Crisis in Health: The Opioid Epidemic

Public health is a multifaceted, constantly changing field that deals with community health. Ranging from pandemics and diseases, to mental health and healthcare disparities, the field is built around supporting communities during times of crisis.¹ Characterized as a drug crisis that has swept the nation since the 1990s (through the increase accessibility of and addiction to Opioids), the Opioid Epidemic is well known throughout public health for its persistence and devastating impact on communities across the United States.

But what exactly are opioids? Classified as synthetic and semisynthetic,² opioids encompass a broad category of drugs that target pain receptors in the brain and spinal cord (the central nervous system) to dull/dampen pain perception. While highly effective, these drugs have extremely addictive properties as they directly affect the brain’s “reward center”, releasing powerful neurotransmitters like endorphins and dopamine. This causes opioid users to experience a sense of elation and euphoria, which, upon the opioids wearing off, causes a “crash” with the decrease in neurotransmitters released.³ Opioids include legal prescription drugs like hydrocodone, oxycodone, fentanyl, and codeine, and illegal drugs like heroin.⁴

The Opioid Epidemic is characterized by 4 main “waves”. The first wave started in the 1990s as a result of increased marketing by pharmaceutical companies on the effectiveness of opioids for pain management. This led to an increased prescription of and subsequent overdependence on opioids, which had devastating effects on thousands of people, families, and communities.⁵ Over the next decade, a rise in opioid addiction led to overuse, misuse, abuse, and overdose deaths. From 1999 to 2010, sales of prescription opioid drugs quadrupled while the rate of overdoses more than doubled from 2.9 to 6.8 deaths per 100,000 people.⁶

The second wave (2002-2013) was characterized by a rapidly expanding illegal drug market, which had a high demand for heroin. As production increased and price decreased, heroin began to be more widely accessible. Those already addicted to opioids were quick to transition to heroin and other highly addictive, illegal drugs. Heroin overdose deaths nearly quadrupled from 0.7 to 2.7 deaths per 100,000 people from 2002 to 2013.⁷

What makes this drug epidemic, in particular, so dangerous is how the waves connect and overlap. Since 2013, the third wave, a result of increased Fentanyl production, has exacerbated opioid effects. Fentanyl’s easy manufacturing and low production costs, in conjunction with its highly addictive, yet fatal nature, make it appealing to the illicit drug market. It is used as a cutting agent within the industry, augmenting other drugs’s quantity and potency.⁸ As a result of boosting the addictive properties of drugs cut with fentanyl, illegal market profits skyrocketed.⁹ From 2019 to 2022, there were approximately 73,000 deaths caused by fentanyl-related drug overdoses, a testament to the dangers of this drug when used in the illicit drug market.¹⁰

The most recent wave of the Opioid Epidemic, the fourth wave (2020-current), is based on the high mortality rate associated with methamphetamines and cocaine combined with opioids.¹¹ This wave is especially dominant in rural communities or those previously untouched by the epidemic, where overdoses have been increasing at an alarming rate akin to that of urban communities.¹² This is due to rural communities often having less access to healthcare because of their geographic distances from medical services, low population densities, and fewer healthcare providers (as seen by the doctor shortage throughout the US).¹³

With each wave characterized by an unprecedented number of deaths, and a rapidly increasing population affected by addiction and opioid abuse, the Opioid Epidemic is considered to be the worst drug epidemic in history and massive failure of US public health regulation. Profit-driven pharmaceutical companies pushed highly addictive drugs (opioids) without proper investigatory measures by US regulatory institutions (i.e. the US Food and Drug Administration). However, while the epidemic rages on, healthcare efforts in the US are focused on spreading awareness about the dangers of opioids and addiction management. Prevention and mitigation efforts, funded through congress legislation, have enabled the development of powerful new tools and strategies to actively save lives. For example, Congress has passed legislation providing over $1 billion dollars annually to the Substance Abuse and Mental Health Services Administration for a new State Opioid Response grant program, with additional funding for the Centers for Disease Control and Prevention and the Health Resources and Services Administration.⁶ Harm reduction programs (such as needle-exchanges) help minimize the spread of harmful, contagious diseases like HIV/AIDS.¹⁴ Additionally, public health approaches work towards making Narcan (an opioid overdose preventing nasal spray) more readily available to help save lives.¹⁵

Though the Opioid Epidemic continues to claim lives, decimating families and communities, public health initiatives have made significant strides in reducing overdose deaths, with reports indicating a 14.5% decrease in opioid-related deaths since 2023.¹⁶ As the US works towards implementing new and innovative opioid-safety measures, we may just be on the cusp of turning the tide for this drug crisis.

