Undereducated about the Unknowns

• The essentials of Nutrition come down to the idea of Energy Balance or how energy is taken into the body, generated, and then expended. A positive energy balance is when more energy is taken in and then stored resulting in weight gain while a negative energy balance is where less energy is taken in than used so fat stores must be used. Remember that the goal of eating food is to make energy which is represented by the molecule ATP (produced by the Mitochondria!). However, depending on the kind of activity done, we may not have enough stored ATP in the body to cover the activity and thus have to use other means of ATP production.
  • When we are at rest, the activities we do such as swiping your thumb on a screen and moving your eyeballs to read do rapidly deplete the amount of stored ATP—this is why you can sit all day without feeling winded. If we perform a more intense activity, such as walking, the stored ATP is used incredibly quickly (lasts <10sec) and we have to use Aerobic Metabolism to create ATP while doing the activity. Aerobic Metabolism utilizes oxygen to make ATP and is incredibly efficient which enables us to do low-impact activities for an extended period, like walking down a hallway. As the impact level of the activity increases or the length of time increases the body switches from Aerobic Metabolism to Anaerobic Metabolism which is ATP production when oxygen is not available. This isn’t to say that your muscles have 0 oxygen when you are running but more that oxygen demand (moving the muscle) is much higher than oxygen supply (oxygen capacity of red blood cells). As such, the body utilizes Anaerobic Metabolism which produces ATP for energy but also Lactic Acid which causes that muscle pain after exercising.

• To make it simple, Aerobic Metabolism is used in low-impact activities while Anaerobic is used short bursts of high-impact (like a 2-min workout) OR prolonged high impact activity (like crossfit or HIIT exercises). Now that we understand that, we can see what kind of energy source is used in what kind of metabolism. As you can see, Fatty Acids are part of Aerobic Metabolism but only after about 1.5-2hrs of activity. What this means is that in order to burn fat you need to burn your Liver glucose stores (called Glycogen) first and then you can start burning fat. So the 20 minute treadmill run while great for raising your mood and improving blood vessel health may not touch the fat in your belly.
• This brings us to the other aspect of Nutrition—diet. Now this is where the lack of words to describe the science is cumbersome. Someone’s food intake, aka their diet, is different from dieting (cutting out certain foods) which is different from following a Diet (capital D), a more strict set of food guidelines. I don’t have the training to discuss what is a good Diet but I can talk about what are the necessary components of what makes up a good diet (lower case d). In general, it is all about ensuring you have the essential nutrients and reduce the intake of weight gaining foods. Essential nutrients like Vitamins, Minerals, Trace Elements, essential Amino Acids are required from our food in order to live and there are lots of sources online about which foods create balanced meals that fit your preferences. What is nonessential is carbohydrates, proteins, and fats (except omega-3 fatty acids). Yeah, kinda weird to think that the main components of our foods are nonessential but what that means is that we can change it up as needed to fit your current need.
  • Carbohydrates are a group of macromolecules that consist of carbon, hydrogen, and oxygen and are very energy rich. Carbs come in two flavors: nondigestible and digestible. Nondigestible carbs are the dietary fiber we need to ensure that our stools can form solidly and move along the intestines. There are lots of types of fibers but the one for weight specifically is Viscous Fiber which forms a gel in the intestines to reduce sugar and fat absorption. Unprocessed oats, flaxseeds, asparagus, beans, and Psyllium Husk are great sources of Viscous Fiber which help reduce the amount of fat and sugar we take in from our food. Digestible carbs on the other hand are the sugar we normally think, the sweet stuff like glucose, sucrose, fructose, and starches. All digestible carbs can result in weight gain but it all depends on the amount you eat. The essential of a diet is not what you eat but how much you eat; so yes you can have some cake one day but you should abstain for the next few days.
  • Unsurprisingly the fat we eat can be absorbed into the body and used to make fat that is stored. Animal products and processed foods are highest in fats that are likely to be stored while plant based fats and oils are less likely to be stored (more likely to be immediately used as energy).
  • Finally proteins which are not required for weight loss but are essential for muscle gain and the best way to promote further energy expenditure after exercise is to promote muscle synthesis. Essentially, when we exercise the muscle is damaged either by the flexing of the muscle or by the lactic acid produced and so needs to recover with protein in our diet. In order to use the protein the body needs to spend energy which can be done in the form of using more stored fat. Thus, eating protein while trying to lose weight can provide additional benefits.
  • So what does this all mean in terms of the exercise we were talking about before? Well remember that in order to burn fat someone needs to exercise about 1.5 hours to burn through stored glucose stores. Now this can be really cumbersome but the way around this is to starve the Liver of glucose to rebuild those glucose stores. By keeping a low-carb diet, your liver wouldn’t be able to use dietary glucose to rebuild the Glycogen stores and instead have to use more fat! As such, keeping the amount of glucose in your diet low aids in getting to the 1.5 hours sooner and can facilitate using fat as a main energy source when you are at rest.
• Now diet and exercise is all well and good but there is a big factor here that we have to consider: ability to diet and exercise. Yes physical ability is a major aspect but this is why this section is titled Undereducated—for individuals who are lower socioeconomic status (SES) they have a harder time achieving the necessary diet and exercise goals to find significant weight loss. Is this because they are uneducated? No, most Obese people of any SES know that eating better and exercising will make them lose weight, but performing those actions uses another major commodity: time. Unfortunately, those of lower SES face several challenges that make it extremely difficult to lose weight: often they are working lower wage jobs meaning that more time is spent working and less time available for exercise. Combine this with the higher cost of living, especially when caring for children, and lower SES correlates heavily with buying cheaper foods which are often not the most nutritious. If a parent has to feed 4 children with a few dollars, they will use sources of food that maximize the value of that dollar—this means processed foods filled with salt and fat to make them taste good. This is part of the benefit of food stamp programs which enable lower earning families to purchase more nutritious foods. But this is where the undereducated part comes in.
  • For many people they think that a weight loss meal is salad, and while its not wrong, its a lot of what is in the meal. Part of my work in college working in a food kitchen was helping families understand how to maximize the benefit of the canned or frozen vegetables and fruits they have access to rather than feeling that healthy food is only fresh produce. A person can accomplish the same nutritive goals on frozen or canned vegetables as they can on fresh or raw foods and often on a smaller budget. I highly encourage those who are on a limited budget to get in touch with their local food bank—often they can connect you with a dietician who can guide you through how to cook nutritious meals on a small budget and for a large family. Please know that diet and exercise is extremely possible even with added time constraints.

