Day: 12/26/2016

Some glioblastoma patients benefit from ‘ineffective’ treatment, researchers say

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glioblastoma multiforme
Highly invasive human brain tumour cells derived from a biopsy in a young patient with glioblastoma multiforme. 

A subgroup of patients with a devastating brain tumor called glioblastoma multiforme benefited from treatment with a class of chemotherapy drugs that two previous large clinical trials indicated was ineffective against the disease, according to a study at the Stanford University School of Medicine.

Specifically, patients in the subgroup who were treated with chemotherapy drugs that block the growth of new blood vessels in the tumor lived an average of about one year longer than those who were given other classes of chemotherapy drugs, the researchers found.

The retrospective study emphasizes the importance of properly categorizing tumors with varied biology in order to best personalize treatment for each patient. Lumping all glioblastoma patients together as one group led to the flawed conclusion that no patients benefited from anti-angiogenesis treatments, the researchers said.

“Traditionally, glioblastoma patients are given this diagnosis based on the histology of their tumor, and then assigned a grade and a stage,” said Daniel Rubin, MD, associate professor of biomedical data science, of radiology and of medicine. “But this information is not always specific enough to clearly inform treatment. We’ve developed a new method of classifying glioblastomas by quantitatively analyzing the magnetic resonance imaging that is routinely performed during diagnosis.”

Rubin is the senior author of the study, which is published in Neuro-Oncology. Postdoctoral scholar Tiffany Ting Liu, PhD, is the lead author of the paper.

A deadly brain tumor

Glioblastoma is one of the most common, and most deadly, brain tumors. About 12,000 people in the United States are diagnosed each year. The median survival is about 15 months after diagnosis. Until recently, clinicians and patients pinned their hopes on a class of chemotherapy drugs called anti-angiogenic compounds that are meant to block the growth of new blood vessels into the tumor. Blocking this growth, they believed, should starve the tumors of oxygen and nutrients. However, two large, phase-3 clinical trials recently reported in The New England Journal of Medicine concluded that one such drug, bevacizumab, conferred no survival benefit on glioblastoma patients.

Liu, Rubin and their colleagues wondered if there might be a subgroup of glioblastoma patients that could still be helped by the treatment. They studied the medical records and diagnostic images of 69 glioblastoma patients who had been treated at a local medical center and 48 patients from a national database known as The Cancer Genome Atlas.

The researchers used specialized software to categorize each patient into one of two groups based on the degree of vascularization of the patients’ brain tumors. Those whose tumors were more highly vascularized—as determined by an imaging technique called perfusion MRI—were significantly more likely to benefit from treatment with anti-angiogenic therapies than those whose tumors were less well vascularized.

Differences in glioblastoma biology

Perfusion MRIs are routinely conducted as part of the diagnostic procedure for brain tumor patients. The researchers found that each of the 117 patients fell neatly into one of two clusters: 51 of the patients had tumors that were highly vascularized, and 66 had tumors that were not as well vascularized. Further investigation showed that the highly vascularized tumors also expressed more genes involved in blood vessel growth and in protecting cells from conditions of low oxygen called hypoxia than tumors of patients in the other group.

The researchers then looked to see what treatments the individual patients had received, and how they fared.

“The most exciting finding was that those members in the highly vascularized group who had received anti-angiogenic treatment lived significantly longer—on average more than a year more—than others in the same group who did not get anti-angiogenic therapy,” said Rubin. “And this analysis was performed using images that already exist as part of the diagnostic procedure for this disease. Our findings speak to the fact that the biology of glioblastoma can vary significantly among individuals, and that certain subgroups of patients may benefit from treatments that appear ineffective when screened across a large unselected mix of patients.”

Rubin and his colleagues hope their study will reignite the conversation about the use of anti-angiogenic therapies in glioblastoma, while also enhancing the understanding of the varied biology of the disease.

“This is a turning point,” said Rubin. “We believe we can identify those people who are likely to benefit from anti-angiogenic treatments, and also begin to think outside the box to identify other types of therapies for those who are unlikely to respond. This shows that subtyping cancers like glioblastoma can have a huge impact on how we treat disease.”

Direct-to-brain chemo better than systemic drugs when immunotherapy is to follow

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mouse brain
Mouse brain, coronal view.

Animal study suggests ‘best practice’ for preserving the immune system –

In experiments on mice with a form of aggressive brain cancer, Johns Hopkins researchers have shown that localized chemotherapy delivered directly to the brain rather than given systemically may be the best way to keep the immune system intact and strong when immunotherapy is also part of the treatment.

The researchers say their study results, reported in Science Translational Medicine, could directly affect the design of immunotherapy clinical trials and treatment strategies for people with a deadly form of brain cancer called glioblastoma.