References

1. What is public health? American Public Health Association - For science. For action. For health. Accessed February 27, 2025. https://www.apha.org/what-is-public-health

2. Opioids. National Institutes of Health. December 3, 2024. Accessed February 27, 2025. https://nida.nih.gov/research-topics/opioids

3. Am I at risk of opioid addiction? Mayo Clinic. July 20, 2024. Accessed February 27, 2025. https://www.mayoclinic.org/diseases-conditions/prescription-drug-abuse/in-depth/how-opioid-addiction-occurs/art-20360372

4. Opioids. Johns Hopkins Medicine. May 11, 2023. Accessed February 27, 2025. https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/opioids

5. Writer B, By, Writer S. What led to the opioid crisis-and how to fix it. Harvard T.H. Chan School of Public Health. November 22, 2024. Accessed February 27, 2025. https://hsph.harvard.edu/news/what-led-to-the-opioid-crisis-and-how-to-fix-it/

6. The Opioid Crisis in the United States: A Brief History. Accessed February 27, 2025. https://crsreports.congress.gov/product/pdf/IF/IF12260

7. Vital signs: Demographic and substance use trends among heroin users - United States, 2002–2013. Centers for Disease Control and Prevention. Accessed February 27, 2025. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6426a3.htm

8. Drugs and Fentanyl Awareness | Fremont Police Department, CA. Accessed February 27, 2025. https://www.fremontpolice.gov/crime-prevention/drugs-and-fentanyl-awareness

9. Understanding heroin cutting agents - the recovery village Palm Beach at Baptist. The Recovery Village Palm Beach at Baptist Health. February 7, 2025. Accessed February 27, 2025. https://www.floridarehab.com/drugs/heroin/heroin-cutting-agents/

10. Drug overdose deaths: Facts and figures. National Institutes of Health. September 30, 2024. Accessed February 27, 2025. https://nida.nih.gov/research-topics/trends-statistics/overdose-death-rates#Fig8

11. Ciccarone D. The Rise of Illicit Fentanyl, Stimulants and the Fourth Wave of the Opioid Overdose Crisis. Current opinion in psychiatry. July 1, 2021. Accessed February 27, 2025. https://pmc.ncbi.nlm.nih.gov/articles/PMC8154745/#:~:text=A%20’fourth%20wave’%20of%20high,with%20the%20ongoing%20opioid%20epidemic

12. Coming wave of opioid overdoses “will be worse than ever been before.” News Center. August 29, 2022. Accessed February 27, 2025. https://news.feinberg.northwestern.edu/2022/08/25/coming-wave-of-opioid-overdoses-will-be-worse-than-ever-been-before/

13. Jenkins R, Ciccarone D, McMahan VM, et al. The fourth wave of the US opioid epidemic and its implications for the rural us: A federal perspective. Preventive Medicine. August 28, 2021. Accessed February 27, 2025. https://www.sciencedirect.com/science/article/pii/S0091743521001250

14. Syringe Services Programs: A Naco opioid solutions strategy brief. National Association of Counties. Accessed February 27, 2025. https://www.naco.org/resource/syringe-services-programs-naco-opioid-solutions-strategy-brief

15. Opioid overdose reversal medications - OORM. SAMHSA. Accessed February 27, 2025. https://www.samhsa.gov/substance-use/treatment/overdose-prevention/opioid-overdose-reversal

16. Overdose Deaths Decline, Fentanyl Threat Looms. DEA. Accessed February 27, 2025. https://www.dea.gov/press-releases/2024/12/16/overdose-deaths-decline-fentanyl-threat-looms

Ultra-Processed Foods and Health: What Happens When You Cut Them Out?

