Archive for the 'Public Health' category

The Obama Administration's 2013 National Drug Control Strategy

Apr 24 2013 Published by under General Politics, Public Health

The ONDCP has been twittering up a storm about the release of the latest National Drug Control Strategy document [ PDF ].

The website touts five bullet points:

  • Prevent drug use before it ever begins through education
  • Expand access to treatment for Americans struggling with addiction
  • Reform our criminal justice system
  • Support Americans in recovery

Whether you think the Obama ONDCP has changed quickly enough for your liking or not, there has clearly been a change in the rhetoric compared with past...all the way back to the Reagan ONDCP. Rhetoric such as this....

While law enforcement will always play a vital role in protecting our communities from drug-related crime and violence, we simply cannot incarcerate our way out of the drug problem. Put simply, an enforcement-centric “war on drugs” approach to drug policy is counterproductive, inefficient, and costly. At the other extreme, drug legalization also runs counter to a public health and safety approach to drug policy. The more Americans use drugs, the higher the health, safety, productivity, and criminal justice costs we all have to bear.

...differs very clearly from the prior ONDCP approaches. Even McCaffrey, as conversant as he was with the science*, still leaned heavily toward the punitive side.

Naturally, I am best pleased that they have a section entitled "The Science":

Throughout much of the last century, scientists studying drug abuse labored in the shadows of powerful myths and misconceptions about the nature of addiction. When science began to study addictive behavior in the 1930s, people addicted to drugs were thought to be morally flawed and lacking in willpower. Those views shaped society's responses to drug abuse, treating it as a moral failing rather than a health problem, which led to an emphasis on punitive rather than preventative and therapeutic responses.

And I would say that we still labor under a great deal of resistance, even though the hard edges may have morphed. We hear people trying to parse "only psychological" addiction from "physiological" addiction...what is this if not more of the "moral failing" argument? We also have attempts to define some substances (and non-substance reinforcers) as being out of consideration for genuine addiction.....again, a similar discounting of the science related to addiction. If you grasp the fact that addictions are disruptions of reward pathways, and that there are a limited set of final-common-mechanisms for reward in the brain then it is no surprise that anything which trips the reward triggers has the potential to cause disruption.

Today, thanks to significant advances in neuroscience, our Nation's responses to drug abuse have begun to change. Groundbreaking discoveries about the brain have revolutionized our understanding of drug addiction, enabling us to respond more effectively to the problem.

Science demonstrates that addiction is a disease of the brain—a disease that can be prevented and treated, and from which people can recover.

Well yes...buuuuuut. Our ability to prevent and treat still has a long way to go. And this, I recognize fully, contributes to public misunderstanding. After all, if it is a disease, surely we must have very specific and mechanistically coherent treatments, right? We don't, for the most part, and so skepticism over the assertion of "a disease of the brain" will continue.

*He was the first Drug Czar I heard address a scientific audience. He was impressive. They guy that came after him during the Bush administration was...not.

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Pondering the Pitbulldenialista


The dog botherers always insist the dog attacks are due to "bad owners". And that presumptively "good owners" will never have a dog that attacks or kills anyone.

We'll leave aside their denialism about their own doggy's noninjurious but threatening behavior and the inherent circularity of their argument for now.

The interesting point is what it takes to be a "good" owner. You have to train and "socialize" the dog. Control it. Keep it in the right circumstances. Train toddlers how to "approach it properly". Leash it. Lock the gate. Etc. never let down your vigilance for one little second.

What is all of this but a frank admission that these alleged domesticated animals are INHERENTLY dangerous to other citizens? If they weren't, the only problem would be "bad owners" who actively train the dog to aggress.

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R.I.P. C. Everett Koop

Feb 25 2013 Published by under Public Health

via Wikipedia

For those of us of a certain age, Dr. C. Everett Koop will always be the iconic Surgeon General of the United States of America.

For me, the reasons that he was also a great Surgeon General is summed up in these few lines in the ABC News item on Koop's passing.

Koop carried out a crusade to end smoking in the United States; his goal had been to do so by 2000. He said cigarettes were as addictive as heroin and cocaine. And he shocked his conservative supporters when he endorsed condoms and sex education to stop the spread of AIDS.

