Additional Thoughts on Acetaminophen & SSRIs [Updated!]

This is a follow-on to my blog: Acetaminophen SSRI interaction Responsible for Dangerous Behavior? which should be read first.

As an indication of the complexity of dosing and schedule along with interactions here are but two relevant studies of several published recently.

Study 1

These results suggest that down-regulation of 5-HT(2A) receptor in response to 5-HT release is a major step in the mechanism underlying analgesia produced by this agent [acetaminophen]. On the contrary, chronic use of acetaminophen may result in 5-HT depletion, which in turn produces re-adaptation of postsynaptic 5-HT(2A) receptors. These data provide further evidence for a central 5-HT-dependent antinociceptive [reducing sensitivity to painful stimuli] effect of acetaminophen.

http://www.nature.com/npp/journal/v38/n6/abs/npp2012258a.html?WT.ec_id=NPP-201305

So, Acetaminophen DOES affect the receptors involved in SSRIs treatment. Further, a reduction in sensitivity to painful stimuli also applies to psychological pain as seen in my previous blog.

Individuals in psychological pain may become chronic users of acetaminophen. It is well known that such individuals seek drugs to alleviate their discomfort and frequently turn to recreational and prescription drugs including prescription pain relievers. 

The possibility that pain relief seeking is an underling cause of some addiction should be investigated. And the chronic use of acetaminophen by those in psychological pain must also be researched!

Study 2

Altogether,  findings from this study provide insights into the serotonergic regulation of executive control processes and suggest that impaired 5-HT_2C receptor signaling during development may predispose to executive function disorders.

http://www.nature.com/npp/journal/v38/n6/abs/npp2012258a.html?WT.ec_id=NPP-201305

Additional Thoughts

Executive function disorders, among their other components, involve a lack of judgment and behavioral dis-inhibition. Such impairment could lead to violent behavior in some individuals.

Executive function disorders can, in my humble opinion, be exacerbated or simply become apparent during final brain maturation (just like adult onset schizophrenia). For those individuals who exhibit the disorder in childhood they may have taken or be taking Ritalin or related drugs. Such a history is likely to significantly effect any acetaminophen/SSRI interaction. And such a history is likely to contribute to violent behavior.

Tylenol May Ease Anxiety Over Death 

Surprise! Science "Proves" Life is Older than the Earth

  Inadvertently posted to "News Mage" Blog

By 2X!

An article in MIT Technology Review [which is based on Life Before Earth by Alexei A. Sharov and Richard Gordon (http://arxiv.org/abs/1304.3381 )]  says that the evidence is clear. “Linear regression of genetic complexity (on a log scale) extrapolated back to just one base pair suggests the time of the origin of life = 9.7 ± 2.5 billion years ago..."

Since the Earth is only 4.5 billion years old, the authors and scientists in general are in a bit of a pickle. If their methodology is sound, one is left with the question, "Where then did life begin?" Apparently it wasn't on earth.

So just how did these well respected, at least until now, scientists dive into this particular pickle barrel?

Their diving board is the curious intersection of genetic evolution and computer development. Intel co-founder Gordon E. Moore, described the trend of increasing complexity in integrated circuits in his 1965 paper. His paper stated that the number of components in integrated circuits had doubled every year from the invention of the integrated circuit in 1958 until 1965. He then predicted that the trend would continue "for at least ten years." This prediction became known as Moore’s Law. 

It's been about forty years beyond his predicted ten and his law still holds. There has continued to be an exponential increase in the number of transistors on microchips.

The MIT article states " if an observer today was to measure this rate of increase, it would be straightforward to extrapolate backwards and work out when the number of transistors on a chip was zero. In other words, the date when microchips were first developed in the 1960s." 

Applying the law in reverse (reverse extrapolation) does, in fact, provide the date of the first integrated circuits.

In a similar fashion one can apply the reverse extrapolation methodology to scientific publications. Using a known pair of dates, 1990 and 1960, one can determine the doubling rate.  Scientific publications doubled in number about every 15 years during that period. Using reverse extrapolation one can find the date for the origin of scientific publication. The date  is 1710. This is about the time of Isaac Newton - a reasonable date for the origin of scientific publication.

Having successfully applied this reverse extrapolation methodology to two deterministic domains, it seems reasonable to apply it to another.

Alexei Sharov at the National Institute on Aging in Baltimore and Richard Gordon at the Gulf Specimen Marine Laboratory in Florida, decided to apply the method to complexity and life.

They argue that they can measure the complexity of life and the rate at which it has increased. They use as their basis data from the development of life's complexity from prokaryotes to eukaryotes to complex animals such as worms, fish and eventually mammals. They state that the data produces a clear exponential increase identical to that behind Moore’s Law. Of course the doubling time is a bit longer than two years -  376 million years to be exact - well, if not exact, approximately 375 give or take a million or two.

Having this data they can reverse extrapolate the complexity of life. The results should give an origin data - plus or minus a few million or billion years.

Unfortunately for science, evolutionary biologists, and our intrepid researchers, the results are unsettling.  “Linear regression of genetic complexity (on a log scale) extrapolated back to just one base pair suggests the time of the origin of life = 9.7 ± 2.5 billion years ago...”

One attack on their finding is that it is unreasonable to assume the complexity of life has increased at the same rate throughout Earth’s history. Some argue that the early steps in the origin of life created complexity much more quickly than evolution does now. Thus, the timescale can be squeezed into the lifespan of the Earth.

According to the MIT article, "Sharov and Gorden reject this argument saying that it is suspiciously similar to arguments that squeeze the origin of life into the time span outlined in the biblical Book of Genesis." 

Ah, isn't it interesting to see the Intelligent Design skeptics hoisted on their own scientific petard?

http://www.technologyreview.com/view/513781/moores-law-and-the-origin-of-life/

http://arxiv.org/abs/1304.3381

Acetaminophen SSRI interaction Responsible for Dangerous Behavior?

Acetaminophen has been found to reduce the psychological effects of fear and anxiety. I think it is highly likely there an interaction with SSRIs. Could this interaction explain dangerous behavior?

Of course it could.

There is a complicated interaction scenario. Consider a 4 way matrix take A or take B cross with stop taking A or stop taking B. Lots of combinations. Add in how long a person has been on each drug and the dosage of each.

Different SSRIs have different effects so any interaction would be different for each SSRI.

In the real world many people cycle through SSRIs looking for one that is effective for them.

Ethnicity, age, prior pain med usage, and gender could all influence effects too.

All these factors make studying possible interactions difficult - especially under controlled conditions.

This may be a break thru in understanding the seemingly random effects of SSRIs and the lack of replication in clinical studies.

http://www.eurekalert.org/pub_releases/2013-04/uobc-aal041613.php