“We understand that our research was done in a mouse model and not in humans, but our evidence is strong that systemic chemotherapy alters the immune system in a way that it never fully recovers,” says Michael Lim, MD, associate professor of neurosurgery and director of brain tumor immunotherapy at the Johns Hopkins University School of Medicine, and member of the Johns Hopkins Kimmel Cancer Center. “With aggressive cancers like glioblastoma, it is important that we don’t handicap the defenses we may need to add alternative treatments, such as immunotherapy, to chemotherapy,” he adds.

Lim’s laboratory in neurosurgery and a team from the Bloomberg~Kimmel Institute for Cancer Immunotherapy led by Drew Pardoll, MD, PhD, performed their studies in a mouse with glioblastoma. In people, glioblastoma is a particularly aggressive form of cancer, with a typical survival time of just over a year after diagnosis. Current treatments include surgical removal of the visible tumor, radiation and chemotherapy. Because the disease is so lethal, even after aggressive standard treatment, neurosurgeons like Lim are looking to add newer immunotherapies that use the body’s own immune system cells to fight the tumor.

However, one challenge to immunotherapy, Lim says, has been the potential toxic effects of systemic therapies that could damage or interfere with the immune system and weaken the chances for success of immunotherapy approaches. With clinical trials being designed to integrate standard of care with immunotherapy, Lim and his team sought to create a way to accurately assess the impact of localized versus systemic chemotherapy on the immune system’s ability to stay healthy, and to see which kind of chemotherapy would actually improve survival time in the test mice.

To determine if one method of chemotherapy delivery was better over another when combined with immunotherapy, the researchers first gave a group of mice with glioblastoma clinically relevant doses the immunotherapy drug anti-PD-1 (200 milligrams per kilogram) and then treated the mice with chemotherapy either throughout the whole body or directly to the brain over two weeks.

For the whole-body, or systemic, chemotherapy, the mice were injected in their bellies with 30 milligrams per kilogram of the chemotherapy drug carmustine—the same drug used against glioblastoma in people—three times a week. Each treatment group contained 15 mice. For the local chemotherapy, the researchers directly implanted a wafer covered in molecules that bound carmustine, allowing sustained release of the drug over a week, into mice with established brain tumors.

The researchers first took blood samples from the rodents’ lymph nodes, brain, bone marrow and blood a couple of days after the end of the chemotherapy treatments, almost two weeks later and at the four-month mark. They focused on counting the number of white blood cells (lymphocytes—T cells) as a way to measure immune system integrity. The mice given systemic chemotherapy had much lower levels of lymphocytes than the mice given the local, long-lasting chemotherapy. For example, two weeks after treatment, mice with systemic chemotherapy had only about a third of the lymphocytes in their circulating blood as mice given the local chemotherapy. The researchers say their findings align with what is observed clinically in patients who received systemic chemotherapy. Lim says the suppression is suggested that the lymphocyte depletion caused by systemic chemotherapy is likely counterproductive to producing an effective antitumor immune response.

Next, the team wanted to see if local versus systemic chemotherapy in conjunction with immunotherapy affected survival in the mice with glioblastoma. The scientists found that when they gave the mice chemotherapy locally, it acted together with the immunotherapy drug to improve survival to about 80 percent after 100 days when compared to mice receiving immunotherapy alone, local chemotherapy alone, or combined systemic chemotherapy and immunotherapy, with a survival rate of about 50 percent after 100 days. Then, they followed up these experiments by assessing the immune system’s memory. They gave mice local chemotherapy or systemic chemotherapy in conjunction with immunotherapy, and then implanted them with more tumors. The mice with the systemic chemotherapy and immunotherapy all died when injected with extra tumors. But the mice with local chemotherapy and immunotherapy survived, essentially immunized against their glioblastoma. The researchers say this suggests that the systemic chemotherapy profoundly weakens the immune system. The researchers showed that the immune system weakening phenomenon isn’t specific to carmustine and happens in multiple types of systemic chemotherapy, such as temozolomide.

The researchers also reversed the treatment protocols, giving the chemotherapy before the immunotherapy to see if that worked better and improved survival. They didn’t notice a difference in survival time whether the immunotherapy was given before or after the brain-specific chemotherapy.

Only 10 percent of people diagnosed with glioblastoma live more than five years, according to the American Brain Tumor Association. Glioblastoma mostly occurs in people over 45 and in men somewhat more often than in woman. An estimated 15 percent of the 78,000 people diagnosed with brain tumors in the U.S. each year will be diagnosed with glioblastoma.

Currently, a large number of immunotherapy trials are underway for patients with glioblastoma. There are only three immunotherapy drugs that are FDA-approved for treating other types of cancer, and they cost over $100,000 annually.

Promising discovery for a non-invasive early detection of Alzheimer’s disease

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tau pathology
Showing brain regions in which gray matter intensity correlates significantly with HMW/LMW tau ratio in Alzheimer’s disease patients.