And a quick buck was made

• First up we have Orlistat, a medication that does not require a prescription in the United States to use. Orlistat is an inhibitor of stomach and pancreas Lipases, a type of enzyme responsible for breaking down dietary fats. This means that when someone takes Orlistat the fats they eat are unable to be broken down for absorption and instead stay in the stool for excretion. When used correctly, about ¼ to ⅓ of dietary fat isn’t absorbed and there is a sizeable reduction in LDL (bad cholesterol). While its nice its over the counter, Orlistat has some…major drawbacks. The biggest is it’s tolerability—because Orlistat prevent fat digestion, most of the fat stays in the intestines causing oily stools, urgent diarrhea, and smelly flatulence. In its official documentation the term “explosive diarrhea” is used. Now, to avoid these unfortunate side effects a person should meals that are high in fat (no more than 30% of their daily recommended fat amount). Now this begs the question: is Orlistat effective in losing weight because of how it works or because people avoid fat like its poison to prevent explosive diarrhea? Either way someone should expect to lose around 15 lbs at 6 months of regular use which is nothing to sneeze at.
  • Speaking of over the counter weight loss aids we should talk about a few. One of the biggest ingredients included in these supplements is Caffeine. Caffeine is thought to work by increasing someone’s metabolic rate or in other words to increase the amount of energy someone uses while at rest. Part of this is because the heart is working harder (Caffeine increases heart rate) but there is some more systemic effects that are not explained by simple increased fight or flight effects. I can’t find the source I heard this from, because I believe I learned it during a seminar, but somewhere near 65% of OTC weight loss supplements have some form of Caffeine in them. Caffeine can be listed by itself or be hidden in an herb like green tea, yerba mate, green coffee beans, kola, guarana, yaupon, and dozens more. I'm not anti-caffeine, I drink plenty of it everyday but these supplements often have people exceeding the safety limit of caffeine by combining these herbs together. Caffeine can worsen anxiety, put significant strain on the heart, and isn’t recommended for pregnant women. Just be careful!

