additional assessment was performed using psychometric measures, physiological
measurement, and experimentation.
Results: Five core, consistent categories of change were uncovered: sense-of-self, cognition, emotion, perception, and memory. Participants’
reports formed clusters in which the types of change in each of these categories were consistent. Multiple clusters were uncovered that formed a range of possible
experiences. The variety of these experiences and their underlying categories may inform the debate between constructivist, common core, and participatory
…Over the course of a week, his father died followed very rapidly by his sister. He was also going through a major issue with one of his children. Over dinner I
asked him about his internal state, which he reported as deeply peaceful and positive despite everything that was happening. Having known that the participant was
bringing his longtime girlfriend, I’d taken an associate researcher with me to the meeting to independently collect the observations from her. My fellow researcher
isolated the participant’s girlfriend at the bar and interviewed her about any signs of stress that the participant might be exhibiting. I casually asked the same
questions to the participant as we continued our dinner conversation. Their answers couldn’t have been more different. While the participant reported no stress,
his partner had been observing many telltale signs: he wasn’t sleeping well, his appetite was off, his mood was noticeably different, his muscles were much tenser
than normal, his sex drive was reduced, his health was suffering, and so forth…It was not uncommon for participants to state that they had gained increased bodily
awareness upon their transition into PNSE. I arranged and observed private yoga sessions with a series of
participants as part of a larger inquiry into their bodily awareness. During these sessions it became clear that participants believed they were far more aware of
their body than they actually were…Many participants discussed the thought, just after their transition to PNSE, that
they would have to go to work and explain the difference in themselves to co-workers. They went on to describe a puzzled drive home after a full day of work
when no one seemed to notice anything different about them. Quite a few chose to never discuss the change that had occurred in them with their families and friends
and stated that no one seemed to notice much of a difference.
There was also a progressively decreasing sense of agency. In the final stage, Location 4, he reports: “These participants reported having no sense of agency or
any ability to make a decision. It felt as if life was simply unfolding and they were watching the process happen. Severe memory deficits were common in these
participants, including the inability to recall scheduled events that were not regular and ongoing.” And yet, almost all of the subjects reported it as a positive
experience. The subjects, at whatever point they were in the scale, were often completely certain about the nature of the experience: “PNSE was often accompanied by a tremendous sense of certainty that participants were experiencing a ‘deeper’ or ‘more true’ reality.
As time passed, this often increased in strength.” They also tended to be dogmatic about their PNSE being the real
thing (whichever location they were at) and descriptions of other people’s different PNSEs as not the real thing.
Another way to say “completely certain” is “unable to doubt”.
Transcranial brain stimulation with low-level light / laser
therapy (LLLT) is the use of directional low-power and high-fluency monochromatic or quasimonochromatic light from lasers or LEDs in the red-to-near-infrared wavelengths to modulate a neurobiological function or induce a neurotherapeutic effect in a
nondestructive and non-thermal manner.
The mechanism of action of LLLT is based on photon energy absorption by cytochrome oxidase, the terminal enzyme in the mitochondrial respiratory chain.
Cytochrome oxidase has a key role in neuronal physiology, as it serves as an interface between oxidative energy metabolism and cell survival signaling pathways.
Cytochrome oxidase is an ideal target for cognitive enhancement, as its expression reflects the changes in metabolic capacity underlying higher-order brain
This review provides an update on new findings on the neurotherapeutic applications of LLLT. The
photochemical mechanisms supporting its cognitive-enhancing and brain-stimulatory effects in animal models and humans are discussed. LLLT is a potential non-invasive treatment for cognitive impairment and other deficits associated with chronic
neurological conditions, such as large vessel and lacunar hypoperfusion or neurodegeneration.
Brain photobiomodulation with LLLT is paralleled by pharmacological effects of low-dose USPmethylene blue, a non-photic electron
donor with the ability to stimulate cytochrome oxidase activity, redox and free radical processes. Both interventions provide neuroprotection and cognitive
enhancement by facilitating mitochondrial respiration, with hormetic dose-response effects and brain region activational specificity.
This evidence supports enhancement of mitochondrial respiratory function as a generalizable therapeutic principle relevant to highly adaptable systems that are
exquisitely sensitive to energy availability such as the nervous system.
