Cav > Books: pharmacology‎ (74)

"..I acknowledge that there are complexities around whether and when we should consider some conditions as “dysfunction” as opposed to a type of neurodiversity that society has wrongly become intolerant to—cases of autism, attention deficit hyperactivity disorder, and depression are all examples. That said, for each of these conditions, a subset of diagnosed individuals suffer in ways that can benefit from treatment. For those individuals, when our existing treatments fall short, we need better ways to help them. With this empathetic spirit, I use the terms “dysfunction” and “disorder” to refer to the conditions of individuals who need better solutions than the ones we can offer them today."

"I am a neuroscientist, and I have been engaged in brain research for over two decades. For a long time, I’ve been convinced that I have the best of all possible jobs: I get paid to think up new questions about how the brain works and answer them. A large part of what inspires my research is my intense curiosity about how the brain gives rise to the mind, and to ourselves. To answer these questions, I focus on memory. I investigate questions like: When we have the experience of remembering that we’ve seen something before, what is happening in our brains? How do our brains manage to remember so much? And how do our brains curate what we remember and forget?
My work is not driven just by curiosity; I believe that a foundational understanding of how memory works will contribute to future treatments and cures for memory dysfunction, including age-related dementias such as Alzheimer’s. In fact, part of my research program focuses on transforming what we’ve learned about memory into the earliest stages of developing a new treatment for memory impairment. Ours is but one example of what is known as the bench to bedside approach, where fundamental research discoveries are the first step toward developing new clinical treatments."

"Hands down, the most profound and important insight I’ve had while writing this book is that the end goal of treating brain dysfunction amounts to one of the most formidable of all possible challenges: controlling a complex system. Not in the creepy or cartoonish sense of “mind control,” but in the sense that treatments require shifting the brain from an unhealthy to a healthier state. This challenge is so formidable that there are questions about whether it can even be done in principle (much less in practice). The answer depends on exactly what type of complex system we’re dealing with.
To illustrate, let’s look at what happened when we tried to control another complex system: the weather. Today, we don’t try to influence the paths of hurricanes. Why not? It’s not because we haven’t tried. Often forgotten about the history of weather research is that we did try, only to realize that it probably won’t work. Thus, we need to ask ourselves: What makes us think that the brain will be any different? After all, an epileptic seizure or psychosis might be likened to a tornado or a hurricane insofar as it’s a complex system gone awry. Under what conditions can we effectively control a complex system?"

"All of us have an abundant microscopic menagerie, collectively known as the microbiota or microbiome.1 They live on our surface, inside our bodies, and sometimes inside our very cells. The vast majority of them are bacteria, but there are also other tiny organisms including fungi (such as yeasts) and archaea, a mysterious group that we will meet again later. There are viruses too, in unfathomable numbers – a “virome” that infects all the other microbes and occasionally the host’s cells. We can’t see any of these minuscule specks. But if our own cells were to mysteriously disappear, they would perhaps be detectable as a ghostly microbial shimmer, outlining a now-vanished animal core."

"This book will open the door fully. We are going to explore the incredible universe that exists within our bodies. We’ll learn about the origins of our alliances with microbes, the counter-intuitive ways in which they sculpt our bodies and shape our everyday lives, and the tricks we use for keeping them in line and ensuring a cordial partnership. We’ll look at how we inadvertently disrupt these partnerships and, in doing so, jeopardise our health. We’ll see how we might reverse these problems by manipulating the microbiome for our benefit. And we’ll hear the stories of the gleeful, imaginative, driven scientists who have dedicated their lives to understanding the microbial world, often in the face of scorn, dismissal, and failure."

"...It can be weird to consider existences that play out in an intestine or in a single cell, or to think about our body parts as rolling landscapes. And yet, they assuredly are. The Earth contains a variety of different ecosystems: rainforests, grasslands, coral reefs, deserts, salt marshes, each with its own particular community of species. But a single animal is full of ecosystems too. Skin, mouth, guts, genitals, any organ that connects with the outside world: each has its own characteristic community of microbes.4 All of the concepts that ecologists use to describe the continental-scale ecosystems that we see through satellites also apply to ecosystems in our bodies that we peer at with microscopes. We can talk about the diversity of microbial species. We can draw food webs, where different organisms eat and feed each other. We can single out keystone microbes that exert a disproportionate influence on their environment – the equivalents of sea otters or wolves. We can treat disease-causing microbes – pathogens – as invasive creatures, like cane toads or fire ants. We can compare the gut of a person with inflammatory bowel disease to a dying coral reef or a fallow field: a battered ecosystem where the balance of organisms has gone awry."

