UNC School of Medicine researchers identified the amino acid responsible for the trip.
- Researchers at UNC's School of Medicine have discovered the protein responsible for LSD's psychedelic effects.
- A single amino acid—part of the protein, Gαq—activates the mind-bending experience.
- The researchers hope this identification helps shape depression treatment.
What is Bicycle Day?<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="d346092205da3c9ed10bad283222c9f1"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/L32mAiLXnLs?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>Back in the world of clinical science, LSD has always showed promise. That trend continues as restrictions are finally easing up. Understanding LSD's effects on our brain's complex system of networks is an important step toward discovering therapeutic actions. As Roth <a href="https://www.inverse.com/mind-body/how-lsd-binds-to-the-brain-study" target="_blank">says</a> of his research,</p><p style="margin-left: 20px;">"Now we know how psychedelic drugs work – finally! Now we can use this information to, hopefully, discover better medications for many psychiatric diseases."</p><p>Using X-ray crystallography, Roth's team discovered a single amino acid—a building block of the protein, Gαq—responsible for binding to serotonin receptors. As LSD is only a partial agonist, they also experimented with a full-agonist designer psychedelic in order to observe complete receptor activation. This amino acid appears to be the master switch for the psychedelic experience. </p><p>While psilocybin has been in the news, the psychedelic renaissance is expanding in all directions. Phase 1 clinical trials on the <a href="https://newatlas.com/science/landmark-clinical-trial-lsd-mdma-mindmed/" target="_blank">combination</a> of LSD, MDMA, and psychotherapy will soon commence. LSD's effects on <a href="https://clinicaltrials.gov/ct2/show/NCT03866252" target="_blank" rel="noopener noreferrer">Major Depressive Disorder</a> and <a href="https://www.sciencealert.com/first-clinical-trial-shows-micro-doses-of-lsd-can-increase-a-person-s-pain-tolerance" target="_blank">pain management</a> are ongoing. With the <a href="https://www.bloomberg.com/news/articles/2020-09-18/-magic-mushroom-company-moves-toward-mainstream-in-nasdaq-ipo" target="_blank" rel="noopener noreferrer">first psychedelics company</a> to IPO on the American stock market, along with hundreds of millions of dollars of investment flowing into similar companies and organizations, the push for legalized psychedelics intensifies. </p>
Credit: ynsga / Shutterstock<p>Researchers are actively attempting to remove the hallucinogenic component of psychedelics for widespread therapeutic usage—<a href="https://www.healtheuropa.eu/could-ibogaine-offer-a-revolutionary-long-term-solution-to-addiction/100635/" target="_blank">trials</a> using ibogaine for addiction treatment, for example. Identifying the chemical effects of psychedelics on our brains is an essential step in that process.</p><p>Of course, believing psychedelics <em>only</em> matters to brain chemistry is problematic as well. The rituals associated with their use are just as relevant. The "<a href="https://en.wikipedia.org/wiki/Set_and_setting" target="_blank">set and setting</a>" model espoused by Timothy Leary reminds us that biology isn't everything; environmental factors play just as important a role in mental health. </p><p>Isolating specific chemicals without understanding the impact of the drug <em>and</em> the environment overlooks the holistic nature of the psychedelic experience. For example, ketamine trials <a href="https://bigthink.com/surprising-science/ketamine-depression" target="_self">were rushed</a> and could potentially backfire; we can't afford to make that mistake again. </p><p>Still, understanding the pathways LSD utilizes is an important step forward. As Roth says, "Our ultimate goal is to see if we can discover medications which are effective, like psilocybin, for depression but do not have the intense psychedelic actions." In a world where more people are growing anxious and depressed by the day, every intervention should be explored.</p><p> --</p><p><em>Stay in touch with Derek on <a href="http://www.twitter.com/derekberes" target="_blank">Twitter</a>, <a href="https://www.facebook.com/DerekBeresdotcom" target="_blank" rel="noopener noreferrer">Facebook</a> and <a href="https://derekberes.substack.com/" target="_blank" rel="noopener noreferrer">Substack</a>. His next book is</em> "<em>Hero's Dose: The Case For Psychedelics in Ritual and Therapy."</em></p>
A team of researchers have discovered the brain rhythmic activity that can split us from reality.
- Researchers have identified the key rhythmic brain activity that triggers a bizarre experience called dissociation in which people can feel detached from their identity and environment.