We propose that human intelligence is composed of multiple independent components
Each behavioral component is associated with a distinct functional brain network
The higher-order g factor is an artifact of tasks recruiting multiple networks
The components of intelligence dissociate when correlated with demographic variables
What makes one person more intellectually able than another? Can the entire distribution of human intelligence be accounted for by just one general factor? Is
intelligence supported by a single neural system? Here, we provide a perspective on human intelligence that takes into account how general abilities or “factors”
reflect the functional organization of the brain. By comparing factor models of individual differences in performance with factor models of brain functional
organization, we demonstrate that different components of intelligence have their analogs in distinct brain networks. Using simulations based on neuroimaging data,
we show that the higher-order factor g is accounted for by cognitive tasks co-recruiting multiple networks. Finally, we confirm the independence of these
components of intelligence by dissociating them using questionnaire variables. We propose that intelligence is an emergent property of anatomically distinct
cognitive systems, each of which has its own capacity.
The gulf in outlook between atheists and adherents of the monotheistic religions is profound. We are fortunate to live under a constitutional system and a code
of manners that by and large keep it from disturbing the social peace; usually the parties ignore each other. But sometimes the conflict surfaces and heats up into
a public debate. The present is such a time.
…In his absorbing new book, Where the Conflict Really Lies, Alvin Plantinga, a distinguished analytic philosopher known for his contributions to
metaphysics and theory of knowledge as well as to the philosophy of religion, turns this alleged opposition on its head. His overall claim is that “there is
superficial conflict but deep concord between science and theistic religion, but superficial concord and deep conflict between science and naturalism.” By
naturalism he means the view that the world describable by the natural sciences is all that exists, and that there is no such person as God, or anything like God.
Plantinga’s religion is the real thing, not just an intellectual deism that gives God nothing to do in the world. He himself is an evangelical Protestant, but he
conducts his argument with respect to a version of Christianity that is the “rough intersection of the great Christian creeds”—ranging from the Apostle’s Creed to
the Anglican Thirty-Nine Articles—according to which God is a person who not only created and maintains the universe and its laws, but also intervenes specially in
the world, with the miracles related in the Bible and in other ways. It is of great interest to be presented with a lucid and sophisticated account of how someone
who holds these beliefs understands them to harmonize with and indeed to provide crucial support for the methods and results of the natural sciences…Faith,
according to Plantinga, is another basic way of forming beliefs, distinct from but not in competition with reason, perception, memory, and the others. However, it
a wholly different kettle of fish: according to the Christian tradition (including both Thomas Aquinas and John Calvin), faith is a special gift from God, not
part of our ordinary epistemic equipment. Faith is a source of belief, a source that goes beyond the faculties included in reason.
God endows human beings with a sensus divinitatis that ordinarily leads them to believe in him. (In atheists the sensus divinitatis is either
blocked or not functioning properly.)2 In addition, God acts in the world more selectively by “enabling Christians to see the truth of the central
teachings of the Gospel.”
If all this is true, then by Plantinga’s standard of reliability and proper function, faith is a kind of cause that provides a warrant for theistic belief, even
though it is a gift, and not a universal human faculty. (Plantinga recognizes that rational arguments have also been offered for the existence of God, but he
thinks it is not necessary to rely on these, any more than it is necessary to rely on rational proofs of the existence of the external world to know just by
looking that there is beer in the refrigerator.) It is illuminating to have the starkness of the opposition between Plantinga’s theism and the secular outlook so
clearly explained. My instinctively atheistic perspective implies that if I ever found myself flooded with the conviction that what the Nicene Creed says is true,
the most likely explanation would be that I was losing my mind, not that I was being granted the gift of faith. From Plantinga’s point of view, by contrast, I
suffer from a kind of spiritual blindness from which I am unwilling to be cured. This is a huge epistemological gulf, and it cannot be overcome by the cooperative
employment of the cognitive faculties that we share, as is the hope with scientific disagreements…The interest of this book, especially for secular readers, is its
presentation from the inside of the point of view of a philosophically subtle and scientifically informed theist—an outlook with which many of them will not be
familiar. Plantinga writes clearly and accessibly, and sometimes acidly—in response to aggressive critics of religion like Dawkins and Daniel Dennett. His
comprehensive stand is a valuable contribution to this debate.
Objectives: Traditional knowledge suggests that Bacopa
monnieri enhances cognitive performance. Such traditional beliefs have now been scientifically tested through a handful of randomized, controlled human
clinical trials. The current systematic review aimed to examine the scientific evidence as to whether Bacopa can enhance cognitive performance in
Design: A systematic review of randomized controlled trials is presented. Multiple databases were systematically searched by multiple authors.
Relevant trials were objectively assessed for methodological quality.
Subjects: The subjects studied were adult humans without dementia or cognitive impairment.
