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Q&A: What Are We Doing About the Opioid Crisis?

Francis Collins

March 14, 2018 -- In 2016, opioids were involved in 42,249 deaths, five times higher than 1999. That figure is expected to exceed 60,000 in 2017, based on preliminary death data, according to research organization Altarum and CDC officials.

Scientists at the NIH, the nation's chief medical research agency, are working on solutions for addressing the public health crisis by investigating new and better ways to prevent opioid abuse, to treat opioid use disorders and to manage pain. Francis Collins, MD, director of the NIH talked about the roots of this epidemic, promising research into both addiction and the treatment of pain, and President Donald Trump's budget proposal for 2019. Here is an edited version of the conversation.

WebMD: You have said that the U.S. got itself into this opioid crisis because there was a belief in the medical community that people with pain would not become addicted to opioids. Where did this belief come from?

Collins: It is a little hard to figure out all the origins of that misconception. I would like to say that some significant part of that was done out of concern for people who were suffering from pain and the desire of benevolent physicians to try to help. That led to a sense (by doctors) that we should be more attentive to pain conditions and led to the idea of pain as the 'fifth vital sign.' (The four vital signs are body temperature, pulse rate, rate of breathing and blood pressure.) And there was a belief that these very powerful pain medications would not be addictive for people who were suffering from pain, but only for people who weren't. In retrospect, we can now look back and say there was no real evidence to support that interpretation, and it started us down a very unfortunate path.

WebMD: Why didn't anyone think it would be addictive? Was it because there was no evidence that it was addictive?

Collins: [There] was the notion that long-acting opioids that didn't give you an immediate high were less likely to result in addiction. That turned out not to be true, either.

WebMD: What is the NIH's role in addressing the opioid epidemic?

Collins: We have been working on these issues for a number of years through our 27 institutes and centers, but particularly amongst those that are part of the NIH Pain Consortium. It is not as if we woke up to this a year ago. Some of the things that have already been done [include] the antidote that is now used for opioid overdoses -- a nasal form of naloxone (brand name Narcan). How did that happen? That was a collaboration between the NIH and a small company. [We] made it possible for naloxone to be distributed as a nasal spray, making it very easy for non-medically trained individuals to deliver it. Now it is the most commonly used [antidote] by first responders. We have also been actively involved in development of medication-assisted treatment for those who suffer from addiction. Buprenorphine is considered to be [an] appropriate intervention [for opioid addiction]. Ideally, you would want multiple different versions of it available to match individuals' needs. NIH has worked with another company to develop a subcutaneous implant that delivers buprenorphine over 6 months, so that someone undergoing treatment doesn't have to remember to take the pill [form] every day.

In the longer term, we need to find better pain treatments than opioids. We have been doing a lot in terms of the basic science of understanding the neural pathways involved in pain. How are they different in somebody with low back pain, or somebody with diabetic neuropathy, or somebody who has pain from osteoarthritis? Basic science understanding about pain will have considerable value for designing the next generation of [pain] treatments that would not be addictive.

WebMD: What do you do about those who are in chronic pain who use opioids appropriately? How do you ensure they get access to opioid pain medication?

Collins: That is a very serious topic of debate right now. [There is] justifiable concern about not having large bottles of opioids prescribed to people who just had their wisdom teeth taken out. But we must not neglect the needs of people with sickle cell disease or osteoarthritis or diabetic neuropathy, for whom at the moment there aren't great alternatives for pain relief. Even though we all would love to set the opioids aside and replace them with something that is not addictive and doesn't cause horrible constipation and all the other things opioids do, we don't have them yet. So we still need to take care of those individuals.

WebMD: What percent of people who take opioids get addicted?

Collins: Physical dependence will develop in most individuals who take opioids chronically, resulting in withdrawal symptoms if the drug is taken away. Addiction is more severe and happens in only a small percentage of those who take opioids chronically.

WebMD: So when is it appropriate to take opioids? Is it only appropriate if you have cancer?

Collins: For cancer, especially when metastatic disease spreads into the bone, excruciating pain can result. Sadly, once cancer has spread to bone, in general, we aren't able to cure it. We would not want individuals to go through excruciating pain during their final months or years. It would be very hard under that circumstance to deny access to appropriate pain medicines.