Researchers in Chile have pioneered technology that detects in human blood platelets the pathological oligomeric forms of brain tau protein in patients with Alzheimer’s disease (AD) and other neurodegenerative disorders. More importantly, the ratio between this anomalous tau and the normal tau protein can discriminate AD patients from normal controls, and are associated with decreased cognitive impairment.

A new research paper on this subject, published in the Journal of Alzheimer’s Disease, stems from the collaboration between the neuroscience laboratory from the International Center for Biomedicine (ICC, Chile) under the leadership of Dr. Ricardo Maccioni and the research teams of Drs. Andrea Slachevsky, Faculty of Medicine, University of Chile, together with Drs. Oscar Lopez and James Becker from University of Pittsburgh, School of Medicine, USA.

The work opens a new avenue in the development of highly sensitive and efficient biomarkers for neurodegenerative disorders.

The fact that pathological forms of tau proteins in platelets correlated with decreased brain volume in areas known to be associated with AD pathology in the brain is one step forward for the use of peripheral biomarkers, not only for clinical purposes, but also for research studies oriented to understand the complexity of AD pathology.

The research proved that the relationship between the pathological and normal variants of tau were associated with the reduction of cerebral volume in key structures linked with the disease. These structures included the left medial and right anterior cingulate gyri, right cerebellum, right thalamus (pulvinar), left frontal cortex, and right parahippocampal region, in agreement with MRI neuroimaging approaches.

tau proteins

Representative immunoblots of platelet tau with tau-5 antibody. High molecular weight tau bands (about 80kDa) can be appreciated, with greater immunoreactivity in patients with AD compared with healthy subjects.

In addition to the enormous utility of this non-invasive technology for the detection and progression of AD, the use of a tau biomarker could lead to the identification of AD pathology before the clinical symptoms are evident, and it could play an essential role in the development of preventive therapies.

Moreover, the determination of peripheral tau markers in platelets can contribute to the understanding of the pathophysiology of multiple neurodegenerative processes where tau proteins play a critical role.

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial

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Abstract

Background:

Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression.

Methods:

In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks.

Results:

Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and anti-depressant effects (approximately 60–80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression.

Conclusions:

In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress.

Chemically-induced synesthesia

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In April 1943, scientist Albert Hoffman ingested 250 micrograms of a substance he had synthesized five years prior. Less than an hour later, he “perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors.”1

Hoffman had discovered lysergic acid diethylamide, a psychedelic drug commonly known as LSD. He had experienced the world’s first acid trip.

Psychedelic drugs like LSD are often associated with experiences that can only be described as synesthesia—the rare neurological phenomenon in which a stimulus produces a second concurrent, involuntary experience—although scientists are still unsure if chemically-induced synesthesia is a genuine synesthetic experience.

The majority of studies on the topic have focused on congenital synesthesia. To date, there have only been four direct studies on chemically-induced synesthesia which were conducted between 1934 and 1966. Indirect studies picked up again in the early 1990s with the work of neurologist Richard Cytowic.

Direct studies suggest it’s possible to chemically-induce synesthesia

In 1934, research conducted by E.L. Kelly and published in the Journal of Experimental Psychology tested auditory-visual synesthesia using five non-synesthetes who first spent seven-weeks being presented with eight different tone-color pairs 1000 to 2000 times. The subjects demonstrated no evidence of developing synesthesia after this initial testing phase. When they consumed 15g of peyote cactus (estimated to contain between 0.15 and 1.2g of the psychoactive stimulant mescaline), four of the participants perceived colorful visual imagery and experienced haptic-visual, kinesthetic-visual, and algesic-color synesthesia. However, the researchers suggested that consumption of mescaline did not enhance trained associations and they observed no evidence of spontaneous auditory-visual synesthesia.2

A second study conducted in 1955 by Simpson and McKeller in the Journal of Mental Science involved two congenital synesthetes (auditory-visual and multiple types). The researchers themselves acted as non-synesthete controls. On separate occasions, subjects were given four mescaline doses (between 0.3 and 0.5g) and were then presented with various stimuli (i.e. visual, auditory, tactile, etc.). Subjects reported experiencing several distinct types of synesthesia, including auditory-visual, kinesthetic-visual, tactile-visual, olfactory-visual, and algesic-visual. Synesthetes and non-synesthetes were equally prone to developing new inducer-concurrent associations. In addition, one of the congenital synesthetes reported enhancements of his regular associations. Once again, the researchers concluded that mescaline seemed to be able to trigger synesthesia among non-synesthetes, but they also suggested that it could enhance the phenomenon in congenital synesthetes.3

A third blind study conducted in 1963 by Hartman and Hollister in Psychopharmacologia compared the effects of mescaline, LSD, and psilocybin (the psychedelic compound found in certain mushrooms). Eighteen participants were given each substance a week apart and were subjected to 16 sonic tones before and after drug administration. Under the influence of LSD and mescaline, but not psilocybin, participants reported significantly more auditory-visual associations compared to baseline levels. Less than 50% of participants experienced auditorily-induced synesthesia under the influence of the drugs.4