Intervention: Bacopa monnieri, including Bacopa extracts, were administered over long-term supplementation periods.
Outcome measures: Any validated cognitive test, whether a primary or secondary outcome.
Results: 6 studies met the final inclusion criteria and were included in review. Trials were all conducted over 12 weeks. Across trials, 3
different Bacopa extracts were used at dosages of 300–450 mg extract per day. All reviewed trials examined the effects of Bacopa on memory, while
other cognitive domains were less well studied. There were no cognitive tests in the areas of auditory perceptual abilities or idea production and only a paucity
of research in the domains of reasoning, number facility, and language behavior. Across studies, Bacopa improved performance on 9 of 17 tests in the
domain of memory free recall. There was little evidence of enhancement in any other cognitive domains.
Conclusions: There is some evidence to suggest that Bacopa improves memory free recall with evidence for enhancement in other
cognitive abilities currently lacking perhaps due to inconsistent measures employed by studies across these cognitive domains. Research into the nootropic effects of Bacopa is in its infancy, with research still yet to investigate the effects of Bacopa across all
human cognitive abilities. Similarly, future research should examine the nootropic effects of Bacopa at varied
dosages and across different extracts.
As a cofactor in numerous enzymatic reactions, magnesium fulfils various intracellular physiological functions. Thus, imbalance in magnesium status—primarily
hypomagnesaemia as it is seen more often than hypermagnesemia—might result in unwanted neuromuscular, cardiac or nervous disorders. Measuring total serum magnesium
is a feasible and affordable way to monitor changes in magnesium status, although it does not necessarily reflect total body magnesium content. The following
review focuses on the natural occurrence of magnesium and its physiological function. The absorption and excretion of magnesium as well as hypomagnesaemia and
hypermagnesemia will be addressed.
Soon after the discovery of lasers in the 1960s it was realized that laser therapy had the potential to improve wound healing and reduce pain, inflammation and
swelling. In recent years the field sometimes known as photobiomodulation has broadened to include light-emitting diodes and other light sources, and the range of
wavelengths used now includes many in the red and near infrared. The term “low level laser therapy” or LLLT
has become widely recognized and implies the existence of the biphasic dose response or the Arndt-Schulz curve. This review will cover the mechanisms of action of
LLLT at a cellular and at a tissular level and will summarize the various light sources and principles of
dosimetry that are employed in clinical practice. The range of diseases, injuries, and conditions that can be benefited by LLLT will be summarized with an emphasis on those that have reported randomized controlled clinical trials. Serious
life-threatening diseases such as stroke, heart attack, spinal cord injury, and traumatic brain injury may soon be amenable to LLLT therapy.
Pharmacological enhancers of cognition promise a bright new future for humankind: more focus, more willpower, and better memory, with applications ranging from
education to military combat. Underlying such promises is a linear, more-is-better vision of cognition that makes intuitive sense. This vision is at odds, however,
with our understanding of cognition’s evolutionary origins. The mind has evolved under various constraints and consequently represents a delicate balance among
these constraints. Evidence of the trade-offs that have shaped cognition include (a) inverted U-shaped performance curves commonly found in response to
pharmacological interventions and (b) unintended side effects of enhancement on other traits. Taking an evolutionary perspective, we frame the above two sets of
findings in terms of within-task (exemplified by optimal-control problems) and between-task (associated with a gain/loss asymmetry) trade-offs, respectively.
With this framework, psychological science can provide much-needed guidance to enhancement development, a field that still lacks a theoretical foundation.
[Keywords: cognitive enhancements, trade-offs, constraints, evolution, side effects]
After consumption of tea, L-theanine enters systemic circulation and is assumed
to enter the brain. Several human studies indicate that L-theanine influences brain functioning. Knowledge about the pharmacokinetics of L-theanine facilitates further study of this health effect.
Volunteers received 25–100 mg of L-theanine as tea, as L-theanine-enriched tea,
and as biosynthetic L-theanine in aqueous solutions. Plasma was analysed for L-theanine content after which data were fitted with a 1-compartment model. For all interventions, the lag time was approximately 10 min
and half-lives of absorption and elimination were approximately 15 and 65 min respectively. After approximately 50 min, maximum plasma concentrations of between
1.0 and 4.4 mg⁄L were achieved. Maximum plasma concentration and area under the plasma-concentration/time curve were dose-proportional.
This knowledge allows prediction of plasma concentrations for various dose regimens supporting further study of a health benefit of L-theanine.
