Does CBD help anxiety, or is it just a placebo effect?

  Recently, it has become fairly common for people to use marijuana to treat anxiety and depression. There are some people, though, who prefer to use CBD alone, one component of marijuana, trying to avoid THC and other compounds that might not help anxiety. I know people who take CBD during acute anxiety which is not extreme enough to cause them to get an anxiety medication, and they believe that it does help to calm them. However, does CBD actually work to treat anxiety, or do people just believe that it would work, making them calmer?

A study done by Spinella et al., in 2021, tested how much of the relief felt by people by CBD was due to the placebo effect, instead of testing the pharmacological effects of CBD. To do the study, they needed people who were at least 19, and these participants had to have used marijuana at least once in their lives to have some familiarity with how they perceived the drug to affect them. Some tests to invoke anxiety included switching between putting their hands in really cold water and having to count backward in odd increments from a high number. They then recorded both heart rate and heart rate variability, as well as asked the participants to rate their stress on a scale of 1 to 10, all after asking how effective they thought CBD was for anxiety. None of the participants consumed any CBD, instead getting hemp seed oil that was without CBD, but one time that they did the tests they were told that it had CBD, and then the other they were told that it did not have any. Overall, they found that the expectation of CBD most likely did help the relaxation that people find when they take it, with the people who believed that CBD would help with their anxiety reporting a higher decrease in stress than those who moderately thought so (Spinella, et al., 2021). 

Overall, it seems like some of the benefits from CBD can come from the placebo effect, which in itself isn’t a bad thing. If more studies are done to make sure that CBD is safe for the brain and doesn’t have any horrible side effects, then it could be a good tool for anxiety for the people who believe that it works, even if it is not as pharmacologically effective as once thought. 

Spinella, T. C., Stewart, S. H., Naugler, J., Yakovenko, I., & Barrett, S. P. (2021). Evaluating cannabidiol (CBD) expectancy effects on acute stress and anxiety in healthy adults: a randomized crossover study. Psychopharmacology, 238(7), 1965–1977. https://doi.org/10.1007/s00213-021-05823-w

Rabies, how it works and how it kills

One of my largest interests as a prospective pharmacy student will be diseases and microbes and how they affect the body. However, the largest mystery for me is an individual's behavior under the effects of rabies lyssavirus, or just rabies for short. Although rabies is very treatable and preventable via vaccines and vaccination of domesticated dogs which make up approximately 99% of cases transmitted to humans via bites or scratch marks (WHO, 2024). It is nearly always fatal when the first symptoms appear, with only a record of 20 individuals surviving after being diagnosed with rabies (Stephenson. C, 2016). At this point, mostly everyone knows the symptoms of rabies via depictions from mainstream media, which typically depict un-ordinarily aggressive behavior, hypersalivation, as well as hydrophobia. But what is largely unknown about the virus is what it is like to live through a rabies diagnosis past the treatment window, such as what it is like to experience the symptoms to explain the loss of rational and terrifying demeanor that is seen sometimes in our beloved pets. The first known survivor of rabies without receiving treatment is Jeanna Giese-Frasseto, who at 15 was first exposed to the viral infection when she was initially bitten on her index finger by a bat she had rescued. A cocktail of experimental drugs now known as the Milwaukee Protocol had placed Jeanna in a medicated comatose state to slow down the viral infection from reaching the brain and eventually death (Stephenson. C, 2016). Even if the Milwaukee Protocol had left her unable to speak, stand, or walk, she was eventually able to relearn these behaviors and as of 2024 has successfully become a mother of twins, due to its success, the Milwaukee Protocol has been used to save 10 other infected patients that had begun showing symptoms (). But how does rabies work? Rabies as many know is transmitted from saliva into an open wound (this explains the hypersalivation and aggressive behavior of the infected individuals due to bite marks or scratches will allow a point of entry for the excess saliva, allowing further propagation within a newly infected individual), the virus then undergoes an incubation period of typically 1-3 months where the virus propagates within affected cells' cytoplasm and uncoats its viral RNA, allowing for virion-associated RNA-dependent RNA polymerase that is translated into 5 viral proteins that lead to the degradation of affected cells (Rupprecht. C, et al. 1996). After multiplication, the virus tends to migrate toward the peripheral nervous system causing irreversible damage (CDC. 2024). The produced protein then attaches to ACh receptors (which we had learned within the class are typically used in the process of memory formation)  within both neurons and immune cells, and when affecting some areas of the brain, the neurological symptoms of rabies can be observed such as the serotoninergic-related motor alterations due to the disruption of cholinergic signaling (Bastos, V, et al. 2023). This gives us insight into how the Milwaukee Protocol works in that it does nothing to prevent the viral protein from binding but rather stalls the virus from affecting critical neurological sites within the brain which gives time for the host's immune system to detect and fend off the virus from doing further damage to the body.

