Tuesday, June 06, 2023

Commentary: As Henry Kissinger turns 100, his hideous legacy still haunts our role in the world

2023/06/06
Former Secretary of State Henry Kissinger responds to opening statements by members of the Senate POW/MIA committee before making his own opening statement on Sept. 22, 1992, in Washington. D.C.. 
- Robert Giroux/AFP/Getty Images North America/TNS

Henry Kissinger celebrated his 100th birthday on May 27, proving once again his remarkable staying power as one of America’s most well-known and influential foreign policy players in modern times. Presidents and other leaders of U.S. national security seek his counsel even today.

But his Machiavellian legacy, which continues to shape America’s foreign policy, is nothing to celebrate, and we continue to pay a price for it.

Kissinger, who served as both secretary of state and national security adviser under President Richard Nixon and his successor Gerald Ford, embodies the impunity of the foreign policy establishment.

Under Kissinger’s leadership, the United States undermined democracy, disdained human rights, and propped up a wide range of brutal and violent dictators. We know this because the paper trail documenting his offenses is long, thanks to his tendency to secretly record his own phone calls in and out of the White House (separate from Nixon’s surreptitious White House tapes).

His foreign policy approach was one in which might makes right, ends justify any means, and long-term consequences are dismissed. In his world, if major states accepted behavior, that behavior was acceptable regardless of the collateral damage along the way.

This worldview shaped Kissinger’s disastrous policies throughout the 1970s. In Chile, at Kissinger’s behest, the United States supported Augusto Pinochet, a Chilean general who launched a coup in 1973, overthrowing Chile’s democratically elected socialist president, Salvador Allende. Following Argentina’s coup in 1976, Kissinger blocked State Department efforts to criticize Argentina’s murderous and destabilizing military leaders. In Indonesia, Kissinger ensured the United States provided political and military support for the military dictator General Suharto in his invasion of East Timor and subsequent slaughter of civilians.

The most memorable of his brutal policies, however, were the bombing campaigns across Vietnam, Cambodia and Laos. The laws of war and even Congress’ oversight role acted as no constraint on his actions. A recent in-depth report into previously classified military documents and interviews with survivors revealed the secret Cambodia campaign to be far more brutal and deadly than previously realized, killing as many as 150,000 civilians. This completely destabilized Cambodia’s government and laid the groundwork for the rise of the Khmer Rouge and its subsequent genocide.

His unaccountable abuses weren’t limited to foreign countries either. In a Nixon-like fashion, Kissinger pressed the FBI director to illegally wiretap his own aides after news of the secret and unauthorized campaigns in Cambodia and Laos were reported in the press. Kissinger undercut any efforts at oversight and accountability, including by wresting foreign affairs leadership from the State Department to the White House, a trend his successors embraced and which continues to this day.

That lack of accountability costs lives, both American and foreign, and Kissinger disregarded the American lives lost just as much as any other. “Military men are dumb, stupid animals to be used” as pawns for foreign policy, Kissinger said, as reported by Bob Woodward and Carl Bernstein, who broke the Watergate case. No country should allow anyone with that attitude within miles of our decisions to go to war.

And yet Kissinger left office with his stature intact. He then cashed in on it, establishing a corporate firm staffed by the country’s national security elites to provide geopolitical consulting services. Today it’s common practice for foreign policy leaders to profit from their prestige after leaving government service, but then it was a novel business idea.

Through this firm, Kissinger and his associates helped undisclosed private clients profit from foreign policy decisions that he and his colleagues continued to informally (and sometimes formally) shape. Kissinger’s (inexplicably strong) reputation is likely what made this clear conflict of interest somehow acceptable and mainstream today.

To those who claim he was our most effective secretary of state in recent history, I would strongly disagree. His foreign policy program not only lacked a moral compass or compassion, but his national security choices helped destabilize and destroy parts of the world that have still not recovered, and many lives in the process. Some estimates put the death toll linked to his policies in the millions.

That history helped shape the perception that persists across the Global South today that America is an imperial power with intentions that cannot be trusted, a legacy that still harms our ability to generate support on everything from Ukraine’s defense to our leadership on climate change.