• One supplement that used to be on the market in the US and is now banned is Ephedra. Ephedra is preparation of the chinese herb Ma Huang which contains the alkaloid Ephedrine and Pseudoephedrine. Both chemicals are part of the stimulant class of medications and when used in large enough doses will cause appetite suppression. Essentially these chemicals stimulate the fight or flight region of the nervous system which suppress the urge to eat. This is actually the reason why stimulants like Amphetamine (Adderall) and Methylphenidate (Ritalin) are used off-label to treat Binge Eating Disorder and help weight loss. Suppressing the urge to eat helps the person eat correct portion of food or prevent binge episodes thus reducing calorie intake. One OTC product that was extremely popular in the late 1990s and early 2000s was Hydroxycut which heavily marketed itself on TV and on the unregulated internet. In 2003 the Missouri Attorney General sued the company over their claims that Hydroxycut was “clinically proven” to burn fat but the case was settled out of court. Later in 2003 the NYT uncovered hidden documents that showed Hydroxycut knew its product didn’t work and have tampered with documents in another lawsuit in Oklahoma to show otherwise. Regardless, the usage of Hydroxycut wasn’t significantly hampered but due to its widespread use and unscrupulous advertising, the FDA banned Ephedra in 2004 after 155 deaths were attributed to the herb. It was the first time a supplement was banned in the US. Hydroxycut then switched to using Hydroxycitric Acid which required a lower dose than the Ephedra based formulations. The company failed to advertise the change in dosing and dozens of cases of serious liver failure resulting in liver transplant were reported and at least one death (19yo male). Hydroxycut is now mostly Caffeine.

• Similar to the stimulants is Bupropion which is combined with the opiate antagonist Naltrexone in the product Contrave. Bupropion is an antidepressant that causes a raise in Dopamine and Norepinephrine in the brain while Naltrexone works by preventing endorphins from binding to the opioid receptor in the brain. Together its thought that Contrave works in Hypothalamus to reduce pro-eating stimulation as well working in the Mesolimbic Dopamine Circuit to reduce the reward feedback someone feels when eating. In a sense, the drugs work by causing someone to be less hungry and then reduce the pleasurability of eating. Contrave can be incredibly useful in people who are mindless snackers (such as eating large quantities of food when not paying attention) or for binge eating disorder. The benefit of using this medication over the stimulants like Adderall or Ritalin because it helps treat the cause of the Obesity (overeating) rather than just preventing the symptom (weight gain). Generally people see around a 25lb weight loss around 6 months.
  • Similar to Contrave is another combination product: Phentermine and Topiramate in the branded product Qsymia. This combo pill utilizes the stimulant Phentermine which comes from the same class as Adderall and Methylphenidate to suppress appetite and Topiramate, originally an anti-epilepsy medication that is thought to suppress appetite, increase satiety, and reducing pleasure from eating. Qsymia produces similar results to Contrave.

• Okay, this brings us to a very controversial medication in the pharmacy world: GLP-1 agonists. If you remember from earlier I described how White Fat releases the appetite-suppressing hormone Leptin due to the stomach and intestine releasing GLP-1. GLP-1 is released when the GI tract detects carbohydrate or fat rich foods and their release triggers a cascade resulting in long term appetite suppression. LIkewise it is believed that the very common side effect of nausea and vomiting reduces the desire to eat. So in a lot of ways, they are working the same as the stimulants are—reducing appetite but not really touching the reason for overeating. GLP-1 agonists like Semaglutide (Wegovy) and Liraglutide (Saxenda) are used primarily for their influence on Insulin in Type 2 Diabetics to help lower blood sugar levels and reduce A1c, a marker of overall health in Diabetes. In diabetes, the clinical benefits of GLP-1s cannot be understated on the heart, kidney, liver and many other organs. In non-Diabetes weight loss? Well…don’t get me wrong they do work—people usually see a 15 lb loss at about 6 months but they miss the mark in the same way that the stimulants do. They prevent symptoms but don’t really help the underlying cause for why someone might be Obese.
  • The other aspect that I am always weary of is when drugs become “popular” in the media and especially with celebrities. Many celebrities and social media influencers are touting the benefits of GLP-1 agonists, i.e. the weight loss, but the consequence of this fad is that Diabetics who rely on this drug are unable to get it anymore. There is a massive shortage in GLP-1 agonists for people who could use another agent with similar efficacy but are using GLP-1s due to the social media presence. Likewise the weight loss isn’t sustained—at about 1 year the weight loss plateaus and after stopping only around 50% maintained the weight loss. Compare this to the other agents we’ve talked about who had a sustained weight loss around 80% and the choice is clear. Another aspect I have against these drugs for weight loss is the use of a side effect as a selling point—the rate of nausea is about 44% which means that someone is making themselves sick in order to lose weight. This is not a life I would put my patients on.