These were both very, very important things for the nation's top health official to do at the time. Especially when the President himself couldn't bear to say "AIDS" in public and many people still believed that smoking was just a 'habit', that low-tar and filtered cigarettes were safer and that the link to cancer had never been "scientifically proven" anyway.

RIP Dr. Koop

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Go Team!!!!!

Feb 03 2013 Published by under Neuroscience, Psychology, Public Health

I've decided I am rooting for neuronal survival during the NFL SuperBowl today.

Go #teamneuron!

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Antivaccaloon learns lesson the hard-ish way; luckily kid survives

Via the New Zealand Herald:

A boy who almost died of tetanus before Christmas is home and on the mend, but his parents are desperate for others to vaccinate their children after they did not.

Auckland couple Ian and Linda Williams thought they had made an informed decision against immunising their three children because of concerns over adverse reactions.

But they regretted their decision when middle child Alijah contracted the potentially fatal disease just before Christmas, and was put in an induced coma on life support at Starship hospital.

They immediately immunised their other children and wrote to Alijah's school to warn parents who had not vaccinated against the disease and others such as whooping cough.

"It was me that put my son in this situation," Mr Williams said.

Yes, yes it was. Don't let it be you who does the same, people. Vaccinate, vaccinate, vaccinate.

h/t: bengoldacre

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First Aid for Mental Health

Dec 15 2012 Published by under Psychology, Public Health

Almost by definition there is something wrong with the mental health of mass shooters like the Aurora cinema guy, the Sikh Temple shooter and the one who just killed 20 elementary school children, 6 staff members, his own mother and ultimately himself.

In parallel with the calls for better gun control in the US we experience calls for improved health care for the brain. But the failing is not the provision of care so much as it is the detection of mental health problems that might lead to mass shootings.

We will never get to a one to one prediction of who is about to become the next news cycle. But then, we don't know who will heal eventually from a given infection, who will recover from stroke without a given intervention...or who will get heart attack save for the cholesterol meds, statins and what not.

So we go with the odds.

And we detect problems with broad screening (annual checkups), acute responses (minor cardiac event perhaps)...and crowdsourcing.

If someone were bleeding in front of you, chances are decent that you would know whether to get a bandaid (even a 5 year old knows to add the antibiotic cream) or stick a finger on the vein while yelling for help. In a crowd? Someone would know CPR if a person stops a pinch you'd have a go based only on what you remember from teevee shows.

What about when someone shows signs of a mental health problem? How does the crowd and pre-FirstResponse do with those situations?

I have only recently been made aware of Mental Health First Aid.

It intrigues me.

28 responses so far

Should NIMH be funding Me-Too drug development?

Hard on the heels of something I just learned about at a recent conference, the NIMH issued a Press Release for a new clinical trial they funded.

A drug that works through the same brain mechanism as the fast-acting antidepressant ketamine briefly improved treatment-resistant patients’ depression symptoms in minutes, with minimal untoward side effects, in a clinical trial conducted by the National Institutes of Health. The experimental agent, called AZD6765, acts through the brain’s glutamate chemical messenger system.

Interesting. The background is that prior studies* have shown that the dissociative anesthetic ketamine is capable of the rapid (within hours) amelioration of depressive symptoms. Yes, ketamine. The recreational drug known as Special K and the veterinary anesthetic they've used on your pet cat or dog. Same ketamine that is approved for human use in pediatric anesthesia, emergency medicine in some cases and for tricky clinical situations.

The same ketamine that has been widely used for decades in humans and nonhuman animals. It has established efficacy, mechanism of action and a huge therapeutic index. A big distance between effective doses and the dose that will kill you. Whether effect is recreational, medical or veterinary. Meaning it is safe.

So why are the studies (cited below*) of effect in depression so exciting? Because traditional drug therapy for depression takes weeks to have effect. Weeks of daily dosing. Selective Serotonin Reuptake Inhibitors (SSRIs) like Prozac are broadly familiar to most of my Readers, I would assume. Efficacy with these front-line meds takes up to three weeks to see effect on depressive symptoms. Trouble is, some cases of depression are acutely suicidal--they may just kill themselves before any SSRI has a chance to make them feel better. And hell, who wants to wait three weeks if another med could make you feel better by tomorrow? Prior to the ketamine work, the only other thing that seemed to have such a rapid effect was ECT. Yeah, ElectroConvulsive Therapy. Which has come a loooooong way from the One Flew Over the Cuckoo's Nest era....but still. A single ketamine dosing seems quite preferable.

