The Problem with Vivitrol®

(https://www.vivitrol.com/opioid-dependence/what-is-vivitrol)

Fascinating post by guest contributor Amy Dunn, graduate student at the Rockefeller University!


What is Vivitrol®? This question is posed in countless ads depicting attractive young people across target states, such as MA, NY, NJ and PA. The ads do little to answer the question – instead just giving a drug name and a website. Vivitrol®, made by the Boston-based company Alkermes, is the brand name for the drug naltrexone and is used to treat both alcohol and opiate addiction.

Opiates like heroin or oxycodone work by stimulating the mu opioid receptor in the brain. This leads to the euphoric and rewarding effects that are characteristic of these drugs. The two most popular medications for treating opiate addictions, methadone and buprenorphine, both work by stimulating that same receptor in a slightly different way. This relieves the cravings, but doesn’t cause the same “high” as heroin or oxycodone. Methadone and buprenorphine are known as agonist, or replacement, medications. Dr. Simon Says Science wrote an excellent article for Addiction Blog that compares methadone and buprenorphine and explains how they work in greater detail. Naltrexone, on the other hand, is an antagonist of that same receptor – meaning that it completely blocks the effects of any opioid. While it seems counterintuitive, medications that stimulate the mu opioid receptor and medications that block the mu opioid receptor have both been proven to be effective treatments for opiate addiction.

Naltrexone was approved by the FDA in the 1980’s and was originally formulated as a daily pill, however it was difficult to get people to adhere to taking their medication. Because naltrexone is a mu opioid receptor antagonist, it can lead to unpleasant feelings that are the opposite of the euphoria felt with an opiate agonist. People with addictions could stop taking the medication if they wanted to get high instead. Because of these adherence issues, the drug bounced around between companies. In addition to these issues with compliance, it was difficult for companies to market an addiction medication because of the social stigma. Addiction is often seen as a moral problem instead of a medical one, which makes selling medications for addictions very difficult.

Naltrexone became far more practical when it was reformulated as an extended-release injection. The extended-release injection lasts for a month, greatly reducing the problem of adherence. Vivitrol®, the brand name for the extended-release naltrexone introduced by Alkermes, was first approved in 2006 for the treatment of alcohol addiction. Following a successful clinical trial in Russia, it was also approved for treatment of opiate addiction in 2010. Despite poor initial sales, the popularity of Vivitrol® has grown rapidly in the past couple years.

Vivitrol® Sales: (https://www.scribd.com/document/351102245/Alkermes-2016-Analyst-and-Investor-Event-Presentation#from_embed)

 

Vivitrol® is still far less utilized than methadone and buprenorphine, but this is expected probably because it is much newer on the market. Importantly, not everyone responds well to methadone or buprenorphine, and having another option for the treatment of opiate addiction should be a good thing for everyone. However, a disturbing pattern has emerged in the past couple years regarding the ethics of Alkermes’ marketing strategies and scientific data. They are missing key scientific data, and actively engaging in strategies to undermine the use of agonist medications that compete with Vivitrol®. While these marketing strategies may or may not be illegal, they still raise important questions about the ethical obligations of pharmaceutical companies to their patients.

The Science on Vivitrol®

In order for the FDA to approve a drug, a drug company must first prove that the drug is effective through a clinical trial. Clinical trials are very tightly regulated in the US which makes sense because you’re testing a drug that is technically still experimental and could be dangerous to people. Not only do you need to prove that your drug is safe, but you also need to prove that it is at least as effective as other drugs out there that treat the same condition. This is where there are holes in the data on Vivitrol®.

The clinical trial that convinced the FDA to approve Vivitrol® was done in Russia.3 Clinical trials are done in other countries for many reasons. Companies may be trying to skirt the tight regulations here in the US, or they might just need to work with a patient population that is found more commonly in other places. The FDA reviews the study design and the data to see if they want to approve the drug regardless of where the study was done. The clinical trial on Vivitrol® was designed to see if Vivitrol® was effective for treating opiate addiction, but did not compare it to either of the other approved medications for opiate addiction (methadone or buprenorphine). Neither of these agonist treatments is available in Russia. In fact, both are illegal because they are opiate agonists. Alkermes only needed to prove that Vivitrol® was more effective than placebo in this case. The results were promising – almost 90% of the addicted persons who received the naltrexone shot remained abstinent during the test period, compared to just over 60% of the control group. This was enough evidence to get FDA approval, however to date there are no clinical trials comparing Vivitrol® to either methadone or buprenorphine. In addition, there was no follow-up study examining the long-term outcomes of the participants of the clinical trial in Russia.

Since it has been approved, there have been several other clinical trials examining the efficacy of Vivitrol® in different populations (although none of these studies compared it to buprenorphine or methadone). There are still concerns about adherence to Vivitro®, as well as the possibility that a person could take a dangerous amount of opioids in order to overcome the blockade effect. Because it’s an antagonist, if an addicted person takes naltrexone while they still have opiates in their system, the naltrexone will both stop the euphoric effects of the opiate and also cause withdrawal symptoms. In fact, a person has to be over a week opiate-free and have already gone through withdrawal before they can begin naltrexone treatment.