Kissinger never paid a price for the many American misdeeds that he led, and the pattern of impunity in the national security establishment has persisted since. Look no further than the slew of immoral, illegal and ineffective policies that made up America’s post-9/11 response and the continued prominence of its architects to understand how this system still works. For all of this, Kissinger paved the way.

Once Kissinger finally bids us adieu, I hope he takes his foreign policy impunity with him to the grave.

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(Elizabeth Shackelford is a senior fellow on U.S. foreign policy with the Chicago Council on Global Affairs. She was previously a U.S. diplomat and is the author of “The Dissent Channel: American Diplomacy in a Dishonest Age.”)

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© Chicago Tribune

NO FIGHTING IN THE WAR ROOM--- DR. STRANGELOVE IS KISSINGER
THE PEOPLES PARTY CANDIDATE
Professor Cornel West launches 2024 presidential run
2023/06/05
Professor Cornel West speaks during a press conference at The National Press Club September 15, 2016, in Washington, D.C. West announced his candidacy for the 2024 presidential race. - Zach Gibson/GETTY IMAGES NORTH AMERICA/TNS

Professor Cornel West announced his candidacy for the 2024 presidential race.

The 70-year-old educator, whose resume includes stints atHarvard, Yale and Princeton, threw his hat into the ring in a video posted to Twitter Monday.

“In these bleak times I have decided to run for truth and justice which takes the form of running for president of the United States as a candidate for the People’s Party,” the 70-year-old scholar said.

West’s nearly three-minute announcement was made to a jazzy soundtrack. He called the presidency “just one vehicle” to advance “truth and justice.” Among his stated concerns were the restrictions of women’s reproductive rights and threats to the democratic process. West’s declaration included a clip of him calling Republican frontrunner Donald Trump a “neo-fascist” and Democratic president Joe Biden a “milquetoast neo-liberal” during an interview with HBO “Real Time” host Bill Maher.

“Do we have what it takes?” West asks supporters in his video. “We shall see. But some of us are going to go down fighting. Go down swinging with style and a smile.”

West supported Vermont Sen. Bernie Sanders for the presidency in 2016 and 2020. He’s been critical of mainstream liberal candidates including Hillary Clinton and Barack Obama, whom he supported but later faulted for his handling of foreign policy and the economy.

The democratic socialist is a long shot to win the White House in 2024. Millard Fillmore, who held office from 1850 to 1853, is the last president to have been affiliated with neither the Democratic or Republican party.

The People’s Party confirmed West’s candidacy onits website with an ad reading “Justice is what love looks like in public.”

On Twitter, West wrote his objectives will be “fighting to end poverty, mass incarceration, ending wars and ecological collapse, guaranteeing housing, health care, education and living wages for all!”

Reactions to his announcement were encouraging and discouraging. Some Twitter users worried West’s candidacy would split the liberal vote and hand the election to the Republican nominee. Many conservatives saw that as a good thing and blasted him for being too liberal. Others commented on his unique sartorial choices, even comparing the California-raised academic’s look to that of a “Scottish Baptist minister” from the past.

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© New York Daily News
Editorial: Who dies, who pays: Different standards of justice for a limo crash and an opioid epidemic

2023/06/06
A judge's gavel rests on a book of law. - Dreamstime/Dreamstime/TNS

Compare and contrast, please.

Wednesday in Upstate New York, Nauman Hussain was sentenced to 5-15 years in prison for his role in the October 2018 deaths of 20 people after the brakes of an enormous stretch limousine failed. Hussain wasn’t driving the car. Rather, he rented out the vehicle — and a jury found evidence beyond a reasonable doubt that before doing so, he failed to ensure it was safe to drive. For that, he was convicted of 20 counts of second-degree manslaughter.

In Manhattan Tuesday, the Second Circuit Court of Appeals ruled that members of the Sackler family, the billionaires who own Purdue Pharma, will get full immunity from all civil lawsuits related to the mass dissemination of powerful pain drugs that have addicted millions and killed thousands. (Though Purdue Pharma has twice pleaded guilty to criminal charges, the Sacklers themselves have never been charged.) The ruling, the culmination of years of legal wrangling, shields the family atop Purdue Pharma and paves the path for the company’s bankruptcy restructuring in exchange for $6 billion in Sackler money that will go to help address the epidemic their company helped fuel.