The last direct study, conducted in 1966 by Masters and Houston in The Varieties of Psychedelic Experience, was extremely informal. In it, participants were interviewed after consuming psychedelic drugs.  The study covered 206 drug sessions and involved a total of 214 subjects.2The researchers reported successfully inducing auditory-visual and auditory-gustatory synesthesia with LSD, but no other details were provided in their report.5

Possible mechanisms for chemically-induced synesthesia

Because the genetic mechanisms underlying congenital synesthesia are still not well understood and chemically-induced studies are so scarce, scientists are unsure if mechanisms influencing chemically-induced synesthetic episodes are—or are similar to—genuine synesthetic experiences.

In congenital synesthesia, very little systematic quantitative research has investigated the neurochemical factors involved. In mechanisms that propose the phenomenon is promoted by disinhibition, y-aminobutyric acid (GABA) plays a role in the disruption of inhibitory activity.2,6In 2008, scientists Brang and Ramachandran suggested serotonin (5-hydroxytryptophan) may also play a role.2,7

According to scientist Christopher Sinke from the University of Hannover, hallucinogens appear to inhibit serotonergic neuron transduction.8 The majority of hallucinogens affect activity in two areas: the locus coeruleus and pyramidal cells in the cortex. Because serotonin is primarily an inhibitory neurotransmitter, when its activity is decreased due to drug intake, the activity of the next neuron in the chain increases when it is no longer inhibited. This mechanism would be similar to the disinhibited feedback models of genuine synesthesia.

Crucial differences between congenital and chemically-induced synesthesia

While any two or more combinations of inducer-concurrent experiences are possible, in congenital synesthesia the grapheme-colour association is the most common type. Meanwhile, auditory-visual synesthesia is the most common form noted in chemically-induced cases (approximately 23%).  Additionally, visual concurrents are more complex in these cases than in congenital cases. Genuine synesthesia is characterized by consistency and automaticity. Currently, there is still no clear evidence that chemically-induced synesthesia is consistent or automatic.

The limitations of scarce research

It is critical to keep in mind when analyzing the existing chemically-induced research that study participants may have been biased to expect synesthesia under the influence of psychedelics and that the drugs increased participant suggestibility. Additionally, as in Albert Hoffman’s initial experience with LSD in 1943, most studies relied on subjects to self-report their experiences rather than using more consistent, objective methods to screen or measure participants.

While the studies discussed here suggest that it is possible to induce synesthesia using psychedelics, a systematic review conducted in 2013 by the University of Greenwich and Oxford recommends more rigorous examination of the subject including placebo-controlled and double blind investigations.2 Promisingly, we have taken steps in this direction with new research attempting to elucidate the mechanisms that may activate chemically-induced synesthesia through more controlled studies.9

Psychedelic therapy re-emerging for anxiety, PTSD and addiction

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psychedelic autum colors

Renewed medical interest in the use of psychedelic drugs for anxiety, posttraumatic stress disorder (PTSD) and addiction has resulted in small research studies that show some success with the controlled use of these drugs, according to an analysis published in CMAJ (Canadian Medical Association Journal).

Psychedelic drugs are substances that have a strong effect on one’s “conscious experience,” such as lysergic acid diethylamide (LSD), psilocybin, found in “magic mushrooms,” dimethyltryptamine (DMT), mescaline and methylenedioxymethamphetamine (MDMA).

“The re-emerging paradigm of psychedelic medicine may open clinical doors and therapeutic doors long closed,” writes Dr. Evan Wood, Professor of Medicine and Canada Research Chair, University of British Columbia, Vancouver, BC, and coauthors.

One small randomized controlled trial indicates that LSD-assisted psychotherapy might help reduce anxiety from terminal illness. Another small study, in which the active molecule in “magic mushrooms” was used as part of therapy for alcohol addiction, shows a significant reduction in the number of days alcohol was used as well as in the amount. A small US study of the drug MDMA shows a reduction in PTSD symptoms in people with chronic, treatment-resistant PTSD.

“Continued medical research and scientific inquiry into psychedelic drugs may offer new ways to treat mental illness and addiction in patients who do not benefit from currently available treatments,” write the authors.

Learnings from research conducted in the 1950s and 1960s, in which there were challenges to conducting studies and ethical breaches, is helping inform current research in the field.

“Although methodological and political challenges remain to some degree, recent clinical studies have shown that studies on psychedelics as therapeutic agents can conform to the rigorous scientific, ethical and safety standards expected of contemporary medical research,” the authors write.

Canadian researchers are leading studies that are looking at psychedelic drugs as treatment for addiction and PTSD.

The authors emphasize that the studies included in their analysis are small and the results preliminary; further research is needed to determine if there is widespread clinical application.