However, no medication is ever perfect. While there are still unanswered questions about Vivitrol®, it is clearly an addition to the toolbox that healthcare providers can use to help people fight addictions. It is important that these scientific concerns are discussed and addressed, and that these issues are clearly presented to the public so that people can make informed decisions about their medications.

The Marketing on Vivitrol®

(www.vivitrol.com)

To understand more about how Alkermes is advertising Vivitrol®, we can look at a screenshot of their main website listed on their advertisements (www.Vivitrol.com). This language – “the first and only once-monthly, non-addictive medication” is problematic.  While they are correct in characterizing naltrexone as “non-addictive”, this wording implies that the other medications that are available (methadone and buprenorphine) somehow are addictive. This same language is often used in a 2016 investor presentation as well, where they describe agonist therapy as “maintain[ing] physiologic dependence on opioids”. This is scientifically correct; a person who is using agonist medication may indeed be dependent on their medication. This simply means that they would experience negative physiological consequences if they abruptly stopped use. It does not mean that they are addicted. “Addiction” is a physiologic dependence combined with compulsive drug-taking despite negative consequences. Alkermes is conflating these two terms in a way that is confusing, and is meant to manipulate the consumer into equating agonist therapies with addicting opiates of abuse. While their statement that agonist therapies lead to dependence is not incorrect, it is still reinforcing a very damaging stereotype that agonist therapy is just “replacing one drug with another.” This stigma against agonist therapies is a major hurdle for the treatment of opiate addictions. Alkermes actively reinforces and uses this stereotype in order to promote Vivitrol® as the “only non-opioid treatment.”

(https://www.scribd.com/document/351102245/Alkermes-2016-Analyst-and-Investor-Event-Presentation#from_embed)

In addition to portraying Vivitrol® as a better and safer alternative to agonist therapies in the public sphere, Alkermes is also deliberately promoting this view in the political realm. This is noted in the slide from an investor presentation that outlines their marketing strategies, above.  NPR and Side Effects Media published an excellent article detailing their investigation into Alkermes’ political involvement.  They describe Alkermes lobbyists presenting to government committees on addiction therapy and promoting the idea that agonist therapies are “replacing one drug with another”. There is overwhelming scientific evidence supporting methadone and buprenorphine as effective treatments for keeping people with addictions off of heroin and able to live their lives without experience frequent drug cravings. Despite this, there are many decision-makers in the government who do not want to support their use in treatment. Republican Rep. Tim Murphy described agonist therapy as “government –supported addiction” at a meeting in March 2015. He has received political donations from Alkermes. Tom Price, the new Health and Human Services Secretary, received a great deal of criticism for his statement that agonist therapy was “substituting one opioid for another” – despite the department’s website explicitly stating that it supports these kinds of evidence-based treatments.

Alkermes’ strategy of reinforcing of this stereotype leads to real policy consequences. The NPR and Side Effects Public Media report describes several bills that contain language steeped in these stereotypes – specifically instructing treatment providers to strive for “the goal of opioid abstinence.” This is beneficial for Alkermes, as Vivitrol® is the only non-opioid treatment available. The science however, does not indicate that opioid abstinence leads to better outcomes for patients than maintaining their agonist therapies. The report includes drafts of several bills that even mentioned Vivitrol® by name, although it was later removed because of ethical concerns. Alkermes lobbyists have also supported tightening regulations for methadone and buprenorphine, which is incredibly problematic given how restrictive the regulations already are for treatment providers.

Alkermes may not be making explicitly false claims in its marketing, but it is certainly playing off of existing harmful biases in order to further their sales. Whether or not this is illegal is debatable; it is illegal under the Federal Trade Commission for companies to “mislead” consumers. At the very least, it is incredibly unethical for a company to be so actively promoting stereotypes and policies that harm the very patients that they claim to be helping. This falls under the larger umbrella of the issues of advertising, pricing and political involvement of the pharmaceutical industry in our country. While there are no easy fixes, it is important that companies like Alkermes are held responsible for their unethical behavior and that consumers are able to make informed decisions about their treatment based on the available research.


About the Author: Hello! I’m currently finishing my 3rd year of graduate school at Rockefeller University. I’m studying the cell signaling changes caused by drugs of abuse and investigating the ways we can use those different pathways to treat addictions. In addition to learning more about the science of addiction through my research, I’m also interested in learning about the different political and social issues surrounding drug addiction. All of the views and opinions here are entirely my own and definitely don’t reflect those of my lab or institution! My email address is adunn@rockefeller.edu.

Response to the June 2017 New Yorker Article on the Opioid Epidemic

At this point, I would think that knowledge about the vastness and seriousness of the prescription opioid and heroin epidemic, the biggest threat to American health and well being since the HIV/AIDS epidemic, would be common knowledge. Of course, given the abundance of shiny Internet things to tantalize easily distracted Americans, this is unfortunately not necessarily the case. Thankfully the New Yorker, with their characteristic excellence in reporting, has just released a superb and humanizing article on the opioid epidemic in their June 5 & 12, 2017 issue.