The cash is no small sum, and will help people in desperate need across America, including here in New York, where opioid deaths have risen from about 1,000 in 2010 to more than 4,000 today. Nationally, opioid deaths now number more than 80,000 per year. Addicted people need counseling, effective medication-based treatment and a range of other services so they don’t wind up part of rising death counts.

It would be facile to call the Sacklers personally responsible for all the deaths and addictions, many of which have been caused by fentanyl. But when their company created and marketed OxyContin, it did more than any other corporate actor to fuel a public health crisis that’s torn America at the seams. Someone once said that one death is a tragedy (or in this case, 20 deaths), while a million deaths is a statistic. It’s not entirely untrue.

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© New York Daily News





CIA knew of Ukraine plan to blow up Nord Stream pipeline: report
Agence France-Presse
June 6, 2023

An aerial photo provided by the Danish Defense Command shows the Nord Stream 2 gas leak near Bornholm. Following the damage to the Nord Stream gas pipelines under the Baltic Sea, authorities in Germany and Denmark continue to search for the cause. Danish Defence Command/dpa

A European spy agency told the CIA it knew of a Ukraine special operations team plan to blow up the Nord Stream gas pipeline three months before explosions damaged the undersea system last year, the Washington Post reported Tuesday.

The newspaper cited US intelligence allegedly leaked earlier this year by a low-level US Air National Guard computer technician who had access to large amounts of highly classified materials.

The leaked documents indicated that an unnamed European intelligence body told the US spy agency in June 2022, four months after Russia invaded Ukraine, that Ukraine military divers reporting directly to the country's military commander-in-chief were planning the attack.

The Nord Stream 1 and 2 pipelines, built to carry natural gas from Russia to Germany, were rocked by underwater explosions on September 26, rendering them useless and cutting off a potential source of billions of dollars in earnings for Russia.

The apparent sabotage sparked a region-wide emergency as it cut off crucial supplies of energy for Europe just as the war had sent the price of oil skyrocketing.

Accusations were made against several countries including Russia, the United States and Ukraine, but all denied responsibility.

The Post, citing unnamed officials, said that after the Central Intelligence Agency learned of the alleged bombing plot, the United States told allies including Germany about it.

It said the original European intelligence on the plot made clear it was not a rogue operation, and that it was overseen by military chief General Valerii Zaluzhnyi without the knowledge of Ukraine President Volodymyr Zelensky.

The Post report is supported by information gathered by German investigators that a six-person team using false passports took a large sailboat from the German port of Rostock last September to undertake the operation.

The sailboat was rented by what appeared to be a front company.

According to German media reports last week, metadata from the emails used to rent a sailboat tie them to Ukraine, and the president of the front company also lives in Kyiv.

However, Danish media recently reported that a Russian navy vessel specialized in submarine operations was photographed near the location of the sabotage just before it happened.

© 2023 AFP




Watch: Republicans literally beg migrants not to leave Florida over DeSantis anti-immigration law

David Edwards
RAW STORY
June 5, 2023, 2:45

Twitter/screen grab

Florida Republicans on Monday met with migrants to urge them not to leave the state in the wake of a new anti-immigration law that is sparking boycotts of the state.

An NPR analysis determined that the law signed by Gov. Ron DeSantis (R) "limits social services for undocumented immigrants, allocates millions more tax dollars to expand DeSantis' migrant relocation program, invalidates driver's licenses issued to undocumented people by other states, and requires hospitals that get Medicaid dollars to ask for a patient's immigration status."

On Monday, state Reps. Alina Garcia (R) and Rick Roth (R) spoke at an event advising migrants of the impacts of SB1718.

Video of the event was obtained by Thomas Kennedy of the Democratic National Committee.

"This bill is 100% supposed to scare you," Roth told the group. "I'm a farmer, and the farmers are mad as hell. We are losing employees. They are already starting to move to Georgia and other states."

