Breakthrough in Making Much Less Addictive Opioids

Important research this is, for it shows that the powerful pain relief opioids provide doesn’t have to be such a dangerous double-edged sword.

In the US, more than one-third of the population experiences some form of acute or chronic pain; in older adults this number rises to 40 percent.

The most common condition linked to chronic pain is chronic depression, which is a major cause of suicide.

To relieve severe pain, people go to their physician for powerful prescription painkillers, opioid drugs such as morphine, oxycodone and hydrocodone.

Almost all the currently marketed opioid drugs exert their analgesic effects through a protein called the “mu opioid receptor” (MOR).

MORs are embedded in the surface membrane of brain cells, or neurons, and block pain signals when activated by a drug.

However, many of the current opioids stimulate portions of the brain that lead to additional sensations of “rewarding” pleasure, or disrupt certain physiological activities. The former may lead to addiction, or the latter, death.

Which part of the brain is activated plays a vital role in controlling pain. For example, MORs are also present in the brain stem, a region that controls breathing.

Activating these mu receptors not only dulls pain but also slows breathing. Large doses stop breathing, causing death.

Activating MORs in other parts of the brain, including the ventral tegmental area and the nucleus accumbens, block pain and trigger pleasure or reward, which makes them addictive. But so far there is no efficient way to turn these receptors “on” and “off” in specific areas.

But there is another approach because not all opioids are created equal. Some, such as morphine, bind to the receptor and activate two signaling pathways: one mediating pain cessation and the other producing side effects like respiratory depression.

Other drugs favor one pathway more than the other, like only blocking pain – this is the one we want.

“Biased opioids” to kill pain

But MOR isn’t the only opioid receptor. There are two other closely related proteins called kappa and delta, or KOR and DOR respectively, that also alter pain perception but in slightly different ways.

Yet, currently there are only a few opioid medications that target KOR, and none that target DOR. One reason is that the function of these receptors in the brain neurons remains unclear.

Recently KOR has been getting attention as extensive studies from different academic labs show that it blocks pain without triggering euphoria, which means it isn’t addictive.

Another benefit is that it doesn’t slow respiration, which means that it isn’t lethal. But although it isn’t as dangerous as MOR, activating KOR does promote dysphoria, or unease, and sleepiness.

This work suggests it is possible to design a drug that only targets the pain pathway, without side effects. These kind of drugs are called “biased” opioids.

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The exciting news is that researchers in the Roth lab have discovered several promising compounds based on the KOR structure that selectively binds and activates KOR, without cavorting with the more than 330 other related protein receptors.

Now our challenge is to transform these molecules into safer drugs.

The Amazing Treatment for Drug Addiction (Medication-Assisted Treatment) Too Rarely Used

Drug addictions need to be treated as health problems instead of as crimes, and in any case, it’d be valuable to direct more resources towards helping people with addictions. That could be rather than using the resources on a senseless or harmful pursuit such as building even more nuclear weapons systems that threaten to cause disasters.

The death toll from the opioids epidemic continues to soar – nearly 64,000 people died in 2016 alone.

Scientists are working to find creative tools to fight it, and President Donald Trump has called the overdose crisis a public health emergency. But he has not yet outlined any targeted solutions aside from calling for drug dealers to be given the death penalty.

A growing cadre of health professionals say we already have a science-backed treatment that works. It’s called medication-assisted treatment, or MAT, and it involves administering FDA-approved medications that help curb cravings and reduce the excruciating symptoms of withdrawal.

“Medications are an effective treatment for opioid addiction,” Kelly J. Clark, president of the American Society of Addiction Medicine, told Business Insider.

The problem is that very few people can get those medications.

Only about half of private-sector treatment programs for opioid use disorder currently offer access to MAT, and of those that offer it, only one third of patients actually receive the medication, according to a study published in the Journal of Addiction Medicine.

There are many reasons for this lack of access to medication. Some stem from a misconception about how the treatments – which can include buprenorphine, methadone, or naltrexone – work.

The stigma surrounding drug use and addiction plays a role, too. Still other issues include federal and state laws that restrict the availability of the medications.

“It’s more of an implementation problem than a basic science problem,” Clark said, “because we know what works.”

Medications do not ‘substitute one drug for another’

In someone with opioid use disorder, using the drugs is often not a pleasurable experience, but rather a practice that has become a necessary fact of life. Being without the drugs leads to painful symptoms that can include severe nausea, shaking, diarrhoea, and depression.