Read the article here.

The piece puts a much-needed human face to the horrors and misery of opioid addiction and the too-frequent death by overdose. Margaret Talbot, the article’s author, zeroes in on Berkeley County, West Virginia, in the heart of a region of the country hardest hit by the epidemic. I don’t want to give away much (because you should actually just read the article) except that the stories are heart wrenching yet balanced, and thorough in way that only the New Yorker can deliver. While the article is largely about the lives of people affected by and fighting against the epidemic, I was disappointed with a couple of points that were either made incorrectly, weakly, or not at all.

First, the article barely talks about how the epidemic arose in the first place. It mentions Purdue pharmaceuticals, the bastards behind Oxycontin (drug name: oxycodone), and that prescription opioid abuse led to heroin addiction but does not describe how the surge in addiction to prescription opioids occurred in the first place. The article describes the main problem with Oxycontin is that it can be crushed and snorted but a 2010 formulation of the drug reduced this risk. While this is indeed true, the article neglects to mention that when someone is first prescribed an opioid like Oxycontin for chronic pain (as was the case in the late 90s and early 2000s despite any evidence for the effectiveness of opioids in the treatment of chronic pain), the addictive potential of opioids often led to opioid substance abuse disorder in people who took it as prescribed (see this comprehensive article for more info). This is the big point, many of the people that eventually abused opioids started down that road by taking the drug as prescribed! Talbot incorrectly frames the big picture problem but she then goes on to correctly describe how those addicted to prescription opioids found their way to the cheaper and more abundant heroin.

The article goes on to mention the CDC’s release of guidelines on opioid prescription but fails to cite that this guidance came out as late as March, 2016, well after the epidemic had already taken root and thousands were already addicted and dying of overdose (I wrote an article on the CDC’s guidelines last year and highly recommend you read that article too if you want to learn more). The CDC’s guidance is mainly about the point I made above, that the over-prescription of opioids is the real cause of the epidemic, not just the crushable version of Oxycontin, and the limitation of opioid prescription is one of the huge policy interventions that is needed.

Later in the article, Talbot introduces us to Dr. John Aldis, a retired U.S. Navy Physician and resident of Berkeley County, WV who took it upon himself to educate people on how to use Narcan (generic drug name: naloxone), the treatment for opioid overdose. Dr. Aldis makes the critical point about the importance of medication-assisted treatments such as Suboxone (generic drug name: buprenorphine) and methadone. I appreciated the point made in the article that some patients may need these vital treatments long-term, or even for life, to combat the all-consuming single-mindedness of opioid addiction. However, beyond this passing mention, I felt that medication-assisted treatment was only weakly covered. There is still a great deal of ignorance about these treatments. Indeed, current HHS secretary Tom Price falsely characterized them as “replacing one opioid with another” and was majorly criticized by addiction experts. The reality is that there is overwhelming scientific evidence (I’ve written plenty on this site) describing the effectiveness of methadone and buprenorphine at 1) keeping addicts off of heroin, 2) allowing them to be able to live their lives without suffering from withdrawals and cravings, and 3) most importantly, keeping them alive. Talbot could have done a much better job of really hammering these points home but she seemed reticent, for some reason, to discuss it in detail in this article.

Finally, the article repeatedly emphasizes the importance of rehab clinics and tells the story of a huge victory for Martinsburg, WV (a town in Berkeley County) when the city council agrees to open a clinic in the town itself. I do not want to discount the importance of an addict assessing their addiction and taking an active role to end it, but this article does miss another critical point: rehab clinics only exist because addiction medicine is not part of medical school curricula and most hospitals are ill-equipped to treat those suffering from addiction. I feel this article could have really made the case for the importance of training for doctors in addiction medicine and the necessary shift that needs to happen for addiction treatment, a move away from overpriced (and often ineffective) private rehab facilities, and to public hospitals. Unfortunately, this point was not made.

Despite these missed opportunities, I commend Talbot and the New Yorker for a well-written article and thank them for this important piece that I encourage all to read.

 

The Laws You Never Heard Of that Will Help to Fight the Opioid Epidemic

When a politician is in his or her final few month in office (because either they lost their re-election or simply decided not to or can’t run), they call this the “lame duck” period. President Obama’s last few months in office were anything but “lame”.

On December 14, 2016, in a rare move of bipartisanship, Obama signed into law the massive 21st Century Cures Act. This law provides a boost in funding for NIH (which includes $1.8 billion for the cancer moonshot initiative), changes to the drug approval process through the FDA, and ambitious mental health reform. This huge bill has the stated purpose of “To accelerate the discovery, development, and delivery of 21st century cures, and for other purposes.”

I’m willing to bet many people were totally unaware of this legislation that could help millions. There are some parts that are controversial and, as with any large piece of legislation, some provision that benefit this interest or that have been worked in (the changes to drug approval at the FDA will likely benefit Big Pharma). I’m not a health policy expert so I’m not about to go through and discuss line-by-line the winners and losers in this law (if you want a more in depth discussion: NPR, Washington Post, and PBS have all written articles on the law).