When we first think of bacteria, we may usually think about the harmful strands and the infections they cause. However, what if I said that some bacteria are actually helpful? In fact, we have over a thousand different species of bacteria in our gut which serve a vital role in ensuring our well being¹. For instance, Lactobacillus reuteri (L. reuteri) is a common bacteria that protects our gut from harmful pathogenic microorganisms, aids in lactose digestion, produces vitamins, and contains several anti-inflammatory properties². If L. reuteri alone plays these roles in maintaining our wellbeing, just imagine the effect of a thousand different bacterial species acting in our gut! However, to see these health benefits, we have to sustain our gut microbiota – something that is becoming increasingly difficult in a society where ultra-processed foods (UPFs) are consumed daily. But what exactly are UPFs and how do they hinder our gut microbiota?

Ultra-processed foods (UPFs) are foods that have been heavily refined, infused with various additives, and contain high amounts of fats, sugars, and salts³. As delicious as these foods may be, they are lacking in essential nutrients and fiber, and constant consumption has negative effects on our well being tied to disruptions to gut microbiota³. Our gut bacteria are highly dependent on the diet we sustain. A healthy diet means our gut bacteria are supplied with essential nutrients to keep them thriving; however, UPFs lack the necessary nutrients to help our microbiota grow⁴. As mentioned before, these foods are high in additives and fat, which means our gut bacteria are not being properly nourished. As a result, there is a reduction in microbiota diversity.

With a decrease in essential gut bacteria, our intestines are more susceptible to harmful pathogens and inflammation⁵. Studies have shown that excess consumption of UPFs have led to several health disorders, among which includes Inflammatory Bowel Disease (IBD), anxiety and depression³. Additionally, excess consumption of UPFs and their high fat content have been linked to a number of brain disorders³. This is because the hippocampus, a region of the brain responsible for memory and learning, is vulnerable to excess saturated fat, and damage to the hippocampus can result in decreased cognitive function and neuroinflammation⁶. On the other hand, the high added sugar content in UPFs can accumulate as fat in our tissues and lead to disorders such as obesity and non-alcoholic fatty liver disease⁶.

Ultra-processed foods, gut microbiota, and overall human wellbeing are all linked together. Our gut bacteria is essential in protecting our body from harmful pathogens and supplies our body with essential nutrients, but the overconsumption of UPFs kills these bacteria and leads to health complications. In order to ensure we take care of our bodies, it is important to be kind to our gut and cognizant of the food we consume.

References

1. Zhang YJ, Li S, Gan RY, Zhou T, Xu DP, Li HB. Impacts of Gut Bacteria on Human Health and Diseases. Int J Mol Sci. 2015;16(4):7493-7519. doi:10.3390/ijms16047493

2. Mu Q, Tavella VJ, Luo XM. Role of Lactobacillus reuteri in Human Health and Diseases. Front Microbiol. 2018;9:757. doi:10.3389/fmicb.2018.00757

3. Song Z, Song R, Liu Y, Wu Z, Zhang X. Effects of ultra-processed foods on the microbiota-gut-brain axis: The bread-and-butter issue.

4. Shi Z. Gut Microbiota: An Important Link between Western Diet and Chronic Diseases. Nutrients. 2019;11(10):2287. doi:10.3390/nu11102287

5. Cuevas-Sierra A, Milagro FI, Aranaz P, Martínez JA, Riezu-Boj JI. Gut Microbiota Differences According to Ultra-Processed Food Consumption in a Spanish Population. Nutrients. 2021;13(8):2710. doi:10.3390/nu13082710

6. Martínez Leo EE, Segura Campos MR. Effect of ultra-processed diet on gut microbiota and thus its role in neurodegenerative diseases. Nutrition. 2020;71:110609. doi:10.1016/j.nut.2019.110609

Turning Waste into Wellness: The Power of Fecal Matter in Medicine

It is not the most pleasant substance. Its notorious smell and inextricable connection to potty humor make it an unappealing subject for many. However, its healing abilities offer a promising treatment for Autism Spectrum Disorder symptoms. What is this mysterious substance? Human fecal matter - also known as poop. 

