A new study identifies cortisol level as an indicator of successful addiction recovery

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A new study conducted by researchers at the Marshall University Joan C. Edwards School of Medicine found that lower baseline cortisol levels may serve as a predictor of retention in substance use disorder treatment programs.

Prospective observational study examined salivary cortisol, stress exposure, adverse childhood experiences (ACE), and treatment retention in men enrolled in residential drug and alcohol recovery programs abstinence Their findings were published last month in Alcoholism: Clinical and Experimental Research, the scientific journal on alcohol abuse and treatment for the Society for Research on Alcoholism and the International Society for Biomedical Research on Alcoholism.

Cortisol levels reflect a physiological response to stress. In this case, the researchers found that participants who stayed in the treatment program for less than 90 days had significantly higher baseline cortisol levels than those who stayed in the program for more than 90 days. In addition, a Cox proportional hazards model indicated that elevated salivary cortisol, marital/relationship status, and ACE score were significantly correlated with the risks of early discontinuation.

“Our hope is that these findings will lead to cortisol as a biomarker that can help clinicians determine which individuals may need a more intensive therapeutic approach,” said Todd H. Davies, Ph.D., associate director of research and John’s development. C. Edwards School of Medicine and corresponding author of the study.

Taylor R. Maddox-Rooper, Kristiana Sklioutouskaya-Lopez, Trenton Sturgill, Caroline Fresch, Charles W. Clements II, MD; Rajan Lamichhane, Ph.D.; and Richard Egleton, Ph.D., were also co-authors of the paper. The research team also collaborated with Recovery Point of West Virginia, a long-term residential recovery program based on the peer-driven recovery model.

The research team, in collaboration with Recovery Point, is currently running a larger follow-up study that seeks to identify clinically significant levels of cortisol. This expanded study also includes a more representative population and examines the hormone oxytocin.

This work was supported by a rural grant from the Marshall University Robert C. Byrd Center for Rural Health through the West Virginia Higher Education Policy Commission. To view this article in its entirety, visit https://doi.org/10.1111/acer.14913.

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About the Marshall University Joan C. Edwards School of Medicine

The Marshall University Joan C. Edwards School of Medicine is a community-based medical school established in 1977. Located in Huntington, West Virginia, the School of Medicine trains physicians, scientists and other professionals to meet the unique needs of health care in rural and disadvantaged areas. communities Learn more at jcesom.marshall.edu.

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$2.7 million grant to find new psychedelic-related addiction treatments

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Evidence from human and animal tests suggests that the brain-altering effects of psychedelics could be repurposed to treat addiction.

Now, researchers at the University of California, Davis and the University of Colorado Anschutz Medical Campus plan to screen hundreds of compounds to discover new non-hallucinogenic treatments for substance use disorders. The research is funded by a $2.7 million grant from the National Institute on Drug Abuse, part of the National Institutes of Health.

Previous work has shown that psychedelic drugs can rewire parts of the brain involved in depression, substance abuse and post-traumatic stress disorder.

David Olson, an associate professor in the departments of Chemistry and Biochemistry and Molecular Medicine at UC Davis, is looking for similar effects among compounds without the hallucinogenic effects of drugs like LSD. He calls these compounds psychoplastogens, because of their ability to modify the brain.

“I am very excited that NIDA is recognizing the potential that psychoplastogens may have for patients with substance use disorders,” said Olson. “This grant will help us understand the basic mechanisms by which these compounds affect addiction, and we hope to develop more effective and better tolerated treatments.”

Olson’s work is part of a growing focus on psychedelic research at UC Davis and UC Davis Health. His laboratory has synthesized hundreds of molecules related to psychedelics in the search for new pharmacological therapies. One such molecule, tabernanthalog or TBG, produces rapid and sustained anti-addictive effects in rodent models of heroin and alcohol self-administration.