- This phenomena is experienced by about 2 percent to 10 percent of the population. Nearly 3 out of 4 individuals who have experienced a traumatic event will slip into a dissociative state either during the event or sometime after.
- The findings implicate a specific protein in a certain set of cells as key to the feeling of dissociation, and it could lead to better-targeted therapies for conditions in which dissociation can occur.
What is dissociation?<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="bd2f1f29418bd4805bf1282001dca814"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/XF2zeOdE5GY?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>Dissociation is an experience commonly described as a feeling of sudden detachment from the individual's identity and environment, almost like an out-of-body experience. This mysterious phenomena is experienced by about 2 percent to 10 percent of the population.</p><p>"This state often manifests as the perception of being on the outside looking in at the cockpit of the plane that's your body or mind — and what you're seeing you just don't consider to be yourself," explained senior author Karl Deisseroth, MD, PhD, <a href="https://med.stanford.edu/news/all-news/2020/09/researchers-pinpoint-brain-circuitry-underlying-dissociation.html" target="_blank" rel="noopener noreferrer">in a Stanford Medicine news release</a>. Deisseroth is a professor of bioengineering and of psychiatry and behavioral sciences, as well as a Howard Hughes Medical Institute investigator.</p><p>Nearly three-quarters of individuals who have experienced a traumatic event will slip into a dissociative state either during the event or in the hours or even weeks that follow, according to Deisseroth. Most of the time, the dissociative experiences end on their own within a few weeks of the trauma. But the eerie experience can become chronic, such as in cases of post-traumatic stress disorder, and extremely disruptive in daily life. The state of dissociation can also occur in epilepsy and be invoked by certain drugs. </p><p>Until now, no one has known what exactly is going on inside the brain triggering and sustaining the feeling of dissociation — and so it has been a challenge to figure out how to stop it and develop effective treatments. </p>
New Research: The Molecular Underpinnings of Dissociation<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDQyNjk3My9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYwNTQ3MTI1NX0._nJoxm1eDcTsHsy1Y27JxNl2uR5hlbEYDWYoQlO0EAU/img.jpg?width=1245&coordinates=0%2C121%2C0%2C121&height=700" id="26e86" class="rm-shortcode" data-rm-shortcode-id="1094af23e35a498a8a6b691f1d0cbfaf" data-rm-shortcode-name="rebelmouse-image" alt="neurons" />
Neurons from a mouse spinal cord
Credit: NICHD on Flickr<p>Last week, in a study published in <a href="https://www.nature.com/articles/s41586-020-2731-9" target="_blank">Nature</a><a href="https://www.nature.com/articles/s41586-020-2731-9">,</a> Deisseroth and his colleagues at Stanford University uncovered a localized brain rhythm and molecule that underlies this state.</p><p>"This study has identified brain circuitry that plays a role in a well-defined subjective experience," said Deisseroth. "Beyond its potential medical implications, it gets at the question, 'What is the self?' That's a big one in law and literature, and important even for our own introspections."</p><p>The authors' findings implicate a specific protein existing in a particular set of cells as key to the feeling of dissociation. </p><p>The research team first used a technique called widefield calcium imaging to record brain-wide neuronal activity in lab mice. They observed and analyzed changes in those brain rhythms after the animals had been administered a range of drugs that are known to cause dissociative states: ketamine, phencyclidine (PCP), and dizocilpine (MK801). At a certain dosage of ketamine, the mice behaved in a way that suggested that they were likely experiencing dissociation. For example, when the animals were placed on an uncomfortably warm surface, they reacted to it by flicking their paws. However, they signaled that they didn't care enough about the unpleasantness to do what they would typically do in such a situation, which is to lick their paws to cool them off. This suggested a dissociation from the surrounding environment.</p><p>The drug produced oscillations in neuronal activity in a region of the mices' brain called the retrosplenial cortex, an area essential for various cognitive functions such as navigation and episodic memory (a unique memory of a specific event). The oscillations occurred at about 1-3 hertz (three cycles per second). The authors then examined the active cells in more detail by using two-photon imaging for higher resolution. This revealed that the oscillations were occurring only in layer 5 of the retrosplenial cortex. Next, the researchers recorded neuronal activity across other regions of the brain. </p><p>"Normally, other parts of the cortex and subcortex are functionally connected to neuronal activity in the retrosplenial cortex," Ken Solt and Oluwaseun Akeju wrote in <a href="https://www.nature.com/articles/d41586-020-02505-z#ref-CR1" target="_blank">Nature</a>. "However, ketamine caused a disconnect, such that many of these brain regions no longer communicated with the retrosplenial cortex."