"It’s commonly said that the average person contains ten microbial cells for every human one, making us rounding errors in our own bodies. But this 10-to-1 ratio, which shows up in books, magazines, TED talks, and virtually every scientific review on this topic, is a wild guess, based on a back-of-the-envelope calculation that became unfortunately enshrined as fact.7 The latest estimates suggest that we have around 30 trillion human cells and 39 trillion microbial ones – a roughly even split. Even these numbers are inexact, but that does not really matter: by any reckoning, we contain multitudes."

"Imagine we’re ten, twenty, maybe thirty years into the future. You see a doctor. You’ve been feeling anxious, so she prescribes a bacterium that’s been shown to affect the nervous system and repress anxiety. Your cholesterol is a little high, so she adds another microbe that makes and secretes a cholesterol-lowering chemical. The levels of secondary bile acids in your gut are unusually low, leaving you vulnerable to a C-diff infection – best to include a strain that produces these acids. Your urine contains molecules that are signs of inflammation, and since you also have a genetic predisposition to IBD, she adds a bug that releases anti-inflammatory molecules. She chooses these species not just for what they can do, but because she predicts that they will interact well with your immune system and your existing microbiome. She also adds a supporting cast of other bacteria chosen to prop up the therapeutic core, and she suggests some dietary plans that will nourish them effectively. And off you go, with a bespoke probiotic pill – a treatment designed to improve not just any old microbial ecosystem but yours in particular. As microbiologist Patrice Cani told me, “The future will be à la carte.”

"...But what happens if you take a tablespoon of dust or dirt and stir it into a quart of water? Add a tablespoon of that slurry into another bottle, then press repeat and dilute it one more time. If you looked at the murky blend through a microscope, you’d start to appreciate the complexity of dust. Tiny crystals and mineral chunks mix with flakes of rotten wood, legs and hairs of insects, soot, odd-looking eggs, and fibers from plants and your clothes. Microscopic algae and protists bump into each other and veer off like windup toys. Dust is alive.
If you treat the diluted mud with a dye that binds to DNA—the chemical compound that makes up the genes of all living things— and shine ultraviolet light through it, microscopic life lights up like the Milky Way, a universe in a drop of water.2 Bacteria and viruses shine like stars. Pollen grains drift by like glowing blimps. And among all these particles are the extending tubular cells, geometrical spores, and budding yeast cells of fungi."

"This book is a journey through the hidden world of fungi and their relationships with humans, other living things, and our environment.
We will look at how we use fungi, and how they use us, as we strive for a sustainable future.
Looking back, I can see that my family history and childhood experiences set me on a path with an unexpected result. I didn’t plan to be a fungus guy—who does?"

"...I had known Stanley Prusiner for some years and had been watching the progress of his laboratory in characterizing this highly unusual “microbe.” I had also seen the tremendous amount of skepticism raised by his outlandish claim that it lacked genes, that it was an infectious protein. Stan’s issue that morning was what to call this unique infectious agent. He had two candidates, he said: “piaf” and “prion.” I forget what piaf stood for, but I said that the name was already taken by a very popular French singer. Fine, he said, in any case he preferred prion, a contraction of protein and infection. I agreed. What I did not say was that prions in my native French tongue means “let us pray,” and that if he persisted with his claim of an infectious protein, he would need prayers. As we know, Stan was right, and for the discovery of prions he was awarded the Nobel Prize in 1997."

"The human brain contains approximately eighty-six billion neurons, which communicate through close to quadrillion (10x15, or one followed by fifteen zeroes) synapses. Those are astronomical numbers. It is difficult, or even impossible, for us to construct a mental image of a quadrillion objects. It is too large. For example, one hundred billion is the number of stars in our galaxy, the Milky Way. The number of synapses in our brain is equivalent to the number of stars in ten thousand Milky Ways!"

"...Because these diseases all cause millions of tiny holes, called vacuoles, in the brain, they are grouped under the name spongiform encephalopathies—diseases that, under the microscope, give the brain the look of a sponge. All of them are caused by a protein called PrP, short for prion protein."

"But there are also “good” prions! An early and most surprising discovery was made at Columbia University in the laboratory of Eric Kandel. This group had been doing pioneering work on the molecular mechanism of memory using a simple model animal, a sea slug named Aplysia. After much work, they concluded that a protein with prion properties, but again different from PrP, was involved in memory storage in this animal. They went on to show that the same protein was involved in memory in the fruit fly and in mice. And there are more and more “good prion” proteins being discovered. It turns out that prion proteins appeared very early, maybe even at the very beginning of the evolution of life on this planet. We will discuss later how they help primitive organisms such as yeast to adapt to changes in their food environment. This field is young, fast-moving, and not devoid of controversy. The nomenclature is not yet settled. Some prefer to use the name prion only for PrP, the protein that causes kuru and the other spongiform encephalopathies. They call the others “prion-like proteins” or “prionoids.” Maybe it is time to resurrect piaf for those! But for the sake of simplicity, I will call all of them “prion proteins” or “prions.”