1. POSTURE i struggle with adhd and this condition as when i zone out all my muscles tighten and i find my self hunched and strained. A few tips even for non adhd. 1.As i do with everything else to remind my monkey brain to get things done set timers, every5-10 mins ( there are also multiple apps and google extensions) to remind yourself to unclench your back and jaw. 2. Stand up and walk around or stretch every 20-30 mins even less if you can. 3. Do postural exercises i will link some that i have found benifical aswell as video reference.
   
2. BOTOX/OTHER MEDICATION botox will work on almost everyone but one thing thats different is, some people need the injection at different doses and places. The injection did nothing for me into my masseter muscle however being injected into my shoulder and neck muscles helped beyond my expectations. FOR MEDICAL CANNABIS/NICOTINE: for a long time i stopped smoking cannabis ( it was the only thing that helped with my anxiety and insomnia) because it would cause a flair up IT IS NOT THE DRUG ITSELF. When you are smoking anything you jaw tends to push backward, if you need to smoke something try keep your jaw forward as you do and you will not receive a flair up( wont work for everyone but in my experience it stopped giving me a flair up. You can also swap to a oil or a small disposable thc vape as the smoke comes out much easier with less effort. FOR ADHD MEDICATION first of ADDERALL will cause a flair up in most cases. RITALIN will cause a flair up ONLY if you take to much and have an empty stomach, i dropped from 2-1 tablets 3 times a day and always eat food before and after taking the tablets and no longer have flair ups. I was actually diagnosed with adhd due to my tmj and constantly saying all i can focus on is the pain and the ritalin helped phenomenally but only in a small dose. CLONIDINE if other medication makes you clench this is what you can try, from the amount of research done on it taking it in adjunction to the other medication has shown to treat bruxism aswell as the pain. I personally only take one tablet before bed and have nit gotten better sleep since my tmj journey started. You can take it during the day (do your own research on when, how much, and how often) keep in mind it can make you drowsy
   

Meth by any other name is still just as… sweet? Addictive?

• The onset and duration of Methamphetamine's rush (the intense euphoria feeling) is entirely dependent on what form is used and how it enters the body. Snorting has an onset within 5 minutes and usually lasts about 30 minutes; IV injection happens within one minute and lasts 10-20 minutes; smoking has an instant effect and lasts for about 5-10 minutes. It should be noted that the rush that someone feels is seconds long the quicker the onset is meaning that someone needs to take multiple hits to continue the euphoric rush. The high, which is the mind/body altering feelings after the rush can last anywhere from 4 to 24 hours with most people landing around 12 hours.

“I’ll be your master, you’ll be my slave. Don’t fear being lonely, I'll walk with you to your grave.”

1. Increasing the Release of Monoamines from their neuronal storage so that their signal is boosted
2. Inhibits Monoamine Ruptake Inhibitors so that any released neurotransmitter is kept in the synapse causing the signal to be boosted.
3. Reverses transporter exchange so any neurotransmitter that is removed from the signal is released again thus boosting the signal
4. Weakly inhibits Monoamine Oxidase which prevents the breakdown of the neurotransmitters to have a longer lifespan and thus boost the signal.

• Central Nervous System - Euphoria, Increased Energy, and Feelings of Power. Some of the main reasons why people misuse stimulants is their ability to increase energy, prevent sleepiness, conquer tasks, and of course the euphoria of a high. One of the most common forms of Amphetamine misuse in young adults ages 18-26 is buying prescription drugs like Adderall and Ritalin to help with studying in college. As I went over in my post about ADHD (link), this condition is not cause by a person having too much energy and so we take a drug to dampen that but rather that the person physically does not have the energy to focus. An analogy would be that it is incredibly hard to focus when you are tired, ADHD is similar except the person is not tired but doesn’t have the energy to focus. In a fatigued state the decision making region of the brain, the Prefrontal Cortex, lacks pro-focus neurotransmitters Dopamine and NorEpi. By administering stimulants we are boosting these neurotransmitters in the brain enabling the person to have enough energy to focus. Now its important to note that this effect of focusing is seen at clinical doses (i.e. prescription dose) but when someone is abusing stimulants for a high, they are taking 5 to 50 times the dose of someone taking their prescribed medication. This means we would see the effect of the medication at the lower dose but also the toxicities of taking the stimulant at these enormously high doses.