Tea ingredients l-theanine and caffeine have repeatedly been shown to deliver unique cognitive benefits when consumed in combination.
The current randomized, placebo-controlled, double-blind, cross-over study compared a combination of l-theanine (97 mg)
and caffeine (40 mg) to a placebo on 2 attention tasks and a self-report questionnaire before, and 10 and 60 min after consumption.
The combination of l-theanine and caffeine statistically-significantly improved attention on a switch task as compared to
the placebo, while subjective alertness and intersensory attention were not improved statistically-significantly.
The results support previous evidence that l-theanine and caffeine in combination can improve attention.
[Alexander defines the “typical mind fallacy”: everyone reasons about their mental experiences as if they are universal. People with vivid visual imagery assume
everyone can see things in “the mind’s eye” while ‘aphantasics’ assume that this is
simply a poetic metaphor; people with color-blindness wonder why other people get so worked up about various shades of gray, and people with anosmia are puzzled by the focus on flowers etc. Further examples include maladaptive daydreaming,
pain insensitivity, the prevalence of visual & auditory hallucinations in mentally-healthy individuals like ‘scintillating scotoma’, misophonia, hearing voices,
inner monologues, facial self-awareness, trypophobia, Severely Deficient Autobiographical Memory, hypermnesia, ASMR,
face blindness/prosospagnosia, musical anhedonia, ‘the call of the void’/intrusive thoughts, hypnagogia, the nasal dilation cycle…
This phenomenon for visual imagery was discovered only recently by Francis
Galton, who asked if the interminable debate between philosophers/psychologists like Berkeley or Behaviorists like Skinner, where neither could accept that
there was (or was not) visual imagery, was because both were right—some people have extremely vivid mental imagery, while others have none at all. He
simply circulated a survey and asked. Turned out, most people do but some don’t.
The typical mind fallacy may explain many interpersonal conflicts and differences in advice: we underappreciate the sheer cognitive diversity of mankind,
because we only have access to our limited personal anecdote, and people typically do not discuss all their differences because they don’t realize they exist nor
have a vocabulary/name.]
Neurogenesis continues through adulthood in the hippocampus and olfactory bulb of mammals. Adult neurogenesis has been implicated in learning and memory, and
linked with depression. Hippocampal neurogenesis is increased in response to a number of stimuli, including exposure to an enriched environment, increased
locomotor activity, and administration of antidepressants. Adult neurogenesis is depressed in response to aging, stress and sleep deprivation. Intriguingly,
caffeine modulates a number of these same stimuli in a dose-dependent manner. We examined the dose and duration dependent effects of caffeine on the proliferation,
differentiation, and survival of newly generated hippocampal neurons in adult mice. Extended, 7-day caffeine administration, alters the proliferation of adult
hippocampal precursors in the mouse in a dose dependent manner; moderate to high doses (20–30mg/kg/day) of caffeine depress proliferation while
supraphysiological doses (60mg/kg/day) increase proliferation of neuronal precursors. Acute, 1-day administration had no affect on proliferation. Caffeine
administration does not affect the expression of early or late markers of neuronal differentiation, or rates of long-term survival. However, neurons induced in
response to supraphysiological levels of caffeine have a lower survival rate than control cells; increased proliferation does not yield an increase in long-term
neurogenesis. These results demonstrate that physiologically relevant doses of caffeine can statistically-significantly depress adult hippocampal neurogenesis.
Evidence in support of the neuroprotective effects of flavonoids has increased significantly in recent years, although to date much of this evidence has emerged
from animal rather than human studies. Nonetheless, with a view to making recommendations for future good practice, we review 15 existing human dietary
intervention studies that have examined the effects of particular types of flavonoid on cognitive performance. The studies employed a total of 55 different
cognitive tests covering a broad range of cognitive domains. Most studies incorporated at least one measure of executive function/working memory, with nine reporting significant improvements in
performance as a function of flavonoid supplementation compared to a control group. However, some domains were overlooked completely (e.g. implicit memory,
prospective memory), and for the most part there was little consistency in terms of the particular cognitive tests used making across study comparisons difficult.
Furthermore, there was some confusion concerning what aspects of cognitive function particular tests were actually measuring. Overall, while initial results are
encouraging, future studies need to pay careful attention when selecting cognitive measures, especially in terms of ensuring that tasks are actually sensitive
enough to detect treatment effects.
Rationale: Although the subjective effects of caffeine abstinence, acute and chronic administration, and tolerance are well described, the
corresponding neurophysiological effects are not.