Although this post is not a "deep-dive" into rabies such as the biochemistry of how the viral proteins bind or interact with the ACh inhibitors, I highly encourage readers to look into random pathogens to further their understanding of how medications work and possibly alleviate any sorry of fear of the unknown.

Citations

Bastos V, V., & Pacheco, V. (2023, October 26). Neuroimmunology of rabies: New insights into an ancient disease. Journal of medical virology. https://pubmed.ncbi.nlm.nih.gov/37885152/

Centers for Disease Control and Prevention. (2024, May 17). Rabies symptoms and specimen collection. Centers for Disease Control and Prevention. https://www.cdc.gov/rabies/hcp/suspected-human-rabies/index.html

From the brink of death to motherhood: First person to ever survive rabies reflects on becoming a mom. Children’s Wisconsin. (2016, May 7). https://childrenswi.org/at-every-turn/stories/jeanna-giese-rabies#:~:text=Jeanna%20Giese%2DFrassetto%2C%20the%20first,did%20not%20seek%20medical%20attention.

Rupprecht, C. E. (1996, January 1). Rhabdoviruses: Rabies virus. Medical Microbiology. 4th edition. https://www.ncbi.nlm.nih.gov/books/NBK8618/

Stephenson, C. (2016, March 29). Motherhood is latest milestone for woman who survived rabies. Journal Sentinel. https://www.jsonline.com/story/news/health/2016/03/29/motherhood-is-latest-milestone-for-woman-who-survived-rabies/84941662/

World Health Organization. (2024, April). Rabies. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/rabies

Six-pack abs, not cans

Alcohol-related myopathy is one of the earliest alcohol-associated pathological tissue changes, whether it’s acute or chronic alcohol use, it leads to change in skeletal muscle mass and function. The detrimental effects of alcohol on human physiology has been well observed affecting many aspects of metabolism, neural function, cardiovascular physiology, thermoregulation and as previously mentioned, skeletal muscle myopathy. The major skeletal muscle anabolic pathway is the mTORC1 pathway leading to muscle protein synthesis. 

Firstly, alcohol inhibits Ca²⁺ transients into the myocyte by inhibiting Sarcolemmal Ca²⁺ channel actions. Alcohol decreases the expression of myosin heavy chain, a major motor protein in the thick filament, and troponin-T – which is necessary for myosin and action binding and positioning. This action impairs the excitation-contraction coupling and overall decreases strength output. The contractile and structural skeletal muscle proteins along with the extracellular matrix play a critical role in regeneration, anabolic signaling and mitochondrial functions. When exposed to ethanol, a decrease in mitochondrial fission factor dynamin-related protein 1 (DRP-1) leads into the mitochondrial unfolded protein response, which finally leads to skeletal muscle weakness. Muscles rely on protein synthesis to repair and grow after activity and injury. Disrupting its anabolic pathway and mechanisms reduces the body’s ability to rebuild muscle tissues, driving the progression of muscle loss. So, in Layman’s term, if you’re exercising using those 5 lb weights and excessive drinking, good luck getting that six-pack. 

 

Metabolically speaking, high levels of alcohol consumption have been shown to impair hepatic gluconeogenesis and glucose output, decreasing the uptake of gluconeogenic precursors lactate and glycerol and decreases muscle glycogen uptake and storage. Neurologically, alcohol is a well-known depressant and reduces central nervous system excitability and cerebral activity. All these things detrimentally effect our bodies and overall quality of life in the long run. Think twice before you get the six-pack at the store versus the gym. 