• One of the biggest effects of abusing Amphetamines is that Dopamine levels will sky rocket. In pop culture we see Dopamine as the happy chemical in the brain but the more accurate way to describe it as the Motivational Salience chemical or in other words it enhances the desirability of doing a task while simultaneously dampening aversion to that same task. We can see this in the Cognitive-Behavioral sense where doing a task becomes pleasurable which encourages us to do it again—taking Methamphetamine would make tasks a more pleasurable experience (the Dopamine concentration rise alone ensures that) and so it drives the brain to seek out those activities more.
  • A parallel to this are the Dopamine Agonists like Ropinirole (Requip), Pramipexole (Mirapex), and Rotigotine (Neupro) which are used primarily in the treatment of Parkinson’s Disease (oh look we have a post on it!). Parkinson’s is caused by the neurodegeneration of Dopamine neurons meaning that there are physically fewer neurons producing Dopamine in the brain. Other than its role in motivation, one of the other main functions of Dopamine receptors is in the initiation and progression of movements. As the illness progresses the number of Dopamine receptors being activated by Dopamine starts to decrease leading to the characteristic movement dysfunction we see in Parkinson’s. This is where the Dopamine Agonists come in—they directly bind to the Dopamine receptor and activate the receptor to replace the Dopamine production that is slowly disappearing.
  • At lower doses, drugs like Ropinirole works primarily with the Dopamine-2 receptor to improve movement but in people who are extra sensitive to the drug we start to see some unwanted side effects. When the drug works on the Dopamine-1 and Dopamine-5 receptors we start to see the feelings of euphoria and behavioral changes in the patient. It is well documented that people who take a Dopamine Agonist are at risk of developing addictions like shopping, gambling, and even sex after they start one of these drugs. Why? Well for similar reasons to an Amphetamine—the drug is activating the Dopamine receptor causing pro-motivation towards those rewarding behaviors thus reinforcing them. In fact there was a big lawsuit in 2012 in France when a patient sued the manufacturers of Ropinirole for his risky hypersexual behaviors and excessive gambling while he was taking the medication from 2003-2010. The behaviors immediately ceased upon discontinuation of the drug and this is why doctors and pharmacists must warn patients to watch out for these extreme behavioral changes.

• Central Nervous System - Feelings of Paranoia. As we have discussed, low doses of Amphetamines allows for an increase in Dopamine and NorEpi in the Prefrontal Cortex allowing them to focus but at abuse levels we see enormous concentrations. The effect of this excess Dopamine in this region of the brain, as well as elevation in the Hippocampus and Amygdala (emotional and fear regions of the brain) is the development of Anxiety and especially Paranoia. Part of this plays into the Reward Circuit of the brain and the addictiveness of the drug but the other is Methamphetamine-Induced Psychosis. Because reward and paranoia are so closely linked, the more someone chases the Euphoria of misuse the more paranoid they are likely to become. Someone can develop visual or auditory hallucinations that can be incredibly scary. All of these are incredibly distressing thoughts but because Methamphetamine can cause a significant withdrawal the person has almost no choice but to continue using the drug else they become incredibly sick.
  • A parallel to the Methamphetamine Psychosis is Schizophrenia—a severe mental illness marked by delusional thoughts, bizarre behaviors, and/or blunted emotions (and yes we do have a post on Schizophrenia found here). It is believed that Schizophrenia is caused by an excess of Dopamine in many different regions of the brain resulting in the wide range of symptoms we see. The hallmark symptom of Schizophrenia is Psychosis or thoughts that do not align with reality—this is where the stereotype that the government is watching the individual come from. The mainstay treatment of Schizophrenia are Antipsychotics (a.k.a Neuroleptics) which act as Dopamine-2 Inhibitors. These drugs block over stimulation of the Dopamine receptor thus preventing overactivation of the Dopamine systems in select regions in the brain to hopefully decrease Psychosis. In a way, Methamphetamine abuse can be seen as a drug-induced Schizophrenia that is very dose dependent.