There’s one piece of the law that I am particularly thrilled about: $1 billion over 2 years for treatment for opioid addiction. That’s rights billion, with a “B”. The money is to be distributed to states in the form of block grants (block grants are in essence a large allocation of federal money to be used for a specific purpose given to states but the details of how that money is used is decided by the states themselves).

This is an unprecedented amount of funding earmarked exclusively to fight the opioid epidemic that is still raging in the US. The funding is to be used for expanding and increasing accessibility to treatment, such as life saving medication-assisted treatments such as methadone and buprenorphine. The federal money will also be used to train healthcare professionals to better care for people dealing with addiction, and a comparatively smaller amount for conducting research on how best to fight the epidemic, and other provisions.

I’ve written about methadone and buprenorphine and their effectiveness ad nauseam on this site and I am personally and thrilled to see a massive federal effort to increase access to these vital tools in the fight against the opioid crisis

The Cures Act comes on the heels of another promising piece of legislation, the Comprehensive Addiction and Recovery Act (CARA), signed into law by President Obama on July 13, 2016. This law includes provisions to expand the availability of naloxone–the medication used to save people from the effects of opioid overdose–to first responders, improve prescription drug monitoring programs, make it easier for healthcare providers to administer, dispense, or prescribe medication-assisted treatments, and other provisions.

The combination of these two pieces of legislation is a promising and much needed initial federal response.

However, this huge boost in funds for treatment in the Cures Act is only for 2-years. President Trump’s budget for FY18 would add $500 million for opioid addiction but most analysts think this is just a sneaky way of making it seem as if he’s supporting addiction treatment when the money has already been written in as part of the Cures Act. Further, his cuts to the Department of Health and Human Services (which contains the NIH and other agencies that administer the Cures and CARA laws) would make it difficult to launch any type of  effective response to the crisis.

Regardless of how things shake out, Trump’s massive cuts for everything that’s not the Department of Defense will likely hurt the fight against the opioid epidemic too. The real question is by how much?

 

5 Facts on the Opioid Epidemic: National Drug and Alcohol Facts Week

Spilled prescription medication --- Image by © Mark Weiss/Corbis
Spilled prescription medication — Image by © Mark Weiss/Corbis

Well, I’m a little late to the punch on this one but National Drug and Alcohol Facts week has been going and ends tonight. This public awareness campaign is now in it’s seventh year and is all about shattering the myths about addiction.ndafw_logoI might as well throw my belated hat in the ring and share 5 facts about the opioid epidemic.

Fact #1: The opioid epidemic in the U.S. has hit all demographic groups, regardless of race, gender, age, location, or socioeconomic status.

Fact #2: Prescription opioid pain medications like oxycodone can be just as addictive as heroin, even if taken as prescribed.

Fact #3: There is no scientific evidence that prescription opioids are effective at managing chronic pain; they are extremely effect for short-term, acute pain.

Naloxone_(1)Fact #4: Naloxone is a drug that counters the effects of opioids and can immediately reverse an overdose; you cannot get addicted to naloxone.

Fact #5: Buprenorphine and methadone are opioids that can help a person to fight their heroin addiction by satisfying their craving for the drug.

To learn more, here’s a short “Best of” from Dr. Simon Says Science on the Opioid Epidemic. Check out the posts below for oodles of info on opioids.

  1. What is naloxone? Should it be available over the counter?
  2. The CDC Fights Back Against the Opioid Epidemic
  3. Is Methadone an Effective Treatment for Heroin Addiction? YES!
  4. Morphine and Oxycodone Affect the Brain Differently
  5. Important: CDC Releases Report on Heroin Epidemic
  6. Methadone Maintenance Therapy Works-End of Story
  7. Paper Review-Initiation into Injection Drug Use and Prescription Opioids
  8. New Review Paper-The Prescription Opioid and Heroin Epidemic

 

The Science of Sexual Orientation

(from psychologicalscience.org)
(from psychologicalscience.org)

Happy New Year!

I figure I’ll kick things off with something a little different than my usual science of addiction posts.

My new job deals with supporting LGBT rights in the developing world and there’s a lot of work be done! In fact, as of June 2016, 77 countries or territories criminalize homosexuality and 13 countries or territories penalize homosexual behavior by death. But why is this? Why is someone who is attracted to and has sex with someone of the same sex so controversial in so much of the world? Well..I’m not about to begin to answer that question because I’ll be writing all week (hint, hint: religion is a huge factor).

Instead, I’ll present some of the key findings from a relatively new (April 2016) review article about the science of sexual orientation by JM Bailey and colleagues in the journal Psychological Science in the Public Interest. This is by far one of the most comprehensive and most even handed review articles written on the subject. The authors take an extremely academic approach because let’s face, the science surrounding sexual orientation has been used and abused by both pro- and anti- gay rights folks. (note: this article does not really discuss with transgenderism or gender identity issues)

This article is too long to go into all the details so instead I’m just going to present the main highlights that I prepared for a research report a few months back. Enjoy!

