8 Search Results for "after opioid"
Posted on by Dr. Francis Collins
Drug overdoses continue to take far too many lives, driven primarily by the opioid crisis (though other drugs, such as methamphetamine and cocaine, are also major concerns). While NIH’s Helping to End Addiction Long-term (HEAL) Initiative is taking steps to address this terrible crisis, new findings serve as another wake-up call that young people battling opioid addiction need a lot more assistance to get back on the right track.
In a study of more than 3,600 individuals, aged 13-22, who survived an opioid overdose, an NIH-funded team found that only about one-third received any kind of follow-up addiction treatment . Even more troubling, less than 2 percent of these young people received the gold standard approach of medication treatment.
The findings reported in JAMA Pediatrics come from Rachel Alinsky, an adolescent medicine and addiction medicine fellow at Johns Hopkins Children’s Center, Baltimore. She saw first-hand the devastating toll that opioids are taking on our youth.
Alinsky also knew that nationally more than 4,000 fatal opioid overdoses occurred in people between the ages of 15 and 24 in 2016 . Likewise, rates of nonfatal opioid overdoses for teens and young adults also have been escalating, leading to more than 7,000 hospitalizations and about 28,000 emergency department visits in 2015 alone .
In the latest study, Alinsky wanted to find out whether young people who overdose receive timely treatment to help prevent another life-threatening emergency. According to our best evidence-based guidelines, timely treatment for youth with an opioid addiction should include medication, ideally along with behavioral interventions.
That’s because opioid addiction rewires the brain—will power alone is simply not sufficient to achieve and sustain recovery. After one overdose, the risk of dying from another one rises dramatically. So, it is critical to get those who survived an overdose into effective treatment right away.
Alinsky and her team dove into the best-available dataset, consisting of data on more than 4 million mostly low-income adolescents and young adults who’d been enrolled in Medicaid for at least six months in 16 states. The sample included 3,606 individuals who’d been seen by a doctor and diagnosed with opioid poisoning. A little over half of them were female; most were non-Hispanic whites.
Heroin accounted for about a quarter of those overdoses. The rest involved other opioids, most often prescription painkillers. However, the researchers note that some overdoses attributed to heroin might have been caused by the powerful synthetic opioid fentanyl. The use of fentanyl, often mixed with heroin, was on the rise in the study’s final years, but it was rarely included in drug tests at the time.
Less than 20 percent of young people in the sample received a diagnosis of opioid use disorder, or a problematic pattern of opioid use resulting in impairment or distress. What’s more, in the month following an overdose, few received the current standard for addiction treatment, which should include behavioral therapy and treatment with one of three drugs: buprenorphine, naltrexone, or methadone.
Drilling a little deeper into the study’s findings:
• 68.9 percent did not receive addiction treatment of any kind.
• 29.3 percent received behavioral health services alone.
• Only 1.9 percent received one of three approved medications for opioid use disorder.
It’s been estimated previously that teens and young adults are one-tenth as likely as adults 25 years and older to get the recommended treatment for opioid use disorder . How can that be? The researchers suggest that one factor might be inexperience among pediatricians in diagnosing and treating opioid addiction. They also note that, even when the problem is recognized, doctors sometimes struggle to take the next step and connect young people with addiction treatment facilities that are equipped to provide the needed treatment to adolescents.
As this new study shows, interventions designed to link teens and young adults with the needed recovery treatment and care are desperately needed. As we continue to move forward in tackling this terrible crisis through the NIH’s HEAL Initiative and other efforts, finding ways to overcome such systemic barriers and best engage our youth in treatment, including medication, will be essential.
 Receipt of addiction treatment after opioid overdose among Medicaid-enrolled adolescents and young adults. Alinsky RH, Zima BT, Rodean J, Matson PA, Larochelle MR, Adger H Jr, Bagley SM, Hadland SE. JAMA Pediatr. 2020 Jan 6:e195183.
 Overdose death rates. National Institute on Drug Abuse, NIH.
 2018 annual surveillance drug-related risks and outcomes—United States: surveillance special report. Centers for Disease Control and Prevention.
 Medication-assisted treatment for adolescents in specialty treatment for opioid use disorder. Feder KA, Krawczyk N, Saloner B. J Adolesc Health. 2017 Jun;60(6):747-750.