I am very excited that NIDA is recognizing the potential that psychoplastogens can have for patients with substance use disorders. This grant will help us understand the basic mechanisms by which these compounds affect addiction, and we hope to develop more effective and better tolerated treatments.—David Olson

The research will include mechanistic studies to understand how TBG affects addiction and the development of new compounds with psychoplastogenic effects, he said. The team will use high-throughput screening to test efficacy, safety and treatment potential. Promising compounds will undergo additional animal testing at CU Anschutz.

Delix Therapeutics, a startup founded by Olson, is also investigating non-hallucinogenic psychoplastogens to treat depression, anxiety and related disorders, but is not involved in the project.

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Black opioid overdose deaths are rising faster than whites, according to the study: shots

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New research shows racial inequalities in the rate of opioid overdose, with a mortality rate among blacks growing faster than in other groups. Researchers are calling for expanded access to drug treatment and education on how to prevent overdoses with the antidote drug, naloxone. Spencer Platt / Getty Images hides the title

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New research shows racial inequalities in the rate of opioid overdose, with a mortality rate among blacks growing faster than in other groups. Researchers are calling for expanded access to drug treatment and education on how to prevent overdoses with the antidote drug, naloxone.

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A study published on Thursday reveals a growing racial disparity in opioid overdose mortality rates. Deaths among African Americans are growing faster than among whites across the country. The study’s authors call for an “anti-racist public health approach” to addressing the crisis of black communities.

The study, conducted in collaboration with the National Drug Abuse Institute of the National Institutes of Health, analyzed overdose data and death certificates from four states: Kentucky, Ohio, Massachusetts, and New York. He found that the rate of opioid deaths among blacks increased by 38% from 2018 to 2019, while the rates of other racial and ethnic groups did not increase.

The study used data collected before the coronavirus pandemic began; Preliminary data show that the global drug overdose increased in 2020.

According to another study published last year in the journal Addiction, African Americans had lower overdose death rates in the first waves of the opioid crisis than whites, and black rates remained the same from 1999 to 2012. No however, in 2013 white rates began to decline while black rates began to rise.

The new NIDA study confirms the trend.

“We’re seeing change in demographics,” says Dr. Nora Volkow, director of NIDA.

Dr. Edwin Chapman, an internal medicine and addiction medicine specialist who serves the African-American community in Washington, DC, says the study is useful because it shows the serious impact of opioid addiction on black Americans.

“It points to the fact that we need to do something different, a more intensive intervention in the African American community,” he says.

What is behind the disparity?

The change raises a number of pressing questions about what is driving the growing gap in addiction treatment and prevention and how it can be closed.

The opioid crisis began with the strong prescription of opioid analgesics, mainly in the white communities of the 1990s. Volkow says the crisis initially affected white Americans more because they are much more likely to be prescribed opioids than black Americans.

“This, in part, reflects on the stigma against blacks that even if they have pain, doctors won’t be as receptive to prescribing them as opioids,” Volkow says.

Structural differences in health care are also to blame for racial disparities in the treatment of addiction, Volkow says. These include access to effective evidence-based treatments.

“If you’re a black American and you have an opioid use disorder, you’re much less likely to be prescribed medications for opioid use disorder,” says Volkow, who notes that medications like buprenorphine have been very effective in protecting patients from overdose. “That’s discrimination,” Volkow says.

The increase in fentanyl, a potent synthetic opioid often found in heroin, has also affected overdose rates among blacks, she says. The main engine of overdose deaths has shifted “from prescription opioids then to heroin and now to fentanyl.”

Overdose deaths in black communities are largely caused by fentanyl.

Other factors are also at play in these mortality rates, Volkow says. It recognizes that the federal government and health care systems, such as hospitals, community clinics, and family physicians, need to put in place mechanisms to collect better data. Currently, many doctors do not detect opioid use disorder, Volkow says.

These data, she said, could “provide us with a better perspective of the nature of the problem and help or guide physicians in interventions.”

In the study, the authors noted that there are also disparities in access to the antidote drug, naloxone, and in training on how to use it to save a life.