Download the article here. It’s Open Access!

jm-bailey-et-al-2016

Brief Summary:

Political controversies pertaining to the acceptance of non-heterosexual (lesbian, gay, bisexual) orientation often overlap with controversies surrounding the science of sexual orientation. In an attempt to clarify the erroneous use of scientific information from both sides of the debate, this article 1) provides a comprehensive review of the current science of sexual orientation, and 2) considers the relevance of scientific findings to political discussions on sexual orientation.

Top Takeaways from the Review:

  • The scientific evidence strongly supports non-social versus social causes of sexual orientation.
  • The science of sexual orientation is often poorly used in political debates but scientific evidence can be relevant to specific, limited number of issues that may have political consequences.
(wikimedia.org)
(wikimedia.org)

The scientific evidence strongly supports non-social versus social causes of sexual orientation (nature vs nurture).

Prevalence of non-heterosexual orientation (analysis of 9 large studies): 5% of U.S. adults.

Summary of the major, scientifically well-founded findings supporting non-social causes:

  • Gender non-conformity during childhood (before the onset of sexual attraction) strongly correlates with non-heterosexuality as an adult.
  • Occurrence of same-sex behavior has been documented in hundreds of species and regular occurrence of such behavior in a few species (mostly primates, sheep).
  • Reported differences in the structure of a specific brain region (SDN-POA) between heterosexual and homosexual men.
  • Hormone-induced changes in the SDN-POA during development in animal studies and subsequent altered adult sexual behavior (the organizational hypothesis).
  • Reports of males reared as females but who exhibit heterosexual attractions as adults.
  • Twin studies suggest only moderate genetic/heritable influence on sexual orientation.
  • Several reports identify a region on the X chromosome associated with homosexuality.
  • The most consistent finding is that homosexual men tend to have a greater number of biological older brothers than heterosexual men. (fraternal-birth-order effect)

The science of sexual orientation is often poorly used in political debates, but scientific evidence can be relevant to a specific, limited number of issues that may have political consequences.

The question of whether sexual orientation is a “choice” is logically and semantically confusing and cannot be scientifically proven. It should not be included in political discussions.

Examples of scientifically reasonable questions include:

  • Is sexual orientation determined by non-social (genetic/hormonal/etc.) or social causes? (nature vs nurture)
  • Is sexual orientation primarily determined by genetics or environment?

Specific cases in which scientific evidence can be used to inform political decisions:

  • The belief that homosexual people recruit others to homosexuality (recruitment hypothesis). This type of belief was espoused by by President Museveni of Uganda in 2014 and was used to justify Uganda’s notorious anti-homosexuality bill (since repealed).
    • No studies exist that provide any type of evidence in support of this hypothesis.
  • Proponents of conversion/reparative “therapies” argue that sexual orientation can be changed through conditioning and reinforcement.  Gov. and VP-elect Mike Pence  allegedly supported these types of bogus “therapies” in Indiana.
    • Studies reporting successful “conversion” suffer from methodological errors such as selection bias and/or unreliable self-report data and are therefore scientifically unfounded.
    • No evidence exists that a person’s sexual orientation can be changed at will.

 

The British Medical Journal (BMJ) Calls for an End to the “War on Drugs”

war-on-drugs-no

A recent editorial in the British Medial Journal (the BMJ) has called for an end to the “War on Drugs”, which costs about $100 Billion/year and has failed to prevent both drug use and drug proliferation.

The article points out how the “War on Drugs”, the term used to collectively describe the laws penalizing drug use, has had a wide-range of negative effects. For example, the US has the highest incarceration rate in the world and about half of those arrests are due to drug-related arrests.

The health effects have been drastic as well. Stigma against opioid replacement therapies like methadone has resulted in increased deaths due to opioid overdose in countries that limit access. Stigma and discrimination against addicts, as well of fear of punishment for for usage, often leads away from health care services to unsafe drug-use practices that can spread HIV and Hepatitis C, and other unintended poor-health outcomes.

Importantly, the editors call for rational, evidence-based, drug-specific approach to regulation and strong involvement of  the scientific and medical communities. Obviously, the risks of something like marijuana are much lower than for heroin but how will drug policy reflect this? Research is required to support any efforts in order to identify the best practices and strategies.

The editors point out that a recent article in the Lancet “concluded that governments should decriminalise minor drug offences, strengthen health and social sector approaches, move cautiously towards regulated drug markets where possible, and scientifically evaluate the outcomes to build pragmatic and rational policy.”

Above all, a change in drug policy must benefit human health and there will be no “one size fits all” approach. The road ahead is difficult but one thing is certain, the road that led us here is a dead end. The “War on Drugs” has failed; the call now is to develop a national and international drug policy that won’t.