Opioid Overdose Crisis (National Institute on Drug Abuse/NIH)
Opioid Overdose (Centers for Disease Control and Prevention, Atlanta)
Decisions in Recovery: Treatment for Opioid Use Disorder (Substance Abuse and Mental Health Services Administration, Rockville, MD)
Rachel Alinsky (Johns Hopkins University Children’s Center, Baltimore)
NIH Support: Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Drug Abuse
Posted on by Dr. Francis Collins
A few weeks ago, I was pleased to take part in the announcement of NIH’s HEALing Communities Study in four states hard hit by the opioid epidemic. This study will test a comprehensive, evidence-based approach—which includes the wide distribution of naloxone to reverse overdoses—with the aim of reducing opioid-related deaths in selected communities by 40 percent over three years.
That’s a very ambitious goal. So, I was encouraged to read about new findings that indicate such reductions may be within our reach if society implements a number of key changes. Among those is the need to arm friends, family members, and others with the ability to save lives from opioid overdoses. Between 2013 and 2016, nine states instituted laws that give pharmacists direct authority to dispense naloxone to anyone without a prescription. However, the impact of such changes has remained rather unclear. Now, an NIH-funded analysis has found that within a couple of years of these new laws taking effect, fatal opioid overdoses in these states fell significantly .
The misuse and overuse of opioids, which include heroin, fentanyl, and prescription painkillers, poses an unprecedented public health crisis. Every day, more than 130 people in the United States die from opioid overdoses . Not only are far too many families losing their loved ones, this crisis is costing our nation tens of billions of dollars a year in lost productivity and added expenses for healthcare, addiction treatment, and criminal justice.
Opioid overdoses lead to respiratory arrest. If not reversed in a few minutes, this will be fatal. In an effort to address this crisis, the federal government and many states have pursued various strategies to increase access to naloxone, which is a medication that can quickly restore breathing in a person overdosing on opioids. Naloxone, which can be delivered via nasal spray or injection, works by binding opioid receptors to reverse or block the effect of opioids. The challenge is to get naloxone to those who need it before it’s too late.
In some states, a physician still must prescribe naloxone. In others, naloxone access laws (NALs) have given pharmacists the authority to supply naloxone without a doctor’s orders. But not all NALs are the same.
Some NALs, including those in Alaska, California, Connecticut, Idaho, New Mexico, North Dakota, Oklahoma, Oregon, and South Carolina, give pharmacists direct authority to dispense naloxone to anyone who requests it. But NALs in certain other states only give pharmacists indirect authority to dispense naloxone to people enrolled in certain treatment programs, or who meet other specific criteria.
In the new analysis, published in JAMA Internal Medicine, a team that included Rahi Abouk, William Paterson University, Wayne, NJ, and Rosalie Liccardo Pacula and David Powell, RAND Corp., Arlington, VA, asked: Do state laws to improve naloxone access lead to reductions in fatal overdoses involving opioids? The answer appears to be “yes,” but success seems to hinge on the details of those laws.
The evidence shows that states allowing pharmacists direct authority to dispense naloxone to anyone have seen large increases in the dispensing of the medication. In contrast, states granting pharmacists’ only indirect authority to dispense naloxone have experienced little change.
Most importantly, the research team found that states that adopted direct authority NALs experienced far greater reductions in opioid-related deaths than states with indirect authority NALs or no NALs. Specifically, the analysis showed that in the year after direct authority NALs were enacted, fatal opioid overdoses in those states fell an average of 27 percent, with even steeper declines in ensuing years. Longer-term data are needed, and, as in all observational studies of this sort, one must be careful not to equate correlation with causation. But these findings are certainly encouraging.
There were some other intriguing trends. For instance, the researchers found that states that allow pharmacists to dispense naloxone without a prescription also saw an increase in the number of patients treated at emergency departments for nonfatal overdoses. This finding highlights the importance of combining strategies to improve naloxone access with other proven interventions and access to medications aimed to treat opioid addiction. Integration of all possible interventions is exactly the goal of the HEALing Communities Study mentioned above.
Successfully tackling the opioid epidemic will require a multi-pronged approach, including concerted efforts and research advances in overdose reversal, addiction treatment, and non-addictive pain management . As I’ve noted before, we cannot solve the opioid addiction and overdose crisis without finding innovative new ways to treat pain. The NIH is partnering with pharmaceutical industry leaders to accelerate this process, but it will take time. The good news based on this new study is that, with thoughtful strategies and policies in place, many of the tools needed to help address this epidemic and save lives may already be at our disposal.
 Association Between State Laws Facilitating Pharmacy Distribution of Naloxone and Risk of Fatal Overdose. Abouk R, Pacula RL, Powell D. JAMA Intern Med. 2019 May 6
 Opioid Overdose Crisis. National Institute on Drug Abuse/NIH. Updated January 2019.