In a procedure known as fecal microbiota transplantation (FMT), human stool from healthy donors is introduced into a patient’s gut through a colonoscopy or a pill (Gupta et al., 2016). The healthy bacteria from the donor’s stool can positively impact the patient’s imbalanced intestinal microbiome. The intestinal microbiome is a collection of countless microorganisms such as bacteria, archaea, and viruses found in the gastrointestinal tract (Gupta et al., 2016). These microorganisms support various bodily processes, but they can be impaired by environmental factors and infectious diseases. FMT is highly effective in treating some of these infectious diseases. For example, it is up to 90% effective in curing recurrent infections of Clostridium difficile bacteria (Wang et al., 2019). 

Recent research has extended the potential applications of FMT to address the symptoms of Autism Spectrum Disorders (ASDs). This diverse group of neurodevelopmental disorders typically leads to distinct patterns of behavior (difficulty in deviating from routines, repetitive movements, and fixations on specific objects or activities) and other social communication issues that impair one’s ability to hold a conversation or detect various social cues (“Autism Spectrum Disorder,” 2018). ASDs affect approximately one in fifty-nine individuals in the United States (Sharon et al., 2019). Many studies indicate a link between abnormal gut microbiota and ASD (Kang et al., 2019). Children with ASD who experience food sensory issues are more likely to face gastrointestinal problems due to deficits in calcium and protein intake. There are not many medical treatments available for these symptoms of ASD (Kang et al., 2019). Behavioral therapy can help improve social skills and issues with communication, but it does not address physical problems in the body. This is where FMT comes into play. 

A study conducted by researchers at Arizona State University found promising results when combining FMT with bowel cleanses and antibiotics to treat children with ASD. After an eighteen-week trial, they observed an 80% reduction in gastrointestinal symptoms of ASD. When they re-evaluated participants two years later they found significant improvements in gastrointestinal and behavioral symptoms (Kang et al., 2019). These findings found support in subsequent studies that investigated the impacts of FMT on gastrointestinal symptoms and metabolic profiles of people with ASD (Martínez-González & Andreo-Martínez, 2020). However, further research is needed to validate this link between FMT and the improved health of patients with ASD. These additional studies should consider the diverse spectrum of ASD severity and the differences in methodologies used to measure ASD behaviors (Martínez-González & Andreo-Martínez, 2020).

These results are not only exciting because they can help such a large number of people, but also because they highlight the potential of treatments derived from readily available materials. The world is in an exciting era of medical innovation and amazingly complex medical technology, but FMT serves as a reminder that we don't always need highly specialized tools to start helping patients in need. Sometimes, using what we already have – in this case, an abundance of human fecal matter – can lead to significant medical breakthroughs.

References

Gupta, S., Allen-Vercoe, E., & Petrof, E. O. (2016). Fecal microbiota transplantation: in perspective. Therapeutic Advances in Gastroenterology, 9(2), 229–239. https://doi.org/10.1177/1756283X15607414

Kang, D. W., Adams, J. B., Coleman, D. M., Pollard, E. L., Maldonado, J., McDonough-Means, S., Caporaso, J. G., & Krajmalnik-Brown, R. (2019). Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota. Scientific Reports, 9(1), 5821. https://doi.org/10.1038/s41598-019-42183-0

Martínez-González, A. E., & Andreo-Martínez, P. (2020). Prebiotics, probiotics and fecal microbiota transplantation in autism: A systematic review. Revista de psiquiatria y salud mental, 13(3), 150–164. https://doi.org/10.1016/j.rpsm.2020.06.002 

Autism Spectrum Disorder. (2018, January 6). Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/autism-spectrum-disorder/symptoms-causes/syc-20352928

Sharon, G., Cruz, N. J., Kang, D. W., Gandal, M. J., Wang, B., Kim, Y. M., Zink, E. M., Casey, C. P., Taylor, B. C., Lane, C. J., Bramer, L. M., Isern, N. G., Hoyt, D. W., Noecker, C., Sweredoski, M. J., Moradian, A., Borenstein, E., Jansson, J. K., Knight, R., Metz, T. O., … Mazmanian, S. K. (2019). Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice. Cell, 177(6), 1600–1618.e17. https://doi.org/10.1016/j.cell.2019.05.004

