ALZHEIMER'S | +80 articles

[mr peabody]

Ayahuasca stimulates brain cells and could treat Alzheimer's

by Olivia Lerche

SCIENTISTS have discovered that a psychedelic substance from the Amazon stimulates the birth of new brains cells and could lead to treatment for neurodegenerative diseases.

The Sant Pau Hospital Barcelona, which worked in collaboration with the Beckley Foundation and Spanish National Research Council in Madrid, has released the findings from a study investigating the potential of ayahuasca to promote neurogenesis - which is the development of new brain cells. The investigators believe that these findings will open up a new avenue of research that may help develop drugs to treat diseases like Alzheimer's, Parkinson's and addiction.

Dr Jordi Riba, lead investigator, presented preliminary data, at the Interdisciplinary Conference on Psychedelic Research in Amsterdam at the weekend. Results showed that two compounds - harmine and tetrahydro harmine - which are found in the psychedelic tea, potently stimulated the transformation of stem cells into new neurons.

Amanda Feilding, director of the Beckley Foundation said: "The images from the Beckley/Sant Pau collaboration showing the birth of new neurons are very interesting and suggest that ayahuasca could lead to a new approach in the treatment of neurodegenerative conditions such as Alzheimer's and Parkinson's, among others."

Experts have believed for years that the brain doesnt make neurons during adulthood. In the 1990s, research changed this finding, showing that new neurons are generated throughout adult life in two regions of the human brain: the area around the ventricles and in the hippocampus. The hippocampus, thought to be the center of emotion and autonomic nervous system, plays a key role in memory. Its function declines with age and in neurological disorders.

Under normal conditions, the rate of the birth of new neurons is very low, and it cannot keep up with the rate of neural death that occurs in diseases such such as Alzheimer's disease. In the study, neural stem cells were isolated from the hippocampus of adult mice. The stem cells were grown in the lab and substances that are present in ayahuasca were added to the cultures and compared with saline a placebo control.

Scientists have described the results as impressive, with ayahuasca substances stimulating the transformation of stem cells into new neurons.

Dr Riba has been studying ayahuasca for twenty years.

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Psilocybin rebuilds damaged neurotransmitters

Dr. Juan R. Sanchez-Ramos has discovered that using large doses of psilocybin allow the brain to create new brain cells. Dr. Ramos is actively seeking alternatives from mainstream medicine to cure Neurodegenerative diseases, Huntington's Disease and Parkinson's Disease.

This is promising news for Alzheimer's patients who suffer with a sloughing of brain cells causing a disruption and permanent loss of memory, and also for people who suffer with depression because of the low serotonin levels. The magic mushrooms rebuild the neurotransmitters responsible for serotonin. Because at the root of many tragic massacres today are psychotropic (Prozac, Paxil, etc.) drugs with side effects like suicide, extreme depression and violence. It appears whenever a natural remedy is applied to alleviate a problem, it does not have these hazardous side effects.​

-Michael Erevna

 

[mr peabody]

Gary Wenk, Ph.D

Cannabinoides found to reduce inflammation, restore cognitive function

Alzheimer’s appears because of inflammation in the brain, and the brain’s inability to remove amyloid beta plaque.

Gary Wenk, Ph.D, professor of neuroscience, immunology and medical genetics at Ohio State University, on marijuana and its link to inflammation:

“I have been trying to find a drug that will reduce brain inflammation and restore cognitive function in rats for over 25 years; cannabinoides are the first and only class of drugs that have ever been effective.”

You know what plaque on your teeth is because of your dentist. He or she tells you to clean your teeth so they won’t be left covered in plaque.

You can watch the dentist scrape plaque off, but what about brain plaque?

Brain plaque is the common term for acetylcholinesterase-associated amyloid β-peptide (Aβ). We can’t see this get wiped away, and even if we could, we wouldn’t. This is because our brains clear themselves out while we’re asleep.

Marijuana helps protect against brain inflammation, which in turn aids in the brain’s waste removal process. Unlike other Alzheimer’s medications, marijuana has been proven to work, does not demean or insult patients, costs considerably less to produce, and eases the brain, mind, and soul.

-Michelle Toole​

 

[mr peabody]

Vitamin K may help ward off Dementia

Experimental Biology | Neuroscience News | 5 Apr 2022

Vitamin K could help reduce or prevent age-related cognitive decline associated with Alzheimer’s and other dementias, a new rat study reveals.

In a new study conducted in rats, scientists report evidence that vitamin K could help protect against aging-related cognitive declines associated with Alzheimer’s disease and other forms of dementia.

“Vitamin K2 demonstrated very promising impact in hindering aging-related behavioral, functional, biochemical and histopathological changes in the senile aging brain,” said Mohamed El-Sherbiny, PhD, of AlMaarefa University in Saudi Arabia, the study’s senior author.

“Vitamin K2 can be proposed to be a promising approach to attenuate age-related disorders and preserve cognitive functions in aging individuals.”

Abdulrahman Aloufi, a medical student working in El-Sherbiny’s laboratory at AlMaarefa University, will present the findings at the American Association for Anatomy annual meeting during the Experimental Biology (EB) 2022 meeting, held in Philadelphia April 2–5.

Dementia is a form of cognitive impairment that interferes with daily life and is different from normal memory lapses that occur with aging. In the U.S., it is estimated that more than six million people are currently living with Alzheimer’s, one of the most common types of dementia.

Vitamin K is a group of compounds that includes vitamin K1, found in leafy greens and some other vegetables, and vitamin K2, found in meats, cheeses and eggs. Previous studies have linked vitamin K with processes involved in brain functioning, and some studies have associated vitamin K deficiencies with Alzheimer’s disease and dementia.

The new study elucidates some of the biological pathways through which vitamin K appears to help preserve cognitive functioning. The researchers investigated the effects of menaquinone-7 (MK-7), a form of vitamin K2, in 3-month-old rats, an age at which rats have reached maturity. One group of rats received supplemental MK-7 for 17 months while the other group did not.

The researchers used validated tests including a maze, swim test and sociability test to assess the rats’ cognitive functioning and depressive-like and anxiety behavior. These tests revealed that rats that received MK-7 performed better than those that did not. Vitamin K supplementation was associated with reduced evidence of cognitive impairment, depression and anxiety, along with improved spatial memory and learning ability.

A diagram illustrating the mechanisms by which vitamin K (MK-7) is thought
to produce a neuroprotective effect in the aged rat.

At the end of the study, the researchers examined the rats’ brain tissues for insights on the biological pathways involved. The results suggest that vitamin K supplementation affects pathways involving the proteins NLRP3, caspase-1, and Nrf-2, which are involved in inflammation and antioxidant activity. It also appears to promote the expression of tyrosine, an amino acid that helps preserve cognitive functions.

In addition to various forms of vitamin K found naturally in foods, vitamin K supplements are commercially available.

However, researchers cautioned that more studies are needed to determine whether the new findings translate from rats to humans and to identify the optimal source and dose of vitamin K to reap potential brain benefits. People taking certain blood thinners and other medications are advised to avoid vitamin K supplements and foods rich in vitamin K.

“Further clinical studies will be required to assess the appropriate dosage for protection against Alzheimer’s, especially in those treated with vitamin K antagonists,” said El-Sherbiny.

Vitamin K May Help Ward Off Dementia - Neuroscience News

Vitamin K could help reduce or prevent age-related cognitive decline associated with Alzheimer's and other dementias, a new rat study reveals.

neurosciencenews.com

 

[mr peabody]

Cannabis may prevent the onset of Alzheimer's

by Steve Elliott

Early use of cannabis apparently delays and might even prevent the onset of Alzheimer's, according to a leading scientist in the field. But the work of longtime researcher Gary Wenk of Ohio State University has come to a halt, despite the promising results.

"We found out that people who smoked cannabis in the 1960s were not getting Alzheimer's," Wenk explained, reports KJ Hiramoto at the Seattle PI. "These 90-year-olds without dementia were telling us things like, 'Well, I drank whiskey and smoked cannabis,' and these are the things they remember. They don't remember habits like how often they ate broccoli."

Maddeningly, Wenk's research ground to a halt due to political, legal and financial reasons.

"The evidence in animals is clear but making the leap to humans means that you have to find a drug company willing to handle the lawsuits and the money," Wenk said.

He faced other hurdles, as well. Scientists who wish to research cannabis have to compete for approval and grants from the National Institute on Drug Abuse (NIDA), for which The University of Mississippi is the only source of cannabis - Mississppi has the only federally legal, grant-funded cannabis garden in the U.S.A.

What makes the situation even worse is that, as admitted even by NIDA Director Nora D. Valkow, M.D., is that the agency is only interested in studying the potential harms of cannabis, not the medicinal benefits.

A spokesperson for the NIDA told the New York Times in 2010 that the agency does not fund research focused on the potential medical benefits of cannabis.

"As the National Institute on Drug Abuse, our focus is primarily on the negative consequences of cannabis use," NIDA spokeswoman Shirley Simson told the Times.

And under federal law, the NIDA must approve all clinical research involving cannabis. It tightly controls which investigators are allowed access to the federal government's Ole Miss cannabis supply, which is grown (and then stored, for years) at the research facility in Oxford, Mississippi.

"I am not funded to do cannabis research," Wenk said. "It cost me about $100,000 to do a whole experiment, $10,000 just to buy the molecule, and every old rat is $150. You can see how it adds up, and individuals can't afford it."

British researchers find corroborating evidence

"A paper published in the British Journal of Pharmacology suggests that the cannabinoids in cannabis are likely not only to prevent the onset of Alzheimer's, but also of Parkinson's disease, Huntington's disease, and age-related dementia," reports Brandon Isaak.