• As discussed in the Schizophrenia post there are two generations of Antipsychotics: the first generation almost exclusively works on the D2 receptors while the later second generation focuses on D2 and a Serotonin receptor 5HT2a and Alpha-2 receptor (A2). Generally we find better efficacy with these later agents because of their broader effects which suggests that Schizophrenia may have some pathology in Serotonin and NorEpi circuits as well. Remember that Amphetamines also increase Serotonin and NorEpi concentrations so its no wonder why we see this drug-induced psychosis that mimics many symptoms of Schizophrenia.
• Now, does this mean we should treat Methamphetamine use with D2 antagonists? When someone is currently using Amphetamines it would be a terrible idea because we would immediately precipitate withdrawal which is why doctors have to be careful when diagnosing true Schizophrenia vs Methamphetamine Psychosis. It is not hard to imagine a scenario in which a person is brought to the ER in an acute psychotic episode and pumped full of Haloperidol (Haldol) immediately causing a Methamphetamine withdrawal which thankfully is not fatal (unlike Alcohol withdrawal). That being said Antipsychotics do have a role in maintaining sobriety from using Methamphetamine and they are increasingly becoming a go-to treatment for helping people stay away from Meth.

• Cardiovascular - Arrhythmias, Hypertensive Crisis, and Heart Attacks. So far we have focused on Dopamine but now we are going to switch focus to the other main neurotransmitter NorEpi. NorEpi is a widely distributed neurotransmitter in the brain and in the rest of the body. We see the effects of NorEpi when the Sympathetic Nervous System (SNS) is activated such as during Fight or Flight; let me set the scene: you just get to class and discover that, shock, you forgot to wear trousers today! You are ass naked in the middle of the lecture hall and desperately need to get back to your dorm to put on the clothes that you somehow forgot. In addition to the stress hormones Cortisol and Epinephrine, the main effect we are going to see is NorEpi to take your wind-chilled butt all the way back home. All of the actions of the SNS are to ensure that you can MOVE QUICKLY to avoid whatever danger you are in (cue bear attack analogy that is normally talked about).
  • In the eyes we see the pupils dilate so that more light can enter to let you see more of your surroundings. Likewise blood is shunted away from the digestive tract (because this is no time for energy to be wasted on something so slow) to the muscles so they can get the extra oxygen delivered. This means that the stomach will secrete less acid, the intestines stop moving waste, and the mouth stops secreting saliva (which is why people get dry mouth when scared). In the lungs the airways dilate to allow more air to be inhaled to oxygenate the blood and the heart is stimulated to beat faster and harder to move that blood to where it's needed, the muscles. We also see smaller blood vessels near the surface of the skin constrict to shunt blood to more important places, like the muscles.

• Running home to get some pants is all well and good but, ahem, what about Methamphetamine? Well remember that Amphetamines cause an increased release and decrease reuptake (removal) of NorEpi in the central nervous system. This means that we are increasing NorEpi concentrations which would simulate Fight or Flight when we don’t need it.

• Even though Methamphetamine will cause a wide range of effects I want to focus specifically on the heart because the relationship between Methamphetamine abuse and Cardiotoxicity is huge. Let me not mince my words: abusing Methamphetamine is incredibly toxic to the heart. (A) Firstly remember that NorEpi causes constriction of blood vessels and we see that Methamphetamine also causes constriction. If the blood vessels that nourish the heart are constricted we see the development of a Myocardial Infarction or Heart Attack which is potentially fatal. This risk of a Heart Attack is cumulative and the risk of having a Heart Attack increases exponentially for every year that someone uses.
  • (C) Next we see the effect of NorEpi on regulating heart rate. The ability for the heart to contract and move blood across the body is an incredibly essential mechanism for us to stay alive. During Fight or Flight more NorEpi is released causing the heart to beat faster and harder so that more blood is moved per minute. Like any muscle the heart can get tired and become dysfunctional if it constantly pushed to its limits—luckily people don’t live in a constant Fight or Flight mode else they would see Cardiomyopathy or weakening heart muscle. With constant Methamphetamine use we see two effects: first the constant stimulation disrupts the very carefully coordinated electrical stimulation on the heart to cause a heart beat. The result is pretty significant arrhythmias or a bad heart beat sequence. Secondly constant stimulation on the heart causes thickening of the heart wall making it more stiff and harder to contract. A stiffer heart means it is less able to move blood in the body and may develop a clot that could potentially cause a stroke. This remodeling is irreversible most of the time and is a real long term consequence of abusing Methamphetamine.

