Explorer - Inside LSD

National Geographic Channel's EXPLORER: INSIDE LSD

National Geographic Channel's EXPLORER: INSIDE LSD puts this mysterious molecule back under the microscope. From psychedelics given to terminally ill patients, to reputedly the "world's purest LSD" administered in lab experiments, find out why some researchers believe this "trippy" drug could become the pharmaceutical of the future  enhancing brain power, expanding creativity and even curing mental illness.
Fifty years ago, psychedelics or "mind-manifesting" drugs like LSD were considered cutting-edge science. Within months of its accidental discovery in 1943 by Hoffman, free samples of LSD were arriving at the doorsteps of scientists and psychiatrists around the world to test its effects on everything from alcoholism to autism. Even the Central Intelligence Agency and the military dosed their own operatives to see if LSD could be weaponized for mind control. But this powerful hallucinogen became a street drug with a dangerous reputation, and it was eventually outlawed. Yet despite its illegality, an estimated 23 million Americans have taken LSD, and more than 600,000 try it each year.

Now, after more than three decades, cutting-edge science takes on psychedelics again. At Purdue University, pharmacology professor Dave Nichols is one of a select group with permission to manufacture and experiment with LSD. His team uses some of the purest LSD ever made to study its molecular structure and effect on the brains of rats, with intriguing results. EXPLORER: INSIDE LSD shows how after chronic dosing, Nichols' rats begin to avoid social contact and mimic schizophrenic behavior in humans. Nichols believes his study may shed light on the chemical mechanisms underlying mental illnesses, potentially leading to cures.

About LSD;
Lysergic acid diethylamide, LSD-25, LSD, formerly lysergide, commonly known as acid, is a semisynthetic psychedelic drug of the ergoline and tryptamine families. LSD is non-addictive, non-toxic, and is well known for its psychological effects which can include closed and open eye visuals, synaesthesia, a sense of time distortion, ego death and profound spiritual experiences, as well as for its key role in 1960s counterculture. It is used mainly by psychonauts as an entheogen and in psychedelic therapy.

A single dose of LSD may be between 100 and 500 micrograms — an amount roughly equal to one-tenth the mass of a grain of sand. Threshold effects can be felt with as little as 25 micrograms of LSD.
Dosages of LSD are measured in micrograms (µg), or millionths of a gram. By comparison, dosages of most drugs, both recreational and medicinal, are measured in milligrams (mg), or thousandths of a gram. For example, an active dose of mescaline, roughly 0.2 to 0.5g, has effects comparable to 100 µg or less of LSD.
Typical doses in the 1960s ranged from 200 to 1000 µg while street samples of the 1970s contained 30 to 300 µg. By the 1980s, the amount had reduced to between 100 to 125 µg, lowering more in the 1990s to the 20–80 µg range.
Estimates for the lethal dosage (LD50) of LSD range from between 200 µg/kg to more than 1 mg/kg of human body mass, though most sources report that there are no known human cases of such an overdose. Other sources note one report of a suspected fatal overdose of LSD occurring in November 1975 in Kentucky in which there were indications that ~1/3 of a gram (320 mg or 320,000 µg) had been injected intravenously. (This is a very extraordinary amount, particularly when compared to the average LSD dosage of ~100 µg).Experiments with LSD were also done on animals; in 1962, an elephant named Tusko died shortly after being injected with 297 mg, but whether the LSD was the cause of his death is controversial
Links;
Wikipedia - LSD
The Mind-Benders: LSD and the Hallucingens, ca. 1970
Experimental Compound MER 17 (Frenquel) and LSD-25: Psychosis, 1955
Bad Acid   The Love Statue LSD Experience  LSD: Problem Child and Wonder Drug
Firing Line with William F. Buckley Jr. "The World of LSD"
The Net: The Unabomber, LSD and the Internet

How the Brain Invents the Mind

Opening Remarks - How the Brain Invents the Mind
A lecture by Dr. Susan Hockfield Rebecca Saxe Ph.D. '03 June 6, 2009;
Running Time: 1:39:22

About the Lecture
In trying financial times, Susan Hockfield remains optimistic and committed to pursuing MIT’s massive, multi-year initiatives in energy and life sciences. She prefaces her “whirlwind” tour of MIT for an alumni audience by referencing the campus-wide relief at the change in presidential administrations, which promises to make science and engineering more central, and to make “MIT values more mainstream.” If it indeed becomes “cool to be smart,” Hockfield believes MIT can count on taking a prominent national role in research, policy and education.

One key area in which MIT hopes to make a major contribution is sustainable energy. The MIT Energy Initiative, two years old, brings together faculty and students across all disciplines to develop a portfolio of new technologies (although the focus seems increasingly to fall on solar). Campus interest is so intense that the Institute has committed to a minor in energy, and it’s seeking five new professorships in the area. The other major enterprise involves fusing biological sciences with engineering, especially in the study of cancer. At the new Koch Institute, cancer biologists and engineers have already made “fundamental discoveries underlying new targeted cancer drugs,” and they are hard at work decoding the disease, and devising new methods for diagnosis and treatment.