Chronic brain inflammation, oxidative stress, and intra-cellular dysfunction are the primary reasons people develop these debilitating neurological diseases, and the study found that both THC and CBD, found in cannabis, help protect nerve cell function in users, significant reducing these harmful conditions.

The cannabinoids tap into the endocannabinoid system, reducing inflammation, protecting brain cells from oxidative damage, and promoting cellular health on multiple levels, according to the researchers.

Showing promise: Old people are going to win

Wenk's research, before it was halted, anyway, was showing promise to middle-aged and older Americans. Cannabinoids found in cannabis may delay the onset of Alzheimer's so effectively that people are more likely to die of old age before showing any signs of dementia.

In the study, Wenk dosed rats in his lab at Ohio State a dosage equivalent to one puff of cannabis every day. In old rats with impaired memory due to brain inflammation, that single puff a day was making them smarter. Not only were they more intelligent, but some of the pathological changes in the rats brains, due to aging, were being reversed.

"Essentially, what we found was that we know that as people get older, their neurogenesis drops to zero," Wenk said, referring to the process through which new brain cells are created. "And that's part of the reason old people have a problem with their memory and depression. What we found was that not only did the single puff a day reverse the memory impairment but also restarted neurogenesis."

According to Wenk, delaying the end of neurogenesis (regeneration of neurons) helps middle-aged Americans and their families in a very easy-to-measure way: in their pocketbooks.

"If we can keep a person out of a nursing home for five years, we've saved that family and their insurance companies an awful lot of money," Wenk said. "No matter how we spin this, old people are going to win."

"I am incredibly excited about it, because this is the first time we have ever had a compound that actually works in the old brain," Wenk said. "Everything works in the young brain, but this is working in old brains. So this means if you are, 60, 70, and you are having problems with mental decline? We might have a mechanism that could target that."

"Very low doses are effective," Wenk said, "Even just one puff of cannabis a day helps," according to his research. "This is just the beginning of what we believe we will uncover as we investigate this line of research," he said.

Blocking endocannabinoids may trigger early Alzheimers

Another study from a team of investigators at the Stanford University School of Medicine led by Daniel Madison has implicated the blocking of endocannabinoids, the brains own internal versions of the active compounds in cannabis, in the early pathology of Alzheimers.

It seems a substance called A-beta, suspected to play a key role in Alzheimers because it is the main part of clumps which dot the brains of Alzheimer's patients, may, in the early stages of the disease, impair learning and memory by blocking the beneficial action of endocannabinoids.

The group at Stanford is now trying to suss out the molecular details of how this occurs. Pinning down the details could pave the path to new ways to stave off the learning disabilities and memory deficits that characterize Alzheimer's and could also help explain how smoking cannabis helps to delay or even prevent its onset.

In the study, published in the June 28, 2014 issue of the scientific journal Neuron, the researchers detail how pyramidal cells in the brain underpin learning and memory. This assures, they learned, that high-intensity input such as falling down or burning your finger tends to stick in your memory, thus presumably help avoid such mishaps in the future.

Pyramidal cells are encouraged to ignore noise signals, they constantly receive random signals from upstream nerve cells by a sort of wet blanket, nerve cells called interneurons. These secret an inhibitory substance, the molecular equivalent of an indifferent shrug or yawn, signaling that the input is not really very important.

But when the news actually is significant, pyramidal cells secrete their own "Now just you wait a minute, these are important" chemicals. And guess what? Those chemicals which signal the importance of incoming information are none other than the endocannabinoids.

Madison speculates that when we smoke cannabis, the phytocannabinoids from the plant have the effect of enhancing the perceived importance of events that happen while we are under the influence of cannabis.

And another likely effect is inhibiting the "wet blanket effect" of interneurons which, in Alzheimers, needs reducing to increase the ability to learn and remember.

Increasing tolerance

The federal Schedule I illegality of cannabis, under which it is officially considered to have no medical uses and a high danger of abuse, has stymied Wenk's research. But the scientist has noticed a refreshing trend, a major shift in the cultural tolerance of cannabis, particularly from young people, including his students.

"I've really seen a shift in 10 years of increased cannabis tolerance," Wenk said. "In my class, people are more than willing to discuss their cannabis use. But they would be embarrassed to mention that they smoke cigarettes."

With Alzheimer's ranking as the sixth leading cause of death in the United States, and with more than five million Americans currently struggling with the disease, which has no known cure, you would think that lab results as promising as Wenk's would have attracted major funding by now. But that is not the case, because, as we have pointed out, the NIDA is not really interested in knowing about the medical benefits of cannabis, just its dangers.​

Wenk, who has researched the effects of Alzheimer's on animals for about 40 years, has shared his findings in his book, Your Brain On Food.

https://tokesignals.com/marijuana-sh...ch-is-stalled/

 

[mr peabody]

Deep sleep helps brain remove waste and toxic proteins linked to Alzheimer’s

by NutritionReview.org | 10 Mar 2019

New research shows how the depth of sleep can impact our brain’s ability to efficiently wash away waste and toxic proteins. Because sleep often becomes increasingly lighter and more disrupted as we become older, the study reinforces and potentially explains the links between aging, sleep deprivation, and heightened risk for Alzheimer’s disease.

“Sleep is critical to the function of the brain’s waste removal system and this study shows that the deeper the sleep the better,” said Maiken Nedergaard, M.D., lead author of the study.
​

“These findings also add to the increasingly clear evidence that quality of sleep or sleep deprivation can predict the onset of Alzheimer’s and dementia.”​

The study, published in the journal Science Advances, indicates that the slow and steady brain and cardiopulmonary activity associated with deep, non-REM sleep (also known as SWS or Slow Wave Sleep) are optimal for the function of the glymphatic system, the brain’s unique process of removing waste. The findings may also explain why some forms of anesthesia can lead to cognitive impairment in older adults.

The previously unknown glymphatic system was first described by Nedergaard and her colleagues in 2012. Prior to that point, scientists did not fully understand how the brain, which maintains its own closed ecosystem, removed waste. The study revealed a system of plumbing which piggybacks on blood vessels and pumps cerebral spinal fluid (CSF) through brain tissue to wash away waste. A subsequent study showed that this system primarily works while we sleep.

Because the accumulation of toxic proteins such as beta amyloid and tau in the brain are associated with Alzheimer’s disease, researchers have speculated that impairment of the glymphatic system due to disrupted sleep could be a driver of the disease.
​

"This squares with clinical observations which show an association between sleep deprivation and heightened risk for Alzheimer’s."​

In the current study, researchers conducted experiments with mice that were anesthetized with six different anesthetic regimens. While the animals were under anesthesia, the researchers tracked brain electrical activity, cardiovascular activity, and the cleansing flow of CSF through the brain. The team observed that a combination of the drugs ketamine and xylazine (K/X) most closely replicated the slow and steady electrical activity in the brain and slow heart rate associated with deep non-REM sleep. Furthermore, the electrical activity in the brains of mice administered K/X appeared to be optimal for function of the glymphatic system.

“The synchronized waves of neural activity during deep slow-wave sleep, specifically firing patterns that move from front of the brain to the back, coincide with what we know about the flow of CSF in the glymphatic system,” said Lauren Hablitz, Ph.D., first author of the study. “It appears that the chemicals involved in the firing of neurons, namely ions, drive a process of osmosis which helps pull the fluid through brain tissue.”

The study further bolsters the link between sleep, aging, and Alzheimer’s disease. It is known that as we age it becomes more difficult to consistently achieve deep non-REM sleep, and the study reinforces the importance of deep sleep to the proper function of the glymphatic system. The study also demonstrates that the glymphatic system can be manipulated by enhancing sleep, a finding that may point to potential clinical approaches, such as sleep therapy or other methods to boost the quality of sleep, for at-risk populations.

Furthermore, because several of the compounds used in the study were analogous to anesthetics used in clinical settings, the study also sheds light on the cognitive difficulties that older patients often experience after surgery and suggests classes of drugs that could be used to avoid this phenomenon. Mice in the study that were exposed to anesthetics that did not induce slow brain activity saw diminished glymphatic activity.

“Cognitive impairment after anesthesia and surgery is a major problem,” said Tuomas Lilius, M.D., Ph.D., with the Center for Translational Neuromedicine at the University of Copenhagen in Denmark and co-author of the study. “A significant percentage of elderly patients that undergo surgery experience a postoperative period of delirium or have a new or worsened cognitive impairment at discharge.”

Deep Sleep Helps Brain Remove Waste and Toxic Proteins Linked to Alzheimer’s

New research shows how the depth of sleep can impact our brain’s ability to efficiently wash away waste and toxic proteins. Because sleep often becomes increasingly lighter and more disrupted…

nutritionreview.org

 

[mr peabody]

Is Alzheimer's a form of diabetes?

The accumulated evidence is now so strong that many specialists are comfortable referring to Alzheimer's as type 3 diabetes.

Insulin doesn't merely signal the body's somatic cells to take up glucose; it also governs the brain's uptake of glucose. And glucose is what powers the brain. It's the brain's primary energy molecule.

We've known for some time that the brain itself makes a certain amount of insulin, and various parts of the brain are rich in insulin receptors. It's also well established that cognitive decline is correlated with both obesity and metabolic abnormalities involving insulin.

Dr. David Perlmutter lays the blame squarely on diet, and details the case for eating more fats and cholesterol (yes, more cholesterol) and cutting gluten from your diet entirely, pointing to studies that have linked low cholesterol to cognitive impairment.

-Kas Thomas

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Studies carried out at Warren Alpert Medical School at Brown University identified the possibility of a new form of diabetes after finding that insulin resistance can occur in the brain.