Objectives: Caffeine withdrawal, acute caffeine effects, caffeine tolerance, and net beneficial effects of chronic caffeine administration were
investigated using cerebral blood flow velocity, quantitative electroencephalography (EEG), and subjective
Materials and Methods: Sixteen regular caffeine users participated in this double-blind, within-subject study during which they received acute
caffeine and placebo challenges (1) while maintained on 400 mg caffeine daily for > or = 14 days and (2) while maintained on placebo for > or = 14 days.
Blood flow velocity was determined for the middle (MCA) and anterior (ACA) cerebral
arteries using pulsed transcranialDoppler sonography. EEG was recorded from 16 scalp sites. Subjective
effects were assessed with questionnaires.
Results: Acute caffeine abstinence (evaluated 24 h after placebo substitution) increased mean, systolic, and diastolic velocity in the
MCA and ACA and decreased pulsatility index in the MCA. Acute caffeineabstinence increased EEG theta and decreased beta 2 power.
Acute caffeine abstinence also increased measures of Tired, Fatigue, Sluggish, and Weary and decreased ratings of Energetic, Friendly, Lively, and Vigor.
Acute caffeine effects were demonstrated across a wide range of measures, including cerebral blood flow, EEG, and
subjective effects. Tolerance and “complete” tolerance were observed on subjective but not physiological measures. Chronic caffeine effects were demonstrated
only on the measure of EEG beta 2 power.
Conclusion: Acute caffeine abstinence and administration produced changes in cerebral blood flow velocity, EEG, and subjective effects. Tolerance to subjective but not physiological measures was demonstrated. There was almost no evidence
for net effects of chronic caffeine administration on these measures. Overall, these findings provide the most rigorous demonstration to date of physiological
effects of caffeine withdrawal.
Objectives: Arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) are essential for brain growth and cognitive development. We have
reported that supplementing pregnant and lactating women with n-3 very-long-chain polyunsaturated fatty acids promotes higher IQ scores at 4 years of age as
compared with maternal supplementation with n-6 polyunsaturated fatty acids. In our present study, the children were examined at 7 years of age with the same
cognitive tests as at 4 years of age. We also examined the relation between plasma fatty acid pattern and BMI in children, because an association between arachidonic acid and adipose
tissue size has been suggested.
Methods: The study was randomized and double-blinded. The mothers took 10 mL of cod liver oil or corn oil from week 18 of pregnancy until 3
months after delivery. Their children were tested with the Kaufman Assessment Battery for Children at 7 years of age, and their height and weight were
Results: We did not find any statistically-significant differences in scores on the Kaufman Assessment Battery for Children test at 7 years of
age between children whose mothers had taken cod liver oil (n = 82) or corn oil (n = 61). We observed, however, that maternal plasma phospholipid
concentrations of α-linolenic acid (18:3n-3) and docosahexaenoic acid during pregnancy were correlated to sequential processing at 7 years of age. We observed no
correlation between fatty acid status at birth or during the first 3 months of life and BMI at 7 years of
Conclusion: This study suggests that maternal concentration of n-3 very-long-chain polyunsaturated fatty acids during pregnancy might be of
importance for later cognitive function, such as sequential processing, although we observed no statistically-significant effect of n-3 fatty acid intervention on
global IQs. Neonatal fatty acid status had no influence on BMI at 7 years of age.
Objectives: Study aims were to evaluate effects of Bacopa monnieri whole plant standardized dry extract on cognitive function and affect and
its safety and tolerability in healthy elderly study participants.
Design: The study was a randomized, double-blind, placebo-controlled clinical trial with a placebo run-in of 6 weeks and a treatment period of
Setting/Location: Volunteers were recruited from the community to a clinic in Portland, Oregon by public notification.
Subjects: Fifty-four (54) participants, 65 or older (mean 73.5 years), without clinical signs of dementia, were recruited and randomized to
Bacopa or placebo. Forty-eight (48) completed the study with 24 in each group.
Interventions: Standardized B. monnieri extract 300 mg/day or a similar placebo tablet orally for 12 weeks.
Outcome Measures: The primary outcome variable was the delayed recall score from the Rey Auditory Verbal Learning Test (AVLT). Other cognitive measures were the Stroop Task assessing the ability to ignore irrelevant information, the Divided
Attention Task (DAT), andthe Wechsler Adult Intelligence Scale (WAIS)
letter-digit test of immediate working memory. Affective measures were the State-Trait Anxiety Inventory, Center for
Epidemiologic Studies Depression scale (CESD)-10 depression scale, and the Profile of Mood States. Vital signs
were also monitored.