"Dopamine, like all neurotransmitters, contains the basic building blocks of life: oxygen, hydrogen, carbon and nitrogen. It exists not only in humans, but in all animals. Primitive lizards and reptiles living tens of millions of years ago had dopamine as part of their neurochemistry. What’s more, dopamine serves a similar role in animals as it does in humans: it modifies behaviours by playing a crucial function in learning and reinforcement from rewards."

"Do you imagine futuristic cityscapes? Do you feel hopeful? Do you picture billowing smokestacks? Do you feel terrified? Does it remind you of school? Does that hold a positive or negative connotation for you?
As to what you envisioned, it may have been any of the above, or something totally different still. But the general consensus of the American public on this matter can be quite easily traced through recent history. In the years following World War II, the American economy was booming. The middle class was gainfully employed, adequately fed and sheltered, and filled with optimism. Because of this, science was viewed as a gleaming obelisk of limitless advancement. It was Disneyland’s Tomorrowland. It was the Jetsons. It was longevity and prosperity."

"Prior to the internet, there were sources of information that were unanimously agreed upon to be trustworthy and reliable. Stories published by newspapers had to be heavily researched by professional journalists. Knowledge from an encyclopedia was not questioned by those who needed to reference a fact, because they were written by top specialists in every discipline, which contributed to their considerable cost. Whether we regard them as good or bad, those times are gone, and they are never coming back. Unlike the encyclopedias of old, the quality of information on the internet is not reliable. It ranges from outstanding to abysmal. For this reason, the internet can serve as a magic mirror, a place where people go to confirm pre-existing bias. Outlets that reflect what we already “know” are correct and trustworthy. Those that do not are ignored, deemed fraudulent, deceitful, paid for by malevolent institutions, or worse. This method of assessment rarely has any respect for the qualifications of those who produce the content we encounter, which has led to what is popularly referred to as the “post-truth era.”

"...I myself became curious about the drug when my father, a retired judge, started to consider giving microdoses of LSD to my mother to treat her Alzheimer’s disease. He had asked me why, if the drug was actually supposed to help, he couldn’t just get it at the pharmacy. This launched me on my research.
The more I dug into the history, the more fascinated I became. I began to see how much of the early history of LSD was shaped by the shadow that lies over the molecule, a result of the personal connection between a Swiss pharmaceutical CEO named Arthur Stoll, a kind of unwilling forefather of psychedelics, and Richard Kuhn, the leading biochemist for the Third Reich. This relationship aided the National Socialists, who were beginning to study the use of psychedelics as potential “truth drugs”—questionable research, which, after the war, sparked the interest of the US military and its intelligence agencies in these substances.
This book is what emerged from my curiosity. In this moment when, after many decades, we are finally reconsidering the nature of our laws surrounding psychedelics, it feels more important than ever to look backward and understand how we arrived at those regulations in the first place."

"...Red light and near-infrared wavelengths is not harmful because treatments occur in a controlled environment such as a licensed spa or medical center, or even using a high-grade red light device at home. This means the chances of the light wavelengths generated by pure red light burning the skin are very dismal."

"...Red light therapy has been around for decades, since the advent of lasers in the 1960s. Currently, there are dozens of FDA-cleared red and near-infrared light therapy devices on the market, mainly for skin care and aches and pains. Some estimates suggest that the light therapy market, including white light devices for seasonal affective disorder and devices of other colors, will reach $1 billion worldwide by 2025."

"The goal of this book is twofold: to inform and inspire curiosity and action. Because light therapy can seem like magic—how, after all, can a form of energy have healing effects on the human body?—this book lays out in plain language the science of this treatment and its possible results. It does not diagnose or treat, but it does explain which conditions respond best to light therapy and how to seek it out."

