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Why LSD Trips Last So Long and Make Everything Seem So Meaningful
Two recent studies reveal the effects of LSD on the brain.
While LSD has been around since 1938, when it was synthesized by the Swiss scientist Albert Hoffman, how exactly it works has continued to be a mystery. As LSD research has picked up, two new studies provide insight on what happens to the brain on LSD, the common name for Lysergic acid diethylamide. One group of scientists figured out the structural changes LSD makes in the brain while the other looks at how LSD makes people create meaning.
Research published in Cell zeroed in at what LSD looks like when attached to a brain receptor.
The team led by Bryan L. Roth, MD, PhD from the UNC School of Medicine used x-ray crystallography to “freeze” and capture images of LSD attached to a serotonin receptor (a protein that senses serotonin, a chemical messenger). The researchers found that the LSD molecule is essentially locked on to that part of the brain as the receptor folds over it like a lid. This explains why the effects of an LSD trip last so long, lingering for 12 hours or more even if LSD molecules are known to clear from the blood in a few hours.
"We think this lid is likely why the effects of LSD can last so long," said Roth, "LSD takes a long time to get onto the receptor, and then once it's on, it doesn't come off. And the reason is this lid."
The answers his team was able to get clears up the question Roth held from his youth.
“When I was younger, and The Grateful Dead was still around, I would occasionally go to Grateful Dead concerts. A lot of people took LSD and similar drugs during concerts, and it would be interesting to be in the parking lot hearing people wondering when their LSD experience was going to end," said Roth. "A lot of people who take the drug are not aware of just how long it lasts."
A molecule of LSD bound to a larger serotonin receptor. The 'lid' that keeps LSD bound so long is the orange bar running through the center. Credit: Lab of Bryan Roth, UNC School of Medicine
The trip ends when LSD molecules get off their receptors, while brain cells eventually pull the receptors into the cell, where they (along with the LSD) get degraded or recycled.
The scientists think their research will help in the development of new treatments, especially considering the recent popularity of LSD microdosing to combat depression or increase creativity.
Another study, this one published in Current Biology, looked at how LSD affects perception. They found specific neurochemicals and receptors in the brain responsible for “loosening” the boundaries of the self and creating a sense of meaning while on an LSD trip. What they were after is to understand why people on LSD paid so much attention to details or objects which normally would not elicit such a focus.
"Our results increase our understanding of how personal relevance attribution is enabled in the brain," said Katrin Preller of the Zürich University Hospital for Psychiatry. "[We now know] which receptors, neurotransmitters, and brain regions are involved when we perceive our environment as meaningful and relevant."
In particular, the researchers studied a group of people on LSD versus a group on placebos, having them rank the meaning of specific songs or musical compositions. It turned out that songs which previously didn’t mean much became very significant to the subjects on LSD. Doing this, while scanning the brains of the participants, allowed the scientists to identify the specific receptors involved in creating that meaningfulness.
"By combining functional brain imaging and detailed behavioral assessments using a specific experimental paradigm to investigate personal relevance or meaning of music pieces, we were able to elucidate the neurobiological correlates of personal relevance processing in the brain," explained Preller. "We found that personal meaning attribution and its modulation by LSD is mediated by the 5-HT2A receptors and cortical midline structures that are also crucially involved in enabling the experience of a sense of self."
Further studies of the identified 5-HT2A receptors may lead to understanding how “excessive stimulation” of these receptors can be responsible for the peculiar feelings and sensations of people on a psychedelic trip. The goal is to develop new treatments for psychiatric illnesses.
Cover photo: Artistic representation of the chemical structure of LSD -- highlighted in yellow -- interlocking into a red-orange ribbon diagram of the serotonin receptor. Credit: Annie Spikes
An open letter predicts that a massive wall of rock is about to plunge into Barry Arm Fjord in Alaska.
- A remote area visited by tourists and cruises, and home to fishing villages, is about to be visited by a devastating tsunami.
- A wall of rock exposed by a receding glacier is about crash into the waters below.
- Glaciers hold such areas together — and when they're gone, bad stuff can be left behind.
The Barry Glacier gives its name to Alaska's Barry Arm Fjord, and a new open letter forecasts trouble ahead.
Thanks to global warming, the glacier has been retreating, so far removing two-thirds of its support for a steep mile-long slope, or scarp, containing perhaps 500 million cubic meters of material. (Think the Hoover Dam times several hundred.) The slope has been moving slowly since 1957, but scientists say it's become an avalanche waiting to happen, maybe within the next year, and likely within 20. When it does come crashing down into the fjord, it could set in motion a frightening tsunami overwhelming the fjord's normally peaceful waters .