</p><p>The scientists then used optogenetics, a method of manipulating living tissue with light to control neural function, to stimulate neurons in the mice's retrosplenial cortex. When the scientists did this at a 2-hertz rhythm, they were able to cause dissociative behavior in the animals analogous to the behavior caused by ketamine without using drugs. The experiments conducted by the team displayed how a particular type of protein, an ion channel, was essential to the generation of the hertz signal that caused the dissociative behavior in mice. Scientists are hopeful that this protein could be a potential treatment target in the future. </p>
What about humans?<p>The researchers also recorded electrical activity from brain regions in an epilepsy patient who had reported experiencing dissociation immediately before each seizure. The sensations experienced right before a seizure is called an aura. This aura for the patient was like being "outside the pilot's chair, looking at, but not controlling, the gauges," Deisseroth said.</p><p>The researchers recorded electric signals from the patient's cerebral cortex and stimulated it electrically aiming to identify the origin point of the seizures. While that was happening, the patient responded to questions about how it felt. The authors found that whenever the patient was about to have a seizure, it was preceded by the dissociative aura and a particular pattern of electrical activity localized within the patient's posteromedial cortex. That patterned activity was characterized by an oscillating signal sparked by nerve cells firing in coordination at 3 hertz. When this region of the brain was stimulated electrically, the patient experienced dissociation without having a seizure. </p><p>This study will have far-reaching implications for neuroscience and could lead to better-targeted therapies for disorders in which dissociation can be triggered, such as PTSD, borderline personality, and epilepsy.</p>
A team at the University of Basel discovered a connection between antidepressants and REM sleep.
- Researchers at the University of Basel measured the efficacy of antidepressants by measuring brain waves during REM sleep.
- Antidepressants take weeks to begin working, and over 50 percent of users don't find success with the first prescription.
- This research could offer a powerful new diagnostic tool for psychiatrists and doctors.
Should you "hack" your sleep pattern? | Vanessa Hill | Big Think<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="af84e812903700afbdc0c73e6b7c619e"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/1Y-qLKZWyDs?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>University of Basel's Dr Thorsten Mikoteit led the research. His team studied 37 volunteers suffering from major depression, with 15 in the control group. Everyone's brain waves were measured while asleep. By gazing at these waves, the researchers identified patterns that could predict whether or not the volunteer would benefit from an antidepressant.</p><p>Through their observations, the researchers were able to suggest a different medication if they did not seem to respond to the first. After five weeks, 87.5 percent of the patients in the treatment group showed an improved response to medication, compared to only 20 percent in the control group. </p><p>It should be noted that this is a pilot study and has not yet been peer reviewed. Still, Mikoteit sees hope in the protocol. </p><p style="margin-left: 20px;">"We have been able to show that by predicting the non-response to antidepressants we were able to adapt the treatment strategy more or less immediately: this enables us to significantly shorten the average duration between start of antidepressant treatment and response, which is vital especially for seriously depressed patients."</p><p>Poor sleep is an indicator of numerous health problems, including anxiety and depression. Getting an inside view of sleep patterns could be a game-changer for the hundreds of millions of people that regularly suffer from depression. If this research holds up, doctors could have a powerful new diagnostic tool at their fingertips. The time, money, and health risks associated with faulty prescriptions could be avoided—a win for patients and the health care system overall. </p><p>--</p><p><em>Stay in touch with Derek on <a href="http://www.twitter.com/derekberes" target="_blank">Twitter</a>, <a href="https://www.facebook.com/DerekBeresdotcom" target="_blank" rel="noopener noreferrer">Facebook</a> and <a href="https://derekberes.substack.com/" target="_blank" rel="noopener noreferrer">Substack</a>. His next book is</em> "<em>Hero's Dose: The Case For Psychedelics in Ritual and Therapy."</em></p>
What exactly does "questions are the new answers" mean?
- Traditionally, intelligence has been viewed as having all the answers. When it comes to being innovative and forward-thinking, it turns out that being able to ask the right questions is an equally valuable skill.