"More than 4,000 PBM lab studies have been conducted, as well as about 700 clinical trials. In total, more than 6,000 papers have been published on the subject—nearly 500 in 2018 alone, signaling a rising interest in the treatment.
Looking back over the last decade or so, we can point to a few particularly important papers. A major report was published in the journal Nature in 2006, highlighting the ability of near-infrared light to flush nitric oxide from cytochrome c oxidase, helping stressed cells return to their normal, healthy function.4 The report noted that “any solution to excessive [nitric oxide] binding might lower the risk of both cancer and degenerative diseases,” since it would encourage sick cells to die off and rejuvenate healthy cells. The following year, the Journal of Rheumatology published a review of research on treatment for chronic neck pain and found that low-level laser therapy effectively reduced pain and improved function in the intermediate term for acute and chronic conditions"

"PBM is also effective at treating wounds and illnesses in animals, which seems relevant to the conversation since there’s no such thing as a placebo effect in animals. As Dr. Praveen Arany, a PBM researcher at the University at Buffalo School of Dental Medicine, explained to me, “Animals do not have placebo. They do not pretend to get better because you’re shining light on them.” Take that, PBM skeptics."

"The global transition to LED lighting seems to be having some concerning impacts on the natural world and human health. These energy efficient artificial lights produce different spectra than older incandescent technology, or the natural light of the Sun that life on Earth evolved with over billions of years. LED lighting is brighter, bluer, and more widely used than incandescent lighting.
Glen Jeffery, a professor of neuroscience from University College London, said that as a result, we may be paying the price with our health due to being oversaturated with blue light and starved of red and infrared light..."

"...While it was once believed that the healing effects of red and near-infrared light could only be obtained using expensive laser devices, science has since established that inexpensive LEDs (light emitting diodes) of the same wavelengths can provide the same remarkable healing benefits at a fraction of the cost."

"I wrote this book because I’ve experienced the benefits of red light therapy firsthand, and I now feel compelled to tell the world and help others find the same healing. The repair and enhancement of my brain function, sexual function, thyroid and overall health due to light therapy have been nothing short of miraculous.
Red light therapy isn’t a cure for all diseases, but by optimizing cellular function, supporting the immune system and accelerating the healing process, there are probably no diseases or conditions that it cannot benefit.
It’s my goal in writing this book to make the most complete resource on red light therapy ever written. One that is based on scientific evidence yet can be easily understood by anybody of any age."

"The global transition to LED lighting seems to be having some concerning impacts on the natural world and human health. These energy efficient artificial lights produce different spectra than older incandescent technology, or the natural light of the Sun that life on Earth evolved with over billions of years. LED lighting is brighter, bluer, and more widely used than incandescent lighting.
Glen Jeffery, a professor of neuroscience from University College London, said that as a result, we may be paying the price with our health due to being oversaturated with blue light and starved of red and infrared light..."

"...Hundreds of millions of people would be told to start taking it by their doctors every day. And doctors all over the world would call it a “miracle drug.”
Here’s the crazy part: That drug exists.
But it’s not a pill. It’s red and near-infrared light.
Red and near-infrared light therapy are one of the biggest breakthrough discoveries in health in the last half century. Scientists have quietly accumulated thousands of studies on the power of red and near-infrared light to enhance human health for the last several decades. And yet, most people have never even heard of it..."

"In this book, you’ll discover the incredible power of red and near-infrared light therapy and how it can help:
* Increase your energy
* Combat aging and make your skin healthier, reduce wrinkles, and help get rid of cellulite
* Speed up fat loss
* Improve muscle recovery and athletic performance
* Improve mood and cognitive function
* Speed healing from injury
* Improve metabolism and hormonal health
Sound too good to be true? Think again! Red and near-infrared light have already been proven in over 3,000 scientific studies to do all that and more!"

"There have now been literally thousands of studies conducted upon both animals and humans. Overall, red light has been repeatedly shown to have positive effects on cell function in animal and human studies and aid in improving a wide range of conditions, improving health in numerous ways. Red and near-infrared (NIR) light therapy devices have been FDA-approved for several purposes so far, including anti-aging, hair-loss reversal, acne treatment, pain relief, slow to heal wounds, fat loss, among other purposes. (This is worth noting as it proves the abundance of research showing benefits—the therapy has to be proven safe and effective in numerous trials to gain FDA approval.)"

"...The chemicals in these products of nature are not a sideshow—they are the main event, and we’ve unwittingly stolen them from a war raging all around us. We use these toxic chemicals to greet our days (caffeine), titillate our tongues (capsaicin), recover from our surgeries (morphine), cure our infections (penicillin), mend our hearts (digoxin), bend our minds (psilocybin), calm our nerves (cannabinol), spice up our food and drink (myristicin), and enhance our social lives (ethanol)."

"This book explores the fascinating and sometimes surprising ways that toxins from nature arose, have been used by us humans and other animals, and have consequently changed the world. We will follow several interrelated threads, or approaches, as we examine how these chemicals have influenced evolution and how they have penetrated each human life, for better and for worse."