The Barry Arm Fjord
Camping on the fjord's Black Sand Beach
Image source: Matt Zimmerman
The Barry Arm Fjord is a stretch of water between the Harriman Fjord and the Port Wills Fjord, located at the northwest corner of the well-known Prince William Sound. It's a beautiful area, home to a few hundred people supporting the local fishing industry, and it's also a popular destination for tourists — its Black Sand Beach is one of Alaska's most scenic — and cruise ships.
Not Alaska’s first watery rodeo, but likely the biggest
Image source: whrc.org
There have been at least two similar events in the state's recent history, though not on such a massive scale. On July 9, 1958, an earthquake nearby caused 40 million cubic yards of rock to suddenly slide 2,000 feet down into Lituya Bay, producing a tsunami whose peak waves reportedly reached 1,720 feet in height. By the time the wall of water reached the mouth of the bay, it was still 75 feet high. At Taan Fjord in 2015, a landslide caused a tsunami that crested at 600 feet. Both of these events thankfully occurred in sparsely populated areas, so few fatalities occurred.
The Barry Arm event will be larger than either of these by far.
"This is an enormous slope — the mass that could fail weighs over a billion tonnes," said geologist Dave Petley, speaking to Earther. "The internal structure of that rock mass, which will determine whether it collapses, is very complex. At the moment we don't know enough about it to be able to forecast its future behavior."
Outside of Alaska, on the west coast of Greenland, a landslide-produced tsunami towered 300 feet high, obliterating a fishing village in its path.
What the letter predicts for Barry Arm Fjord
Moving slowly at first...
Image source: whrc.org
"The effects would be especially severe near where the landslide enters the water at the head of Barry Arm. Additionally, areas of shallow water, or low-lying land near the shore, would be in danger even further from the source. A minor failure may not produce significant impacts beyond the inner parts of the fiord, while a complete failure could be destructive throughout Barry Arm, Harriman Fiord, and parts of Port Wells. Our initial results show complex impacts further from the landslide than Barry Arm, with over 30 foot waves in some distant bays, including Whittier."
The discovery of the impeding landslide began with an observation by the sister of geologist Hig Higman of Ground Truth, an organization in Seldovia, Alaska. Artist Valisa Higman was vacationing in the area and sent her brother some photos of worrying fractures she noticed in the slope, taken while she was on a boat cruising the fjord.
Higman confirmed his sister's hunch via available satellite imagery and, digging deeper, found that between 2009 and 2015 the slope had moved 600 feet downhill, leaving a prominent scar.
Ohio State's Chunli Dai unearthed a connection between the movement and the receding of the Barry Glacier. Comparison of the Barry Arm slope with other similar areas, combined with computer modeling of the possible resulting tsunamis, led to the publication of the group's letter.
While the full group of signatories from 14 organizations and institutions has only been working on the situation for a month, the implications were immediately clear. The signers include experts from Ohio State University, the University of Southern California, and the Anchorage and Fairbanks campuses of the University of Alaska.
Once informed of the open letter's contents, the Alaska's Department of Natural Resources immediately released a warning that "an increasingly likely landslide could generate a wave with devastating effects on fishermen and recreationalists."
How do you prepare for something like this?
Image source: whrc.org
The obvious question is what can be done to prepare for the landslide and tsunami? For one thing, there's more to understand about the upcoming event, and the researchers lay out their plan in the letter:
"To inform and refine hazard mitigation efforts, we would like to pursue several lines of investigation: Detect changes in the slope that might forewarn of a landslide, better understand what could trigger a landslide, and refine tsunami model projections. By mapping the landslide and nearby terrain, both above and below sea level, we can more accurately determine the basic physical dimensions of the landslide. This can be paired with GPS and seismic measurements made over time to see how the slope responds to changes in the glacier and to events like rainstorms and earthquakes. Field and satellite data can support near-real time hazard monitoring, while computer models of landslide and tsunami scenarios can help identify specific places that are most at risk."
In the letter, the authors reached out to those living in and visiting the area, asking, "What specific questions are most important to you?" and "What could be done to reduce the danger to people who want to visit or work in Barry Arm?" They also invited locals to let them know about any changes, including even small rock-falls and landslides.
Eating veggies is good for you. Now we can stop debating how much we should eat.
- A massive new study confirms that five servings of fruit and veggies a day can lower the risk of death.
- The maximum benefit is found at two servings of fruit and three of veggies—anything more offers no extra benefit according to the researchers.
- Not all fruits and veggies are equal. Leafy greens are better for you than starchy corn and potatoes.
The famous cognition test was reworked for cuttlefish. They did better than expected.
- Scientists recently ran the Stanford marshmallow experiment on cuttlefish and found they were pretty good at it.
- The test subjects could wait up to two minutes for a better tasting treat.
- The study suggests cuttlefish are smarter than you think but isn't the final word on how bright they are.
