The term “drugs of abuse” gets thrown around when trying to specify drugs that are detrimental in nature. This is opposed to the “drugs of use” that would include over-the-counter and prescription medication. It is far too often that these abusive drugs lead one into a path of addiction, and it is far too often that this path of addiction leads to death. So I must ask, why are “drugs of abuse” drugs of addiction?
Our remarkable human bodies have evolved in such fascinating ways. We, as a species, have honed in on the most practical ways to learn about the world, and remember what we learn, so that we might apply it in, ultimately, reproducing and raising our offspring. A result of this evolution is our ability to remember what gave us a “good” experience.
When I say “good”, I mean in the sense that the experience will increase one’s likelihood of creating and rearing successful offspring. This “good” experience can manifest itself in multiple ways: the awareness that comes along with a cup of morning coffee, the relaxation of a massage, the satisfaction in eating a pastry, or the intrinsic pleasure of sexual activity. It is such that all of these activities increase the odds of making successful children (some more directly than others).

Thanks to evolution, our brains devised incredible ways to “lock on to” these events, remembering exactly how they felt, and the specific steps taken to allow them to occur. Because of this, we get remarkably good at reproducing these feelings of pleasure, and most of the time, it is a very good thing.
The brain must transmit its signals somehow, and since the basic building blocks of life are chemicals, it chooses to transmit the signals as chemicals. Neurotransmitters, as they are called, are the chemicals released within the synapses of the brain, and they give us the ability to be humans. During the aforementioned “periods of pleasure”, many of these neurotransmitters are released, but the most important (and plentiful) of these is dopamine.

Dopamine is used colloquially as the “feel-good” hormone, and indeed it produces pleasurable effects. It is important in other aspects, however. As was mentioned, our brains are very good at remembering exactly how pleasurable events were created. It is dopamine that locks down these memories.
This is where drugs of abuse play such an important role. Nearly every abusive drug increases dopaminergic receptor agonism (“extra dopamine release”). This is either done in a direct (mescaline and amphetamine) or indirect (most other drugs of abuse) manner. Regardless of the process, the brain is receiving signals of pleasure from an unnatural source. Note, I use the term “unnatural” to mean that the brain is not triggering its own dopamine release, but rather substances from outside the body are.
Since these drugs can be administered in any dosage, it is quite common for internal dopamine levels to increase past the point of any natural setting. This incredibly high concentration of dopamine creates the “high” felt by abusers, as well as the second effect of dopamine: the formation of intense memories associated with obtaining the feeling of pleasure.
It is well-hypothesized that these “memory-forming” effects of dopamine play just as important of a role in addiction as the pleasurable effects do. While the pleasurable effects are likely more important in the development of withdrawal symptoms, the intense memories give addicts the urge that cannot be erased from their minds. When we look at the two together, we can see why the road to addiction is far too short.

Since extra dopamine is flooding the synapses, the brain thinks something is wrong, and down-regulates its dopamine receptors. This is, again, a result of evolution as it is meant to “reset” the brain to a normal state. But once the drug wears off, and dopamine levels return to normal, the brain cannot activate as many receptors as it normally would have. The result of this is initially depression, but follows with all sorts of horrendous symptoms which the reader may look up for themselves. This process is characterized as withdrawal.
The sad case of the matter is that eventually addicts do not seek the drug to experience a high, but rather to avoid a low.
The memory-effects of dopamine also come into play here, for just as the drug wears off, an abuser will remember the “good ol’ times” vividly. It will cease to matter whether the process of getting the drug is detrimental (expensive or dangerous); the addict will seek out a repeat experience nonetheless. And of course, each time the process “works”, the abuser will have strengthened the memory further. It is through this process that the “cravings” of addiction are created.
And so, terrible withdrawal symptoms, coupled with cravings, arises from repeated abuse of drugs. The well-known saying that drugs “hijack the body’s reward mechanism” are completely true. There is little escape from the self-administration of “dopamine” because of its grip on creating habits, and when administered in high concentrations, our bodies cannot prepare. What was meant to reinforce habits capable of creating life, in the end creates habits capable of destroying it.

A diagnosis of ALS is often accompanied by feelings of fear, frustration, sadness, and anger. Amyotropic lateral sclerosis (ALS) affects about 6,000 Americans every year and usually appears in midlife. In order to better cope with a diagnosis or help a loved one going through it, education is important. Understanding what we do know about the disease can be beneficial. The image below outlines some of the potential contributing factors to ALS.

ALS can be difficult to clinically diagnose because there is no test for it. It is diagnosed by ruling out other options such as: thyroidtoxicosis, cervical spondylosis, diabetes affecting brachial plexus, carpal tunnel syndrome or lesion on the elbow, neuropathy, chronic inflammation, myasthenia gravis, sclerosis, spastic paraplegia. Only about 10-15% of people have a false positive diagnosis.

After a diagnosis you visit the doctor every 3-6 months. At an ALS Association Certified Center of Excellence, your team typically consists of the neurologist, RN, speech pathologist, respiratory therapist, physical therapist, occupational therapist, dietician, rehab tech, and a social worker. You can participate in clinical trials for new drug treatments if you fit the criteria.

The current understanding of the pathology of the disease is limited and there are many factors affecting the onset of ALS. We know that oxidative stress causes changes in the cell that contribute to the death of motor neurons. As you can see in the drawing, in the presence of oxidative stress, stress granules form and remove TDP43 and FUS from the nucleus (information center) of the cell. TDP43 and FUS are critical to cell function, and when they are removed from the nucleus and clump up in the cell, it causes damaging effects seen in ALS patients.