The need to use is simultaneously a physical and emotional compulsion – the lines between those kinds of pain are blurred.

One of the main misconceptions about medication-assisted treatment is that medications simply replace the drugs that hooked users – leading to more highs and fuelling a pattern of repeated use.

But that view is outdated and ill-informed, experts say. Instead, the drugs work by staunching cravings and reducing or preventing withdrawal and relapse.

Buprenorphine and methadone help suppress cravings, while naltrexone blocks the euphoric and sedative effects of opioids so users don’t experience a high.

“People ask me all the time, ‘well, aren’t they just substituting one drug for another?’ The answer is no. These are evidence-based treatments and they work,” Patrice A. Harris, the former president of the American Medical Association and a board certified psychiatrist, told Business Insider.

Several large studies suggest that as access to MAT rises, drug overdose deaths fall.

A study of heroin overdose deaths in Baltimore between 1995 and 2009 published in the American Journal of Public Health, for example, found a link between the increasing availability of methadone and buprenorphine and a roughly 50 percent decrease in the number of fatal overdoses.

“These treatments are life saving and they work,” Sarah Wakeman, the medical director of the substance use disorder initiative at Massachusetts General Hospital and an assistant professor at Harvard, told Business Insider.

From jail to court to rehab, medication-assisted treatment is hard to find

Despite the evidence demonstrating MAT’s effectiveness, it is surprisingly difficult to obtain.

One of the hardest-to-access forms of medication for recovery is methadone. In the US, the medication can only be accessed in specialised clinics; because of the way the treatment works, people on MAT must come to a facility to be injected daily.

But those facilities typically have negative reputations because of policies that restrict them to locations considered seedy or run-down.

And patients who come for treatment often have to push past active drug users – a big trigger for someone with substance use disorder – on their way to and from the clinic.

“You can access heroin pretty easily, yet we make it really hard to get a treatment that’s life-saving and allows you to live healthily,” Wakeman said.

On Friday, the US Food and Drug Adminstration issued a new set of guidelines aimed at underlining the important role MAT should play treating opioid use disorder.

“Unfortunately, far too few people who suffer from opioid use disorder are offered an adequate chance for treatment that uses safe and effective medications,”commissioner Scott Gottlieb said.

Other countries take a very different approach to medication-assisted treatment that makes the treatments easier to obtain. In Canada, for example, methadone is distributed in pharmacies.

Rehabilitation facilities and courts in the US often don’t offer medication-assisted treatment either. Instead, most operate on an abstinence-based model, in which patients must detox and then are offered counseling.

They’re encouraged to attend 12-step meetings like Narcotics Anonymous, which remains opposed to MAT despite the growing body of evidence behind it.

Vaccines to Treat Opioid Abuse and Prevent Overdoses in Development

It should be beneficial once it’s developed. For today, it’s not widely known, but needles aren’t the only way to deliver Narcan (what’s used to respond to opioid overdoses) — there’s actually a nasal spray that exists now too.

Heroin and prescription opioid abuse and fatal overdoses are a public health emergency in the United States. Vaccines offer a potential new strategy to treat opioid abuse and prevent fatal opioid overdoses.
A team of scientists from the University of Minnesota Medical School and Minneapolis Medical Research Foundation at Hennepin Healthcare is developing vaccines against heroin and prescription opioids, such as oxycodone and fentanyl. These vaccines function by using the immune system to produce molecules (antibodies) that target, bind, and prevent opioids from reaching the brain (the site of drug action).
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Pre-clinical studies show that both heroin and oxycodone vaccines are effective in blocking heroin and oxycodone distribution to the brain when subjects are challenged with clinically-relevant opioid doses. Vaccination prevents addiction-relevant behaviors, including opioid self-administration that models human abuse patterns. These vaccines appear to be safe and may help in preventing opioid-induced respiratory depression, a hallmark of an opioid fatal overdose.

Importantly, vaccination does not prevent use of currently approved addiction treatment medications such as methadone, naltrexone, buprenorphine, and naloxone.

The research team is also working on biologics against other opioid targets, such as fentanyl, and developing more effective next-generation vaccine formulations.

“Opioid vaccines show promising pre-clinical efficacy, but the road from the laboratory to the clinic is still long,” said Principal Investigator Marco Pravetoni, Ph.D., Minneapolis Medical Research Foundation senior investigator and associate professor of medicine at the University of Minnesota Medical School.