But fortunately, most causes of chronic pain are not as severe or life-threatening as metastatic cancer. In those situations, opioids should not be the place to start. Other alternatives can and should be utilized, such as nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, which can actually be quite effective if given at reasonable doses. Nobody should move onto opioids if relief can be obtained from something safer like an NSAID. But there will be times where that doesn't do it and under that circumstance, unless and until we have alternatives that we know are safe and effective, opioids are going to continue to need to be accessible to those on the most severe end of the spectrum of chronic pain.

WebMD: The NIH is also working on an opioid initiative to work with public and private organizations to identify areas where drug companies could accelerate the development of drug treatments to treat pain and opioid use disorders. Would you talk more about that?

Collins: Many companies have been interested in the development of effective and non-addictive pain treatments, [but] it has turned out to be difficult to achieve success. In part [it is] because we didn't understand [the] neuroscience of pain. It is also because there [is] a very high bar set for safety of drugs that might be used for somebody who has chronic pain, where you want to be reassured that side effects are quite minimal. That can be a hard standard to meet. Industry has developed dozens of promising leads for new forms of pain medicine; a couple have made it to human trials, but most are still in the pre-clinical stage. We have been working quite avidly, over the course of almost a year, to identify how NIH and industry can work together to speed up that pipeline.

WebMD: Is there anything that will come out of this public/private partnership in the coming year?

Collins: In the short term, I think the things we might be able to accomplish, when the partnership is launched, would include coming up with more potent antidotes for overdose. With fentanyl having found its way into the heroin supply, there are many stories of individuals who overdosed for whom the naloxone antidote wasn't strong enough to bring them around and keep them from falling back into respiratory arrest. So it looks as if we may need a longer-lasting antidote. Now with some additional assurance of resources from both the Congress and the administration, we will be pushing very hard on that. Clearly, we also need to have other alternatives for treating addiction beyond the fairly limited set [we have], so we'll be working on that as well. For instance, individuals who have recovered from addiction but are at very high risk for relapse can take advantage of an injectable form of naltrexone. The [brand name is] Vivitrol, and it blocks the opioid receptor. Someone with naltrexone in their system will not get a high from opioids because the receptor is blocked. It's a good insurance policy to strengthen determination to stay opioid-free, but it only lasts for a month, and the risk of relapse after that month continues to be high. If we had a version of naltrexone that lasted for 6 months, that would be really, really powerful.

WebMD: How much of addressing the opioid epidemic is understanding the science of addiction?

Collins: A lot. Part of NIH's research agenda is to understand what are the factors that predispose some people to become addicted, and not others. Some of those are genetic, some are environmental, and some are social. A significant correlation exists between individuals who have been suffering from some kind of mental health condition, [particularly depression] and the risk of becoming addicted to opioids. So we need to understand that. Something like 40% of people who are addicted to opioids have a mental health diagnosis.

WebMD: You also have funded a new long-term study to research the brains of adolescents to determine how addiction and pain might develop?

Collins: This “ABCD” study is enrolling more than 10,000 kids across the country, and will follow them over 10 years. Already we have released the first set of data on kids that are 9 to 10 years old, 7,500 of them. The study includes extensive information about their behavior but also includes sophisticated MRI scans of the brain. If they are typical of other kids in that age group, some of them will begin to experiment with drugs and alcohol in the coming years, and we'll have a chance, because of this longitudinal survey, to see what changes occur in their performance and even in their brain anatomy. Those are the types of data that we haven't really had before on this scale.

WebMD: Did President Trump's budget proposal provide the resources you need for addressing the opioid epidemic?

Collins: The president's budget for fiscal year 2019 included a $10 billion figure for the management of the opioid epidemic across all agencies. Of this, $3 billion was specifically allocated, and $750 million was assigned to NIH. We already had $100 million proposed in an earlier version of the 2019 budget, so that makes $850 million altogether. Of that, the money targeted for the public-private partnership is $500 million. Then there is $350 million for other needs that we have for research on opioids and mental health. To have the administration put a very significant resource commitment into the budget is exactly what we hoped might happen. And rest assured that we know exactly how those dollars could be spent on the most pressing research needs, after all the planning we have done over the last year.


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