Wang, J. W., Kuo, C. H., Kuo, F. C., Wang, Y. K., Hsu, W. H., Yu, F. J., Hu, H. M., Hsu, P. I., Wang, J. Y., & Wu, D. C. (2019). Fecal microbiota transplantation: Review and update. Journal of the Formosan Medical Association, 118 Suppl 1, S23–S31. https://doi.org/10.1016/j.jfma.2018.08.011 

From Induced Bacterial Infections to Revolutionary Cancer Treatment: The History of Immunotherapy

It’s the late 1800s. You’ve been diagnosed with an untreatable form of bone cancer, and an experimental approach is your best bet. Fortunately, you’ve been lucky enough to be treated by the best of the best, Dr. William Coley: head of the Bone Tumor Service at Memorial Hospital in New York City (McCarthy, 2006). However, the course of treatment is not what you’d expect: injecting a bacterial mixture known as“Coley’s Toxins” (McCarthy, 2006).

While late 19th century hospitals were a major advancement in offering accessible medical care, they were also petri dishes offering the perfect environment for the spread of disease. Prior to the development of modern sterilization, known as aseptic technique, a bacterial infection called erysipelas, coined “St. Anthony’s Fire,” commonly plagued hospitals (Gianfranco et al, 2021). This skin infection, eventually serving as the inspiration for Coley’s toxin mixture, was named to describe both the burning sensation that patients experienced as well as the speed through which it swept through hospitals (Graeber, 2018). 

In 1891, Coley was tasked with performing a surgery on a patient’s bone cancer after a similar surgery seven years prior (2006). After a successful surgery, the patient fell ill with erysipelas. Although frequently fatal, the patient not only survived the infection, but his tumor shrunk significantly (2006). Coley hypothesized that there may be a connection between the bacterial infection and the rapid tumor eradication, and dedicated his career to the development of “Coley’s Toxins” (Graeber, 2018). As Coley’s experiments preceded a strong understanding of the immune system, their potential was limited. Although controversial and unethical, Coley’s contributions opened a door into curiosity about the immune system and led toa foundational understanding upon which many treatment options would be based. Today, scientists can understand that the bacterial infection was somehow activating the immune system and serving as a catalyst for a response against the patient’s cancer.

Notably, some of the greatest modern immunotherapeutic developments are checkpoint inhibitors and CAR T-cell therapy. Checkpoint inhibitors act on the cell growth and division cycle. This cycle is regulated by checkpoints that allow the body to trigger apoptosis (cell death) if the cell is too damaged to divide. But, cancer cells have mechanisms to sneak through these checkpoints, and continue to pass on their damaged DNA to create more cancer cells. Checkpoint inhibitors allow the immune system to recognize and destroy cancer cells (Eno, 2017). Conversely, CAR T-cell therapy allows for a personalized immunotherapeutic approach. In this process, a patient’s T-cells (cells that attack threats in the body) are collected and genetically modified with a Chimeric Antigen Receptor (CAR) gene specific to the patient’s cancer cells. Then, these T-cells are allowed to proliferate, and finally returned to the patient's body to fight their particular cancer cells (NIH, 2022). 

Although historical procedures like “Coley’s Toxins” may seem outlandish at times, they provide the grounds for generating questions: the fabric of scientific investigation. Experiments being conducted today, although we may not fully understand their results, could provide foundational insight into the treatments of tomorrow.

References:

Cervellin, Gianfranco et al. “One holy man, one eponym, three distinct diseases. St. Anthony's fire revisited.” Acta bio-medica : Atenei Parmensis vol. 92,1 e2021008. 11 Sep. 2020, doi:10.23750/abm.v92i1.9015

Dobosz, Paula, and Tomasz Dzieciątkowski. “The Intriguing History of Cancer Immunotherapy.” Frontiers in immunology vol. 10 2965. 17 Dec. 2019, doi:10.3389/fimmu.2019.02965

Eno, Jessica. “Immunotherapy Through the Years.” Journal of the advanced practitioner in oncology vol. 8,7 (2017): 747-753.

Graeber, Charles. The Breakthrough: Immunotherapy and the Race to Cure Cancer. New York, Twelve, 2018. 

McCarthy, Edward F. “The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas.” The Iowa orthopedic journal vol. 26 (2006): 154-8.

National Institute of Health. “CAR T Cells: Engineering Patients' Immune Cells to Treat Their Cancers.” National Cancer Institute. https://www.cancer.gov/about-cancer/treatment/research/car-t-cells. 10 Mar, 2022.