New study discovers biological basis for magic mushroom ‘mind expansion’

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New research shows that our brain displays a similar pattern of activity during dreams as it does during a mind-expanding drug trip.

Psychedelic drugs such as LSD and magic mushrooms can profoundly alter the way we experience the world but little is known about what physically happens in the brain. New research, published in Human Brain Mapping, has examined the brain effects of the psychedelic chemical in magic mushrooms, called psilocybin, using data from brain scans of volunteers who had been injected with the drug.

The study found that under psilocybin, activity in the more primitive brain network linked to emotional thinking became more pronounced, with several different areas in this network – such as the hippocampus and anterior cingulate cortex – active at the same time. This pattern of activity is similar to the pattern observed in people who are dreaming. Conversely, volunteers who had taken psilocybin had more disjointed and uncoordinated activity in the brain network that is linked to high-level thinking, including self-consciousness.

Psychedelic drugs are unique among other psychoactive chemicals in that users often describe ‘expanded consciousness,’ including enhanced associations, vivid imagination and dream-like states. To explore the biological basis for this experience, researchers analysed brain imaging data from 15 volunteers who were given psilocybin intravenously while they lay in a functional magnetic resonance imaging (fMRI) scanner. Volunteers were scanned under the influence of psilocybin and when they had been injected with a placebo.

“What we have done in this research is begin to identify the biological basis of the reported mind expansion associated with psychedelic drugs,” said Dr Robin Carhart-Harris from the Department of Medicine, Imperial College London.  “I was fascinated to see similarities between the pattern of brain activity in a psychedelic state and the pattern of brain activity during dream sleep, especially as both involve the primitive areas of the brain linked to emotions and memory. People often describe taking psilocybin as producing a dream-like state and our findings have, for the first time, provided a physical representation for the experience in the brain.”

The new study examined variation in the amplitude of fluctuations in what is called the blood-oxygen level dependent (BOLD) signal, which tracks activity levels in the brain. This revealed that activity in important brain networks linked to high-level thinking in humans becomes unsynchronised and disorganised under psilocybin. One particular network that was especially affected plays a central role in the brain, essentially ‘holding it all together’, and is linked to our sense of self.

In comparison, activity in the different areas of a more primitive brain network became more synchronised under the drug, indicating they were working in a more co-ordinated, ‘louder’ fashion. The network involves areas of the hippocampus, associated with memory and emotion, and the anterior cingulate cortex which is related to states of arousal.

Lead author Dr Enzo Tagliazucchi from Goethe University, Germany said: “A good way to understand how the brain works is to perturb the system in a marked and novel way. Psychedelic drugs do precisely this and so are powerful tools for exploring what happens in the brain when consciousness is profoundly altered. It is the first time we have used these methods to look at brain imaging data and it has given some fascinating insight into how psychedelic drugs expand the mind. It really provides a window through which to study the doors of perception.”

Dr. Carhart-Harris added: “Learning about the mechanisms that underlie what happens under the influence of psychedelic drugs can also help to understand their possible uses. We are currently studying the effect of LSD on creative thinking and we will also be looking at the possibility that psilocybin may help alleviate symptoms of depression by allowing patients to change their rigidly pessimistic patterns of thinking. Psychedelics were used for therapeutic purposes in the 1950s and 1960s but now we are finally beginning to understand their action in the brain and how this can inform how to put them to good use.”

The data was originally collected at Imperial College London in 2012 by a research group led by Dr Carhart-Harris and Professor David Nutt from the Department of Medicine, Imperial College London. Initial results revealed a variety of changes in the brain associated with drug intake. To explore the data further Dr. Carhart-Harris recruited specialists in the mathematical modelling of brain networks, Professor Dante Chialvo and Dr Enzo Tagliazucchi to investigate how psilocybin alters brain activity to produce its unusual psychological effects.

As part of the new study, the researchers applied a measure called entropy. This was originally developed by physicists to quantify lost energy in mechanical systems, such as a steam engine, but entropy can also be used to measure the range or randomness of a system. For the first time, researchers computed the level of entropy for different networks in the brain during the psychedelic state. This revealed a remarkable increase in entropy in the more primitive network, indicating there was an increased number of patterns of activity that were possible under the influence of psilocybin. It seemed the volunteers had a much larger range of potential brain states that were available to them, which may be the biophysical counterpart of ‘mind expansion’ reported by users of psychedelic drugs.

Previous research has suggested that there may be an optimal number of dynamic networks active in the brain, neither too many nor too few. This may provide evolutionary advantages in terms of optimising the balance between the stability and flexibility of consciousness. The mind works best at a critical point when there is a balance between order and disorder and the brain maintains this optimal number of networks. However, when the number goes above this point, the mind tips into a more chaotic regime where there are more networks available than normal. Collectively, the present results suggest that psilocybin can manipulate this critical operating point.