- The difference between the right and wrong questions is not simply in the level of difficulty. In this video, geobiologist Hope Jahren, journalist Warren Berger, experimental philosopher Jonathon Keats, and investor Tim Ferriss discuss the power of creativity and the merit in asking naive and even "dumb" questions.
- "Very often the dumb question that is sitting right there that no one seems to be asking is the smartest question you can ask," Ferriss says, adding that "not only is it the smartest, most incisive, but if you want to ask it and you're reasonably smart, I guarantee you there are other people who want to ask it but are just embarrassed to do so."
Construction is nearly complete for a camera that will take 3,200-megapixel panoramas of the southern night sky.
Building a bigger focal plane<p>The tech involved in the focal plane is incredibly sophisticated and its assembly is downright harrowing.</p><p>The sensors that capture 16-megapixel images in high-end digital cameras are called <a href="https://en.wikipedia.org/wiki/Charge-coupled_device" target="_blank">charge-coupled devices</a>, or CCDs. (Our phones and tablets instead use <a href="https://lifeinlofi.com/2015/05/06/how-does-your-iphone-cmos-shutter-work/" target="_blank" rel="noopener noreferrer">CMOS</a> sensors.) The LSST camera contains 189 CCD sensors. The sensors are arranged into 21 squares of nine CCDs each — each square is called a "science raft." The 2-foot-tall, 20-pound rafts are mounted in a grid inside the camera. This all adds up to 3.2 billion pixels, each of which is tiny at 10 microns in size, about a tenth of the width of a human hair.</p><p>As you might expect, assembling such sophisticated hardware is not for the faint of heart. The rafts must be precisely positioned in the grid so that they're separated by a width equivalent to just five human hairs. If they touch they crack, and down the drain goes $3 million per raft. The SLAC team practiced the assembly operation for a year before the six-month assembly process commenced.</p><img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDMwNzk5Mi9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYwNjc0ODQyNH0.JGSUxAHw3ZaqyyeO_ZeYxt0CBKTxyKqOTAB9QTE7pfo/img.jpg?width=980" id="9d15d" class="rm-shortcode" data-rm-shortcode-id="3d35e06eb183e93b8c2f549194477e23" data-rm-shortcode-name="rebelmouse-image" />
One CCD raft in place, plus a smaller non-imaging raft to its left.
Amazingly detailed images<p>The camera will be worth the effort.</p><p>The flatness of its giant focal plane — over 2 feet wide, as opposed to 1.4 inches in a consumer camera — will allow it to capture images of the heavens about 40 moons across. Zoomed in, the team says an image it produces will be so clear it will be like seeing a golf ball from 15 miles away. The camera will also be highly sensitive to dim objects, so it will be able to take pictures of things that are more than 100 million times dimmer than what we can see with our eyes — it's comparable to being able to see a candle from 1,000 miles away. Project scientists Steven Ritz sums it up: "These specifications are just astounding."</p><p>Once assembled, the focal plane was put inside a custom-built cryostat for cooling — the required operating temperature is -150° F.</p><span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="32a84ac359d1e08caf87ad1d1f0f8fce"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/IP3TUneJ0ho?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span>
Broccoli, say "cheese."<p>Broccoli's surface is packed with tiny details, making it a sensible candidate for testing out the focal plane. The camera housing hasn't yet been completed, so the scientists <a href="https://youtu.be/qc_iscV1uA0?t=62" target="_blank">created a pinhole device</a> that projected the broccoli's image onto the focal plane.</p><p>The man in charge of assembling and testing the LSST focal plane is Aaron Roodman, who says that "taking these images is a major accomplishment. With the tight specifications we really pushed the limits of what's possible to take advantage of every square millimeter of the focal plane and maximize the science we can do with it." </p><a href="https://www.slac.stanford.edu/~tonyj/osd/public/romanesco.html" ><img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDMwODA5MS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY1MDEwNTEyNX0.nszfZqSEKmPZabqaYBziJOQetJ6VAowQ7678QB4G6a0/img.jpg?width=980" id="0c7cc" class="rm-shortcode" data-rm-shortcode-id="dc13ce1e827f4380684bb21aa006d47c" data-rm-shortcode-name="rebelmouse-image" alt="broccoli image captured by LSST camera" /></a>
(Click image to explore the image at full resolution.)