The NIH Announces a Commitment to Research on LGBT Health

lgbt-med

Every person has a right to live a healthy life. One part of that vision is equal access to health care for all. But unsurprisingly, not everyone have the same ability to receive health care due to things like socioeconomic status, race, gender, or even sexual orientation. Indeed, LGBT people often have less access to health care than their non-LGBT counterparts, most often due to discrimination and stigma [1].

The Director of the National Institute on Minority Health and Health Disparities, part of the National Institutes of Health (NIH), announced “the formal designation of sexual and gender minorities (SGMs) as a health disparity population for NIH research.” Read the full announcement here.

What does this mean? That the NIH is officially recognizing that LGBT people have less access to health care and that improved research on LGBT-specific (defined here broadly as sexual and gender minorities) health issues is essential to improved health care.

The long-overdue announcement was supported by an important report released by the non-partisan National Academies of Science (NAS) in 2011. The report identified gaps in the research on the health of LGBT persons and made recommendations for improving this research that could benefit not just LGBT people, but the health care system overall.

LGBT individuals have unique health challenges that many doctors do not understand or address. For example, certain types of cancer seem to be more prevalent among gay men compared to straight men, which means different cancer screenings would be important for gay men [2].

The new designation by NIMHD will hopefully increase research and knowledge about the health challenges of LGBT people and will hopefully result in improved health care for all people, regardless of sexual orientation, gender identity, or gender expression.

Selected References

  1. Hatzenbuehler ML, Bellatorre A, Lee Y, Finch BK, Muennig P, Fiscella K. Structural stigma and all-cause mortality in sexual minority populations. Social science & medicine. 2014;103:33-41. doi: 10.1016/j.socscimed.2013.06.005.
  2. Quinn GP, Sanchez JA, Sutton SK, Vadaparampil ST, Nguyen GT, Green BL, et al. Cancer and lesbian, gay, bisexual, transgender/transsexual, and queer/questioning (LGBTQ) populations. CA: a cancer journal for clinicians. 2015;65(5):384-400. doi: 10.3322/caac.21288.

Rapping About Replication

science-scienceLast year, a paper came out in the journal Science that made waves in the scientific community and the public at large (it was even voted the #5 most publicly cited paper of 2015 by Altmetric).

replication-study

So why am I writing about a paper over a year old and one that has already received plenty of public attention? Well, because this paper is a huge deal. Why you may ask? One of the most important words in the entire scientific enterprise: Replication.

In brief, this study was done by the Open Science Collaboration (OSC), a massive consortium of hundreds of researchers. The OSC team attempted to replicate 100 research papers in the experimental psychology field. The scientists decided which studies were to be included in the analysis, shared methods and tools, and agreed on criteria for how they would critically evaluate the studies (in some cases, the original authors provided the original test materials).

Unfortunately, the results were not good. The authors found that 2/3 of the original findings could not be replicated with any degree of statistical confidence. When taken as group, the effect sizes of the 100 replication studies compared to the originals were only about half as a great. In other words, more than half of the 100 papers could not be replicated.

But what does this mean and why is it a big deal?

Science is all about uncovering “how stuff works” but at a far more fundamental level, what science really is, is a method or system to figure out “how stuff works” and “what causes what” and uncovering the underlying principles of nature, etc.

And how does a scientist know that why they discovered about how this or that works is actually real? Well, one way is for other scientists to run the same experiment. If they get the same result, then it’s a pretty good chance then the discovery is “real”.

One of the biggest challenges the scientific research field has been grappling with is this issue of replication and ability to replicate other people’s work. If what people are reporting in papers is real, then why are so many findings so difficult to replicate?

There’s about a million ways to answer that question but the simplest answer is that doing science is really, really hard. Even if you think you designed the perfect experiment, collected the best data you could, and analyzed it the best way you know how, you might have gotten something wrong. You might have forgotten to control for a variable that you never thought of or even more mundanely, you forgot to report some crucial detail that other scientists need to know but you have taken for granted.

The failure to replicate is NOT about making up results (though a few bad apples have done that) is about not having time and money to thoroughly consider the results of the field. Science has a way of weeding out ideas that just don’t hold water but it requires other scientists to delve into the work of their colleagues and try to expand on their initial colleagues.

And just to be clear, there’s plenty of outstanding work being done that has been replicated and is scientifically solid.

Regardless, scientists need to resolve how to solve this problem with replication.

As bad as it is can be in biology, it’s a whole lot worse for a “soft science” like psychology. Many psychological studies have either been discredited or shown to be outright frauds (one of the more sensational stories involved years of forged data by the psychologist Diederik Stapel).

Thankfully, the field as a whole is trying to acknowledge their past failings and improving the integrity of their discipline. It would be a huge step forward for other fields, such as in the biomedical research field, to also take on such an endeavor.

And in the end, this is why this paper is so ground breaking and worth talking about (again). The field acknowledged they had a problem, did a systematic analysis of all available studies, and tried to replicate which ones are good and which are bad.

But there’s one more layer to this too. There’s also no incentive to replicate findings either. The pressure to publish only “sexy” results and get the big research grant almost prohibits scientists from trying to replicate each others work.