Psilocybin inhibits the processing of negative emotions in the brain

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When emotions are processed in a negatively biased manner in the brain, an individual is at risk to develop depression. Psilocybin, the bioactive component of the Mexican magic mushroom, seems to intervene positively in the emotion-processing mechanism. Even a small amount of the natural substance attenuates the processing of negative emotions and brightens mood as shown by University of Zurich (UZH)  researchers using imaging methods.

Emotions like fear, anger, sadness, and joy enable people to adjust to their environment and react flexibly to stress and strain and are vital for cognitive processes, physiological reactions, and social behaviour. The processing of emotions is closely linked to structures in the brain, i.e. to what is known as the limbic system. Within this system the amygdala plays a central role – above all it processes negative emotions like anxiety and fear. If the activity of the amygdala becomes unbalanced, depression and anxiety disorders may develop.

Researchers at the Psychiatric University Hospital of Zurich have now shown that psilocybin, the bioactive component in the Mexican magic mushroom, influences the amygdala, thereby weakening the processing of negative stimuli. These findings could “point the way to novel approaches to treatment” comments the lead author Rainer Krähenmann on the results which have now been published in the renowned medical journal “Biological Psychiatry”.

Psilocybin inhibits the processing of negative emotions in the amygdala

The processing of emotions can be impaired by various causes and elicit mental disorders. Elevated activity of the amygdala in response to stimuli leads to the neurons strengthening negative signals and weakening the processing of positive ones. This mechanism plays an important role in the development of depression and anxiety disorders. Psilocybin intervenes specifically in this mechanism as shown by Dr. Rainer Krähenmann’s research team of the Neuropsychopharmacology and Brain Imaging Unit led by Prof. Dr. Franz Vollenweider.

Psilocybin positively influences mood in healthy individuals. In the brain, this substance stimulates specific docking sites for the messenger serotonin. The scientists therefore assumed that psilocybin exerts its mood-brightening effect via a change in the serotonin system in the limbic brain regions. This could, in fact, be demonstrated using functional magnetic resonance imaging (fMRI). “Even a moderate dose of psilocybin weakens the processing of negative stimuli by modifying amygdala activity in the limbic system as well as in other associated brain regions”, continues Krähenmann. The study clearly shows that the modulation of amygdala activity is directly linked to the experience of heightened mood.

Next study with depressive patients

According to Krähenmann, this observation is of major clinical importance. Depressive patients in particular react more to negative stimuli and their thoughts often revolve around negative contents. Hence, the neuropharmacologists now wish to elucidate in further studies whether psilocybin normalises the exaggerated processing of negative stimuli as seen in neuroimaging studies of depressedpatients – and may consequently lead to improved mood in these patients.

Rainer Krähenmann considers research into novel approaches to treatment very important, because current available drugs for the treatment of depression and anxiety disorders are not effective in all patients and are often associated with unwanted side effects.

78 years ago, a journalist who studied 500 millionaires realized something about relationships that is just as relevant today.

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bill melinda gates

Nearly a century ago, journalist Napoleon Hill set out on a mission to uncover and document the strategies used by the wealthiest and most successful businessmen in in America.

He studied more than 500 self-made millionaires over a span of 20 years, and his research culminated in the 1937 bestseller, ” Think and Grow Rich ,” which shares what he calls the “money-making secret” in 13 principles .

His tenth principle – “the mystery of sex transmutation” – suggests that love, romance, and sex are critical factors in the determination of one’s success and wealth.

Hill writes:

Sex desire is the most powerful of human desires …

When harnessed, and redirected along other lines, this motivating force maintains all of its attributes of keenness of imagination, courage, etc., which may be used as powerful creative forces in literature, art, or in any other profession or calling, including, of course, the accumulation of riches …

Love, romance, and sex are all emotions capable of driving men to heights of super achievement … When combined, these three emotions may lift one to an altitude of a genius.

Hill makes some bold claims: “the men of greatest achievement are men with highly developed sex natures,” and “the men who have accumulated great fortunes … were motivated by the influence of a woman.”

While this principle may seem a little far-fetched, there is something to be said about having a supportive partner to achieve financial success – an idea that has surfaced and gained relevance today, 78 years later.

Sheryl Sandberg

“The most important career choice you’ll make is who you marry,” Facebook COO Sheryl Sandberg, whose estimated net worth is $1.1 billion, said at the 2011 IGNITION conference in New York .

Many people echo this sentiment, including Catherine Alford of The Simple Dollar , who wrote : “If I’d selected a different spouse, my life would look very different … My spouse, whether I realized it or not at the time, has been the best money decision of my life.”

It makes sense. As motivational speaker Jim Rohn famously said: We are the average of the five people we spend the most time with , which is especially true when it comes to our spouses.

These claims are backed by research. One s tudy , by Brittany C. Solomon and Joshua J. Jackson of Washington University in St. Louis, shows thathaving a conscientious spouse can boost your salary significantly.