 

Simon, L., Bourgeois, B. L., & Molina, P. E. (2023). Alcohol and Skeletal Muscle in Health and Disease. Alcohol research : current reviews, 43(1), 04. https://doi-org.dml.regis.edu/10.35946/arcr.v43.1.04

 

Vella, L. D., & Cameron-Smith, D. (2010). Alcohol, athletic performance and recovery. Nutrients, 2(8), 781–789. https://doi-org.dml.regis.edu/10.3390/nu2080781

Hangovers are HORRIBLE

  I'm sure we all have been at the hardest point in our lives where we are blowing chunks into the toilet because we overestimated our tolerance. Since my 21st birthday was on October 28, I figured I should delve into the research on why hangovers happen and how to get rid of them seeing as I will more than likely have many in the future.

For those of you who can't relate A hangover is the experience of various unpleasant physiological and psychological effects that occur after consuming alcohol, such as fatigue, weakness, headache, nausea, and sensitivity to light and sound. Hangover symptoms often begin when your blood alcohol content drops and is at or near zero. As stated by  The Royal Society of Medicine Health Encyclopedia Alcohol promotes diuresis by causing the pituitary gland to produce less of the antidiuretic hormone vasopressin. Which means we actively become dehydrated after drinking any alcohol because we are now filtering more toxins in the kidneys as well and are trying to get rid of it.

The most compelling theory, at the moment, is that hangovers result from a buildup of acetaldehyde, a toxic compound, in the body. As the body processes alcohol, acetaldehyde is the very first byproduct, and it's estimated to be between 10 and 30 times as toxic as alcohol itself. In controlled studies, it's been found to cause symptoms such as sweating, skin flushing, nausea and vomiting this experiment can be proven by Harvard health complications. There is also a strong correlation that's been proven in the  The Royal Society of Medicine Health Encyclopedia between high levels of cytokines which are —molecules that the immune system uses for signaling—and hangover symptoms (. Normally, the body might use cytokines to trigger a fever of inflammatory response to battle an infection, but it seems that excessive alcohol consumption can also provoke cytokine release, this was proven in Smithsonian magazine. 

Popular opinions on prevention and care can be   seen in Harvard Medical School Commentaries on Health they suggest hydrating during the drinking, and make sure to drink lots of electrolytes. Along with electrolytes a hefty meal is needed preferably carbs and greasy meals. 

Hangover is the worst and should be taken more seriously to prevent them 

When you are of legal age to do these activities, it is important to take care and know yourself well enough to see how much you can endure. Orrrr, you can absolutely wreck your stomach and push your limits, but that would lead to alcohol poisoning and be an overall unwise decision 

Works Cited 

Stromberg, J. (2013, December 31). Your complete guide to the science of hangovers. Smithsonian Magazine. https://www.smithsonianmag.com/science-nature/your-complete-guide-to-the-science-of-hangovers-180948074/

Harvard Health Publications (Ed.). (2019). Why do we get hangovers? In Harvard Medical School Commentaries on Health (1st ed.). Harvard Health Publications. https://search.credoreference.com/articles/Qm9va0FydGljbGU6NDY3OTkwNg==?aid=98655

Hangover. (2000). In R. M. Youngson, The Royal Society of Medicine Health Encyclopedia (2nd ed.). Bloomsbury. https://search.credoreference.com/articles/Qm9va0FydGljbGU6MTU0OTU5Ng==?aid=98655

Neurogenesis as a Therapy

        Strokes are a common way for a large amount of neurons to die due to vasculature occlusions in the periphery or in the cortical regions that lead to a deprived oxygen and glucose source to the brain. Neurons do not have glucose storages like most cells, so they depend on a constant supply to oxygen and glucose through the blood in order to carry out an oxidative reaction which will allow for the production of ATP and carry out other cellular functions. The lack of oxygen to the brain is known as an ischemic event and some of the most common symptoms are unilateral facial drooping, slurred speech, confusion, and muscle weakness typically on one side of the body as well. If these symptoms are detected on time and the patient is rushed immediately to the hospital, they are able to receive a treatment known as tPA or tissue plasminogen activator which will break the thrombus that is occluding the blood supply to the brain, and symptoms will resolve almost immediately. However, patients who are actively having a stroke will only have a short amount of time to receive this treatment in order to minimize potential neurological deficits. If a patient is out of the time range, which is about 1-4.5 hours after the onset of symptoms, they will no longer be eligible to receive tPA and other treatment options have to be considered such as surgically removing the occlusion. In a lot of cases, patients will suffer from neurological deficits following a stroke. 