Lead researcher, Dr Suzanne de la Monte, carried out a further study in 2012 to further investigate the link.

The researchers pinpoint resistance to insulin and insulin-like growth factor as being a key part of the progression of Alzheimer’s disease.

Whereas type 1 and type 2 diabetes are characterized by hyperglycemia (increased blood sugar), a separate study, carried out by the University of Pennsylvania and published in 2012, excluded people with a history of diabetes, indicating that Alzheimer’s can develop without the presence of significant hyperglycemia in the brain.

People that have insulin resistance, in particular those with type 2 diabetes have an increased risk of suffering from Alzheimer's disease estimated to be between 50% and 65% higher.

Researchers have discovered that many type 2 diabetics have deposits of a protein called amyloid beta in their pancreas which is similar to the protein deposits found in the brain tissue of Alzheimer's sufferers.

-diabetes.co.uk

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New research shows insulin resistance is one of the major factors that starts the brain-damage cascade, which robs the memory of over half the people in their 80s, leading to a diagnosis of Alzheimer’s disease.

Eating sugar and refined carbs can cause pre-dementia and dementia. But cutting out the sugar and refined carbs and adding lots of fat can prevent, and even reverse, pre-dementia and early dementia.

Studies show people with diabetes have a four-fold risk for developing Alzheimer’s. People with pre-diabetes or metabolic syndrome have an increased risk for having pre-dementia or mild cognitive impairment (MCI).

You don’t have to have full blown type 2 diabetes to develop brain damage and memory loss from high insulin levels and insulin resistance.

-Dr. Mark Hyman​

 

[mr peabody]

Ayahuasca stimulates brain cells and could treat Alzheimer's

by Olivia Lerche

SCIENTISTS have discovered that a psychedelic substance from the Amazon stimulates the birth of new brains cells and could lead to treatment for neurodegenerative diseases such as Alzheimer's. The tea called Ayahuasca, is also used as a traditional spiritual medicine in ceremonies in Peru, South America.

The Sant Pau Hospital Barcelona, which worked in collaboration with the Beckley Foundation and Spanish National Research Council in Madrid, has released the findings from a study investigating the potential of ayahuasca to promote neurogenesis - which is the development of new brain cells. The investigators believe that these findings will open up a new avenue of research that may help develop drugs to treat diseases like Alzheimer's, Parkinson's and addiction.

Dr Jordi Riba, lead investigator, presented preliminary data, at the Interdisciplinary Conference on Psychedelic Research in Amsterdam at the weekend. Results showed that two compounds - harmine and tetrahydro harmine - which are found in the hallucinogenic tea, potently stimulated the transformation of stem cells into new neurons.

Amanda Feilding, director of the Beckley Foundation said: "The images from the Beckley/Sant Pau collaboration showing the birth of new neurons are very interesting and suggest that ayahuasca could lead to a new approach in the treatment of neurodegenerative conditions such as Alzheimer's and Parkinson's, among others."

Experts have believed for years that the brain doesnt make neurons during adulthood. In the 1990s, research changed this finding, showing that new neurons are generated throughout adult life in two regions of the human brain: the area around the ventricles and in the hippocampus. The hippocampus, thought to be the center of emotion and autonomic nervous system, plays a key role in memory. Its function declines with age and in neurological disorders.

Under normal conditions, the rate of the birth of new neurons is very low, and it cannot keep up with the rate of neural death that occurs in diseases such such as Alzheimer's. In the study, neural stem cells were isolated from the hippocampus of adult mice. The stem cells were grown in the lab and substances that are present in ayahuasca were added to the cultures and compared with saline a placebo control.

Scientists have described the results as impressive, with ayahuasca substances stimulating the transformation of stem cells into new neurons.

Dr Riba has been studying ayahuasca for twenty years.​

 

[mr peabody]

Cannabis shown to Reverse Cognitive Decline and fight Alzheimer’s*

by Nick Cherbanich & Valerie Bonnelle | Beckley Foundation​

Cannabis has the reputation of impairing memory, attention and motivation, especially in young people. But what if it could actually protect the brain and prevent neurodegenerative disorders like Alzheimer’s and other types of dementia from developing?

Although cannabis has been used for its medicinal properties for many thousands of years, scientific research into the plant and its derivatives (pioneered by the Beckley Foundation and others) has only recently started to acknowledge and investigate some of its health benefits. Among many therapeutic applications, results gathered over the last decade have unveiled some extremely promising brain-protective and restorative properties.

The effects of cannabis are caused by chemical compounds produced by the plant known as cannabinoids. These include tetrahydrocannabinol (THC) and cannabidiol (CBD). Cannabinoid-like molecules – called endocannabinoids – occur naturally in the brain, and are involved in a diverse range of processes including appetite, energy regulation, and sleep. Indeed, cannabinoid receptors are some of the most abundant receptors found in the body.

Fig.1 – Humans have been using cannabis therapeutically for thousands of years – it is here illustrated in a 6th-century medical textbook (Wikimedia)

The endocannabinoid system develops gradually throughout childhood and is most active during adolescence, but as we age, its activity declines. Compelling evidence suggests this may be one of the root causes of some of the detrimental aspects of normal and pathological aging. One possibility seems particularly worth exploring – that supplementing the aging endocannabinoid system with exogenous plant cannabinoids may mitigate some of the damage that occurs in the brain as we grow older.

Recent experimental research seems to support this notion. In a study published last year, THC – the molecule in cannabis responsible for its psychoactive effects – was found to reverse age-related cognitive decline in old mice. The study also found that THC increased the number of connections between brain cells in the hippocampus, a brain region which plays a key role in memory.

THC, administered on consecutive days, significantly increased the speed at which mature
and old mice completed a maze task

This is not an isolated report; several other studies have found that THC-like substances improve memory and cognition in rodents. The positive effects of cannabis and cannabinoids on sleep and appetite, and on reducing stress and anxiety, may constitute other indirect ways in which these substances can ward off cognitive decline.

Perhaps even more profound is the implication that cannabinoids may treat more serious age-related disorders such as Alzheimer’s Disease. Despite the diagnosis of Alzheimer’s in millions of people every year, there is yet no definitive treatment for the condition. The disease involves accumulation of the toxic protein amyloid-beta (Aβ) in the brain. The insoluble Aβ plaques also cause further damage when the bodies own inflammatory response attacks cells in an attempt to clear them, leading to further death of brain tissue.

The idea that a component of cannabis – a natural, easily-grown substance with a known, positive safety profile – could be used to treat a disease which is afflicting more and more people in an aging population is a very attractive one.

Though the science is still at an early stage, pre-clinical research is promising. A study using neuronal cell cultures that had been genetically altered to over-produce Aβ – effectively a test-tube model of Alzheimer’s Disease – found that by adding increasing doses of THC, less of the toxic protein accumulated, and cells were less likely to die. These findings are also reflected in animal studies, which found that cannabinoids similar to THC and CBD improved cognition and decreased cellular damage in a mouse model of the disease.
​

Fig.3 – THC increased survival of Aβ-producing neurones (left), and decreased the accumulation of Aβ (right) in a dose-dependent manner (Currais et al. 2016)

There are various proposed mechanisms for the neuroprotective effect of cannabinoids in degenerative disorders such as Alzheimer’s. Symptoms of these diseases are partially a result of the body’s own immune system overreacting to diseased neurones. In chronic brain diseases, excessive immune response to neurones can further damage them, a process known as pathological neuroinflammation. The endocannabinoid system is involved in regulating the inflammatory response by inducing changes in pro-inflammatory proteins, limiting possible damage caused by their over-activation.

Another potential mechanism via which cannabinoids may exert their neuroprotective effects could be through inhibiting excitotoxicity. If neurones activate for too long and too often (excitation), they become damaged (toxicity). Damaged neurones then release chemicals that further activate and damage neurones near them, creating a positive feedback loop of spreading cellular damage. Activation of the cannabinoid system by endocannabinoids decreases the release of these potentially harmful molecules, limiting the spread of damage from an initial injury. By introducing plant cannabinoids in addition to those naturally produced by the body, it may be possible to boost these effects and further minimise brain damage.

Fig.4 – Some of the proposed mechanisms by which cannabinoids may mitigate neurodegenerative damage in conditions like Alzheimer’s Disease (Sasha Frost)

Cannabis derivatives hold great medical potential – not only for the treatment of neurodegenerative diseases such as Alzheimer’s, but for epilepsy, addiction, pain, and a host of other conditions. Unfortunately, this potential is limited by anti-scientific laws and policies. Cannabis is currently on Schedule I of the UN’s global drug conventions; of ‘little or no therapeutic value’, despite the overwhelming amount of evidence to the contrary. This strict legal scheduling means that research into the plant is severely underfunded and limited by bureaucratic restrictions which do little to quell recreational use of cannabis, but which do prevent doctors prescribing it to patients.

We are actively campaigning to reform the current system of drug legislation, and hope that both UK and global policy will soon change to reflect the scientific evidence. The Beckley Foundation and other research groups are dedicated to fully unravelling the therapeutic benefits of cannabis and other psychoactive compounds – something that everyone will benefit from.

*From the article here :
http://beckleyfoundation.org/2018/06...ne-alzheimers/​

 

[mr peabody]

Waves of fluid bathe the sleeping brain*

Neuroscience News | Boston University | Nov 1 2019

New research from Boston University suggests that tonight while you sleep, something amazing will happen within your brain. Your neurons will go quiet. A few seconds later, blood will flow out of your head. Then, a watery liquid called cerebrospinal fluid (CSF) will flow in, washing through your brain in rhythmic, pulsing waves.

