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Groundbreaking new research suggests removing drug-associated memories could prevent relapse
The 2020 study successfully removed memories associated with morphine from the brains of mice with very promising results.
- Once the mice in the study had become dependent on the morphine, "switching off" (or silencing) that PVT pathway completely abolished their preference for the morphine.
- Stanford associate professor Xiaoke Chen's team was able to precisely control the activity of various pathways at different points of the animals' drug-use experience.
- Extinction training attempts to reduce the strength of those cue-drug memories which, if successful, could decrease the number of factors that induce cravings and aid in relapse. This new "erasure" method could eventually be considered an alternative to that - erasing the cues altogether instead of training your mind to forget them.
"The most difficult part of treating addiction is to prevent relapse, especially for opioids," explains Xiaoke Chen, an associate professor at Stanford University's School of Humanities and Sciences and lead for a new study."To prevent relapse, we really need to deal with the withdrawal."
According to Chen, both the reward of the high and the alleviation of agonizing withdrawal symptoms can serve as memory cues that trigger the drug cravings that lead to relapse. Because of this, he and his team have taken a look at drug addiction as a memory problem.
A study of morphine and mice show promising results for the battle against addiction
This study of mice and morphine shows very promising results for the battle of addiction in the human population.
Photo by Rudmer Zwerver on Shutterstock
The mice in this groundbreaking 2020 study were introduced to a two-sided chamber that was differentiated by tactile and visual cues. One side of the chamber had a drug-free saline solution and the other a small dose of morphine.
Over the course of four days, the mice went through a kind of "training" - associating the two sides of the chamber with either saline or morphine. When their memories were tested on the fifth day, the mice had already developed a compulsive preference for the chamber containing morphine.
Prior to this study, Chen's team had traced the animals' learning and memory abilities to a node in the brain known as the paraventricular thalamus (PVT for short). This area of the brain connects to multiple brain regions that are also involved in drug addiction.
By using a light-based technique (called optogenetics), Chen's team was able to precisely control the activity of various pathways at different points of the animals' drug-use experience.
Once the mice had become dependent on the morphine, "switching off" (or silencing) the PVT pathway that had previously been found to be important for withdrawal completely abolished their preference for the morphine. A day later, the mice were tested once more without the PVT silencing technique. There was still no preference for the chamber with morphine in it. This is a very surprising and potentially groundbreaking study in the world of addictions.
Even when the morphine was reintroduced to the mice, they still did not prefer the morphine-paired chamber — even as long as two weeks later.
"Our data suggest that after silencing this PVT pathway, environmental cues will not work to reactivate this memory," explains Chen. "We haven't tested a later time point than two weeks but we think it's very likely the memory is just gone."
What could this mean for the struggle of addictions in humans?
What could this mean for addiction in the human population?
Photo by Olivier Le Moal on Shutterstock
For a little more of an in-depth understanding of the future implications of this study, we should take a look at what the paraventricular thalamus is in the human brain and how it relates to drug addiction.
A brief explanation of the paraventricular thalamus in humans
According to Science Direct, "brain circuits that regulate reward and motivation are considered to be the neural substrate of drug addiction. An increasing body of literature indicates that the paraventricular thalamic nucleus (PVT) could serve as a key node in the neurocircuits that control goal-directed behaviors."
The PVT receives input from the brain stem and hypothalamus and is also connected to the limbic system. Neurons in the PVT are impacted by drug exposure as well as cue and context that become associated with drug-taking. You can see then how silencing the PVT could potentially impact the need for continued drug use.
"Erasure" and silencing of the PVT pathway
The scientists attached to this study have dubbed the silencing of this PVT pathway to be called "erasure" because it appears that the drug-associated memory is effectively erased from the brain (of mice).
Two crucial components for memory erasure are location and timeframe. Manipulation of this pathway must be done while the animal is inside the memory-associated environment (which, in this case, is the drug-associated chamber where the morphine was) and that the animal must be experiencing withdrawal at the time of erasure for this to be effective.
"The memory first needs to be reactivated to provide an opportunity for precise memory manipulation," said Chen. "You don't want to erase the entire memory; you only want to erase the part that's associated with the drug."
Once reactivated, there is a window of opportunity for updating the drug-associated memory, suggesting that scientists could strengthen and reinforce the memory by providing the drug or weaken the memory by changing the brain's association with the drug.
Extinction training versus erasure
There is already the practice of "extinction training", where the brain effectively "learns to forget" about addiction as a process of treating addiction. When environmental stimuli or cues become associated with drug use, they become powerful motivators of continued drug use. Extinction training attempts to reduce the strength of those cue-drug memories which, if successful, could decrease the number of factors that induce cravings and aid in relapse.
This new "erasure" method could eventually be considered an alternative to that - erasing the cues altogether (by silencing the PVT pathway) instead of training your mind to forget them.