Need for a true “public health response”

“It’s downtown communities that have been hardest hit by addiction, where the problem was put aside for four decades,” says Dr. Andrew Kolodny, medical director of opioid policy research at the Heller School for Social Policy and Management at Brandeis University. “It wasn’t until we saw a drug crisis affecting white communities that we began to see the resources of Congress.”

He says it’s important that addiction resources go to the communities that need them most.

“One of the problems here is that we have terrible surveillance of the opioid crisis,” Kolodny says. He notes that nationwide, tracking data on drug addiction has been a mosaic, with some federal agencies focusing exclusively on overdose deaths, others on treatment, and others on research. “Surveillance fell through the cracks,” he says.

For COVID-19, the U.S. tracks cases, deaths, and hospitalizations at the county level, and generally on a daily basis, Kolodny says. “But for the opioid crisis, we don’t have a good estimate of how many Americans are opioid addicts or the communities that have the most impacts or incidence rates. We don’t know how many people become opioid addicts.” says Kolodny. “We’re still in the dark era.”

“Opioid addiction is a disease that can be prevented and treated and you need a public health response that is similar even to an outbreak of a communicable disease like COVID.”

He says that in addition to overdose data by race, the U.S. should track demographics such as gender and age and whether those affected live in rural or urban areas. “We need data on which we can act. And that’s not here,” says Kolodny, referring to the new NIDA study, which calls it “far too little, too late.”

Improve access to treatment

Addiction specialist Edwin Chapman has worked his life to fight the drug epidemic in the black community. He says drug addiction in these communities has always been treated differently. “Whether it’s racism or cultural incompetence, we need to correct that,” he says.

NPR outlined Dr. Chapman’s work in 2018 when the opioid crisis began to escalate in urban black communities across the country.

Chapman knows all too well the problems facing the African American population when it comes to drug addiction and treatment, “starting with the fact that our epidemic was largely ignored, followed by insurance barriers and access to treatment, ”he says.

“Our population has always been treated as a moral and criminal problem, which means that the patients we treat in the African American community have this added burden,” he says.

From his experience at his clinic, he says he has found it more complex to treat black patients, as additional resources are needed, such as helping to navigate the health care system, advising and helping to find housing or a job.

Chapman says black communities also have a “provider access problem.” He notes that relatively few addiction treatment specialists focus their practice on treating black patients. “In addition, there is stigma within the provider community about the treatment of these patients because they are always perceived to have a criminal inclination or are not desirable as patients,” he says.

On the contrary, Chapman adds, “there is the shame and stigma that patients carry, so patients do not seek treatment.”

Chapman says the number of patients he is currently treating has decreased during the pandemic, “some died of COVID, others from overdose,” he says by early 2020, his clinic was seeing 270 patients, now the number of patients is 230.

The COVID-19 crisis increased overdose deaths in Washington, DC, according to the chief medical examiner’s office. In 2019, which was previously the highest peak, there were 281 overdose deaths, but in 2020 there were around 408, and there have been a total of 157 overdoses this year.

Finding solutions to these problems will not be easy, Chapman says. “What we need is what I call a Marshall Plan that is basically a cut and funded by taxpayers in this subset of high-risk, high-cost patients,” he says.

Ignoring the African American population will ultimately be more costly for the country, he says. It gives him renewed optimism to see a new focus on these disparities and he will continue to treat people and talk about how to solve the problem, he says.

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As Overdoses Rise in Rural America, More Doctors Prescribe Addiction Drugs

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MARSHALLTOWN, Iowa – Andrea Storjohann is glad to see she’s becoming a rarity in rural America.

The nurse practitioner prescribes medication to dozens of patients trying to recover from addiction to heroin or opioid pain relievers.

The general practice where he works, located in a repurposed supermarket building, has no sign designating it as a place where people seek treatment for drug addiction, which is how Storjohann wants it.

“You could come here for OB-GYN care. You could come here for a sore throat. You could come here for any number of reasons,” and no one in the waiting room would know the difference, he said.