The study, published on October 31 in Science, is the first to illustrate that the brain’s CSF pulses during sleep, and that these motions are closely tied with brain wave activity and blood flow.

“We’ve known for a while that there are these electrical waves of activity in the neurons,” says study coauthor Laura Lewis, a BU College of Engineering assistant professor of biomedical engineering and a Center for Systems Neuroscience faculty member. “But before now, we didn’t realize that there are actually waves in the CSF, too.”

This research may also be the first-ever study to take images of CSF during sleep. And Lewis hopes that it will one day lead to insights about a variety of neurological and psychological disorders that are frequently associated with disrupted sleep patterns, including autism and Alzheimer’s disease.

The coupling of brain waves with the flow of blood and CSF could provide insights about normal age-related impairments as well. Earlier studies have suggested that CSF flow and slow-wave activity both help flush toxic, memory-impairing proteins from the brain. As people age, their brains often generate fewer slow waves. In turn, this could affect the blood flow in the brain and reduce the pulsing of CSF during sleep, leading to a buildup of toxic proteins and a decline in memory abilities. Although researchers have tended to evaluate these processes separately, it now appears that they are very closely linked.

To further explore how aging might affect sleep’s flow of blood and CSF in the brain, Lewis and her team plan to recruit older adults for their next study, as the 13 subjects in the current study were all between the ages of 23 and 33. Lewis says they also hope to come up with a more sleep-conducive method of imaging CSF. Wearing EEG caps to measure their brain waves, these initial 13 subjects were tasked with dozing off inside an extremely noisy MRI machine, which, as anyone who has had an MRI can imagine, is no easy feat.

“We have so many people who are really excited to participate because they want to get paid to sleep,” Lewis says with a laugh. “But it turns out that their job is actually–secretly–almost the hardest part of our study. We have all this fancy equipment and complicated technologies, and often a big problem is that people can’t fall asleep because they’re in a really loud metal tube, and it’s just a weird environment.”

But for now, she is glad to have the opportunity to take images of CSF at all. "One of the most fascinating yields of this research," Lewis says, "is that they can tell if a person is sleeping simply by examining a little bit of CSF on a brain scan."

“It’s such a dramatic effect,” she says.

As their research continues to move forward, Lewis’ team has another puzzle they want to solve: How exactly are our brain waves, blood flow, and CSF coordinating so perfectly with one another? “We do see that the neural change always seems to happen first, and then it’s followed by a flow of blood out of the head, and then a wave of CSF into the head,” says Lewis.

This shows the CSF in the brain during sleep. During sleep, the brain exhibits large-scale waves:
waves of blood oxygenation (red) are followed by waves of cerebrospinal fluid (blue).

"One explanation may be that when the neurons shut off, they don’t require as much oxygen, so blood leaves the area. As the blood leaves, pressure in the brain drops, and CSF quickly flows in to maintain pressure at a safe level."

“But that’s just one possibility,” Lewis says. “What are the causal links? Is one of these processes causing the others? Or is there some hidden force that is driving all of them?”

*From the article here :

Are we 'brainwashed' during sleep? - Neuroscience News

Study reveals as we sleep, cerebrospinal fluid pulses in the brain in rhythmic patterns.

neurosciencenews.com

 

[mr peabody]

THC found to promote the removal of toxic clumps of amyloid beta

The finding supports the results of previous studies that found evidence of the protective effects of cannabinoids, including THC, on patients with neurodegenerative disease.

"Although other studies have offered evidence that cannabinoids might be neuroprotective against the symptoms of Alzheimer's, we believe our study is the first to demonstrate that cannabinoids affect both inflammation and amyloid beta accumulation in nerve cells," says one of the team, David Schubert from the Salk Institute for Biological Studies in California.

Schubert and his colleagues tested the effects of THC on human neurons grown in the lab that mimic the effects of Alzheimer's disease.

If you're not familiar with this special little compound, it's not only responsible for the majority of marijuana's psychological effects, including the high, thanks to its natural pain-relieving properties, it's also been touted as an effective treatment for the symptoms of everything from HIV and chemotherapy to chronic pain, post-traumatic stress disorder, and stroke.

In fact, THC appears to be such an amazing medical agent, researchers are working on breeding genetically modified yeast that can produce it way more efficiently than it would be to make synthetic versions.

The compound works by passing from the lungs to the bloodstream, where it attaches to two types of receptors, cannabinoid receptor (CB) 1 and 2, which are found on cell surfaces all over the body.

In the brain, these receptors are most concentrated in neurons associated with pleasure, memory, thinking, coordination and time perception, and usually bind with a class of lipid molecules called endocannabinoids that are produced by the body during physical activity to promote cell-to-cell signaling in the brain.

But THC can also bind to them in much the same way, and when they do, they start messing with your brain's ability to communicate with itself. The can be a good and a bad thing, because while you might forget something important or suddenly be incapable of swinging a baseball bat, you'll probably feel amazing, and want to eat all the snacks:

Over the years, research has suggested that by binding to these receptors, THC could be having another effect on aging brains, because it appears to helps the body clear out the toxic accumulations, or plaques, of amyloid beta.

No one's entirely sure what causes Alzheimer's disease, but it's thought to result from a build-up of two types of lesions: amyloid plaques and neurofibrillary tangles.

Amyloid plaques sit between the neurons as dense clusters of beta-amyloid molecules, a sticky type of protein that easily clumps together, and neurofibrillary tangles are caused by defective tau proteins that clump up into a thick, insoluble mass in the neurons.

It's not clear why these lesions begin to appear in the brain, but studies have linked inflammation in the brain tissue to the proliferation of plaques and neurofibrillary tangles. So if we can find something that eases brain inflammation while at the same time encourages the body to clear out these lesions, we could be on the way to finding the first effective treatment for Alzheimer's ever.

Back in 2006, researchers at the Scripps Research Institute found that THC inhibits the formation of amyloid plaques by blocking the enzyme in the brain that produces them, and now Schubert and his team have demonstrated that it can also eliminate a dangerous inflammatory response from the nerve cells, ensuring their survival.

"Inflammation within the brain is a major component of the damage associated with Alzheimer's disease, but it has always been assumed that this response was coming from immune-like cells in the brain, not the nerve cells themselves," says one of the team, Antonio Currais.

"When we were able to identify the molecular basis of the inflammatory response to amyloid beta, it became clear that THC-like compounds that the nerve cells make themselves may be involved in protecting the cells from dying."

It's exciting stuff, but it's so far only been demonstrated in neurons in the lab, so the next step will be for Schubert and his team to observe the link between THC and reduced inflammation and plaque build-up in a clinical trial. And they've reportedly already found a drug candidate called J147 that appears to have the same effects as THC, so this might be the way they can test the effects of THC without the government getting in the way.​

https://www.nature.com/articles/npjamd201612

 

[mr peabody]

Blocking endocannabinoids may trigger early Alzheimer's

Another study from a team of investigators at the Stanford University School of Medicine led by Daniel Madison has implicated the blocking of endocannabinoids, the brains own internal versions of the active compounds in cannabis, in the early pathology of Alzheimer's.

It seems a substance called A-beta, suspected to play a key role in Alzheimer's because it is the main part of clumps which dot the brains of Alzheimer's patients, may, in the early stages of the disease, impair learning and memory by blocking the beneficial action of endocannabinoids.

The group at Stanford is now trying to suss out the molecular details of how this occurs. Pinning down the details could pave the path to new ways to stave off the learning disabilities and memory deficits that characterize Alzheimers and could also help explain how smoking cannabis helps to delay or even prevent its onset.

In the study, published in the June 28, 2014 issue of the scientific journal Neuron, the researchers detail how pyramidal cells in the brain underpin learning and memory. This assures, they learned, that high-intensity input such as falling down or burning your finger tends to stick in your memory, thus presumably help avoid such mishaps in the future.

Pyramidal cells are encouraged to ignore noise signals, they constantly receive random signals from upstream nerve cells by a sort of wet blanket nerve cells called interneurons. These secret an inhibitory substance, the molecular equivalent of an indifferent shrug or yawn, signaling that the input is not really very important.

But when the news actually is significant, pyramidal cells secrete their own Now just you wait a minute, these are important chemicals. And guess what? Those chemicals which signal the importance of incoming information are none other than the endocannabinoids.

Madison speculates that when we smoke cannabis, the phytocannabinoids from the plant have the effect of enhancing the perceived importance of events that happen while we are under the influence of pot.

And another likely effect is inhibiting the wet blanket effect of interneurons which, in Alzheimer's, needs reducing to increase the ability to learn and remember.

Increasing tolerance

The federal Schedule I illegality of cannabis, under which it is officially considered to have no medical uses and a high danger of abuse, has stymied Wenk's research. But the scientist has noticed a refreshing trend, a major shift in the cultural tolerance of cannabis, particularly from young people, including his students.

Ive really seen a shift in 10 years of increased cannabis tolerance, Wenk said. In my class, people are more than willing to discuss their cannabis use. But they would be embarrassed to mention that they smoke cigarettes.

With Alzheimers ranking as the sixth leading cause of death in the United States, and with more than five million Americans currently struggling with the disease, which has no known cure, you would think that lab results as promising as Wenk's would have attracted major funding by now. But that is not the case, because, as we have pointed out, the NIDA is not really interested in knowing about the medical benefits of cannabis, just its dangers.

Wenk, who has researched the effects of Alzheimers on animals for about 40 years, has shared his findings in his book, Your Brain On Food.​

https://tokesignals.com/marijuana-sh...ch-is-stalled/

 

[mr peabody]

UT Southwestern’s O’Donnell Brain Institute

The “Big Bang” of Alzheimer’s: Genesis of the disease identified

Neuroscience News, July 10, 2018

Scientists have discovered a “Big Bang” of Alzheimer’s disease – the precise point at which a healthy protein becomes toxic but has not yet formed deadly tangles in the brain.