Results: Controlling for baseline cognitive deficit using the Blessed Orientation-Memory-Concentration test, Bacopa participants had
enhanced AVLT delayed word recall memory scores relative to placebo. Stroop results were similarly significant,
with the Bacopa group improving and the placebo group unchanged. CESD-10 depression scores, combined state plus
trait anxiety scores, and heart rate decreased over time for the Bacopa group but increased for the placebo group. No effects were found on the DAT, WAIS digit task, mood, or blood pressure. The dose was well tolerated with few adverse
events (Bacopa n = 9, placebo n = 10), primarily stomach upset.
Conclusions: This study provides further evidence that B. monnieri has potential for safely enhancing cognitive performance in the aging.
Background: In patients undergoing dialysis, therapy with calcitriol or paricalcitol or other vitamin D agents is associated with reduced
mortality. Observational data suggests that low 25-hydroxyvitamin D levels (25[OH]D) are associated with diabetes mellitus, hypertension, and cancers. However,
whether low serum 25(OH)D levels are associated with mortality in the general population is unknown.
Methods: We tested the association of low 25(OH)D levels with all-cause, cancer, and cardiovascular disease (CVD) mortality in 13 331 nationally representative adults 20 years or older from the Third National Health and Nutrition
Examination Survey (NHANESIII) linked mortality files. Participant vitamin D levels
were collected from 1988 through 1994, and individuals were passively followed for mortality through 2000.
Results: In cross-sectional multivariate analyses, increasing age, female sex, nonwhite race/ethnicity, diabetes, current smoking, and higher
body mass index were all independently associated with higher odds of 25(OH)D deficiency (lowest quartile of 25(OH)D level,
<17.8 ng/mL [to convert to nanomoles per liter, multiply by 2.496]), while greater physical activity, vitamin D supplementation, and nonwinter season were
inversely associated. During a median 8.7 years of follow-up, there were 1806 deaths, including 777 from CVD. In
multivariate models (adjusted for baseline demographics, season, and traditional and novel CVD risk factors), compared
with the highest quartile, being in the lowest quartile (25[OH]D levels <17.8 ng/mL) was associated with a 26% increased rate of all-cause mortality
(mortality rate ratio, 1.26; 95% CI, 1.08–1.46) and a population attributable risk of 3.1%. The adjusted models of
CVD and cancer mortality revealed a higher risk, which was not statistically-significant.
Conclusion: The lowest quartile of 25(OH)D level (<17.8 ng/mL) is independently associated with all-cause mortality in the general
It has been suggested that the recent rapid developments in the fields of neuroscience and psychopharmacology have increased the possibilities for
pharmacological enhancement of mental functioning. Here, evidence is reviewed which shows that drugs acting on a variety of neurotransmitter systems can indeed
enhance cognition, and to a lesser extent mood and pro-social behavior. Moreover, it seems possible to interfere with the (re)consolidation of traumatic memories.
There are, however, a number of caveats: first, as cognition-enhancing drugs can simultaneously exert both linear and quadratic (U-shaped) effects, doses most
effective in facilitating one behavior could at the same time exert null or even detrimental effects on other cognitive domains. Second, individuals with a ‘low
memory span’ might benefit from cognition-enhancing drugs, whereas ‘high span subjects’ are ‘overdosed’. And finally, evidence suggests that a number of trade-offs
could occur. For example, increases of cognitive stability might come at the cost of a decreased capacity to flexibly alter behavior. A short overview of ethical
issues raised by the use of cognition and mood enhancing drugs demonstrates the tremendous variety in views and opinions regarding the subject.
Background: Brahmi (Bacopa monniera) is a traditional Indian medicinal plant which causes multiple effects on the central nervous system. The
standardized extract of this plant has shown enhanced behavioural learning in preclinical studies and enhanced information processing in healthy volunteers.
Aim: To study the efficacy of standardized Bacopa monniera extract (SBME) in subjects with
age-associated memory impairment (AAMI) without any evidence of dementia or psychiatric disorder.
Methods: A double-blind, placebo-controlled randomized study design was employed. The subjects received either 125 mg of SBME or placebo twice a day for a period of 12 weeks followed by a placebo period of another 4 weeks (total duration of the trial 16
weeks). Each subject was evaluated for cognition on a battery of tests comprising mental control, logical memory, digit forward, digit backward, visual
reproduction and paired associate learning.
Results: SBME produced significant improvement on mental control, logical memory and paired
associated learning during the 12-week drug therapy.