"It's urgent that you talk to all of your people and convince them that you have resources, state representatives, and other people that can explain the bill to you," he continued.

Garcia said she agreed with Roth.

"This is a bill basically to scare people from coming to the state of Florida," she insisted. "I think that it's done its purpose. This bill really doesn't have any teeth."

Tree-mendous ride: Wooden Citroen 2CV sells for 210,000 euros
Agence France-Presse
June 5, 2023, 6:42 AM ET

Michel Robillard spend five years handbuilding the wooden 2CV Citroen(
AFP)

A Citroen 2CV made of wood, thought to be the only one of its kind, has sold for 210,000 euros ($225,000) at auction in France, setting a new price record for the iconic vehicle.

The car, in full working order and registered in France, beat expectations when it went under the hammer in the central town of Tours on Sunday.

The body of the 2CV was hand-crafted out of wood with the same famous curves as the post-war French classic.

It was snapped up by Paris-based collector Jean-Paul Favand, who owns a museum of vintage fairground attractions.

"I'm having difficulty talking after this bet," Favand told AFP by telephone afterwards.

The auction house had issued a guide price of 150,000-200,000 euros, saying it was "much more than a car -- it's a work of art".

Auctioneer Aymeric Rouillac declared the sale a record as he brought down the hammer.

The previous high for a 2CV was set in 2016, when an extremely rare 1961 2CV Sahara in almost mint condition was sold for 172,800 euros by Paris-based auction house Artcurial.

Carpenter Michel Robillard crafted the wooden 2CV's wings out of walnut and its chassis from pear and apple tree wood.

He used a single block of cherry wood for the bonnet, shaped with just chisels and sandpaper.

- 'Crazy project' -

Robillard told AFP he spent five years and approximately 5,000 hours creating the car, beginning in 2011.

"It's like my daughter," he said as he polished the vehicle before the auction. "I had three boys and this was my little daughter."


The 2CV -- which stands for "deux chevaux", meaning "two horsepower" -- was launched in 1948 as Citroen's answer to the Volkswagen Beetle.

Robillard's model is equipped with an original engine from Citroen's later 3CV model, giving it the extra power needed to propel the naturally heavier wooden structure.

He said he had another "crazy project" in mind for the next few years.

He intends to make a wooden version of another French classic -- the Citroen DS, which in 2025 will celebrate 70 years of existence.

A woodworker since the age of 14, Robillard began making miniature wooden replicas of the world's famous automobiles in the 1990s.

He has won several prizes for his intricate work, including for a Harley Davidson motorcycle and its sidecar, which took more than 500 hours to complete.
Divers fish deadly 'ghost nets' from Santorini's depths

Agence France-Presse
June 5, 2023

A diver retrieves a 'ghost net' from the seabed off the Greek island of Santorini (Will Vassilopoulos)


Off the spectacular Greek tourist island of Santorini, divers drag deadly "ghost nets" from the depths of the Aegean Sea which have claimed the lives of thousands of fish.

"These abandoned nets are like fish traps," said diver Mika Panagiotopoulou, one of a group of volunteers who have been descending up to 45 meters to fish out discarded nets, tyres and plastic bags from the crystalline blue waters.

"For half a century the build-up of these abandoned nets has swept up thousands of fish and caused incalculable damage to the flora and fauna of our seas," said Santorini's mayor Antonis Sigalas, as the rubbish was gathered up at the little port of Vlychada before being recycled.


Some of the nets and plastic fished from the sea off Santorini
 ARIS MESSINIS

"For World Environment Day we want to highlight the dangers of abandoned fishing nets for our seas," said George Sarelakos, co-founder of Aegean Rebreath, the Greek NGO behind the clean-up.

"Discarded fishing nets account for about a tenth of the world's marine pollution and it's a real challenge because up to now it has been invisible -- because most people have no idea of what in hidden in the depths," he added.

Over the last five years, Aegean Rebreath's 300 volunteer divers have removed more than 28 tonnes of nets and hundreds of thousands of plastic bags -- one of the greatest scourges of the aquatic world -- from Greek waters.