Privacy is an important part of treatment. And so is the medication Storjohann prescribes: buprenorphine, which curbs cravings and prevents withdrawal symptoms for people who have stopped abusing opioids. The central Iowa clinic, owned by the nonprofit agency Primary Health Care, has offered buprenorphine since 2016. “We were like a unicorn in this part of the state,” Storjohann said, but that’s changing.

Unlike methadone, the traditional withdrawal drug for heroin or other opioids, buprenorphine can be prescribed in primary care clinics and dispensed at neighborhood pharmacies. Federal and state authorities have encouraged more frontline health care professionals to prescribe Suboxone and other medications containing buprenorphine to patients trying to overcome opioid addiction. Federal regulators have made it easier for doctors, nurse practitioners and physician assistants to become certified to provide the service.

The opioid crisis has deepened over the past decade with the illicit distribution of fentanyl, a powerful and extremely addictive opioid. Its prevalence has complicated the use of drugs to treat opioid addiction. Patients who have misused fentanyl can experience severe withdrawal symptoms when they start taking buprenorphine, so healthcare professionals must be careful when initiating treatment.

In Iowa, officials designated $3.8 million of the state’s initial share of opioid lawsuit settlement money for a University of Iowa program that helps health care providers understand how use the medicines.

Federal agencies are spending millions to expand access to drugs to treat addiction, even in rural areas. The Health Services and Resources Administration, which aims to improve health care for disadvantaged people, offers many of these grants.

Carole Johnson, the agency’s top administrator, said she hopes more training on opioid addiction treatment will encourage health care providers to learn about the latest ways to treat other types of addiction, such as methamphetamine dependence and alcoholism, which many rural states suffer from. “We’re making people aware of substance use disorder in a big way,” he told KHN.

In 2016, only 40 percent of rural counties nationwide had at least one health care provider certified to prescribe buprenorphine, according to a University of Washington study. The study found that this number rose to 63% in 2020.

The study credited the increase to changes in federal regulations that allow nurse practitioners, physician assistants and other mid-level health care providers to prescribe buprenorphine. In the past, only doctors could do this, and many rural counties had no doctors.

Buprenorphine is an opioid that pharmacies most often sell as a tablet or film that dissolves under the tongue. It doesn’t cause the same kind of high as other opioid drugs, but it can prevent the debilitating withdrawal effects experienced with these drugs. Without this help, many people relapse into risky drug use.

The idea of ​​opioid “maintenance treatment” has been around for over 50 years, mostly in the form of methadone. This drug is also an opioid that can reduce the chances of relapsing into heroin or painkiller abuse. But the use of methadone for addiction treatment is strictly regulated, due to concerns that it can be abused.

Only specialist clinics offer methadone maintenance treatment, and most are located in cities. Many patients starting methadone treatment must travel daily to clinics, where staff watch them swallow their medication.

Federal regulators approved Suboxone in 2002, paving the way for addiction treatment in cities without methadone clinics.

Storjohann said buprenorphine offers a practical alternative for Marshalltown, a city of 27,000 surrounded by rural areas.

The practice nurse spends about half of her time working with patients who are taking drugs to prevent relapse into drug abuse. The other half of her practice is mental health care. A recent appointment with patient Bonnie Purk included a bit of both.

Purk, 43, sat in a small exam room with the nurse practitioner, who asked her about her life. Purk described the family struggles and other stressors he faces while trying to abstain from abusing painkillers.

Storjohann asked if Purk felt desperate. “Or are you just frustrated?”

Purk thought for a moment. “I had a week where I was just crying,” she said, wiping her eyes with a tissue. But she said she has not been seriously tempted to relapse.

Storjohann praised her persistence. “You’re riding a roller coaster,” he said. “I think you should give yourself some grace.”

Bonnie Purk, left, meets with nurse Andrea Storjohann at the primary health care clinic in Marshalltown, Iowa.Courtesy Tony Leys/KHN

Purk knows that Suboxone is not a miracle cure. He has been on the medication for years and has relapsed twice by abusing pain pills. But he has avoided a relapse since the spring and said the medication is helping.