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Health officials in China reported that a man was infected with bubonic plague, the infectious disease that caused the Black Death.
- The case was reported in the city of Bayannur, which has issued a level-three plague prevention warning.
- Modern antibiotics can effectively treat bubonic plague, which spreads mainly by fleas.
- Chinese health officials are also monitoring a newly discovered type of swine flu that has the potential to develop into a pandemic virus.
Bacteria under microscope
needpix.com<p>Today, bubonic plague can be treated effectively with antibiotics.</p><p style="margin-left: 20px;">"Unlike in the 14th century, we now have an understanding of how this disease is transmitted," Dr. Shanthi Kappagoda, an infectious disease physician at Stanford Health Care, told <a href="https://www.healthline.com/health-news/seriously-dont-worry-about-the-plague#Heres-how-the-plague-spreads" target="_blank">Healthline</a>. "We know how to prevent it — avoid handling sick or dead animals in areas where there is transmission. We are also able to treat patients who are infected with effective antibiotics, and can give antibiotics to people who may have been exposed to the bacteria [and] prevent them [from] getting sick."</p>
This plague patient is displaying a swollen, ruptured inguinal lymph node, or buboe.
Centers for Disease Control and Prevention<p>Still, hundreds of people develop bubonic plague every year. In the U.S., a handful of cases occur annually, particularly in New Mexico, Arizona and Colorado, <a href="https://www.cdc.gov/plague/faq/index.html" target="_blank">where habitats allow the bacteria to spread more easily among wild rodent populations</a>. But these cases are very rare, mainly because you need to be in close contact with rodents in order to get infected. And though plague can spread from human to human, this <a href="https://www.healthline.com/health-news/seriously-dont-worry-about-the-plague#Heres-how-the-plague-spreads" target="_blank">only occurs with pneumonic plague</a>, and transmission is also rare.</p>
A new swine flu in China<p>Last week, researchers in China also reported another public health concern: a new virus that has "all the essential hallmarks" of a pandemic virus.<br></p><p>In a paper published in the <a href="https://www.pnas.org/content/early/2020/06/23/1921186117" target="_blank">Proceedings of the National Academy of Sciences</a>, researchers say the virus was discovered in pigs in China, and it descended from the H1N1 virus, commonly called "swine flu." That virus was able to transmit from human to human, and it killed an estimated 151,700 to 575,400 people worldwide from 2009 to 2010, according to the Centers for Disease Control and Prevention.</p>There's no evidence showing that the new virus can spread from person to person. But the researchers did find that 10 percent of swine workers had been infected by the virus, called G4 reassortant EA H1N1. This level of infectivity raises concerns, because it "greatly enhances the opportunity for virus adaptation in humans and raises concerns for the possible generation of pandemic viruses," the researchers wrote.
So far, 30 student teams have entered the Indy Autonomous Challenge, scheduled for October 2021.
- The Indy Autonomous Challenge will task student teams with developing self-driving software for race cars.
- The competition requires cars to complete 20 laps within 25 minutes, meaning cars would need to average about 110 mph.
- The organizers say they hope to advance the field of driverless cars and "inspire the next generation of STEM talent."
Indy Autonomous Challenge<p>Completing the race in 25 minutes means the cars will need to average about 110 miles per hour. So, while the race may end up being a bit slower than a typical Indy 500 competition, in which winners average speeds of over 160 mph, it's still set to be the fastest autonomous race featuring full-size cars.</p><p style="margin-left: 20px;">"There is no human redundancy there," Matt Peak, managing director for Energy Systems Network, a nonprofit that develops technology for the automation and energy sectors, told the <a href="https://www.post-gazette.com/business/tech-news/2020/06/01/Indy-Autonomous-Challenge-Indy-500-Indianapolis-Motor-Speedway-Ansys-Aptiv-self-driving-cars/stories/202005280137" target="_blank">Pittsburgh Post-Gazette</a>. "Either your car makes this happen or smash into the wall you go."</p>
Illustration of the Indy Autonomous Challenge
Indy Autonomous Challenge<p>The Indy Autonomous Challenge <a href="https://www.indyautonomouschallenge.com/rules" target="_blank">describes</a> itself as a "past-the-post" competition, which "refers to a binary, objective, measurable performance rather than a subjective evaluation, judgement, or recognition."</p><p>This competition design was inspired by the 2004 DARPA Grand Challenge, which tasked teams with developing driverless cars and sending them along a 150-mile route in Southern California for a chance to win $1 million. But that prize went unclaimed, because within a few hours after starting, all the vehicles had suffered some kind of critical failure.</p>
Indianapolis Motor Speedway
Indy Autonomous Challenge<p>One factor that could prevent a similar outcome in the upcoming race is the ability to test-run cars on a virtual racetrack. The simulation software company Ansys Inc. has already developed a model of the Indianapolis Motor Speedway on which teams will test their algorithms as part of a series of qualifying rounds.</p><p style="margin-left: 20px;">"We can create, with physics, multiple real-life scenarios that are reflective of the real world," Ansys President Ajei Gopal told <a href="https://www.wsj.com/articles/autonomous-vehicles-to-race-at-indianapolis-motor-speedway-11595237401?mod=e2tw" target="_blank">The Wall Street Journal</a>. "We can use that to train the AI, so it starts to come up to speed."</p><p>Still, the race could reveal that self-driving cars aren't quite ready to race at speeds of over 110 mph. After all, regular self-driving cars already face enough logistical and technical roadblocks, including <a href="https://www.bbc.com/news/technology-53349313#:~:text=Tesla%20will%20be%20able%20to,no%20driver%20input%2C%20he%20said." target="_blank">crumbling infrastructure, communication issues</a> and the <a href="https://bigthink.com/paul-ratner/would-you-ride-in-a-car-thats-programmed-to-kill-you" target="_self">fateful moral decisions driverless cars will have to make in split seconds</a>.</p>But the Indy Autonomous Challenge <a href="https://static1.squarespace.com/static/5da73021d0636f4ec706fa0a/t/5dc0680c41954d4ef41ec2b2/1572890638793/Indy+Autonomous+Challenge+Ruleset+-+v5NOV2019+%282%29.pdf" target="_blank">says</a> its main goal is to advance the industry, by challenging "students around the world to imagine, invent, and prove a new generation of automated vehicle (AV) software and inspire the next generation of STEM talent."