Despite a tax being levied on plastic bags in Greece since 2018, shops still hand them out with abandon.

However, Sarelakos said there has been some progress. "There has been a change of mentality among fisherman and now they are handing (nets) over to be recycled."

"It is hard for a fisherman to survive so they put down more and more nets, which leads to fewer fish. It's a vicious circle," he said.

The Barron's news department was not involved in the creation of the content above. This story was produced by AFP. For more information go to AFP.com.
'We will not hire Jews': Prominent LA lawyers busted for blatant anti-Semitism

Brad Reed
June 5, 2023, 

Attorneys John Barber, left, and Jeff Ranen, right

Two attorneys who until recently worked at big-name law firm Lewis Brisbois Bisgaard & Smith have been exposed for making years' worth of anti-Semitic comments in emails to one another.

In emails between the two that were obtained by Forward, attorneys John Barber and Jeff Ranen are seen to routinely mock Jews and, in one exchange, even said, "we will not hire Jews" in response to a letter of recommendation they had received.

The pair also used the word "Jew" as a verb to denote stinginess with money.

"I might be able to Jew them down," wrote Ranen in one email where he discussed getting a hotel to lower its prices.

Other instances of blatant anti-Semitism include an email in which Barber mocked Ranen for bringing bagels into work by labeling him a "Jew c--t"; Ranen responding to a submitted invoice by saying, "This is the reason why people don’t like Jews"; and a complaint from Ranen about society frowning upon anti-Semitism by lamenting, "Since when can we not make Jew jokes?"

Lewis Brisbois tells Forward that they found the emails between the two lawyers after receiving a formal complaint leveled against them and that the firm is now conducting a formal review of their behavior.

"We are deeply troubled by their us of prejudiced language and racial and cultural slurs aimed at colleagues, clients, attorneys from other firms, and even Judges,” the firm said in a prepared statement.
People systematically overperceive the level of moral outrage expressed in political tweets, study finds

2023/06/03


People tend to misperceive others on Twitter as being more outraged than they actually are, according to new research published in Nature Human Behaviour. The findings suggest that the prevalence of divisive content on social media platforms might be a result of our tendency to misperceive others as angrier than they actually are online.

The new study was motivated by the importance of accurate social knowledge in functional democracies and the role of online social networks in shaping social knowledge of morality and politics. The researchers aimed to investigate how social media platforms, as currently designed, may contribute to the overperception of moral outrage, which could distort individuals’ understanding of collective moral attitudes.

“There is a growing body of research that examines how social media – whether through our psychology or algorithmic amplification, or both – increases the production of moral and political content,” said study author William Brady, an assistant professor of Management and Organizations at Northwestern University’s Kellogg School of Management.

“Some research including my own suggests that there are several features of social media that in fact increase its production, and this turns out to be very important because our knowledge of morality and politics is increasingly being constructed in online settings. But much less research has looked at the other side of this picture, which is the perception of moral and emotional content.”

“One striking finding in U.S. politics that highlights the importance of perception, for example, is that some portion of the growing levels of affective polarization can actually be explained by misperceptions of how polarized we really are (the idea of ‘false polarization’),” Brady explained. “We hypothesized that the overperception of certain types of political content like moral outrage in the context of social media may actually be an important building block of phenomenon such as false polarization.

“Thus, we designed field studies on Twitter to test whether our perceptions of moral outrage can be skewed online, and whether this has downstream consequences for group perceptions (e.g. norms of outrage and polarization).

For the three field studies, the researchers implemented a research pipeline consisting of multiple phases. In the author phase, the researchers used Twitter’s application programming interface (API) to collect public tweets about contentious topics in American politics. They then classified the collected tweets to determine whether they contained moral outrage expression.

Direct messages (DMs) were sent to users who expressed moral outrage or non-moral outrage, requesting them to report the emotions they experienced when they posted their tweet. The DMs were sent shortly after the users’ tweets were posted to capture their emotions at that specific moment.

In the observer phase, politically partisan participants were recruited to rate the level of outrage and happiness expressed by the authors of the collected tweets. Each participant judged a selection of 30 tweets, including both outrage and non-outrage tweets. The researchers used generalized linear models to analyze the data and test for overperception of outrage and happiness in the authors’ tweets.