Blue Blood: How Horseshoe Crabs Revolutionized Medicine

Endotoxins are contaminants in the cell walls of some bacteria [4]. Medications and vaccines intravenously given to patients that may contain these endotoxins pose a risk of serious infection, septic shock, and death. Researchers and manufacturers initially avoided this catastrophe with animal testing on rabbits, but in the 1970's a new endotoxin detection solution was found in organisms older than dinosaurs: horseshoe crabs [3].

Horseshoe crabs are not actually crabs, but arthropods, like spiders and scorpions [2]. A blue, blood-like fluid called hemolymph flowing through the bodies of these "living fossils" is the key to testing all injectable drugs for endotoxins. This is because the blue hemolymph contains special immune system cells, called amebocytes, that are extra sensitive to molecules found in endotoxins, called lipopolysaccharides (LPS) [1]. Researchers have used these special cells to develop Limulus amebocyte lysate (LAL). 

LAL is named after North America's horseshoe crab species (Limulus polyphemus)[2], the special cells in their hemolymph (amebocytes), and the process used to make the compound (lysis, or breaking down, of the amebocyte cells). When LAL comes in contact with endotoxins secreted by bacteria, a sequence of reactions, called a coagulation cascade, occurs between proteins. This cascade ends in the activation of a protein called coagulogen which is turned into a gel called coagulin. This protein-gel forms visible clots, which are used to identify bacterial contamination of medical supplies from water and catheters to transplantable tissues and COVID-19 vaccines [1].

In order to synthesize LAL, scientists have to catch and drain the blood of about half a million horseshoe crabs. Of these crabs, only about 87% are returned to the ocean, after which about 15% to 30% of the creatures die due to blood loss and the disorienting amount of time spent outside of their aquatic environment. Overall, it is estimated that 130,000 horseshoe crabs are killed by this process each year [3].

Because of this harm to horseshoe crabs, and high demand for LAL, synthetic alternatives have been in development. One group of researchers used horseshoe crab DNA to make an alternative that fluoresces when it comes in contact with endotoxins present in contaminated medical supplies like vaccines, drugs, and syringes. Beyond taking stress off of horseshoe crabs, this synthetic alternative may also return more reliable results. Because horseshoe crab hemolymph and LAL react to many more molecules than just LPS from endotoxins, samples of drugs may clot even if they are not contaminated, but the synthetic alternative reacts more specifically to endotoxins [3]. 

Horseshoe crabs and their blue "blood" have been essential to the pharmaceutical industry. But, after half a century of harvesting the creatures for their hemolymph, synthetic alternatives may modernize endotoxin detection while sparing the horseshoe crabs.

1. Ashrafuzzaman, M.; Razu, M. H.; Showva, N.-N.; Bondhon, T. A.; Moniruzzaman, M.; Rahman, S. A.; Rabby, M. R.; Akter, F.; Khan, M. Biomolecules of the Horseshoe Crab’s Hemolymph: Components of an Ancient Defensive Mechanism and Its Impact on the Pharmaceutical and Biomedical Industry. Cellular Microbiology 2022, 2022, 1–17.

2. Horseshoe Crab. https://www.nwf.org/Educational-Resources/Wildlife-Guide/Invertebrates/Horseshoe-Crab (accessed Nov 14, 2022).

3. Maloney, T.; Phelan, R.; Simmons, N. Saving the Horseshoe Crab: A Synthetic Alternative to Horseshoe Crab Blood for Endotoxin Detection. PLOS Biology 2018, 16 (10).

4. Tamura, H.; Reich, J.; Nagaoka, I. Outstanding Contributions of Lal Technology to Pharmaceutical and Medical Science: Review of Methods, Progress, Challenges, and Future Perspectives in Early Detection and Management of Bacterial Infections and Invasive Fungal Diseases. Biomedicines2021, 9 (5), 536.

5. Jimenez, Darcy. Pharma’s reliance on horseshoe crabs is threatening the species. Pharmaceutical Technology. https://www.pharmaceutical-technology.com/features/pharma-horseshoe-crabs-threatening-species/ (accessed Aug 8, 2023)