    Neurogenesis is the process by which new neurons are created. This involves an immature neuron proliferating, migrating to a different part of the brain, differentiating, and finish maturing. There has been evidence in post stroke instances where neurogenesis has taken place. Neural stem cells from the subventricular zone (SVZ) and the dentate gyrus, which are typical places where immature neurons can be found, will travel to the damaged area and then differentiate. Although this process sounds effective, there have been some concerns regarding the new neurons ability to survive due to the increase in inflammation and other factors in the brain that take place after a stroke. In majority of cases, inflammation in the brain will prevent neurogenesis from taking place, however, there has been some evidence to show that it can trigger neurogenesis. 

    Proteins such as SDF-1 and MCPI are involved in inflammation but there has also been evidence to show that these proteins are also associated to the neurogenesis. MMPs, is a particular protein that is involved in the repairing of the cellular matrix after a stroke, and this has been seen to be involved in migration to promote neurogenesis. With this in mind, the timing of inflammation is also an important factor when it comes to neurogenesis. There has been an attempting to target neuroinflammation when trying to target neurogenesis, GSK inhibitors are particularly used but more needs to be researched on these inhibitors. 

    Another factor that is considered for neurogenesis are microglia. There has been some evidence to show that they are involved in neurogenesis as they can secrete trophic factors which help neurons to survive and migrate. In studies where there is a decrease in microglia, have also demonstrated that there has been a decrease in neurogenesis. There is a similar mechanism observed  in angiogenesis where endothelial cells that are closely involved in creating more vasculature secrete trophic factors VEGF, SDF01, and angiopoeitin-1 which have also been seen to be involved in neurogenesis; particularly in the differentiation step and ultimately survival of the newly formed neuron. With this, angiogenesis can also be targeted when attempting to target neurogenesis. Another type of glial cell involved can be the astrocyte as they are neuron precursors. They can release factors that will help neurons survive. Upon division of these astrocytes, a precursor is developed and a neuron will also be created; this has been considered as a potential treatment. It is important to note that many of these discoveries were done on mice and rats who underwent surgical occlusion, there is still more that needs to be investigated in humans. 

    With neurogenesis, there is an issue that newly formed neurons might not survive. For this, there has been research done using stem cells promote neurogenesis while also helping neurons survive. A study done on mice showed that implanting stem cells into the hippocampus 24 hours after an ischemic episode showed improved recovery when it came to their behavior and also decreasing the size of the infarct, or the area where the stroke took place. Within this same study, it was also noted that the blood brain barrier improved. This same group of researchers also noted that stem cell implantation with tPA showed a decrease in pro-inflammatory cytokines (proteins involved in an inflammatory response), in addition to a decrease in TNF-alpha, and IL-6 which are known to decrease neurogenesis when there are excessive amounts present. However, there are still ethical concerns regarding this potential therapy as many stem cells obtained are human fetal stem cells, so more research has to be done. 

    The field of neurogenesis is very fascinating as it can be used as a potential treatment following a stroke. There is still more research that needs to be done, but this form of therapy can yield favorable results. 

Reference:

Rahman AA, Amruta N, Pinteaux E, Bix GJ. Neurogenesis After Stroke: A Therapeutic Perspective.Transl      Stroke Res. 2021 Feb;12(1):1-14. doi: 10.1007/s12975-020-00841-w. Epub 2020 Aug 29. PMID:              32862401; PMCID: PMC7803692. 

Puff or Poison

Electronic cigarettes (E-cigs) were initially marketed as a smoking cessation aid for addicted adults with the promise of a safer product, but the flavored cartridges heavily attracted the adolescent population fairly quickly. The concern for how nicotine impacts the developing brain of a young adult can be traced back to the usage of these e-cigs. Nicotine is the primary psychoactive and addictive component of tobacco. It acts on the nicotinic acetylcholine receptors found in the brain and peripheral nervous system (PNS). Overtime, nicotine induced changes in the neuronal circuitry, which alters the sensitivity of the receptors to the drugs and higher doses of nicotine are needed to satisfy the rewarding effects that you feel. Modifications were made such as nicotine salts were introduced to enhance the sensory quality of e-cigs. But, this wasn’t much of a modification, because it only made it worse. 