A new Harvard study finds that the language you use affects patient outcome.
- A study at Harvard's McLean Hospital claims that using the language of chemical imbalances worsens patient outcomes.
- Though psychiatry has largely abandoned DSM categories, professor Joseph E Davis writes that the field continues to strive for a "brain-based diagnostic system."
- Chemical explanations of mental health appear to benefit pharmaceutical companies far more than patients.
Challenging the Chemical Imbalance Theory of Mental Disorders: Robert Whitaker, Journalist<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="41699c8c2cb2aee9271a36646e0bee7d"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/-8BDC7i8Yyw?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>This is a far cry from Howard Rusk's 1947 NY Times editorial calling for mental healt</p><p>h disorders to be treated similarly to physical disease (such as diabetes and cancer). This mindset—not attributable to Rusk alone; he was merely relaying the psychiatric currency of the time—has dominated the field for decades: mental anguish is a genetic and/or chemical-deficiency disorder that must be treated pharmacologically.</p><p>Even as psychiatry untethered from DSM categories, the field still used chemistry to validate its existence. Psychotherapy, arguably the most efficient means for managing much of our anxiety and depression, is time- and labor-intensive. Counseling requires an empathetic and wizened ear to guide the patient to do the work. Ingesting a pill to do that work for you is more seductive, and easier. As Davis writes, even though the industry abandoned the DSM, it continues to strive for a "brain-based diagnostic system." </p><p>That language has infiltrated public consciousness. The team at McLean surveyed 279 patients seeking acute treatment for depression. As they note, the causes of psychological distress have constantly shifted over the millennia: humoral imbalance in the ancient world; spiritual possession in medieval times; early childhood experiences around the time of Freud; maladaptive thought patterns dominant in the latter half of last century. While the team found that psychosocial explanations remain popular, biogenetic explanations (such as the chemical imbalance theory) are becoming more prominent. </p><p>Interestingly, the 80 people Davis interviewed for his book predominantly relied on biogenetic explanations. Instead of doctors diagnosing patients, as you might expect, they increasingly serve to confirm what patients come in suspecting. Patients arrive at medical offices confident in their self-diagnoses. They believe a pill is the best course of treatment, largely because they saw an advertisement or listened to a friend. Doctors too often oblige without further curiosity as to the reasons for their distress. </p>
Image: Illustration Forest / Shutterstock<p>While medicalizing mental health softens the stigma of depression—if a disorder is inheritable, it was never really your fault—it also disempowers the patient. The team at McLean writes,</p><p style="margin-left: 20px;">"More recent studies indicate that participants who are told that their depression is caused by a chemical imbalance or genetic abnormality expect to have depression for a longer period, report more depressive symptoms, and feel they have less control over their negative emotions."</p><p>Davis points out the language used by direct-to-consumer advertising prevalent in America. Doctors, media, and advertising agencies converge around common messages, such as everyday blues is a "real medical condition," everyone is susceptible to clinical depression, and drugs correct underlying somatic conditions that you never consciously control. He continues,</p><p style="margin-left: 20px;">"Your inner life and evaluative stance are of marginal, if any, relevance; counseling or psychotherapy aimed at self-insight would serve little purpose." </p><p>The McLean team discovered a similar phenomenon: patients expect little from psychotherapy and a lot from pills. When depression is treated as the result of an internal and immutable essence instead of environmental conditions, behavioral changes are not expected to make much difference. Chemistry rules the popular imagination.</p>