• (D) We also see Methamphetamine being directly toxic to heart cells leading to induced cell death and necrosis. This means patches of the heart are dead and won’t be repaired even if the person stops using Meth. This process takes place by Methamphetamines binding to the Sigma-1 Receptor on the Mitochondrion (makes energy for the cell, but you already knew that) and the Endoplasmic Reticulum (remember this one from biology? It makes and stores proteins) which are essential for the continued survival of the cell. No Mitochondria or ER? Dead cell.

• Teeth and Skin — Meth Mouth and Crank Bugs. Now that we have talked about the effects of Dopamine and Norepinephrine we can talk about the most recognizable signs of Methamphetamine use. I want to talk about it not to shame a user but because it's important to understand the complications related to the teeth and skin to avoid serious infections and further health complications. Despite how shocking they appear, its important to know that these conditions don’t happen overnight and through repeated misuse they get worse. Let’s dive in.
  • “Meth Mouth” as it is known is the characteristic breaking, decay, and loss of teeth and gums in those who use Methamphetamine. The mouth (which is featured in this post about sugar) is both tough and sensitive to the different conditions we put it under—in a lot of ways it is incredibly dynamic to the very different kinds of things we put in it. For instance we can put exceptionally acidic foods like lemonade which wears away teeth, too hot food that burns the palate, and not brush for weeks at a time without dying. Seriously, humans have been neglecting their dental health for all of time except for 60 years ago and we made it! Well barely, there is a lot of evidence that says good oral health is good general health (seriously go brush AND FLOSS). Looking at the cause of mouth damage due to Methamphetamine is multifactorial with the outcome being more of AND than one or the other.

• 1) Meth is acidic — Okay this is a bit of a misnomer because any chemist will tell you that an amine is very basic BUT bear with me. Acidic foods wreak havoc on the teeth because they erode the protective enamel on the teeth allowing for them to become very sensitive and potentially damaged. Meth itself is not acidic but Crystal Meth is manufactured via the Red, White, and Blue Method which uses primarily Red Phosphorus (usually sourced from matches or flares), Pseudoephedrine tablets (white in color), Iodine (blue in color) in addition to a whole list of unsafe and toxic solvents. This manufacturing process utilizes the strong acid Hydroiodic Acid which may be left in the final product thus eroding the teeth.“Meth mouth” typically begins with the yellowing of the user’s teeth and rapidly deteriorating enamel “flaking” off from the underlying tooth structure. Repeated use of the drug eventually leaves the user’s teeth looking grayish-brown or black stained, decayed to the gum line, and often non-restorable. The rapid destruction of tooth enamel is thought to be a result of the heated vapors released by toxic chemicals produced while smoking methamphetamine.
• 2) Meth dries out the mouth — remember how I said that Methamphetamine turns on the Sympathetic Nervous System which turns off digestion? Well one of the effects is that the salivary glands stop producing saliva which dries out the mouth. Saliva is protective because it dilutes any acid in the mouth AND washes away bacteria on the teeth that could be doing damage.
• 3) Meth users clench and grind their teeth — similar to another Amphetamine, Ecstasy, people who use Methamphetamine are activating Dopamine receptors that cause the muscles in the jaw the clench. Sometimes the person is clenching so hard that they can crack and break their teeth and if the teeth are already weakened from erosion then the likelihood of breaking is greater.
• 4) Addicts are concerned with their next high not about dental health — probably most sadly is that the engrossing nature of Meth addiction is that it removes any motivation for anything other than the drug. Someone who is in the middle of their addiction is less likely to take care of their teeth because it's just not a priority for them.
• Moving onto the skin we encounter “Crank Bugs.” Remember that Methamphetamine causes a hyper-Dopaminergic state that is similar to the pathology of Schizophrenia which can result in intense hallucinations. This can result in pretty significant disordered thinking, especially Delusional Parasitosis or the idea that the body is infested with parasites and bugs leading to severe agitation. A person using Methamphetamine may start to scratch their skin to remove the bugs from their skin which can lead to lesions that can become infected very quickly. If someone does not have the delusions they may still pick at their skin like a tic (which is also a hyper-Dopaminergic state) causing skin lesions. Like the teeth, someone using Meth is not likely to care about the lesions when they are looking for their next high. Likewise someone who chooses to inject Methamphetamine may have degradation of the tissue around the injection site. Also remember that Methamphetamine causes vasoconstriction of the blood vessels of the skin shunting blood away from it which means its not being nourished with oxygen and nutrients that it needs preventing adequate repair.