“With every standard-deviation increase in a spouse’s conscientiousness, an employee is likely to earn about $4,000 more a year ,” reported theHarvard Business Review . “An employee with an extremely conscientious spouse (two standard deviations above the mean) is 50% more likely to get a promotion than an employee with an extremely unconscientious spouse (two standard deviations below the mean).”

Conscientious spouses tend to allow their partner to focus more on their career. Also, people with conscientious spouses generally feel more satisfied with their marriage, and this absence of stress and drama at home allows them to bring more emotional and physical energy to work, the researchers concluded.

While parts of Hill’s philosophy are outdated – he only analyzed rich men, and wrote for a predominantly male audience – he was onto something when he suggested relationships are a crucial step toward accumulating wealth.

The True Reason behind The 40-Hour Work Week And Why We Are Economic Slaves

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What is the true reason behind the 40-hour work week?

Economic slavery, or wage slavery, refers to one’s total and immediate dependence on wages to survive.

 Although people throughout history have had to work to get by, we now live in a culture where we are led to believe we have economic freedom, when unbeknownst to most citizens, we are in fact bound in servitude. We automatically accept a 40-hour workweek with meager hourly pay as normal, even though many work overtime and still struggle to survive. There are also those who make enough to live comfortably but are unable to request less hours—you either work 40 hours a week, or you don’t get to work at all. We submit when told what to wear, when we have to arrive and depart, when we’re allowed to eat, and even when we’re allowed to use the restroom. How is it we have come to allow this?

The 40-hour-work week came about during the Industrial Revolution in Britain when at one point workers were putting in 10 to 16 hour days and began to protest. Working situations for Americans began to worsen as well, and by 1836, labor movement publications were also calling for a 40-hour workweek. Citizens in both situations were so overworked, an eight-hour day was easily accepted. This system is unnecessary now, if it ever was, but we still accept it due to the effects of our capitalist society.

There are many contributing factors that have led to our current economic system and continued acceptance of the 40-hour workweek, three major factors being consumerism, inflation, and debt. First, it’s important to understand exactly what inflation is, how it works, and how it leads to debt.

Inflation:

To put inflation simply, let’s say the U.S. government needs money for whatever war they’ve decided to wage this year. They ask the Federal Reserve for a loan, and the Fed agrees to buy bonds (sort of like IOU’s) from the government in the amount of the requested loan. The U.S. government then prints up a bunch of pieces of paper that say “Treasury Bond” while at the same time, the Federal Reserve prints up a bunch of little pieces of paper that we know as money. A trade is made between the government and the Federal Reserve—the bonds for the money—and the U.S. government directly deposits this newly printed money in a different bank, which in turn, takes its cut in fees and interest. Voilà, money has been created out of thin air.

Although this process takes place electronically now (only 3% of money is in physical form, the other 97% exists in computers) the problem either way is that it depletes the worth of the dollar. At one point in time, currency was worth gold. That was what gave money its value, but now the value of money is trusted to the Federal Reserve who has no moral objections to reducing that value by printing more money (basically legal counterfeit). For the cost of printing, the Federal Reserve creates money that the U.S. government has promised to pay back—money that didn’t even exist in the first place.

It works like this with private bank loans to citizens as well. Each time a transaction of this sort happens, it reduces the value of actual currency, and thus we have inflation. One dollar in 1913 required $21.60 in 2007 to match its value. That’s a 96% devaluation since the Federal Reserve came into existence. How does this lead to economic slavery? By the debt inflation has caused.

Debt:

Since money is created through loans, that means it’s created through debt. Money equals debt, and debt equals money. So the more money there is, the more debt there is, and vice versa. What this means is, if somehow the government and every citizen in debt were able to pay back those loans, there would not be a single dollar in circulation.

Interest plays an important role in this equation as well. When you take out a loan and the bank gives you money that technically doesn’t exist, they also expect you to pay additional interest with it. If the money loaned is coming from the Federal Reserve, where is the money for the interest supposed to come from?

The answer is nowhere.

That means no matter what, the nation will never be able to get out of debt, and that is exactly the purpose of this meticulously orchestrated system. Like a toss of the coin, somebody somewhere will always go bankrupt to make up for the interest that is being paid with even more debt. And so, as the nation sinks further in the hole while the cost of living increases, surviving in the economy becomes more difficult. This desperation to survive, coupled with the fact that we were born into this system, is ultimately what causes us to accept the 40-hour workweek without a moment’s thought.

 So now we understand the element that forces us to accept our predicament, but how does the 40-hour workweek benefit banks and corporations? After all, studies show that the average office worker gets less than three hours worth of work done in an 8-hour work shift, and according to reports, US corporate profits are soaring while wages are declining. Bureau of Labor Statistics figures show that productivity has increased at a 2.3 percent annual rate in the third quarter, while hourly pay only increased 1.3 percent in the third quarter, and this has been the basic pattern for some time—it adds up after a while. Corporate profits are at their highest level in at least 85 years, so why aren’t we being paid more, working less, and providing additional jobs to those who need them? This brings us to consumerism.