Researchers have identified the exact point at which healthy proteins become toxic in Alzheimer’s disease. The findings could help to detect Alzheimer’s before the disease progresses and develop treatments to stabilize tau proteins.

A study from UT Southwestern’s O’Donnell Brain Institute provides novel insight into the shape-shifting nature of a tau molecule just before it begins sticking to itself to form larger aggregates. The revelation offers a new strategy to detect the devastating disease before it takes hold and has spawned an effort to develop treatments that stabilize tau proteins before they shift shape.

“We think of this as the Big Bang of tau pathology. This is a way of peering to the very beginning of the disease process.”

Dr. Mark Diamond, Director for UT Southwestern’s Center for Alzheimer’s and Neurodegenerative Diseases “This is perhaps the biggest finding we have made to date, though it will likely be some time before any benefits materialize in the clinic. This changes much of how we think about the problem,” said Dr. Marc Diamond, Director for UT Southwestern’s Center for Alzheimer’s and Neurodegenerative Diseases and a leading dementia expert credited with determining that tau acts like a prion – an infectious protein that can self-replicate.

The study published in eLife contradicts the previous belief that an isolated tau protein has no distinct shape and is only harmful after it begins to assemble with other tau proteins to form the distinct tangles seen in the brains of Alzheimer’s patients.

Scientists made the discovery after extracting tau proteins from human brains and isolating them as single molecules. They found that the harmful form of tau exposes a part of itself that is normally folded inside. This exposed portion causes it to stick to other tau proteins, enabling the formation of tangles that kill neurons.

“We think of this as the Big Bang of tau pathology,” said Dr. Diamond, referring to the prevailing scientific theory about the formation of the universe. “This is a way of peering to the very beginning of the disease process. It moves us backward to a very discreet point where we see the appearance of the first molecular change that leads to neurodegeneration in Alzheimer’s. This work relied on a close collaboration with my colleague, Dr. Lukasz Joachimiak.”

Despite billions of dollars spent on clinical trials through the decades, Alzheimer’s disease remains one of the most devastating and baffling diseases in the world, affecting more than 5 million Americans alone.

Dr. Diamond is hopeful the scientific field has turned a corner, noting that identifying the genesis of the disease provides scientists a vital target in diagnosing the condition at its earliest stage, before the symptoms of memory loss and cognitive decline become apparent.

His team’s next steps are to develop a simple clinical test that examines a patient’s blood or spinal fluid to detect the first biological signs of the abnormal tau protein. "But just as important," Dr. Diamond said, "efforts are underway to develop a treatment that would make the diagnosis actionable."​

Abnormal accumulations of a protein called tau can collect inside neurons, forming tangled threads
—eventually harming the synaptic connection between neurons.

He cites a compelling reason for cautious optimism: Tafamidis, a recently approved drug, stabilizes a different shape-shifting protein called transthyretin that causes deadly protein accumulation in the heart, similar to how tau overwhelms the brain.

“The hunt is on to build on this finding and make a treatment that blocks the neurodegeneration process where it begins,” Dr. Diamond said. “If it works, the incidence of Alzheimer’s disease could be substantially reduced. That would be amazing.”

Dr. Diamond’s lab, at the forefront of many notable findings relating to tau, previously determined that tau acts like a prion – an infectious protein that can spread like a virus through the brain. The lab has determined that tau protein in the human brain can form many distinct strains, or self-replicating structures, and developed methods to reproduce them in the laboratory. He said his newest research indicates that a single pathological form of tau protein may have multiple possible shapes, each associated with a different form of dementia.​

https://neurosciencenews.com/alzheimers-genesis-9547/

 

[mr peabody]

Alzheimer's: Molecular study clarifies link to high blood sugar

A new molecular study reveals for the first time that high blood sugar or glucose damages an important enzyme that is involved with how the immune system responds in the early stages of Alzheimer's disease. The researchers say the findings will help map the progression of the devastating disease to better identify those at risk and perhaps find new ways to treat or prevent it.

Abnormally high blood sugar, or hyperglycemia, is a well-known characteristic of diabetes and obesity.

However, apart from the fact that people with diabetes have a higher risk of developing Alzheimer's disease, the link between hyperglycemia and this common cause of dementia has been less clear.

Now, researchers show that macrophage migration inhibitory factor (MIF) - an enzyme that plays an important role in immune function and insulin regulation - undergoes damage associated with high glucose in early Alzheimer's disease.

The team - from the University of Bath and King's College London, both in the United Kingdom - describes the findings in a paper published in the journal Scientific Reports.

Toxic changes in the brain

Alzheimer's is a progressive brain-wasting disease that erodes people's ability to remember, think, perform daily tasks, and lead an independent life.

Among older adults, Alzheimer's disease is the most common cause of dementia, a condition that affects 46 million people worldwide.

As more studies are done, scientists are gradually unraveling the complex changes that happen in the brain during the onset and development of the disease.

Many experts believe the damage caused by Alzheimer's disease starts 10 years or more before the cognitive decline becomes apparent.

During this preclinical stage, when people appear symptom-free, toxic changes are taking place in the brain.

One of the main changes occurring in the brain is the accumulation of abnormal proteins into toxic plaques and tangles, causing once-healthy cells to stop working, lose connections with other cells, and die.

Scientists already knew that glucose and its metabolic byproducts can damage proteins through a reaction called glycation, which has also been linked to Alzheimer's disease, and is a known feature of the hyperglycemia induced by diabetes.

For the new study, the researchers used a sensitive technique to detect glycation in brain samples from people with and without Alzheimer's disease.

Sugar damage to the enzyme "MIF" could be 'tipping point'

The team found evidence that the enzyme MIF undergoes glycation damage in the early stages of the disease. It also seems that the extent of MIF glycation increases as the disease progresses.

MIF is involved in how brain cells called glia respond to the buildup of the abnormal proteins during Alzheimer's disease.

The team suggests that sugar damage to MIF reduces some of the enzyme's functions and blocks others completely, and this could be the "tipping point" that allows Alzheimer's to develop.

"We've shown that this enzyme is already modified by glucose in the brains of individuals at the early stages of Alzheimer's disease," says Jean van den Elsen, one of the senior investigators and professor in biology and biochemistry at Bath.

He and his colleagues are now investigating if they can detect similar changes in the blood.

"Excess sugar is well known to be bad for us when it comes to diabetes and obesity, but this potential link with Alzheimer's disease is yet another reason that we should be controlling our sugar intake in our diets." -Dr. Omar Kassaar​

https://www.medicalnewstoday.com/art...oday_TrendMD_1

 

[mr peabody]

Evidence for person-to-person transmission of Alzheimer's

Study raises question about whether proteins implicated in the disease are capable of spreading through medical procedures.

Prions are the misshapen proteins that replicate by inducing normal proteins to misfold and aggregate in the brain, leading to rare diseases such as mad cow and kuru. In recent years, scientists have discovered that similar processes of protein misfolding are at work in many neurodegenerative disorders, including Alzheimer’s, Parkinson’s and Lou Gehrig’s disease. Now, a study in Nature reveals the first evidence for human-to-human transmission of the misfolded proteins that underlie the pathology of Alzheimer’s disease.

The new findings draw upon earlier research conducted on a prion disease. Between 1958 and 1985, a number of individuals with short stature received shots of human growth hormone extracted from the pituitary glands of cadavers. The gland is a pea-sized structure that sits at the base of the brain. Some of these samples were contaminated with prions that caused certain patients to develop Creutzfeldt-Jakob disease (CJD), a rare and fatal brain disorder. Treatments ceased once these reports came to light, but by that time an estimated 30,000 people had already received the injections. As of 2012, researchers have identified 450 cases of CJD worldwide that are the result of these growth hormone injections and other medical procedures, including neurosurgery and transplants.

Misfolding of the amyloid-beta proteins is a hallmark of Alzheimer’s. Previous studies have shown that minute amounts of amyloid-beta injected into animals such as mice or monkeys act as seeds that initiate a chain reaction of protein misfolding that resembles the pathology of Alzheimer’s. However, until now, no studies have found evidence that this process occurs in humans.

To explore the question of human transmission, John Collinge, a neuroscientist at University College London and his colleagues, conducted an autopsy study of eight patients who died from CJD after treatment with cadaver-derived growth factor. To their surprise, they found that six of the brains had the amyloid-beta pathology found in Alzheimer’s patients, and four exhibited some degree of cerebral amyloid angiopathy, in which amyloid deposits build up on the walls of blood vessels in the brain.

The patients were between the ages of 36 and 51—typically too young to exhibit Alzheimer’s pathology—and none of the individuals bore genetic mutations associated with early onset of the disease. All evidence pointed toward one possibility: Like prions, amyloid-beta seeds were in the growth hormone injections and infected these individuals. Although none of the brains showed any other Alzheimer’s disease markers, such as buildup of another misfolded protein called tau, the researchers suggest that had the patients not died young, they would have developed the disease later in life.

The research may be a first step toward answering the question of whether human-to-human transmission of pathological proteins is possible. “This is an observational study,” Collinge says. “We’re simply describing what we see in these patients and we are trying to explain that. This study alone," he says, "does not suffice to prove that the Alzheimer’s disease process can be induced in one individual through contact with another’s brain tissue." In a follow-up study, the researchers are hoping to obtain archived batches of the cadaver-derived human growth hormone to look for the presence of telltale, small clusters of amyloid-beta.