Hockfield also candidly describes the impact of the economic downturn on the Institute, acknowledging that “most revenue streams have been compromised,” except for research. With the endowment down by 20-25%, departments across the board are making significant but strategic cuts for the next two to three years. MIT will not compromise on providing financial aid to needy students, a cost that understandably has risen in the past year, nor on hiring faculty. Hockfield hopes that private philanthropy will help MIT “preserve core strengths and values.” At the end of the recession, she says, “We want to come out with a leaner, stronger Institute.”

Fellow neuroscientist Rebecca Saxe outlines her research investigating the neural basis for a Theory of Mind -- how the human mind seems geared to “glean what others are thinking and feeling.” From her work with children and adults, Saxe has determined that there’s a very specific region of the brain -- the right temporal-parietal junction -- dedicated to thinking about how others think. This area lights up in the fMRI scanner when people read stories involving another person’s beliefs and moral judgments, but not when they digest other kinds of written material. The RTPJ develops this special function slowly (young children don’t have it), and Saxe has discovered that she can interfere with this region’s activities, altering her subjects’ sense of what constitutes morally permissible behavior. She’s exploring whether these distinct neural networks develop differently in children with autism, with the hope of finding therapies that might someday help treat the disorder.

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The Autistic Neuron

The Autistic Neuron A Lecture by Mark Bear; May 4, 2009
Running Time: 0:35:11
About the Lecture

This self-described “basic neuroscientist” confesses he never thought he’d give a talk on autism, but as Mark Bear recounts, decades of research in the basics are now paying off with important insights into the etiology and treatment of brain disorders, including autism.

Bear provides a primer on this developmental disorder, noting that its roots are biological, it is highly heritable, and astonishingly prevalent: one in 150 people express some of the symptoms of autism. These fall on a spectrum, from severely reduced social behavior, abnormal language, repetitive movements, seizures and mental retardation, to the milder Asperger’s Syndrome, where individuals are often academically successful, but socially awkward. Particularly significant to Bear: Autism’s underlying genetic changes manifest themselves in problematic communication between neurons.

To unravel autism, researchers are examining its clinical heterogeneity, “genetic risk architecture,” and how it alters brain connections and function. One of the difficulties in approaching autism is that a variety of genetic mutations can result in autistic behaviors, and only a few of these mutations have been identified. Bear himself has been probing the single gene disorder, Fragile X syndrome (responsible for about 5% of the cases “of full-blown autism.”) In Fragile X, the FMR1 gene is silenced, leading to a missing protein that serves as a key regulator of brain proteins involved in neuron communication. Without FMR1, “the brakes are missing,” and there’s excessive protein synthesis leading to altered brain function.

Bear hypothesized that it might be possible to correct Fragile X by bringing the system back in balance. He created mice models of the disease, and found that by reducing the number of neurotransmitter receptors that respond to the excessive brain proteins, he could ameliorate or correct Fragile X defects. These receptors are “druggable targets,” and, says Bear, “if the treatment works in fly, fish or mouse, it better work in humans or Darwin was wrong.”

Based on this work, drug companies are devising compounds to test in human clinical trials of Fragile X syndrome. In addition, Bear notes, colleagues have discovered that other mutations connected with autism also involve protein regulation problems. “This gets us excited, because it looks like a common pathway that causes synaptic dysfunction in different diseases that may ultimately manifest as autism. If that’s the case, then treatment for the disorder may be efficacious in multiple disorders.”

Link; mitworld.mit.edu

How the Brain Encodes Reward

How the Brain Encodes Reward - a lecture by Okihide Hikosaka
May 7, 2009 - Running Time: 0:51:02

About the Lecture
As Ann Graybiel puts it, “basal ganglia were dark basement structures” until Okihide Hikosaka began his classic 1980s research demonstrating how these neuronal clusters influenced eye movements. Hikosaka has deepened and broadened his work in this once neglected area of the brain, and brings a McGovern audience up to date on his latest discoveries.

Hikosaka briefly sketches what is known about the basic pathways leading in, around and out of the basal ganglia, circuits that have been associated with stress, pain, mood, memory and arousal. This specialized cluster of neurons seems especially attuned to the neurotransmitter dopamine, and Hikosaka has been investigating “a number of unsolved questions,” including how dopamine neurons form circuits for movement control, whether such neurons encode “motivational values,” and what other parts of the brain guide them.

Hikosaka describes research demonstrating that certain dopamine neurons become excited if a visual cue indicates a future reward, and become inhibited with a visual cue indicating no reward. Dopamine also increases after an action delivers a reward and decreases when an action produces no reward. Research began to explore whether dopamine neurons “encode motivational values, including reward and punishment.” After others’ studies yielded contradictory or uncertain conclusions, Hikosaka designed a set of studies on monkeys involving classical Pavlovian conditioning, with juice rewards and air puffs as aversive stimuli.

Among Hikosaka’s findings: some dopamine neurons were excited primarily by positive, reward-predicting stimuli, others inhibited by air puff-predicting stimuli. But he also found another group of dopamine neurons excited both by positive and negative reward-predicting stimuli (as well as the stimuli themselves). Hikosaka posited two types of neurons that react in very different ways to motivational signals, which he described as value-coding and salience-coding. He also determined that the lateral habenula, a part of the brain sitting at one end of the thalamus, seems to regulate dopamine pathways involved in some motivational responses. By sending a weak electric pulse through the lateral habenula, Hikosaka saw a very strong inhibition of the dopamine neurons that “encode mostly motivational values.”

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