As someone who has spent that last 10+ years in academic research labs, I’ve heard the concerns from friends and colleagues about how quickly they need to publish their results out of fear of being “scooped” by a competing lab working on the same topic. And I and anyone in the academic research knows the the near constant anxiety about how to come up with new exciting ideas for the big grant that your entire livelihood is dependent upon (maybe a little over-dramatic but seriously, only a little).

If a scientist is under pressure to publish a new finding as quickly as possible, sometimes mistakes are made or a critical control was overlooked on accident. One facet of the replication crisis may be this competitive drive between labs. In business, competing tech companies are pressured to release a product that may be cheaper or more appealing to the public. However, competition has the exact opposite effect in scientific research. Increased competition may actually hurt scientists. And of course, the root cause of competition to publish is competition for a limited pool of grant money, without which there would be no basic research at all.

The replication study is an important milestone and idealizes the self-correcting tradition of the scientific enterprise in general. Scientists are supposed to be the most critical of their own work and the community should be able to recognize if an initially exciting finding cannot be replicated.

With increased funding and reduced pressure to publish only “sexy” results in top-tier journals, perhaps the scientific community will turn away from competition and prestige and return to the spirit of openness, sharing, and collaboration. Maybe then the failure to replicate will become unable to be replicated.

Update: Changes to site, Cocaine review article

Good-bye NYC! (Photo © Derek Simon 2015)
Good-bye NYC!
(Photo © Derek Simon 2015)

Change is coming!

After a several month hiatus, I’m happy to be posting again!

I wanted to announce that I recently switched fields from basic neuroscience research to a fellowship position in the LGBTI Office at the US Agency for International Development (USAID)!

This means good-bye NYC and hello Washington DC! It also means that the scope, style, and range of topics I’ll write about will greatly expand beyond just drug addiction. I’m still figuring out those details….

But in the mean time:

Cocaine Addiction Review Article

About two years ago I wrote a review article for a new academic book about addiction. Finally, the book and the article have been published!

The book is Neuropathology of Drug Addictions and Substance Misuse. My article appears in Volume 2.

Feel free to download a pdf of my article for free!

PDF of Cocaine Review Article.

I first present an overview of the pathology and neurobiology of cocaine addiction and then discuss some of the research findings about changes that occur in the brain because of cocaine addiction.

A summary of key points discussed in the article:

  • Cocaine is a widely abused drug that has significant economic, medical, and social costs and no effective pharmacotherapeu­tic treatments.
  • Cocaine addiction progresses from initial use to repetitive cycles of heavy, short-term use (“binge” use), abstinence, and relapse.
  • Unlike other drugs of abuse (which only primarily affect DA release), cocaine’s mechanism of action consists of blocking the reuptake of all monoamine neurotransmitters (DA, 5HT, and NE) by antagonizing the monoamine transporters (DAT, SERT, and NET) thus leading to an accumulation of these neu­rotransmitters in the synapse of the mesolimbic reward path­way and other regions of the brain.
  • Genetic and environmental factors contribute to the suscepti­bility of an individual to becoming addicted to cocaine, and based on twin studies, it has been estimated that genetics may account for 30–60%, and as high as 78% of this susceptibility.
  • Acute cocaine use activates the HPA axis while chronic cocaine use sensitizes the HPA axis and blunts the stress response, which contributes to relapse behavior.
  • Accurate behavioral models used to study cocaine addiction, such as self-administration and the “binge” model, are useful because they attempt to recapitulate the human disease.
  • Cocaine use results in upregulation of dynorphin mRNA and protein and subsequent elevation of KOPR/dynorphin tone in the VTA/CPu/NAc circuit in virtually every behavioral model tested.
  • Modulation of the KOPR/dynorphin system may represent a viable pharmacotherapeutic target for treatment of cocaine addiction.

The Consequences of Childhood Abuse Last Until Adulthood: What are the Implications for Society?

(© Derek Simon 2015)
(© Derek Simon 2015)

One of the great questions in the addiction field is why do some people become full-blown addicts while other people can use drugs occasionally without progressing to anything more serious? One part the answer definitely has to do with the drug itself. For example, heroin causes a more intensely pleasurable high than cocaine and people that try heroin are more likely to become addicted to it than cocaine. But that’s not the whole story.

I’ve written previously about how a negative, stressful environment can have long-lasting negative impacts on the development of a child’s brain (also known as early-life stress of ELS). ELS such as childhood abuse (physical or sexual) and neglect can increase the risk for a whole host of problems as an adult such as depression, bipolar disorder, PTSD, and of course drug and alcohol abuse. There’s even a risk for more physical ailments like obesity, migraines, cardiovascular disease, diabetes, and more.

Childhood abuse/neglect = psychological and physical problems as an adult.

Attitudes towards childhood development have certainly changed! Child coal miners ca. 1911 (wikipedia.org).
Attitudes towards childhood development have certainly changed! Child coal miners ca. 1911 (wikipedia.org).