One prominent Alzheimer’s investigator—John Trojanowski of the University of Pennsylvania, who was not involved in the study—asserted that the research does not provide a clear answer about whether Alzheimer’s pathology can spread between humans. Trojanowski says that "the study will generate more confused thinking and stoke unreasonable concerns by the public about the infectivity of Alzheimer’s, which I think does not help the field of prion and AD research.”

He points to the small size of the study and the fact that the subjects did not show other signs of Alzheimer’s. “Also, studies show that plaques and tangles begin to deposit as early as the second and third decade of life, which means the subjects could merely have aging-related deposition of amyloid-beta.”

But other researchers found the study to be an important contribution to the growing body of research showing that many neurodegenerative diseases may be induced through prion-like processes. All direct evidence of transmission was conducted in animal studies, Collinge says, raising questions about whether the same pathology was present in humans. “The best evidence for the transmissibility of amyloid-beta lesions comes from animal studies, in which various factors are carefully controlled and competing hypotheses are ruled out,” says Lary Walker, a neuroscientist at Emory University not involved in the study. “This study adds an important dimension to the establishment of the prion paradigm.”

Collinge emphasized that Alzheimer’s and prion diseases such as CJD cannot be “caught” through direct contact and previous epidemiological studies have found no evidence that a history of blood transfusion is associated with increased risk of Alzheimer’s disease. However, the possibility remains that certain medical procedures, such as transplants and neurosurgery, may expose individuals to amyloid-beta seeds, and the possibility of transmitting them through blood will likely become an avenue of further research.

In another study, published today in Nature Neuroscience, Mathias Jucker from the University of Tuebingen in Germany and colleagues, including Lary Walker, found that amyloid-beta seeds have the ability to persist in the brain for months and regain pathogenic properties when introduced to the right environment. Together with the evidence that Alzheimer’s pathology can be transmitted between humans, scientists are starting to look carefully at the ways in which a range of neurodegenerative diseases may develop over the course of decades—and the role that transmission between humans may play. “I think we all agree that more systematic research in this area is necessary,” says Jucker.​

https://www.scientificamerican.com/...person-transmission-of-alzheimer-s-pathology/

 

[mr peabody]

Cannabis compound removes toxic Alzheimer's protein from the brain

THC has been found to promote the removal of toxic clumps of amyloid beta protein in the brain, which are thought to kickstart the progression of Alzheimer's disease.

The finding supports the results of previous studies that found evidence of the protective effects of cannabinoids, including THC, on patients with neurodegenerative disease.

"Although other studies have offered evidence that cannabinoids might be neuroprotective against the symptoms of Alzheimer's, we believe our study is the first to demonstrate that cannabinoids affect both inflammation and amyloid beta accumulation in nerve cells," says one of the team, David Schubert from the Salk Institute for Biological Studies in California.

Schubert and his colleagues tested the effects of THC on human neurons grown in the lab that mimic the effects of Alzheimer's disease.

If you're not familiar with this special little compound, it's not only responsible for the majority of cannabis' psychological effects - including the high - thanks to its natural pain-relieving properties, it's also been touted as an effective treatment for the symptoms of everything from HIV and chemotherapy to chronic pain, post traumatic stress disorder, and stroke.

In fact, THC appears to be such an amazing medical agent, researchers are working on breeding genetically modified yeast that can produce it way more efficiently than it would be to make synthetic versions.

The compound works by passing from the lungs to the bloodstream, where it attaches to two types of receptors, cannabinoid receptor (CB) 1 and 2, which are found on cell surfaces all over the body.

In the brain, these receptors are most concentrated in neurons associated with pleasure, memory, thinking, coordination and time perception, and usually bind with a class of lipid molecules called endocannabinoids that are produced by the body during physical activity to promote cell-to-cell signalling in the brain.

But THC can also bind to them in much the same way, and when they do, they start messing with your brain's ability to communicate with itself.

Over the years, research has suggested that by binding to these receptors, THC could be having another effect on ageing brains, because it appears to helps the body clear out the toxic accumulations - or 'plaques' - of amyloid beta.

No one's entirely sure what causes Alzheimer's disease, but it's thought to result from a build-up of two types of lesions: amyloid plaques and neurofibrillary tangles.

Amyloid plaques sit between the neurons as dense clusters of beta-amyloid molecules - a sticky type of protein that clumps together - and neurofibrillary tangles are caused by defective tau proteins that clump up into a thick, insoluble mass in the neurons.

It's not clear why these lesions begin to appear in the brain, but studies have linked inflammation in the brain tissue to the proliferation of plaques and neurofibrillary tangles. So if we can find something that eases brain inflammation while at the same time encourages the body to clear out these lesions, we could be on the way to finding the first effective treatment for Alzheimer's ever.

In 2006, researchers at the Scripps Research Institute found that THC inhibits the formation of amyloid plaques by blocking the enzyme in the brain that produces them, and now Schubert and his team have demonstrated that it can also eliminate a dangerous inflammatory response from the nerve cells, ensuring their survival.

"Inflammation within the brain is a major component of the damage associated with Alzheimer's disease, but it has always been assumed that this response was coming from immune-like cells in the brain, not the nerve cells themselves," says one of the team, Antonio Currais.

"When we were able to identify the molecular basis of the inflammatory response to amyloid beta, it became clear that THC-like compounds that the nerve cells make themselves may be involved in protecting the cells from dying."

It's exciting stuff, but so far it has only been demonstrated in neurons in the lab, so the next step will be for Schubert and his team to observe the link between THC and reduced inflammation and plaque build-up in a clinical trial.

They've reportedly already found a drug candidate called J147 that appears to have the same effects as THC, so this might be the way they can test the effects of THC without the government getting in the way.

Though it's worth adding that more recent legal changes since the time of this research around cannabis use in the USA may be making further research in this area a lot easier.​

https://www.sciencealert.com/marijua...ein-from-brain

 

[mr peabody]

High-fat diet in utero protects against Alzheimer’s later

Temple University Health System | Neuroscience News | Aug 27 2019

A high-fat diet can carry health risks, but for mothers-to-be, it may make all the difference when it comes to Alzheimer’s disease prevention for their children. In a report published online August 26 in the journal Molecular Psychiatry, researchers at the Lewis Katz School of Medicine at Temple University show for the first time in animals that high maternal fat consumption during gestation protects offspring against changes in the brain that are characteristic of late-onset Alzheimer’s disease.

“In humans, it has been known that individuals whose mothers develop Alzheimer’s disease after age 65 are at increased risk of also developing the disease around the same age,” said senior investigator Domenico Praticò, MD, Scott Richards North Star Foundation Chair for Alzheimer’s Research, Professor in the Departments of Pharmacology and Microbiology, and Director of the Alzheimer’s Center at Temple at the Lewis Katz School of Medicine.

Genetic factors transmitted by mothers to their offspring seem like an obvious explanation behind this phenomenon, but so far no genes have been identified that could explain the maternal transmission of Alzheimer’s disease. This fact would suggest that environmental factors, such as lifestyle and diet, adopted during the gestation period, a time in which mother and baby are in tight interaction, could significantly influence the offspring’s risk of developing the disease later in life.

Diet is of particular interest as a risk factor, especially a diet rich in animal fat and cholesterol. High-fat intake previously has been shown in young/adult mice to directly exacerbate the types of changes in brain function that ultimately may contribute to Alzheimer’s disease.

To better understand the unique relationship between maternal Alzheimer’s disease and risk in her offspring, Dr. Praticò and colleagues looked at maternal fat intake specifically during the gestation period in mice engineered to develop Alzheimer’s disease. Pregnant mice were fed a high-fat diet from the beginning until the end of gestation. The moment offspring were born, mothers were switched to a regular diet, which was maintained during the lactation period. Offspring of these mothers were always kept at the same regular, or standard, diet throughout their life.

At 11 months of age, offspring underwent behavioral tests to assess learning ability and memory. “Surprisingly, we found that animals from mothers fed a high-fat diet during gestation had better learning and memory skills than their counterparts born to mothers fed a regular diet during gestation,” Dr. Praticò said.

The observed improvements in memory and learning were associated with the maintenance of good synaptic integrity. In fact, offspring from mothers exposed to a high-fat diet had significant improvement of synapse function when compared with offspring from mothers on a regular diet. Synapses, the places where neurons come together to relay information, play a vital role in learning and memory formation.

In addition, compared to animals born to mothers fed a regular diet, offspring from mothers on a high-fat diet had lower levels of amyloid-beta, an abnormal protein that builds up in neurons, contributing to nerve cell dysfunction and eventually significant impairments in memory and learning.

When the team searched for possible mechanisms responsible for the beneficial effect, they discovered that offspring from mothers fed a high-fat diet exhibited reduced levels of three important genes involved in Alzheimer’s disease: beta-secretase, tau, and the pathological tau-regulating gene CDK5. Dr. Praticò’s team found that already in the early developmental stages, the three genes were effectively switched off in offspring because the high-fat diet had increased activity of a protein called FOXP2. They demonstrated that the repressive activity of FOXP2 on these genes ultimately protected offspring from later declines in brain function and Alzheimer’s disease development.

“Our findings suggest that, to be effective, Alzheimer’s disease prevention probably needs to start very early in life, during gestation,” Dr. Praticò said. “Diet at this specific life stage can have critical, but underestimated, long-term impacts on brain health.”