In an interview after his monthly appointment with Storjohann, Purk said the drug dampens cravings and blocks withdrawal symptoms. She recalled terrible night sweats, insomnia, diarrhea and jitters she experienced when trying to stop abusing pills without taking Suboxone.

“Don’t focus on anything but the next solution. ‘Where am I going to get it? How am I going to get it?'” he said. “You just feel like a train wreck, like you’re going to die without him.”

Purk said mental health counseling and frequent drug testing have also helped her stay sober.

Patients may remain on buprenorphine for months or even years. Some skeptics claim that it is trading one drug addiction for another and should not be seen as a substitute for abstinence. But advocates say that skepticism is waning as more families see how treatment can help people regain control of their lives.

Dr. Alison Lynch, a specialist in addiction medicine at the University of Iowa, warned about the risks of fentanyl and buprenorphine at a recent conference for health professionals in training.

Lynch explained that fentanyl stays in the body longer than other opioids, such as heroin. When someone with fentanyl in their system takes buprenorphine, it can cause nausea, muscle pain and other particularly harsh symptoms, he said. “It’s not dangerous. It’s just miserable,” he said, and it can discourage patients from continuing their medication.

Lynch noted that drug dealers are incorporating fentanyl into other drugs, so people don’t always realize they’ve taken it. “I just assume that if people are using any drug that they’ve bought off the street, it’s probably got fentanyl in it,” he said. That’s why, he said, he’s been using smaller starting doses of buprenorphine and increasing the dose more gradually than before.

Nationally, the number of healthcare professionals certified to prescribe buprenorphine has more than doubled in the past four years to more than 134,000, according to the federal Substance Abuse and Mental Health Services Administration. Efforts to expand access to treatment come as drug overdose deaths have more than doubled in the US since 2015, led by overdoses of fentanyl and other opioids.

Storjohann would like to see more general practitioners seek training and certification to prescribe buprenorphine at least occasionally. For example, she said, emergency room doctors might prescribe a few days of the medication for a patient who comes to them in crisis and then refer the patient to a specialist like her. Or a patient’s primary physician might take over buprenorphine treatment after an addiction treatment specialist stabilizes a patient.

Dr. Neeraj Gandotra, chief medical officer of the federal Substance Abuse and Mental Health Services Administration, said he sees potential in expanding these arrangements, known as a “hub and spoke” model of care. Family practice providers who agree to participate would have the assurance that they could always refer a patient to an addiction treatment specialist if problems arose, he said.

Gandotra said he hopes more primary care providers will seek certification to prescribe buprenorphine.

Johnson, the administrator of the Health Resources and Services Administration, said states can also increase access to medication-assisted treatment by expanding their Medicaid programs to provide health insurance coverage to more low-income adults. The federal government pays most of the cost of the Medicaid expansion, but 11 states have declined to do so. That leaves more people without insurance, which means clinics are less likely to be reimbursed for treating them, he said.

Health care providers are no longer required to take special classes to obtain a federal certification — called a “waiver” — to treat up to 30 patients with buprenorphine. But Lynch said even veteran health care professionals could benefit from training on how to properly manage the treatment. “It’s a little daunting to start prescribing a drug that we didn’t get a lot of training on in med school or AP school or nursing school,” he said.

Federal officials have created a public database of health care providers certified to offer buprenorphine treatment for addiction, but the registry only lists providers who agree to include their names. Many don’t. In Iowa, only one-third of certified providers have agreed to be listed in the public registry, according to the Iowa Department of Health and Human Services.

Lynch speculated that some health care professionals want to use the drug to help current patients who need addiction treatment, but aren’t looking to make it a major part of their practice.

Storjohann said some health professionals believe that treating addiction would lead to frustration, because patients can relapse repeatedly. She doesn’t see it that way. “This is a field where people really want to improve,” he said. “It’s really rewarding.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism on health issues. Along with policy analysis and surveys, KHN is one of the three main operational programs of KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization that provides information on health issues to the nation.