This idea doesn’t sound too controversial but believe it or not, the idea that a bad or stressful situation as a child would do anything to you as an adult was laughed away as not possible. It’s only within the last decade or so that a wealth of research has supported this idea that ELS can physically change the brain and that these changes can last through the abused child’s entire life.

This recent review paper (published in the journal Neuron) is an excellent, albeit technical, summary of dozens research papers done on this subject and the underlying biology behind their findings.

Paradise lost childhood abuse review 2016 title

I especially love the quotes the author included at the beginning of the article:

Paradise lost childhood abuse review 2016 quotes

And even more recently, yet another research paper has come out that highlights how important childhood is for the development of the brain and how a stressful childhood environment can impact the function of a person as an adult.

Childhood abuse paper 2016

This most recent report, published in the journal Neuropscyhopharmacology concludes that early childhood abuse affects male and females differently. That is to say that the physical changes that occur in the brain are distinct for men and women who were abused as children.

Studies like this one are done by examining the brains of adults who were abused as kids and then comparing the activity or structure of different parts of the brain to the brains of adults who were not abused. The general technique of examining the structure or activity of the brain in a living human being is called neuroimaging and includes a range of techniques such as MRI, PET, fMRI, and others. (I’ve written about some of these techniques before. In fact, the development of better methods to image the brain is a huge are of research in the neuroscience field).

However, this study did not examine behavioral differences in the subjects, but as I said above, a great number of many other studies have looked at the psychological consequences of ELS. But this paper is really primarily interested in the gender differences in the brains of adults that have been abused as kids.

*Note: the following discussion is entirely my own and is not mentioned or alluded to by the author’s of this study at all.

This work—and the many studies that preceded it—has important implications because as a society, we have to realize that part of our personality/intelligence/character/etc. is determined by our genetics while the other part totally depends on the environment we are born into. I don’t want to extrapolate too much but the idea that childhood abuse can increase the risk of psychological problems as an adult also supports the broader notion that a great deal of a person’s success is determined by entirely random circumstances.

The_ACE_Pyramid
The Adverse Consequences Pyramid perfectly illustrates how ELS/abuse/neglect (the bottom of the pyramid) leads to much greater problems in later life. (wikimedia.org).

The science shows that a child born into a household rife with abuse will have more chance of suffering from a psychological problem (such as addiction) as an adult than someone who was born into a more stable life. The psychological problem could hurt that person’s ability to study in school or to hold down a job. And the tragic irony, of course, is that no child gets to choose the conditions under which they are born. A child, born completely without a choice of any kind over whether or not he or she will be abused, can still suffer the consequences of it (and blame for it) as an adult.

As a society, we often always blame a person’s failures as brought on by his or her own personal failings, but what if a person’s childhood plays an important role in why that person might have failed? How, as a society, do we incorporate this information into the idea of ourselves as having complete control over our minds and our destinies, when we very clearly do not? As an adult, how much of a person’s personality is really “their own problem” when research like this clearly show that ELS impacts a person well after the abuse has ended?

If the environment a child is born into has a tangible, physical effect on how the brain functions as an adult, than this problem is more than a social or an economic one: this is a matter of public health. Studies that support findings such as these provide empirical significance for public policy and public services for child care such as universal pre-K, increased availability of daycare, health insurance/medical access for children, increased and equitable funding for all public schools regardless of the economic situation of the district that school happens to be located in, etc.

One of our goals as a society (if indeed we believe ourselves to be a functioning society…the success of Donald Trump’s candidacy raises some serious doubts…but I digress) is the improvement of the lives of ALL of our citizens and securing the prosperity of the society for future generations. Reducing childhood poverty and abuse quite literally could help secure the future generations themselves and improve the ability of any child to grow up to become a successful and productive adult.

Public programs are essential because the unfortunate reality for many people born into poverty is that they must work all the time at low paying jobs in order to simply survive and may not be able to give their children all the advantages of a wealthier family. And this is where government and public policy step in, to correct the imbalances and unfairness inherent to the randomness of life and level the playing field for all peoples. Of course, the specific programs and policies to reduce childhood poverty and abuse would need to be evaluated empirically themselves to guarantee an important improvement in development of the brain and health of the child when he/she grows up.

And this is the real power of neuroscience and basic scientific research papers like this one. Research into how our brains operate in real-life situations reveal a side of our minds and our personalities that we never may have considered before and the huge implications this can have for society. The brain is a complex machine and just like other machines it can be broken.

Of course, we shouldn’t extrapolate too much and say that, for example, a drug addict who was abused as a child is not responsible for anything they’ve ever done in between. But is important to recognize all the mitigating factors at play in a person’s success and simply dismiss someone’s problems as “their own personal responsibility.” As a neuroscientist, I might argue that that phrase and the issues behind it are way more nuanced than the how certain politicians like to use it.

Special endnote Due to some recent shifts in my career, Dr. Simon Says Science will be expanding the content that I write about. Addiction and neuroscience will still be prominently featured but I plan to delve into a variety of other topics that I find interesting and sharing opinions that I think are important. I hope you will enjoy the changes! Thanks very much!