The first field study focused on tweets about William Barr and President Donald Trump’s popularity. The second field study focused on tweets about Amy Coney Barrett’s Supreme Court confirmation and the 2020 U.S. presidential election. The third study aimed to replicate the findings from the previous studies and also examine the relationship between perceiving outrage and using social media for political purposes. The studies included 333 tweet authors and 650 observers in total.

The studies found consistent evidence of overperception of outrage, with observers perceiving higher levels of outrage than reported by the authors. Although people tended to overestimate the level of moral outrage conveyed by authors in their tweets, this overperception did not occur when perceiving happiness.

“Our key finding was that the social media users in our study who observed political Twitter posts systematically overperceived the level of moral outrage expressed by the message author,” Brady told PsyPost. “Our method actually allowed us to classify Twitter messages in real-time so we knew who was expressing moral outrage, and then send them a message prompting consenting users to self-report their actual level of outrage at the time of composing the tweet (within 15 minutes of their posting).

The researchers also conducted additional experiments to explore the consequences of overperception of outrage. They manipulated the overperception of individuals’ outrage in a simulated Twitter newsfeed and found that participants who viewed a newsfeed containing overperceived outrage expressions perceived higher levels of collective outrage in the social network. They also found that viewing overperceived outrage messages amplified participants’ beliefs about norms of outrage expression, affective polarization, and ideological extremity present in the network.

“We also find, in experimental settings where we create social media feeds that manipulate levels of overperception of outrage, that when we overpercieve individual’s outrage is directly amplifies users group level judgments,” Brady explained. “Compared to newsfeeds that induce less overperception of outrage because of the messages our ‘algorithm’ amplifies, the newsfeeds that induces more overperception of outrage cause users to think their social network is more collectively outraged, to think that expressing outrage in the context of politics is more normative, and to think their group dislikes the political outgroup more (affective polarization).”

Furthermore, the researchers found that individuals who engage in frequent political social media use were more likely to overperceive outrage. This suggests that people who spend more time using social media to learn about politics are more prone to overperceive outrage.

“One key question is what are the variables that predict when a user is most likely to overperceive moral outrage in social media messages?” Brady told PsyPost. “This is a complicated question that requires further research both in terms of what the author is motivated to do and what biases observers have, but one variable we find to explain significant variance consistently: the amount of time that observers spent on social media to learn about politics.”

“Users who spent more time on social media to learn about politics were much more likely to overperceive outrage. We believe that this is because these users are spending more time around politically active users who are much more likely to express high levels of outrage, and this experience forms their priors of outrage expression that creeps into their judgment of any given person’s emotion expression.”

The study has certain limitations, including the selection of specific Twitter users for the experiments and the focus on language cues without considering other factors that influence emotion perception on social media. The researchers called for further research to validate the findings across different platforms and media channels and to explore the effects of overperception on topics beyond politics and morality.

“Further research is required to disentangle effects of authors vs observers that together produce overperception effects,” Brady said. “For example, is our finding mostly because authors are motivated to express high outrage when they are not actually feeling it? Our initial data suggest that this explanation cannot fully explain our effect, yet our study was not designed to precisely pull apart author motivations vs observer perceptual bias.”

The study, “Overperception of moral outrage in online social networks inflates beliefs about intergroup hostility“, was authored by William J. Brady, Killian L. McLoughlin, Mark P. Torres, Kara F. Luo, Maria Gendron, and M. J. Crockett.

© PsyPost
Your body naturally produces opioids without causing addiction or overdose – studying how this process works could help reduce the side effects of opioid drugs

The Conversation
June 5, 2023, 

Opioid neurotransmitters (Shutterstock)

Opioid drugs such as morphine and fentanyl are like the two-faced Roman god Janus: The kindly face delivers pain relief to millions of sufferers, while the grim face drives an opioid abuse and overdose crisis that claimed nearly 70,000 lives in the U.S. in 2020 alone.