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Heroin antibodies fare better than previous therapies that targeted its metabolites

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A monoclonal antibody targeting heroin (11D12) is effective in blocking the euphoric and lethal effects of this widely abused opioid, reported a study in mice by scientists at the Scripps Research Institute in La Jolla, CA. The findings offer a promising new strategy for treating heroin addiction and overdose.

Kim Janda, PhD, professor of chemistry at Scripps Research is the lead author of the study

“Our results suggest that a monoclonal antibody-based therapy will be more effective than a vaccine and should target heroin itself rather than its psychoactive metabolites,” said Kim Janda, PhD, Ely R. Callaway, Jr. ., professor of chemistry. , director of Scripps Research’s Worm Institute for Research & Medicine and lead author of the study.

“The work of Dr. Janda and colleagues is very interesting and timely given the importance of developing new strategies to address the opioid epidemic and the dramatic increase in fatal overdoses attributable to opioids or mixtures of opioids and stimulants like cocaine and methamphetamine,” he said. Marco Pravetoni, PhD, a professor in the department of psychiatry and behavioral medicine at the University of Washington School of Medicine, whose team is developing vaccines and monoclonal antibodies (mAbs) against heroin, oxycodone, fentanyl, and analogs of fentanyl. “The results show that target selection is critical to advancing effective therapy.” Pravetoni did not participate in the current study. “

“This work provides compelling data that challenge our current understanding of the pharmacodynamics of heroin. It continues to show the utility of high-affinity antibodies, not only as biological tools, but as viable therapeutics to combat the opioid crisis in course,” said Nicholas Jacob, PhD, senior research scientist at Cessation Therapeutics. Jacob did not participate in the current study.

Political and scientific leaders around the world have been trying to quell the exponentially growing opioid epidemic for decades. However, current medications and behavioral interventions have failed to reduce this public health crisis. Instead, cases of opioid abuse and overdose have increased to unprecedented levels since the start of the COVID-19 pandemic.

Small molecule medications approved by the FDA for opioid use disorders (METADONE, buprenorphine, naltrexone, and naloxone) are limited by adverse side effects, short half-lives, limited availability, high cost, lack of adherence to medication regimen, potential for abuse and relapse to addiction once the medication is discontinued. Immunopharmacotherapy offers a viable alternative. This treatment approach uses antibodies to block the action of illicit substances, keeping the compounds in the peripheral circulation.

Decades of studies have attributed the psychoactive and lethal effects of heroin to its metabolites: 6-monoacetylmorphine (6-AM) and morphine. Therefore, previous immunopharmacotherapeutics have used active and passive vaccines to target heroin metabolites rather than heroin itself. “Passive vaccines” often involve the injection of monoclonal antibodies (mAbs) against the target or its metabolites, while active vaccines use immunostimulatory proteins that mimic the target or its metabolites to activate the patient’s own immune system. However, these therapies have had limited success, underscoring the need to reassess the selection of therapeutic targets.

That the anti-heroin vaccines that Janda’s team and others were developing failed to succeed in clinical trials prompted Janda to step back and assess perceptions and misperceptions in the drug addiction field. drugs

“Most researchers saw heroin as simply a ‘prodrug’ that crosses the blood-brain barrier very quickly and that its ‘prodrug’ ability was simply to transport the major mu opioid receptor drugs, 6-acetylmorphine and , finally, morphine, in the brain.” Janda said. “Based on that reasoning, targeting heroin was an afterthought.”

When previous heroin vaccines failed to counteract the effects of a dose of heroin as expected, poor adjuvants in the vaccine cocktail were pointed to as the culprit.

Janda said, “Actually, the general formulation of the vaccines was correct, but the targeting of 6-acetylmorphine and morphine with the antigen was wrong.”