Study: Legal Medical Cannabis Lowers Opioid Use

The pharmaceutical industry is generally among the biggest opponents of legalized marijuana for a reason. Interestingly enough, legal marijuana now polls at 55 to 60 percent majority support in the United States. If the country was a democracy instead of mainly a plutocracy, issues with majority support such as that one would be acted on much differently than is done today.

States that have approved medical cannabis laws saw a dramatic reduction in opioid use, according to a new study by researchers at the University of Georgia.

In a paper published today in the Journal of the American Medical Association, Internal Medicine, researchers examined the number of all opioid prescriptions filled between 2010 and 2015 under Medicare Part D, the prescription drug benefit plan available to Medicare enrollees.

In states with medical cannabis dispensaries, the researchers observed a 14.4 percent reduction in use of prescription opioids and nearly a 7 percent reduction in opiate prescriptions filled in states with home-cultivation-only medical cannabis laws.

“Some of the states we analyzed had medical cannabis laws throughout the five-year study period, some never had medical cannabis, and some enacted medical cannabis laws during those five years,” said W. David Bradford, study co-author and Busbee Chair in Public Policy in the UGA School of Public and International Affairs. “So, what we were able to do is ask what happens to physician behavior in terms of their opiate prescribing if and when medical cannabis becomes available.”

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The researches concede that if medical cannabis is to become an effective treatment, there is still much work to be done. Scientists are only just beginning to understand the effects of the compounds contained in cannabis, and an effective “dose” of cannabis would need to be defined clearly so that each patient receives a consistent dose.

“Regardless, our findings suggest quite clearly that medical cannabis could be one useful tool in the policy arsenal that can be used to diminish the harm of prescription opioids, and that’s worthy of serious consideration,” David Bradford said.

It should also be noted that marijuana can come with its own harms, particularly if smoked. Competent studies have consistently found for the last few years that marijuana smoke is about as harmful and perhaps even more harmful than tobacco smoke. In light of this, non-combustible alternatives such as the marijuana edibles should be recommended much more for those needing pain relief.

Giving Big Pharma Public Hearings, Inspired by the Big Tobacco Hearings

The U.S. Congress – in its decay over the last four decades after being further corrupted by big business interests – rarely has held public hearings in the last several years. It should hold many more public hearings, however, and it should do so on the most important issues facing society today.

Senator Sanders though provides yet another example of why he’s justifiably the most popular U.S. politician, as he continues to focus on the real problems (healthcare, wages, the opioid crisis, etc.) instead of on the regressively McCarthyist and largely nonsensical Russia drama that drains too much news focus. The proposal he has about making the pharmaceutical corporations pay to reimburse the communities they ruined is also clear-sighted and sensible.

Sen. Bernie Sanders (I-Vt.) called Monday for the Senate to hold pharmaceutical companies accountable for any role they’ve played in fueling the opioid epidemic that has spread despair in his state and across the U.S.

In a letter to Sen. Lamar Alexander (R-Tenn.), the chairman of the committee on health, education, labor and pensions, Sanders encouraged him to hold hearings on the matter just as the Senate had once compelled Big Tobacco executives to testify about the deadly hazards of smoking.

“That committee had the courage to demand that the leading executives of the tobacco industry tell the American people what they knew and when they knew that tobacco was addictive … and had killed millions of people,” Sanders wrote. “Though all denied under oath believing tobacco was addictive, we now know they were lying. But the hearing eventually led to real change,” with the Food and Drug Administration regulating tobacco and the rate of smoking in the U.S. at a record low.

Sanders pointed out that the hearing helped states reach massive settlements with the tobacco industry. Several local jurisdictions have already filed lawsuits against painkiller manufacturers. Some have already received settlements. The opioid crisis, Sanders, wrote, “did not happen in a vacuum.” He praised investigative journalists for exposing Big Pharma’s lies about opioid painkillers not being addictive and how small-town pharmacies were flooded with opioids.

“Yet, while some of these companies have made billions each year in profits, not one of them has been held fully accountable for its role in this crisis,” Sanders wrote. “Individual states have received small settlements from companies after taking legal action, but not nearly enough to pay for the costs associated with the opioid epidemic. The states cannot do it alone.”

Sanders sees an economic cost as well as a human cost to the epidemic. And he wants the industry to be liable for the economic costs. Sanders noted in his letter that he plans to introduce legislation that would in part require companies to reimburse communities for the devastating economic consequences that their painkillers have caused.