So.....on to the me-too drug development! Woot!
Zarate CA Jr, Mathews D, Ibrahim L, Chaves JF, Marquardt C, Ukoh I, Jolkovsky L, Brutsche NE, Smith MA, Luckenbaugh DA. A Randomized Trial of a Low-Trapping Nonselective N-Methyl-D-Aspartate Channel Blocker in Major Depression. Biol Psychiatry. 2012 Nov 30. pii: S0006-3223(12)00941-9. doi: 10.1016/j.biopsych.2012.10.019. [Epub ahead of print][Publisher, PubMed]

This AZD6765 compound is, as you might deduce from the letters, property of AstraZeneca Pharmaceuticals and indeed one of the authors lists this as his affiliation. The rest of the folks are from the NIMH intramural program which, presumably, provided the majority of the funding for the study.

The conclusions appear to be that this novel compounds, with a similar mechanism of action as ketamine worked but less well. From the Presser:

About 32 percent of 22 treatment-resistant depressed patients infused with ASD6765 showed a clinically meaningful antidepressant response at 80 minutes after infusion that lasted for about half an hour – with residual antidepressant effects lasting two days for some. By contrast, 52 percent of patients receiving ketamine show a comparable response, with effects still detectable at seven days. So a single infusion of ketamine produces more robust and sustained improvement, but most patients continue to experience some symptoms with both drugs.

However, depression rating scores were significantly better among patients who received AZD6765 than in those who received placebos. The researchers deemed this noteworthy, since, on average, these patients had failed to improve in seven past antidepressant trials, and nearly half failed to respond to electroconvulsive therapy (ECT).

So this is good. Anything that shows promise as a rapid-alleviator of depression is good by my lights.

But why is NIMH spending taxpayer dollars to develop me-too drugs? Look, I recognize that drugs within a class of pharmacological mechanism, like the SSRIs, may be differentially effective for different patients. And it is a good thing if we have more options to tailor medication to the individual patient. ADHD is another situation where an array of monoamine transporter inhibitors, including methylphenidate and amphetamine, are used with success and failure. One drug works for one patient, another works for a different patient....and they might describe the other medication as even worse than not being treated. So...great.

But make no mistake. The central feature driving me-too drug development is profit. Drug companies decide they can take a big enough slice of the market away from the market-leader to make it worth their while. Perhaps they had development in parallel and had sunk enough cost in by the time their competitor gained FDA approval that there was no turning back. Whatever. Point being that they are in it for the money and not for some noble cause of serving that subset of patients that do not gain relief from their competitor's drug.

Over the past few years the side-chatter about the ketamine effect on depression has frequently been a lament about the lack of financial motive for companies to push forward with ketamine. Push forward with specific clinical trials to gain on-label approval for the indication of depression. Push forward with marketing campaigns. Push forward with physician education and stroking like they do with their proprietary stuff.

The Zarate paper took a stab at claiming the reason for developing something else was an attempt to avoid the adverse effects of ketamine. The dissociative type effects can be unpleasant and recovery doesn't look fun. So there's some toehold there to claim one is motivated to find a "perfect" drug which somehow produces the therapeutic effect with nothing else. Color me skeptical, given what I know about existing NMDA channel blockers like ketamine (and PCP, did I mention that? Yeah, angel dust might work for depression....).

So I smell profit motive in this effort.

What I don't understand is why NIMH is involved with this. Why not just pursue the evidence body for ketamine?
*References pulled out of the paper
R.M. Berman, A. Cappiello, A. Anand, D.A. Oren, G.R. Heninger, D.S. Charney et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry, 47 (2000), pp. 351–354

N. Diazgranados, L. Ibrahim, N.E. Brutsche, A. Newberg, P. Kronstein, S. Khalife et al. A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression. Arch Gen Psychiatry, 67 (2010), pp. 793–802

C.A. Zarate Jr, N.E. Brutsche, L. Ibrahim, J. Franco-Chaves, N. Diazgranados, A. Cravchik et al. Replication of ketamine’s antidepressant efficacy in bipolar depression: A randomized controlled add-on trial Biol Psychiatry, 71 (2012), pp. 939–946

G.W. Valentine, G.F. Mason, R. Gomez, M. Fasula, J. Watzl, B. Pittman et al. The antidepressant effect of ketamine is not associated with changes in occipital amino acid neurotransmitter content as measured by [(1)H]-MRS Psychiatry Res, 191 (2011), pp. 122–127

M. aan het Rot, K.A. Collins, J.W. Murrough, A.M. Perez, D.L. Reich, D.S. Charney et al. Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression Biol Psychiatry, 67 (2010), pp. 139–145

7 responses so far

"Chemical Free" is bullshit. But you knew that already.....