Conclusion: SBME is efficacious in subjects with age-associated memory impairment.
There is a general belief among doctors, in part grounded in experience, that patients with arthritis need nonsteroidal anti-inflammatory drugs
(NSAIDs). Implicit in this view is that these patients require the symptomatic relief provided by inhibiting synthesis
of nociceptive prostaglandin E2, a downstream product of the
enzyme cyclo-oxygenase (COX), which is inhibited by NSAIDs. However, the
concept of ‘safe’ NSAIDs has collapsed following a multiplicity of observations establishing increased risk for
cardiovascular events associated with NSAID use, especially but not uniquely with the newCOX-2-selective NSAIDs. This mandates greater parsimony in the use ofthese agents. Fish
oils contain a natural inhibitor of COX, reducereliance on NSAIDs, and reduce
cardiovascular risk through multiple mechanisms. Fish oil thus warrants consideration as a component of therapy for arthritis, especially rheumatoid
arthritis, in which its symptomatic benefits are well established. A major barrier to the therapeutic use of fish oil in inflammatory diseases is ignorance of its
mechanism, range of beneficial effects, safety profile, availability of suitable products, effective dose, latency of effects and instructions for administration.
This review provides an evidence-based resource for doctors and patients who may choose to prescribe or take fish oil.
To use sensory information efficiently to make judgments and guide action in the world, the brain must represent and use information about uncertainty in its
computations for perception and action. Bayesian methods have proven successful in building computational theories for perception and sensorimotor control, and
psychophysics is providing a growing body of evidence that human perceptual computations are ‘Bayes’ optimal’. This leads to the ‘Bayesian coding hypothesis’: that
the brain represents sensory information probabilistically, in the form of probability distributions. Several computational schemes have recently been proposed for
how this might be achieved in populations of neurons. Neurophysiological data on the hypothesis, however, is almost non-existent. A major challenge for
neuroscientists is to test these ideas experimentally, and so determine whether and how neurons code information about sensory uncertainty.
A failure to adapt to novel or changing environmental demands is a core feature of a wide variety of neuropsychiatric disorders as well as the normal states of
stress and fatigue. We review the neurochemistry of cognitive control, which has been associated primarily with the prefrontal cortex. Many drugs affect the
functioning of the prefrontal cortex, but the direction and extent of drug effects vary across individuals and tasks. Apparently paradoxical effects are often
observed, where the same medication causes both cognitive enhancement as well as cognitive side effects. We review neurobiological research that is beginning to
elucidate the nature of these contrasting effects and the factors underlying the large variability across individuals and behaviours. The work has considerable
implications for the understanding of and treatment development for abnormalities such as Parkinson’s disease, attention deficit hyperactivity disorder and drug
Aims: Ulcerative colitis is predominantly a disease of nonsmokers and transdermal nicotine has therapeutic value in active disease; however
side-effects are troublesome. The aim of this study was to develop an oral formulation of nicotine which would be slowly released in the colon over 6 h, and to
examine its pharmacokinetic profile in 12 healthy volunteers, with measurements of serum nicotine and cotinine, its principal metabolite.
Methods: Nicotine was combined with a polyacrylic carbomer, Carbopol 974P which was incorporated into 13 different vehicles and their release
profiles examined in vitro. The polyglycolized glyceride, Gelucire 50/13, was chosen for subsequent kinetic studies because it consistently produced a suitable
release pattern which was linear. Capsules containing 3 mg nicotine, combined with carbomer in Gelucire 50/13, were coated with an acrylic resin Eudragit L; this
ensured the capsule would remain intact until the ileum. On 2 separate days, 6 and 15 mg nicotine, contained in 2 and 5 capsules, respectively, were
administered to 12 subjects, all nonsmokers, mean age 28 years. Serial blood measurements were taken for 36 h, serum nicotine and cotinine concentrations were
measured by gas liquid chromatography.
Results: There was considerable intersubject variability in the nicotine and cotinine values. Plasma nicotine levels began to rise about 4 h
after ingestion of the capsules, corresponding with the oro-caecal transit time. Cmax nicotine values were 2.2 and 5 ng ml−1, obtained 7 h
after the ingestion of 6 and 15 mg, respectively, of the formulation. The corresponding Cmax values for cotinine were 37 and 94.4 ng ml−1,
occurring after 9–10 h. The mean for elimination half-lives in the 24 studies, including the 6 and 15 mg doses, for nicotine were 4.3±2.7 h and for cotinine
16.8±7.5 h. With 6 mg nicotine-carbomer, only 1 of 12 volunteers had possible side-effects, but with the 15 mg dose 11 out of the 12 reported adverse effects which
were systemic or gastrointestinal in nature-their timing corresponded with peak serum concentrations of nicotine.