Treatment of ALS is very difficult to find because of the complicated nature of the disease. Researchers have not been able to find the key target that would stop or reverse the effects of the disease. The current drug on the market Riluzole only prolongs life by 2-3 months and is an antiglutamate drug acts by reducing levels of excess glutamate found in the nervous system. Current clinical trials are in progress for trying to use stem cells to promote neuron survival and growth. Because 90-95% of cases are sporadic it is difficult to pin down a genetic sequence that is inherited to explain the cause of the disease. It also tends to be found in Caucasians and is more common in males than in females.

While this disease is scary, it needs to be talked about to raise awareness and help work toward finding a cure. In order to better cope, it is helpful to join a support group and learn as much as you can about the disease. It is recommended to maintain a good lifestyle, healthy eating, exercise and time with loved ones.

For more information see: http://www.alsa.org/

Just three weeks ago, I purchased A Brief History of Time, by Stephen Hawking, and less than two weeks ago, I finished the book. From what I hear, Stephen Hawking’s persona is equally linked to ALS (amyotrophic lateral sclerosis) as it is to black holes, quantum mechanics, and general relativity. The “pop culture” idea of the man is as the wheelchair-bound genius. Thus, I found it remarkably coincidental that the following Monday I was required to read a recent journal review of ALS for my neurochemistry course.

The review highlighted recent research regarding RNA dysregulation and oxidative stress as main culprits for the debilitating disease. It insisted that the two were inexplicably linked through the processes of two nuclear (i.e. pertaining to the nucleus of the cell) proteins, FUS and TDP43. The overarching theory was that oxidative stress would cause these proteins to leave the nucleus, and find their way to other parts of the cell where they would cause problems with RNA (think of it as the link between DNA and proteins). Basically, oxidative stress was destroying the cell’s ability to properly make proteins. This would in turn lead to more oxidative stress which would just start the cycle over again, eventually the cell (a motor neuron, the body’s way of telling muscles to move) would die, and thus we have ALS.
This is truly a remarkable theory, and certainly there is evidence to support it, but there is a competing theory: excitotoxicity of motor neurons. Excitotoxicity is a big word. It means that the cell is getting too much stimulation, and thus eventually dies. (Too much of anything is bad it may seem.) Indeed, the best pharmaceutical drug prescribed to ALS, riluzole, is a glutamatergic inhibitor (prevents excitotoxicity). However, even this drug is thought to extend the average life expectancy of a patient, which is only 2-3 years usually, by only a few extra months.

If the drug works at all, it must be targeting something that is causing the disease, so we can readily assume that excitotoxicity is a culprit. But the drug certainly does not cure ALS, so it cannot be giving us the full story. Perhaps the review I mentioned gives the other half of the story, though that is highly doubtful. In the end, we must agree that there is no single answer to solving this problem.
I then look back at Hawking, and his book, A Brief History of Time, and again notice a coincidence. Hawking argues that our knowledge of the universe is likewise incomplete, as there may indeed be no singular answer to the problem. He argues for more collaboration, and ultimately more research. If this is to be the case, however, I wonder if perhaps our research into the workings of the universe would be misplaced.

Let us imagine, for a second, what kind of world we would live in if instead of wasting hours on end mathematically modeling the trajectories of black holes spiraling into one another, we put our efforts into saving lives medically. We spend enormous amounts of time on understanding the maddeningly large, and the unthinkably small, that we forget about the in-between where lives may be saved. How is it that we can say how much slower time may progress for a relativistic traveler, but we cannot discover the causes of ALS? Could Hawking himself have, if not cured, perhaps contributed to his own disease’s salvation? Educated human beings place so much effort into things that will likely never save lives. And I constantly wonder if my own pursuit of mathematics will do “harm” to the world in the sense that I am not doing as much “good” as I could in chemistry.
Without a doubt, we (as a species) could have saved millions of lives from countless diseases if we had put our efforts into medical technology, instead of other pursuits. And yet we continue to do otherwise. Why? Indeed, there can only be one answer. Human lives cannot be quantified as “better” by the amount of time they exist. What I mean to say is, saving a life is not saving a life if one has instead thrown away one’s own life in the process. We are only here for a fleeting moment, and as such it is important for each of us to make the most of the fleeting moment. That may indeed consist of saving lives medically, but it may also consist of “saving lives” in other ways. Perhaps an article written by a journalist prompts a young boy to enter politics, wherein he pushes to allocate more money to NASA, who in turn create a nano-scale polymer to shed heat on rockets reentering the atmosphere, but indeed that nano-scale science is published and gives medical researchers the ability to create cancer-targeting drugs, wherein countless lives are saved. The journalist, perhaps dead for twenty years, has just saved lives, by doing what she loved best. A scenario like this, can be represented by the butterfly effect, which states that the smallest change in initial conditions can have unforeseeable consequences for the future.
In the end, then, we can at least agree that our actions, however we decide to make them, will certainly change, and possibly even save, lives. Stephen Hawking may likely still be bringing about his disease’s salvation, just in an obscure way. But at the same time, he is following his own path and immensely impacting the world for the better. It is not only our right, but our duty to pursue our own passions, even at the extent of others’ deaths.