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Big Pharma is pulling out of CNS indications, NIMH to the rescue?

Jan 06 2012 Published by under Neuroscience, NIH, Public Health, Uncategorized

A recent blogpost from NIMH Director (and Acting NCATS Director) Tom Insel details the grim future for private sector development of drugs for the brain and behavior disorders.

But change is coming from another direction as well, especially for psychiatric medications. Over the past year, several companies, including Astra Zeneca, Glaxo-Smith-Kline, Sanofi Aventis, and recently Novartis, have announced either a reduction or a re-direction of their programs in psychiatric medication R&D. Some of these companies (such as Novartis) are shifting from clinical trials to focus more on the early phases of medication development where they feel they can identify better targets for treating mental disorders. Others are shifting from psychiatry to oncology and immunology, which are viewed by some as lower risk.

There are multiple explanations for these changes. For instance, many of the blockbuster psychiatric medications are now available in inexpensive generic form. In addition, there are few validated new molecular targets (like the dopamine receptor) for mental disorders. Moreover, new compounds have been more likely to fail in psychiatry compared to other areas of medicine. Studying the brain and the mind has proven to be much more difficult than the liver and the heart. Most experts feel the science of mental disorders lags behind other areas of medicine. The absence of biomarkers, the lack of valid diagnostic categories, and our limited understanding of the biology of these illnesses make targeted medication development especially difficult for mental disorders.

As I may have mentioned already, this sort of change in the development "system*" gives me a better reason to agree with the creation of NCATS and the earlier noises about the NIH taking a more active role in therapy development. There are lots of indications that don't receive enough attention because there is no route to sufficient profit. Drug abuse is one of those indications. Part of the reason we aren't more advanced in pharmacotherapy for substance abuse is on us, the basic science folks. Sure. But a big part is also on private industry which never saw where the paycheck was going to come from. So there was never much enthusiasm for pursuing anti-substance abuse programs. No program, no drugs. Remember, estimates run some 10-20,000 compounds evaluated in a drug development pipeline to arrive at each approved medication.

I don't believe the NIH can improve this by being smarter, that is a foolish conceit of many. But not having to seek blockbuster returns does change the calculus for what indications are worthy of serious drug development effort.

And that would be a GoodThing.
*such as it is

10 responses so far

Annual Use of Cannabimimetic (Spice/K2, etc) Products in 12th Graders

Dec 22 2011 Published by under Cannabis, Public Health, Uncategorized

The Monitoring the Future study has added the synthetic marijuana products (see here, here, here for additional) to their annual survey. Data on annual use rates are now available for the 12th grader segment. I have taken the liberty of graphing the annual use rates for a selection of the more common drugs in this 2011 dataset.
What you can see (click on the graph to see a bigger version) is that these products are more popular than a host of drugs that have a considerably longer history. These packets of plant material spritzed with one or more full endocannabinoid CB1 receptor agonists (see dr leigh here, here for details) only really appeared on the US market in 2010 in broad availability.

Not too shabby to already be beating these other drugs, eh?

Unfortunately the full monographs aren't available yet and the update tables for "lifetime" and "30 day" do not appear to include the synthetic marijuana category yet. Nevertheless, it's a good thing that this drug category has been added to the survey. As we go forward it will be interesting to see if popularity continues or if this was a brief flash in the pan related to broad quasi-licit availability of these products.

These data will also provide a nice comparison to more limited investigations such as this one. Hu et al (2011) report 8% cannabimimetic use in a sample of 852 college students collected in September of 2010.
The Annual Prevalence table is here.

MtF 2011 update page

To the Maximus Foundation (@FakeWeed)

21 responses so far

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