Scientists like me who study pain and opioids have been seeking a way to separate these two seemingly inseparable faces of opioids. Researchers are trying to design drugs that deliver effective pain relief without the risk of side effects, including addiction and overdose.

One possible path to achieving that goal lies in understanding the molecular pathways opioids use to carry out their effects in your body.

How do opioids work?

The opioid system in your body is a set of neurotransmitters your brain naturally produces that enable communication between neurons and activate protein receptors. These neurotransmitters include small proteinlike molecules like enkephalins and endorphins. These molecules regulate a tremendous number of functions in your body, including pain, pleasure, memory, the movements of your digestive system and more.

Opioid neurotransmitters activate receptors that are located in a lot of places in your body, including pain centers in your spinal cord and brain, reward and pleasure centers in your brain, and throughout the neurons in your gut. Normally, opioid neurotransmitters are released in only small quantities in these exact locations, so your body can use this system in a balanced way to regulate itself.

The opioids your body produces and opioid drugs bind to the same receptors.

The problem comes when you take an opioid drug like morphine or fentanyl, especially at high doses for a long time. These drugs travel through the bloodstream and can activate every opioid receptor in your body. You’ll get pain relief through the pain centers in your spinal cord and brain. But you’ll also get a euphoric high when those drugs hit your brain’s reward and pleasure centers, and that could lead to addiction with repeated use. When the drug hits your gut, you may develop constipation, along with other common opioid side effects.

Targeting opioid signal transduction


How can scientists design opioid drugs that won’t cause side effects?


One approach my research team and I take is to understand how cells respond when they receive the message from an opioid neurotransmitter. Neuroscientists call this process opioid receptor signal transduction. Just as neurotransmitters are a communication network within your brain, each neuron also has a communication network that connects receptors to proteins within the neuron. When these connections are made, they trigger specific effects like pain relief. So, after a natural opioid neurotransmitter or a synthetic opioid drug activates an opioid receptor, it activates proteins within the cell that carry out the effects of the neurotransmitter or the drug.

Cells communicate with one another in multiple ways.


Opioid signal transduction is complex, and scientists are just starting to figure out how it works. However, one thing is clear: Not every protein involved in this process does the same thing. Some are more important for pain relief, while some are more important for side effects like respiratory depression, or the decrease in breathing rate that makes overdoses fatal.

So what if we target the “good” signals like pain relief, and avoid the “bad” signals that lead to addiction and death? Researchers are tackling this idea in different ways. In fact, in 2020 the U.S. Food and Drug Administration approved the first opioid drug based on this idea, oliceridine, as a painkiller with fewer respiratory side effects.

However, relying on just one drug has downsides. That drug might not work well for all people or for all types of pain. It could also have other side effects that show up only later on. Plenty of options are needed to treat all patients in need.



This figure shows the structure of Hsp90. 
Laguna Design/Science Photo Library via Getty Images

My research team is targeting a protein called Heat shock protein 90, or Hsp90, which has many functions inside each cell. Hsp90 has been a hot target in the cancer field for years, with researchers developing Hsp90 inhibitors as a treatment for many cancer types.



We’ve found that Hsp90 is also really important in regulating opioid signal transduction. Blocking Hsp90 in the brain blocked opioid pain relief. However, blocking Hsp90 in the spinal cord increased opioid pain relief. Our recently published work uncovered more details on exactly how inhibiting Hsp90 leads to increased pain relief in the spinal cord.

Our work shows that manipulating opioid signaling through Hsp90 offers a path forward to improve opioid drugs. Taking an Hsp90 inhibitor that targets the spinal cord along with an opioid drug could improve the pain relief the opioid provides while decreasing its side effects. With improved pain relief, you can take less opioid and reduce your risk of addiction. We are currently developing a new generation of Hsp90 inhibitors that could help realize this goal.

There may be many paths to developing an improved opioid drug without the burdensome side effects of current drugs like morphine and fentanyl. Separating the kindly and grim faces of the opioid Janus could help provide pain relief we need without addiction and overdose.

John Michael Streicher, Associate Professor of Pharmacology, University of Arizona Health Sciences

This article is republished from The Conversation under a Creative Commons license. Read the original article.