"...That is why we go to the edge of uncertainty: to quest, and question, and fight with ourselves and others until we have an answer. Then, aware that we have brushed against other questions and surprises, we stow our new discoveries safely, and dive back into the dark waters to wrestle more things into the light. We have been doing it for centuries, and we can only hope we will be doing it for centuries to come. This is, after all, the best thing humans have ever done.
This is how those mysterious and powerful brains compel us to behave: they endow us with the curiosity, the bravery and the tenacity to hunt out the truth as best we can. It’s not an easy way to live. By the end of this journey to the frontiers of human certainty and beyond, your brain will feel battered and bruised. But it will also cry out for more. Adventuring is addictive. You have been warned..."

"...It is the source of creativity and, further along the spectrum, madness; it is the key to addiction and the path to recovery; it is the bit of biology that makes an ambitious executive sacrifice everything in pursuit of success, that makes successful actors and entrepreneurs and artists keep working long after they have all the money and fame they ever dreamed of; and that makes a satisfied husband or wife risk everything for the thrill of someone else. It is the source of the undeniable itch that drives scientists to find explanations and philosophers to find order, reason, and meaning.
It is why we look into the sky for redemption and God; it is why heaven is above and earth is below. It is fuel for the motor of our dreams; it is the source of our despair when we fail. It is why we seek and succeed; it is why we discover and prosper.
It is also why we are never happy for very long..."

"Look down. What do you see? Your hands, your desk, the floor, maybe a cup of coffee, or a laptop computer or a newspaper.
What do they have in common? These are things you can touch.
What you see when you look down are things within your reach, things you can control right now, things you can move and manipulate with no planning, effort, or thought. Whether it’s a result of your work, the kindness of others, or simple good fortune, much of what you see when you look down is yours. They’re things in your possession.
Now look up. What do you see? The ceiling, perhaps pictures on a wall, or things out the window: trees, houses, buildings, clouds in the sky—whatever is in the distance. What do they have in common? To reach them, you have to plan, think, calculate. Even if it’s only a little, it still requires some coordinated effort. Unlike what we see when we look down, the realm of up shows us things that we have to think about and work for in order to get..
Sounds simple because it is. Yet to the brain this distinction is the gateway between two wildly different ways of thinking—two utterly different ways of dealing with the world. In your brain the down world is managed by a handful of chemicals—neurotransmitters, they’re called—that let you experience satisfaction and enjoy whatever you have in the here and now. But when you turn your attention to the world of up, your brain relies on a different chemical—a single molecule—that not only allows you to move beyond the realm of what’s at your fingertips, but also motivates you to pursue, to control, and to possess the world beyond your immediate grasp. It drives you to seek out those things far away, both physical things and things you cannot see, such as knowledge, love, and power. Whether it’s reaching across the table for the salt shaker, flying to the moon in a spaceship, or worshipping a god beyond space and time, this chemical gives us command over every distance, whether geographical or intellectual."

"From dopamine’s point of view, having things is uninteresting. It’s only getting things that matters. If you live under a bridge, dopamine makes you want a tent. If you live in a tent, dopamine makes you want a house. If you live in the most expensive mansion in the world, dopamine makes you want a castle on the moon. Dopamine has no standard for good, and seeks no finish line. The dopamine circuits in the brain can be stimulated only by the possibility of whatever is shiny and new, never mind how perfect things are at the moment. The dopamine motto is “More.”

"HUMANS EVOLVED TO seek comfort. We instinctually default to safety, shelter, warmth, extra food, and minimal effort. And that drive through nearly all of human history was beneficial because it pushed us to survive.
Discomfort is both physical and emotional. It’s hunger, cold, pain, exhaustion, stress, and any other trying sensations and emotions.
Our comfort drive led us to find food. To build and take shelter. To flee from predators. To avoid overly risky decisions. To do anything and everything that would help us live on and spread our DNA. So it’s really no surprise that today we should still default to that which is most comfortable."

"...He called this “prevalence-induced concept change.” Essentially “problem creep.” It explains that as we experience fewer problems, we don’t become more satisfied. We just lower our threshold for what we consider a problem. We end up with the same number of troubles. Except our new problems are progressively more hollow...
...This creep phenomenon applies directly to how we now relate to comfort, said Levari. Call it comfort creep. When a new comfort is introduced, we adapt to it and our old comforts become unacceptable. Today’s comfort is tomorrow’s discomfort. This leads to a new level of what’s considered comfortable."

“In our model of misogi, there are only two rules,” said Elliott. “Rule number one is that it has to be really fucking hard. Rule number two is that you can’t die.”