Building on previous efforts to develop an effective immunopharmacotherapeutic to treat heroin abuse, the current study analyzed four unique mAbs that target heroin, 6-AM, or morphine, or both heroin and 6-AM. The development of these mAbs using a deutero-heroin hapten with broad-spectrum affinity for heroin and its metabolites was reported in a previous study by the same group. The researchers profiled the binding affinities of these mAbs using surface plasmon resonance (SPR), which allowed them to select four different antibody clones with superior abilities to bind heroin or one of the metabolites.

“By using these antibodies, we were able to dissect which of these three drugs was important for (antibody) vaccine development,” Janda said.

The researchers then performed pharmacokinetic assays, overdose assays, and hot-plate and tail-flick assays for pain perception, to identify targets that would effectively neutralize the behavioral, toxic, and lethal effects of heroin. These in vitro and in vivo tests showed that mAb 11D12 targeting heroin was, unexpectedly, the optimal therapeutic to suppress the effects of heroin, compared to the other mAbs that targeted its two main metabolites.

This study reveals that the monoclonal antibody 11D12 abolishes the psychoactive and lethal effects of heroin in mice. [Adapted from Lee et al., ACS Central Science]The authors showed that 11D12 blocks the analgesic effects of heroin and prevents heroin from slowing breathing and heart rate, the direct causes underlying heroin’s lethality. mAb 11D12 achieved this with a high degree of potency required for human clinical trials.

Pravetoni said, “Lee et al., provide evidence that mAb can be used to reverse opioid overdose and to reduce lethality after exposure. These results are consistent with our work on anti-opioid mAbs (Baehr et al., JPET 2020; Baehr et al., JPET 2022; Hicks et al., HVI 2022) and support the idea that the vaccine and mAb warrant clinical investigation.”

In addition, the researchers found that 11D12 remained active in circulation for weeks, unlike previous therapies that were cleared from circulation within hours. This is a key advantage against poor patient adherence to treatment regimens, which is common among patients with addiction.

The effectiveness of 11D12 in counteracting the effects of heroin surprised Janda and his team because, unlike the other three antibodies tested, it targets heroin with the highest binding affinity and does not to its metabolites. Because esterase enzymes in the blood rapidly convert heroin to morphine and 6-acetylmorphine through sequential deacetylation, scientists have so far identified the metabolites as better targets.

“The focus on metabolites fundamentally misled the field: our report will reset research in a direction where successful clinical trials can now be achieved,” said Janda. The current findings shed light on the reasons underlying the failure of previous attempts to develop therapeutics targeting only heroin metabolites.

“From work in the field, we know that targeting heroin, 6 AM, and morphine may be equally important. However, the impact of individual vaccines or mAb formulations remains to be assessed eventually in human subjects through clinical trials,” said Pravetoni. “For example, targeting heroin and 6-AM would be important to reduce the acute toxicity and reward of heroin, but it is unclear whether targeting morphine would also be necessary to counteract the chronic effects of heroin metabolites. heroin in patients with OUD”.

“We are always trying to optimize the ability of opioids and other drugs of abuse to generate antibodies, as high levels of antibodies are needed to counteract the toxic and lethal effects of drugs of abuse, especially fentanyl-related opioids.” , said Thomas Kosten. , MD, the Wagoner Professor of Psychiatry, Pharmacology, Neuroscience and Immunology at Baylor College of Medicine. “While this work focuses on heroin and this class of opioids, similar work by this research group has greatly contributed to our ability to develop vaccines and monoclonals for other classes of drugs of abuse, including fentanyl-related opioids, which are the most lethal and resistant. to our existing FDA-approved treatments of methadone, buprenorphine, and depot naltrexone. This article provides an excellent contribution to our field of immunotherapy for addictions”. Kosten did not participate in the current study.

In future studies, the team will test a human version of the mouse monoclonal antibody 11D12 and parallel mAbs to neutralize the synthetic opioids fentanyl, carfentanil, and other related compounds.

Janda said, “Our heroin antibody could, in theory, have translational value for clinical trials if humanized.”

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