Dr. Praticò and colleagues plan next to compare the effects of a high-fat diet to those of other diets, including diets high in sugar and protein and diets resembling the Mediterranean diet in humans. “We also want to see whether our findings can be replicated in wild-type animals,” Dr. Praticò added.​

High-fat diet in utero protects against Alzheimer's later - Neuroscience News

High-fat diets during pregnancy may protect the developing brain from Alzheimer's in those with genetic risk factors.

neurosciencenews.com

 

[mr peabody]

Ohio State University

Cannabinoides reduce inflammation, restore cognitive function

Alzheimer’s appears because of inflammation in the brain, and the brain’s inability to remove amyloid beta plaque.

Gary Wenk, Ph.D, professor of neuroscience, immunology and medical genetics at Ohio State University, on marijuana and its link to inflammation:

“I have been trying to find a drug that will reduce brain inflammation and restore cognitive function in rats for over 25 years; cannabinoides are the first and only class of drugs that have ever been effective.”

You know what plaque on your teeth is because of your dentist. He or she tells you to clean your teeth so they won’t be left covered in plaque.

You can watch the dentist scrape plaque off, but what about brain plaque?

Brain plaque is the common term for acetylcholinesterase-associated amyloid β-peptide (Aβ). We can’t see this get wiped away, and even if we could, we wouldn’t. This is because our brains clear themselves out while we’re asleep.

Marijuana helps protect against brain inflammation, which in turn aids in the brain’s waste removal process. Unlike other Alzheimer’s medications, marijuana has been proven to work, does not demean or insult patients, costs considerably less to produce, and eases the brain, mind, and soul.

-Michelle Toole​

 

[mr peabody]

Virus and bacteria identified as major causes of Alzheimer’s

A worldwide team of senior scientists and clinicians have come together to produce an editorial which indicates that certain microbes – a specific virus and two specific types of bacteria – are major causes of Alzheimer’s Disease. Their paper, which has been published online in the highly regarded peer-reviewed journal, Journal of Alzheimer’s Disease, stresses the urgent need for further research – and more importantly, for clinical trials of anti-microbial and related agents to treat the disease.

This major call for action is based on substantial published evidence into Alzheimer’s. The team’s landmark editorial summarises the abundant data implicating these microbes, but until now this work has been largely ignored or dismissed as controversial – despite the absence of evidence to the contrary. Therefore, proposals for the funding of clinical trials have been refused, despite the fact that over 400 unsuccessful clinical trials for Alzheimer’s based on other concepts were carried out over a recent 10-year period.

Opposition to the microbial concepts resembles the fierce resistance to studies some years ago which showed that viruses cause certain types of cancer, and that a bacterium causes stomach ulcers. Those concepts were ultimately proved valid, leading to successful clinical trials and the subsequent development of appropriate treatments.

Professor Douglas Kell of The University of Manchester’s School of Chemistry and Manchester Institute of Biotechnology is one of the editorial’s authors. He says that supposedly sterile red blood cells were seen to contain dormant microbes, which also has implications for blood transfusions.

“We are saying there is incontrovertible evidence that Alzheimer’s Disease has a dormant microbial component, and that this can be woken up by iron dysregulation. Removing this iron will slow down or prevent cognitive degeneration – we can’t keep ignoring all of the evidence,” Professor Douglas Kell said.

Professor Resia Pretorius of the University of Pretoria, who worked with Douglas Kell on the editorial, said “The microbial presence in blood may also play a fundamental role as causative agent of systemic inflammation, which is a characteristic of Alzheimer’s disease – particularly, the bacterial cell wall component and endotoxin, lipopolysaccharide. Furthermore, there is ample evidence that this can cause neuroinflammation and amyloid-β plaque formation.”

The findings of this editorial could also have implications for the future treatment of Parkinson’s Disease, and other progressive neurological conditions.

...

This makes total and complete sense to me. I immediately connected it to the chickenpox/shingles correlation. the possible causes of AD listed in this article are definitely appropriate to my husband. my husband was diagnosed with age related dementia/AD in June 2012 by MRI (at age 80, when he was still actively pastoring a church). he had had several mri over a period of years showing progressive plaque build up with some symptomatology. after major open heart surgery in may 2013 there was a major change in his status mentally for the worse and with a slow downhill slide, along with physical weakening, such as in his balance & hearing, even tho he now exercised on a regular basis – something he had not done in more than 30 years. as of January 2016, he is now on dialysis, with another drop in mental status. he lost a sister diagnosed with AD in April 2015 at the age of 95 and has a sister with mild dementia who just reached the age of 99. we did almost not accept going on the dialysis due to the AD, even knowing it would have meant imminent death. living with this disease on a daily basis, the current ‘meds’ for it are worse than the disease itself, are too expensive, & many times of no use. we need to find a way to stop this disease. these clinical trials must be funded. the treatments are there for us to find & are probably already on our shelves now.

-redhvn56

...

In the editorial of the Journal of Alzheimer Disease , published in 8 March 2016 with the title “MICROBES AND ALZHEIMER’S DISEASE”,the dozens of prestigeous researchers of prestigeous universtities of dozens of countries around the world that wrote the milestone text of it very interesting editorial , agree that herpes simplex virus type 1 , Chlamydia pneumoniae, and several types of spirochaete (as Borrelia of Lyme disease) , fungal infections,etc. can be related as some triggers (but NOT as causes) of Alzheimer disease.Extra Virgin Coconut Oil is empirically used as mitochondrial function improver and as alternative fuel to the brain in AD and others dementias , still without scientific foundation, but with hundreds of empirical testimonies by patients , caregivers and relatives of patients that gives some improve in dementias as AD.

-Carlos Oliveira

...

The findings that AD has a microbial etiology is indeed a significant finding. Microbiologists can possibly try using probiotics for the prevention and treatment of AD. Recent research outputs have shown that the human intestinal microbiome composition plays an important role in orchestrating the overall health and well-being of an individual. Probiotics have already been used for the prevention of certain nutritional deficiencies, hyperlipidemia, colorectal cancer and hopefully even diabetes.

-Teddy Quark

...

This may be a situation where the infecting/offending organism does the damage to start the process in motion and once established antimicrobial therapy is not effective. Examples include Hepatitis C or B virus where treated early causes limited liver damage but over time may lead to cirrhosis or liver cancer. At that later time treating the virus is too late. Trials might want to focus on very early AD or better yet if one can make the definite link between an organism and AD treat before symptoms develop. As a microbiologist I believe it warrants much more study.

-Ray

...

Two Spriochetal Infections -

Borrelia spirochetes (Blood and Tissue pathogens) Transmitted by insect bites and Treponemal spirochetes from the oral cavity (Periodontal disease pathogens) are linked to Alzheimer’s Disease pathogenesis.

I offer in support of the Chronic Borrelia spirochete brain infections in Alzheimer’s disease, the following two links to lectures which describe images of the Borrelia in Autopsy Alzheimer’s Brain tissue from the Harvard Medical School Brain Bank.
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Link:; Original 37 min Powerpoint without narration:
https://www.dropbox.com/s/nthxi50btu...tion.pptx?dl=0
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Link:: Video with Narration 44 min.:
Final Lecture German Borreliosis Society Alan B MacDonald Lecture March 11 2016

Borrelia brain infections provide the most Photographic documentation of The Cause of Alzheimer’s Disease, as proven by direct Photographs of these microbes by DNA probe imaging in autopsy Alzheimer’s disease Brains.

-Alan B. MacDonald, MD​

 

[mr peabody]

Alzheimer’s : The early warning sign everyone should know

This Alzheimer’s early warning sign could provide a way of warding off the neurodegenerative disease.

Poor sleep could be an early sign of Alzheimer’s in people who are otherwise healthy, new research finds.

Scientists have found links between certain biological markers of Alzheimer’s and sleep disturbances. Dr Barbara B. Bendlin, who led the study, said:

“Previous evidence has shown that sleep may influence the development or progression of Alzheimer’s disease in various ways.For example, disrupted sleep or lack of sleep may lead to amyloid plaque buildup because the brain’s clearance system kicks into action during sleep. We looked not only for amyloid but for other biological markers in the spinal fluid as well.”

The study was carried out on 101 people with an average age of 63. All were at risk of Alzheimer’s, although none had any symptoms. The results showed that those with the worst sleep quality also had biological markers of Alzheimer’s in their spinal fluid. Dr Bendlin said:

“It’s important to identify modifiable risk factors for Alzheimer’s given that estimates suggest that delaying the onset of Alzheimer’s disease in people by a mere five years could reduce the number of cases we see in the next 30 years by 5.7 million and save $367 billion in health care spending.”

Not everyone with sleep problems had the biological markers, though, said Dr Bendlin:

“It’s still unclear if sleep may affect the development of the disease or if the disease affects the quality of sleep. More research is needed to further define the relationship between sleep and these biomarkers. Improving sleep could be one way of helping to ward off Alzheimer’s," said Dr Bendlin. "There are already many effective ways to improve sleep. It may be possible that early intervention for people at risk of Alzheimer’s disease may prevent or delay the onset of the disease.”

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Coffee may reduce risk of Alzheimer’s and Parkinson’s

Alzheimer’s disease is the most common neurodegenerative disease and a leading cause of dementia.

Studies have shown that coffee drinkers have up to a 65% lower risk of developing Alzheimer’s disease.

Parkinson’s is the second most common neurodegenerative disease and caused by the death of dopamine-generating neurons in the brain.

Coffee drinkers have a 32-60% lower risk of Parkinson’s disease. The more coffee people drink, the lower the risk.

Bottom Line: Several studies show that coffee drinkers have a much lower risk of dementia, Alzheimer’s disease and Parkinson’s disease in old age.

-Kris Gunnars​

 

[mr peabody]

Microdosed LSD: Finally a breakthrough for Alzheimer’s

by Abbie Rosner

After decades of effort and untold millions invested in the search for an effective treatment for Alzheimer’s, the disease remains unchecked and rampant. Most recently, the New York Times reported that researchers declared defeat after the failure of yet another experimental drug designed to fight the formation of the disease’s signature amyloid plaque in the brain.