Proof that some people are less patient than invertebrates<iframe width="730" height="430" src="https://www.youtube.com/embed/H1yhGClUJ0U" frameborder="0" allow="accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture" allowfullscreen></iframe><p> The common cuttlefish is a small cephalopod notable for producing sepia ink and relative intelligence for an invertebrate. Studies have shown them to be capable of remembering important details from previous foraging experiences, and to adjust their foraging strategies in response to changing circumstances. </p><p>In a new study, published in <a href="https://royalsocietypublishing.org/doi/10.1098/rspb.2020.3161" target="_blank" rel="noopener noreferrer">The Proceedings of the Royal Society B</a>, researchers demonstrated that the critters have mental capacities previously thought limited to vertebrates.</p><p>After determining that cuttlefish are willing to eat raw king prawns but prefer a live grass shrimp, the researchers trained them to associate certain symbols on see-through containers with a different level of accessibility. One symbol meant the cuttlefish could get into the box and eat the food inside right away, another meant there would be a delay before it opened, and the last indicated the container could not be opened.</p><p>The cephalopods were then trained to understand that upon entering one container, the food in the other would be removed. This training also introduced them to the idea of varying delay times for the boxes with the second <a href="https://www.sciencealert.com/cuttlefish-can-pass-a-cognitive-test-designed-for-children" target="_blank" rel="noopener noreferrer">symbol</a>. </p><p>Two of the cuttlefish recruited for the study "dropped out," at this point, but the remaining six—named Mica, Pinto, Demi, Franklin, Jebidiah, and Rogelio—all caught on to how things worked pretty quickly.</p><p>It was then that the actual experiment could begin. The cuttlefish were presented with two containers: one that could be opened immediately with a raw king prawn, and one that held a live grass shrimp that would only open after a delay. The subjects could always see both containers and had the ability to go to the immediate access option if they grew tired of waiting for the other. The poor control group was faced with a box that never opened and one they could get into right away.</p><p>In the end, the cuttlefish demonstrated that they would wait anywhere between 50 and 130 seconds for the better treat. This is the same length of time that some primates and birds have shown themselves to be able to wait for.</p><p>Further tests of the subject's cognitive abilities—they were tested to see how long it took them to associate a symbol with a prize and then on how long it took them to catch on when the symbols were switched—showed a relationship between how long a cuttlefish was willing to wait and how quickly it learned the associations. </p>
All of this is interesting, but what use could it possibly have?<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNTcxNzY2MS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY2MTM0MzYyMH0.lKFLPfutlflkzr_NM6WmnosKM1rU6UEIHWlyzWhYQNM/img.jpg?width=1245&coordinates=0%2C10%2C0%2C88&height=700" id="77c04" class="rm-shortcode" data-rm-shortcode-id="7eb9d5b2d890496756a69fb45ceac87c" data-rm-shortcode-name="rebelmouse-image" data-width="1245" data-height="700" />
A diagram showing the experimental set up. On the left is the control condition, on the right is the experimental condition.
Credit: Alexandra K. Schnell et al., 2021<p> As you can probably guess, the ability to delay gratification as part of a plan is not the most common thing in the animal kingdom. While humans, apes, some birds, and dogs can do it, less intelligent animals can't. </p><p>While it is reasonably simple to devise a hypothesis for why social humans, tool-making chimps, or hunting birds are able to delay gratification, the cuttlefish is neither social, a toolmaker, or is it hunting anything particularly <a href="https://gizmodo.com/cuttlefish-are-able-to-wait-for-a-reward-1846392756" target="_blank" rel="noopener noreferrer">intelligent</a>. Why they evolved this capacity is up for debate. </p><p>Lead author Alexandra Schnell of the University of Cambridge discussed their speculations on the evolutionary advantage cuttlefish might get out of this skill with <a href="https://www.eurekalert.org/pub_releases/2021-03/mbl-qc022621.php" target="_blank" rel="noopener noreferrer">Eurekalert:</a> </p><p style="margin-left: 20px;"> "Cuttlefish spend most of their time camouflaging, sitting and waiting, punctuated by brief periods of foraging. They break camouflage when they forage, so they are exposed to every predator in the ocean that wants to eat them. We speculate that delayed gratification may have evolved as a byproduct of this, so the cuttlefish can optimize foraging by waiting to choose better quality food."</p><p>Given the unique evolutionary tree of the cuttlefish, its cognitive abilities are an example of convergent evolution, in which two unrelated animals, in this case primates and cuttlefish, evolve the same trait to solve similar problems. These findings could help shed light on the evolution of the cuttlefish and its relatives. </p><p> It should be noted that this study isn't definitive; at the moment, we can't make a useful comparison between the overall intelligence of the cuttlefish and the other animals that can or cannot pass some variation of the marshmallow test.</p><p>Despite this, the results are quite exciting and will likely influence future research into animal intelligence. If the common cuttlefish can pass the marshmallow test, what else can?</p>