The next epidemic? Or just an old one becoming worse?

• The domestic use of Amphetamines in the US starts a bit differently than the military however. As I detailed in the ADHD post, the original use of Amphetamines was in the diagnosis of a type of encephalitis vs flu in children. By the 1950s Amphetamines were marketed towards housewives for weight loss, athletes and students for performance enhancers, and truck drivers to stay awake on long hauls. In 1959 the FDA banned Amphetamine inhalers to curb the rise in abuse and in 1962 we saw the first use of “Speed Freak” to describe users of Amphetamines. To combat the continued rise of Ampethamine misuse among biker gangs, the Controlled Substances Act of 1970 established Amphetamine-derivatives as Schedule II classified substances which designated them as highly addictive prescription drugs. In 1980 the federal government tightly regulated the movement and sale of Phenyl-2-Propanone (P2P), the original precursor, meaning that home Meth cooks had to turn to other sources to make Meth.

• In the early 1980s, Mexican Cartels, bike gangs, and home cooks turned to the drugs Ephedrine and Pseudoephedrine (Sudafed) as a better precursor thus birthing the Red, White and Blue Method we talked about earlier. This enabled the DEA to regulate Ephedrine and Pseudoephedrine but big pharma companies pushed back against any regulation so the DEA compromised by regulating powdered Ephedrine and Pseudoephedrine but not finished tablets in the pharmacy in 1986. The switch to using Ephedrine tablets instead of powders was not difficult for home Meth labs and by 1993 the majority of home labs were using over the counter Sudafed tablets to make meth OR purchasing it in bulk from Mexico.
• In 1993 legislation was passed to require pill sellers, like pharmacies, to register with the DEA to hopefully catch and stop any major diversion. Meth cooks switched to using Psuedoephedrine tablets which required flammable solvents to extract the ingredients from the tablet—the Meth task force said that 60% of explosions and fires in labs was due to this switch. In 1996 the DEA required all Pseudoephedrine to be sold in blister packs believing it would be too much hassle for people to acquire enough precursor. It did not and up to 73% of raided labs showed evidence of blister packs being used int he cook. FINALLY in 2004 Oklahoma was the first state to require the purchaser to show ID and sign at the register when buying Pseudoephedrine. By 2005, 35 other states passed similar laws and the federal government passed the Combat Methamphetamine Epidemic Act of 2005 to move Pseudoephedrine behind the counter and require ID.

• When we look at the trends of Methamphetamine we see an alarming increase. In the last 10 years, especially since the beginning of the pandemic, we have seen a sharp increase in the use of Methamphetamine. Methamphetamine use remains incredibly high and the drug of choice in the Western half of the United States (West of the Mississippi River) while the East is mostly Fentanyl. When compared to other drugs, Methamphetamine remains one of the highest rated harmful drugs, and is one drug that is most likely to cause harm to the user. \

• In just 20 years we have seen overdose and death due to Methamphetamine skyrocket as seen in this graph from Utah. Methamphetamine was associated with a 16,200% increase in mortality in urban Black users when compared against urban White users. Perhaps scariest is that the rate of Methamphetamine deaths independent of other drugs has sharply risen meaning that the Meth Epidemic is becoming a distinct issue outside of the Opiate Epidemic. This has led some public health officials to state that we are seeing the rise of a Second Wave, the first being in the 1990s to 2000s. Right now there is heavy lobbying in the US to combat Meth production inside and outside of the states but progress is extremely slow. Some states that instituted the electronic system to track Pseudoephedrine purchases by showing ID have seen no decrease in Meth use since the program started. So where does this leave us? Well we are stuck at the beginning of a second wave that we may not be prepared for because we have yet to recognize the danger that is looming. Should there be more done to combat the Meth Epidemic? Yes, no doubt but it's plotting the right course that is extremely tricky. And those solutions will have to wait for another post. Cheers!