But according to Shlomi Raz, CEO and founder of biomedical startup, Eleusis, the problem with conventional, single-target approaches to Alzheimer’s is that they don’t take into account the multiple dysregulated processes in the disease’s complex pathobiology.

And Raz’s company’s approach to the disease is anything but conventional.

Eleusis is investigating the anti-inflammatory potential of psychedelics as medicines, specifically the application of sub-perceptual doses of LSD in halting the progression of Alzheimer’s disease at its earliest detectable stage.

I spoke with Raz about the origins of this novel application of LSD, and the company’s strategy for developing this potentially game-changing therapy for Alzheimer’s disease.

You started out in finance, working at Goldman Sachs. How did you end up in the field of drug development?

In 2008 I decided to leave Goldman and pursue a lifelong interest in psychology. I enrolled in a graduate program at NYU with the intention of becoming a psychotherapist. There I came across research out of Johns Hopkins on the profound psychiatric impacts of psychedelic drugs.

My curiosity led me into the basic science surrounding the serotonin 2A receptor, which is the target of most psychedelics. And I found that the psychiatric potential of psychedelics was only the visible part of the iceberg - that there was a whole submerged therapeutic potential that hadn't been realized.

Also, being an outsider to pharmaceuticals and biotechnology, I didn't realize that serotonin 2A receptors were an anti-target for purposes of development - because no sane drug developer would think to target a receptor that could give rise to profound psychoactive effects.

But I read the work of Professor Charles Nichols at Louisiana State University, who found that some psychedelics potently reduced inflammation at levels that would be predicted not to be psychoactive or even perceptible, via activation of the serotonin 2A receptor, which besides being expressed in the brain, is also highly expressed throughout the body. And this got me very excited.

I continued to dig into the literature, and found that the same receptor that mediates the psychoactivity of psychedelics is also implicated in the effects these compounds have in terms of providing protection against oxidative stress, enhancing neuroplasticity, and alleviating depression and anxiety. And because these compounds are anti-inflammatory, they address a constellation of dysregulated functions in aging.

Digging further, I found research indicating that this receptor, if it was engaged by a psychedelic drug, would also reduce the amount of toxic amyloid that was produced in an organism. And I thought that was interesting, because at the time, and certainly for the prior decade, amyloid was the primary target for Alzheimer's disease.

When I put together the entire picture of what psychedelics were doing, it became quite clear that this could be a therapy to modify the course of Alzheimer's disease. LSD in particular seemed like an attractive candidate for such a therapeutic approach, as it is capable of potent and prolonged activation of the serotonin and dopamine neurotransmission receptors implicated in Alzheimer’s disease, and specifically the serotonin 2A receptor.

If you look at the symptoms of Alzheimer's and the disease progression, not only is the loss of 2A receptor expression correlated with cognitive impairment and toxic amyloid burden, but you also have a significant increase in the incidence of depression and anxiety, which are psychiatric conditions known to be significantly influenced by serotonin 2A receptor function.

Given the extensive clinical evidence of LSD’s efficacy in treating alcoholism, depression, anxiety, and other indications, could all this just be a coincidence?

When you combine all of the effects which LSD or other psychedelics have been observed to have, in vitro, in animal models, and in patients, they check all the boxes for an attractive multi-target drug candidate with the potential to halt the progression of Alzheimer’s disease. It was based on this revelation that I decided to found Eleusis, with the mission to develop the full therapeutic potential of psychedelics.

What makes your approach different from conventional drug development?

Most biotechnology companies try to develop a drug that hits a single target and nothing else. But Alzheimer's is a complex disease with multiple therapeutic targets, and as single target approaches continue to fail, there is a growing and widespread belief that a successful therapeutic approach will have to hit multiple targets simultaneously. And that's exactly what a conventional drug developer doesn't want to hear because that exponentially increases the complexity and cost of drug development.

I learned that developing a multi-target drug relies, to a significant extent, upon serendipity, when a drug is accidentally found to have therapeutic effects despite hitting two or more targets at the same time. And I found this quite curious because in the history of pharmacology, the discovery of LSD is considered to be one of the greatest serendipities of all time.

Then LSD could be that multi-target therapeutic?

Yes. It hits all of these different targets, not only the serotonin 2A receptor which has all the effects which I described, but other serotonin and dopamine receptors implicated as either targets to slow the progression of Alzheimer's disease or treat its psychiatric and cognitive symptoms. And the interesting thing about LSD is that it has a very well established safety record. It has muted physiological effects, and one primary liability, which is its psychoactivity.

But the fact that you could have demonstrable engagement in the brain at dose levels that were either at the borderline of, or below perception, indicated to me that the dazzle of LSD in psychiatry obscured its potential use to modify the course of Alzheimer's disease.

How has Eleusis pursued this opportunity?

I founded Eleusis in 2013, and our first clinical trials in 2015 were exploring exactly that hypothesis, that low doses of LSD could be detectable in patients, without giving rise to psychoactivity.

Stepping back, was it the wisest idea to start with LSD? Probably not. Because from a commercial perspective, you want to pick a drug and an indication with the cheapest and most effective path to market. And the problem is that, when developing a drug for Alzheimer's, it's a very expensive process.

So what we've done recently is prioritize the development of a new “not-so-psychedelic psychedelic” drug candidate for use in ophthalmology, for the treatment of retinal disease. The idea is that it will be a much more cost-effective path for demonstrating the anti-inflammatory and neuroprotective effects of this drug class.

This approach would also set the foundation for us, both commercially as well as scientifically, to advance LSD into Phase 2 trials for Alzheimer's.

So that was a long winded way of saying that we chose LSD first because it has the best safety profile, it hit all the targets in Alzheimer's disease, and we wanted to demonstrate the viability of transforming psychedelics into medicine at sub-perceptual dose levels.

Did LSD’s status as a Schedule 1 substance make it difficult to get approvals for your clinical studies?

People often believe that there are institutional and governmental barriers to conducting research with scheduled compounds, and with cannabis that may have actually been the case. We conducted our trials in the UK, and did not encounter any obstacles. In fact, we found the regulators to be very supportive. But to be clear, I don't think we would have had a different experience in the United States.

Can you describe your most recent clinical trial, published in the journal Psychopharmacology, and its outcomes?

That was our Phase 1 double-blind, placebo-controlled, randomized trial where we explored the safety and tolerability of low dose LSD on healthy older adults. What we found was that it was safe and tolerable, although I think that being able to discern the effects is a little bit confounded by the fact that we were administering the drug in a clinical hospital setting.

Some people believe, anecdotally, that these compounds have different effects in different environments. We only really evaluated the effects in one environment.

So now that you have established safety and efficacy in the Phase I study, what is the next step for the company?

With LSD, that study establishes the safety of repeated dosing. It’s unclear if the regulators will require any additional studies before we can conduct the next logical study, which would be in individuals at risk of progressing from a state of mild cognitive impairment to Alzheimer's disease.

Given the fact that those types of studies require anywhere from 400 to 800 patients to prove if a drug is having a disease modifying effect, they're very expensive. For a startup company to finance a study of that size would be extremely difficult.

So we thought it would be easier to first advance a new drug that was not scheduled, that we had developed for a different indication – in this case for retinal disease – which would have a much more cost-effective path to getting clinical approval. Once that drug was demonstrated to be potentially successful both therapeutically and commercially, we'd be in a position to raise the capital required to conduct a Phase 2 study of LSD in patients at risk of progressing to Alzheimer's.

So you could extrapolate from this other drug that you would test for the ophthalmological application to the LSD/Alzheimer’s model?

Alzheimer’s has no good animal model. Companies have spent untold fortunes testing their drugs in pre-clinical models that reliably overexpressed amyloid for example. But then, sure enough, they don’t translate into the clinic.

Our view is that, if we can first prove the overarching hypothesis that these compounds can be administered at sub-perceptual dose levels and have therapeutic anti-inflammatory effects, including cellular protection, up-regulation of mitochondrial function, etc., then validation of that scientific hypothesis would give investors confidence to pursue Phase 2 studies of LSD in Alzheimer’s disease.

Now the effects of LSD in the brain are complicated, well beyond our current comprehension. But with ophthalmology, being able to observe the effects of our new drug candidates in the retina, we're getting a very simplified assessment of how psychedelics, at low dose levels, would exert therapeutic effects in the brain. Because in many ways, the retina represents a “window to the brain”, with many types of cells that are similar to, or exactly the same as, the cells in the brain. And many of the same dysregulated processes associated with inflammation in retinal disease are also found in Alzheimer’s disease.

And to conclude, if one of the big Alzheimer's associations came to you tomorrow and said, we're ready to fund that clinical trial, would you jump at the opportunity?

Oh, absolutely. We think the science is sufficiently compelling. The interesting thing here is that LSD, as well some other psychedelics, have already been extensively studied, and their safety profile is well understood.

We have tried to engage some of the not-for-profit funders in this space. As you can imagine, LSD still carries a lot of stigma, but we remain optimistic about this prospect.

In the meantime, it seems like we are starting to see a shift in the public perception of psychedelic drugs and a growing recognition of their therapeutic potential. So maybe your timing is also serendipitous.

I certainly hope so, for the sake of the patients and their families. There is such an incredible unmet need. I have family who suffered through dementia, and I think almost everyone has.

Conventional drug development will continue down a path of single target therapeutics. But if we’re right, and you need a multi-target therapeutic to beat Alzheimer’s, LSD may be the best one we've got.​