Opioid Crisis Killing More People Than Breast Cancer

The opioid crisis is largely a result of greedy, profit-driven pharmaceutical corporations such as Purdue Pharma mass producing highly addictive opioids and then flooding economically weak (and thus despairing) communities with them. The problem must be attacked at the root — significantly alter the function of the pharmaceutical industry and fix much of the economic weakness that it thrives on. If neither of those solutions are applied, the problem will keep becoming worse, with all the innocent lives lost that go with it.

More than 63,600 lives were lost to drug overdose in 2016, the most lethal year yet of the drug overdose epidemic, according to a new report from the National Center for Health Statistics, part of the US Centers for Disease Control and Prevention.

Most of those deaths involved opioids, a family of painkillers including illicit heroin and fentanyl as well as legally prescribed medications such as oxycodone and hydrocodone. In 2016 alone, 42,249 US drug fatalities — 66% of the total — involved opioids, the report says. That’s over a thousand more than the 41,070 Americans who die from breast cancer every year.

Much of the increase was driven by the rise in illicit synthetic opioids like fentanyl and tramadol. The rate of deadly overdoses from synthetic opioids other than methadone has skyrocketed an average of 88% each year since 2013; it more than doubled in 2016 to 19,413, from 9,580 in 2015.

Heroin also continues to be a problem, the report says. Since 2014, the rate of heroin overdose deaths has jumped an average of 19% each year.

The opioid crisis has raised significant awareness of prescription painkillers. Between 1999 and 2009, the rate of overdoses from such drugs rose 13% annually, but the increase has since slowed to 3% per year.

In 2009, prescription narcotics were involved in 26% of all fatal drug overdoses, while heroin was involved in 9% and synthetics were involved in just 8%. By comparison, in 2016, prescription drugs were involved in 23% of all deadly overdoses. But heroin is now implicated in about a quarter of all drug fatalities, and synthetic opioids play a role in nearly a third.

These increases have contributed to a shortening of the US life expectancy for a second year in a row.

The states with the highest rates of overdose in 2016 were West Virginia, Ohio and New Hampshire, the report said. The rate of overdose in West Virginia was over 2.5 times the national average of 19.8 overdose deaths for every 100,000 people.

While the outlook nationwide is fairly bleak, it’s particularly bad in some states. Twenty-two states and the District of Columbia had overdose rates significantly higher than the national average.

While overdose rates increased in all age groups, rises were most significant in those between the ages of 25 and 54.

Provisional data for 2017 from the CDC show no signs of the epidemic abating, with an estimate of more than 66,000 overdose deaths for the year. “Based on what we’re seeing, it doesn’t look like it’s getting any better,” said Bob Anderson, chief of the mortality statistics branch at the National Center for Health Statistics.

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According to the 2016 Surgeon General’s Report on Alcohol, Drugs, and Health, 30% of Americans do not seek any sort of addiction treatment because they do not have insurance and cannot afford treatment.

The opioid epidemic is of course worst in West Virginia because of how economically ravaged the state has been by decades of neoliberalism, the increase in deaths being worst among those 25 to 54 notably follows the ages that are regularly considered to be those of prime age workers, and the lack of a national single-payer healthcare system shows itself as a flaw yet again.

Feature on the Opioid Crisis

The Empire Files program did a feature on the opioid crisis that focuses on the behavior of criminogenic pharmaceutical corporations. It is particularly notable for noting that big pharmaceutical corporations have targeted and still do target economically ravaged places suffering from significant despair.

Economic despair is at the core of the opioid epidemic. A lot of those people addicted to opioids would have done much better if they had meaningful work to occupy their time and give them a sense of purpose. Unfortunately though, in many sectors the economic system is so dysfunctional that it fails to provide even basic elements of meaningful community work for people.

There’s a disturbing graph that shows utilization of capacity, and it reveals that there are many, many billions of dollars being lost due to capacity such as buildings not being used. It isn’t because there’s a lack of needed work — on the contrary, looking around plenty of places will have a reasonable person saying that there’s a lot that needs to be done. So there’s a lot of work that needs to be done and a lot of capacity (23 percent in the graph) pointlessly sitting idle, and there’s an economic system that isn’t putting them together for productive benefits.

Screenshot-2017-12-5 Capacity Utilization Total Industry

The U.S. government could enact a massive infrastructure project that would create millions of jobs and/or it could provide low interest loans to support worker cooperatives in economically downtrodden communities. There are other solutions too, and they also need significant will to be applied. The point to make here though is that the situation doesn’t have to be that bleak for the communities, and there’s actually a clear enough method to reconstruct what has been mismanaged.