Consumerism:

Consumerism is defined by the Merriam-Webster dictionary as: the belief that it is good for people to spend a lot of money on goods and services. At one point in time this belief may have rang true, but with the current capitalist system and cost of living, consumerism has begun to have negative effects on our society, especially when you take inflation and the increasing debt into consideration. The more we buy, the more we feed the corporations and banks who are in turn pushing us into economic slavery.

Related Article: 10 Painfully Obvious Truths Everyone Forgets Too Soon

Since the 1800’s and the Industrial Revolution, “consumers” have been spending increasing amounts of money on frivolous purchases. This over-indulgence has been nurtured and fed by the corporations using commercialism (the attitude or actions of people who are influenced too strongly by the desire to earn money or buy goods rather than by other values—Merriam-Webster) as a tool. Psychological insinuations have been planted into society’s subconscious for generations through consumer advertisements which have ultimately led to certain habits and beliefs. Some examples are:

“Buy now pay later” – The General Motors Acceptance Corporation (GMAC) started this mindset when it was established in 1919 and began to promote giving loans to people who bought cars. Americans eventually started to use the new credit plans on just about everything.

“Keeping up with the Joneses” – Commonly thought to be the beginning of the American consumer culture, this mindset began when GM introduced the yearly automobile model change. People wanted to have the latest model each year, and soon this idea spread out. Most of us, whether we want to admit it or not, are familiar with this mentality. Rather than keeping our old toaster that works perfectly fine, we want the new retro-style stainless steel model because it looks swanky sitting on our kitchen counter.

“1929-1945 Depression and War” – Soon after The Depression came WWII, during which advertisers promised products to be available when there was peace. As a result, customers (consumers) were eager to take up spending immediately after the war was over.

“Peace” – When the war ended, consumer optimism and economic growth accompanied victory.

“Charge it!” – Credit cards were first promoted through the Diners Club—a charge card company that services affluent and well-travelled individuals from around the world. Other companies followed suit and started advertising credit cards as a “time-saving device” rather than a way to spend money that wasn’t actually there.

“Bigger is better” – During the 1970’s, companies began to send credit cards out by the masses to those who had not requested them. While Americans had already been developing the idea that “bigger is better”, the credit card boom ended up exploiting that idea. Now people had the means to obtain extravagant items they couldn’t before, even though it put many in colossal debt. Congress soon had to regulate the credit card boom, and ban sending cards to those who never requested them in the first place.

Companies in all kinds of industries hold a huge stake in the public’s penchant to be careless with their money, and they encourage this habit of casual or non-essential spending when they can. For example, in the documentary The Corporation, a marketing psychologist discussed a method she used to increase sales that involved encouraging children to nag their parents to buy toys. Studies showed that 20% to 40% of purchases of this sort resulted after children nagged their parents.

“You can manipulate consumers into wanting, and therefore buying, your products. It’s a game.” Lucy Hughes, co-creator of “The Nag Factor”.

The 40-hour workweek is the ultimate tool for corporations to sustain this culture of over-indulgent spending. Under our current working conditions, people are forced to build a life in the evenings and their days-off. We find ourselves more inclined to spend heavily on entertainment and conveniences because we rarely have any free time. When we do have time to ourselves, it’s usually fleeting, and we eventually find ourselves neglecting those activities which are free—walking, exercising, reading, meditating, sports, hobbies, etc.—because they take too much time.

While having extra money comes at the sacrifice of personal time for some, for others they not only are robbed of their personal freedom, but they struggle to make ends meet on top of it. The “perfect” consumer works full-time, earns a fair amount of money, indulges during their free time, and somehow just makes it by each month. However, even those who don’t earn fair wages sometimes find themselves wasting small increments of money on unnecessary items for the wrong reasons—a cup of Starbucks here, a McDonald’s cheeseburger there, and those really cool fuzzy dice hanging from the rear-view of your 1993 Honda Civic.

Any way you look at it, we have become an unhappy, mindless, over-worked society. We buy silly items for a few moments of happiness before getting bored and moving on. We feel a need to keep up with fads, or to fulfill our childhood vision of what adulthood would be like. We hide our insecurities, avoid issues, and replace psychological needs with material items. By keeping society’s free time scarce, people will pay more for convenience, gratification, and any other relief they can buy.

Keeping America unhealthy has become extremely profitable for big-business, and so far their efforts have paid-off beautifully. Our society has been transformed into an industry fueled by economic slavery, and consumerism is a key factor in this corrupt system—one the people have direct influence over. Consumers are the only ones who can stop consuming.

Source: Anonhq