 

Nicotine salts have a stronger inflammatory effect on the lung epithelium than regular nicotine-containing e-liquids. The inflammatory effect usually involves a high regulated cascade of molecular events, which is meant to be short-lived, but when inflammatory signaling is made long-term and becomes chronic, the effects are damaging and are associated with tumorigenesis. If the inflammation remains unresolved or stimulated for long periods of time, it can promote carcinogenesis by provoking DNA damage and oxidative stress and the inhibitions of immune cell activity. E-cigs do just that. The thermal degradation starting in the mouth carry pro-inflammatory effects on all aspects of the respiratory system by increasing airway resistance, depositing ultrafine particles and heavy metals in airway, and decreasing innate immunity and response to infection in the airways. Lung damage is one of the primary pathologies associated with the use of tobacco products, but we already knew this, right? Well, it has been shown that cellular damage from e-cigs was more extensive than the damage imposed by traditional cigarettes. The health risks associated with vaping affect multiple organs: oral cavity, vascular system, respiratory system, and brain to name a few. So, next time you’re thinking about hitting your friend’s vape, think about the dangers in the puff (dab pens count too). 

 

Auschwitz, E., Almeda, J., & Andl, C. D. (2023). Mechanisms of E-Cigarette Vape-Induced Epithelial Cell Damage. Cells, 12(21), 2552. https://doi-org.dml.regis.edu/10.3390/cells12212552

 

Jonas A. Impact of vaping on respiratory health BMJ 2022;  378 :e065997 doi:10.1136/bmj-2021-065997

Feed your focus, not your face

Did you know you could be on the fast track to a sharper mind? How, you may ask? Intermittent fasting. Intermittent fasting (IF) is not just the idea of not eating for hours on end, there is some science to it. Intermittent fasting has three variants, namely: time-restricted eating (TRE), alternate day fasting (ADF), and periodic fasting (PF). Now, let’s break these down. TRE is characterized by a time window of food intake that only lasts 8 hours per day; ADF is characterized as alternating between eating regularly on one day and restrain from eating the next; PF is characterized by cycles of abstinence or strong limitation of food for two days a week with no restrictions for the remaining five days of the week. 

Now, what these variants of IF all have in common is when it is sustained long enough, a process called “the metabolic switch” or “G-to-K switch” occurs. This transition occurs 12-36 hours after the fasting period begins and initiates the transition of using carbohydrates and glucose to fatty acids and ketones as the major cellular fuel source. The decreased availability of glucose and increase ketone levels (specifically B-hydroxybutyrate) can upregulate the expression of brain-derived neurotrophic factor (BDNF) which in result, promotes mitochondrial biogenesis, synaptic plasticity, and cellular stress resistance. So, why should we care about this switch? 

This switch has revealed remarkably complex and coordinated adaptation of the brain and body that have enabled an individual to maintain and even enhance their cognitive and physical performance for extended periods of time. Intermittent fasting leads to lower levels of circulating insulin in the bloodstream, which enhances neuroplasticity and protection against metabolic and oxidative stress. It has been shown that IF enhances a little something we like to call long-term potentiation (LTP) at hippocampal synapses. This LTP strengthens the synaptic connections between neurons and plays a key mechanism for learning and memory. So, with finals coming up, perhaps you should give intermittent fasting a chance because we love LTP. 

Gudden, J., Arias Vasquez, A., & Bloemendaal, M. (2021). The Effects of Intermittent Fasting on Brain and Cognitive Function. Nutrients, 13(9), 3166. https://doi.org/10.3390/nu13093166

 

Mattson, M. P., Moehl, K., Ghena, N., Schmaedick, M., & Cheng, A. (2018). Intermittent metabolic switching, neuroplasticity and brain health. Nature reviews. Neuroscience, 19(2), 63–80. https://doi.org/10.1038/nrn.2017.156