Naloxone for Opioid Overdose (National Institute on Drug Abuse/NIH)
NIH Support: National Institute on Drug Abuse
Posted on by Dr. Francis Collins
Gene editing has shown great promise as a non-heritable way to treat a wide range of conditions, including many genetic diseases and more recently, even COVID-19. But could a version of the CRISPR gene-editing tool also help deliver long-lasting pain relief without the risk of addiction associated with prescription opioid drugs?
In work recently published in the journal Science Translational Medicine, researchers demonstrated in mice that a modified version of the CRISPR system can be used to “turn off” a gene in critical neurons to block the transmission of pain signals . While much more study is needed and the approach is still far from being tested in people, the findings suggest that this new CRISPR-based strategy could form the basis for a whole new way to manage chronic pain.
This novel approach to treating chronic pain occurred to Ana Moreno, the study’s first author, when she was a Ph.D. student in the NIH-supported lab of Prashant Mali, University of California, San Diego. Mali had been studying a wide range of novel gene- and cell-based therapeutics. While reading up on both, Moreno landed on a paper about a mutation in a gene that encodes a pain-enhancing protein in spinal neurons called NaV1.7.
Moreno read that kids born with a loss-of-function mutation in this gene have a rare condition known as congenital insensitivity to pain (CIP). They literally don’t sense and respond to pain. Although these children often fail to recognize serious injuries because of the absence of pain to alert them, they have no other noticeable physical effects of the condition.
For Moreno, something clicked. What if it were possible to engineer a new kind of treatment—one designed to turn this gene down or fully off and stop people from feeling chronic pain?
Moreno also had an idea about how to do it. She’d been working on repressing or “turning off” genes using a version of CRISPR known as “dead” Cas9 . In CRISPR systems designed to edit DNA, the Cas9 enzyme is often likened to a pair of scissors. Its job is to cut DNA in just the right spot with the help of an RNA guide. However, CRISPR-dead Cas9 no longer has any ability to cut DNA. It simply sticks to its gene target and blocks its expression. Another advantage is that the system won’t lead to any permanent DNA changes, since any treatment based on CRISPR-dead Cas9 might be safely reversed.
After establishing that the technique worked in cells, Moreno and colleagues moved to studies of laboratory mice. They injected viral vectors carrying the CRISPR treatment into mice with different types of chronic pain, including inflammatory and chemotherapy-induced pain.
Moreno and colleagues determined that all the mice showed evidence of durable pain relief. Remarkably, the treatment also lasted for three months or more and, importantly, without any signs of side effects. The researchers are also exploring another approach to do the same thing using a different set of editing tools called zinc finger nucleases (ZFNs).
The researchers say that one of these approaches might one day work for people with a large number of chronic pain conditions that involve transmission of the pain signal through NaV1.7. That includes diabetic polyneuropathy, sciatica, and osteoarthritis. It also could provide relief for patients undergoing chemotherapy, along with those suffering from many other conditions. Moreno and Mali have co-founded the spinoff company Navega Therapeutics, San Diego, CA, to work on the preclinical steps necessary to help move their approach closer to the clinic.
Chronic pain is a devastating public health problem. While opioids are effective for acute pain, they can do more harm than good for many chronic pain conditions, and they are responsible for a nationwide crisis of addiction and drug overdose deaths . We cannot solve any of these problems without finding new ways to treat chronic pain. As we look to the future, it’s hopeful that innovative new therapeutics such as this gene-editing system could one day help to bring much needed relief.
 Long-lasting analgesia via targeted in situ repression of NaV1.7 in mice. Moreno AM, Alemán F, Catroli GF, Hunt M, Hu M, Dailamy A, Pla A, Woller SA, Palmer N, Parekh U, McDonald D, Roberts AJ, Goodwill V, Dryden I, Hevner RF, Delay L, Gonçalves Dos Santos G, Yaksh TL, Mali P. Sci Transl Med. 2021 Mar 10;13(584):eaay9056.
 Nuclease dead Cas9 is a programmable roadblock for DNA replication. Whinn KS, Kaur G, Lewis JS, Schauer GD, Mueller SH, Jergic S, Maynard H, Gan ZY, Naganbabu M, Bruchez MP, O’Donnell ME, Dixon NE, van Oijen AM, Ghodke H. Sci Rep. 2019 Sep 16;9(1):13292.
 Drug Overdose Deaths. Centers for Disease Control and Prevention.
Congenital insensitivity to pain (National Center for Advancing Translational Sciences/NIH)
Opioids (National Institute on Drug Abuse/NIH)
Mali Lab (University of California, San Diego)
Navega Therapeutics (San Diego, CA)
NIH Support: National Human Genome Research Institute; National Cancer Institute; National Institute of General Medical Sciences; National Institute of Neurological Disorders and Stroke