Conclusions: An oral formulation of nicotine has been developed; in the ileum and colon, this becomes available for slow linear release over 6
h and delivers high concentrations of nicotine for topical effect on the colon. 6 mg Nicotine was well tolerated, whilst 15 mg gave both systemic and
gastrointestinal side-effects. High concentrations of topical nicotine in the colon are achieved with relatively low systemic bioavailablity-reflected by the
Cmaxand AUC values for nicotine. This, or comparable formulations, may be of therapeutic value in
The purpose of this paper is to study the responses given to a questionnaire by subjects who received a tap water ‘placebo’ instead of lysergic acid
diethylamide (LSD-25), and to relate the number of responses to other variables. These variables are: body weight,
number of responses on a health questionnaire, arithmetic test scores, scores on the Wechsler-Bellevue Intelligence Scale, and Rorschach test responses.
…Figure 4 shows for each question the percentage and number of subjects out of 28 who gave a positive response at least once during the 0.5,
2.5, and 4.5-hour intervals. The questions appear in the figure in the order of decreasing percentages of response to them. The time of the response and the
magnitude are disregarded in this tabulation. The question receiving the greatest percentage response was (Subject 24), “Are your palms moist?” As many as
60.7% reported this symptom. Half of the subjects reported headache (Subject 13), fatigue (Subject 44), and drowsiness (Subject 45). About 36% reported
anxiety (Subject 47). Illness (Subject 1), and dizziness (Subject 15) were reported by 28.6 per cent of the group and 25% indicated a dream-like feeling
(Subject 46), increased appetite (Subject 6), unsteadiness (Subject 16), a hot feeling (Subject 22), heaviness of hands and feet (Subject 30), and
weakness (Subject 43). There were 19 questions which received positive responses from between 10 and 22 per cent of the subjects. Less than 10% of the group (or no
more than two subjects) responded positively to the remaining questions, but each question received a positive response from at least one subject.
…The findings point out that a substance such as tap water, which is generally considered chemically and pharmacologically inactive, is capable of eliciting
certain responses from certain subjects who believe they have received lysergic acid diethylamide. These observations emphasize once more the need for placebo
controls in studies investigating the effects of drugs; without them changes which are produced merely by the situation and not by the drug are frequently falsely
attributed to the action of the drug…Most subjects who respond to a placebo tend to do so most markedly during the first 0.5 hour after receiving the substance. At
this time their anticipation of, and anxiety about, the effects of LSD-25 are probably greatest. Gradually the
effects wear off, as the anticipation wears off. Individual differences exist in the time of peak effect, but this is the most common finding. The questions which
elicited the greatest percentage response from the group were those related to anxiety (moist palms and feeling anxious) or to phenomena which commonly occur
without the presence of any foreign agent (drowsiness, fatigue, and headache). The remaining questions received random responses. The fact that there is a wide
range in the number of positive responses made to the questionnaire is of major interest.
With due allowance for style and age, Hadamard ably describes and defends the basic model of ‘work, incubation, illumination, verification’, with reference to his own discoveries,
his many famous acquaintances, Poincaré’s lecture, and a very interesting survey of mathematicians. In fact, it’s a little depressing that we don’t seem to have
gone much beyond that in the half-century since this was published back in 1945 or so. While at least we no longer need his defense of the unconscious as a
meaningful part of cognition, much of the rest is depressingly familiar—for example, his acute observations on mental imagery & people who solely think in words,
and mention of Francis Galton’s survey (little-known outside of psychology), could be usefully read by many who commit the typical mind
If Hadamard comes to no hard and fast conclusions, but merely raises many interesting points and criticizes a number of theories, we can hardly hold that
against him, as we can do little better and so it becomes our failing to followup, not his.]
Volumetric dosing is the process of dissolving a compound in a liquid to make it easier to measure. In the interest of harm reduction, it is
important to use volumetric dosing with certain compounds that are too potent to measure with traditional weighing scales.
This technique makes it possible to use a cheap $40$302013 scale and still measure accurately to a few milligrams.
Many psychoactive substances, including benzodiazepines and certain psychedelics, are active at less than a single milligram. Such small quantities cannot be
accurately measured with common digital scales, so the drug must instead be dosed volumetrically by weighing out larger amounts of the compound and dissolving it
in a calculated volume of a suitable liquid.