Author Archives: Zuzanna Walter

Cannabis for Pain Management in Sickle Cell Disease Cases

Sickle cell disease, a red blood cell disorder that causes cellular deformation resulting in cells similar in shape to sickles, is the most common inherited blood disorder in the United States and affects approximately 100,000 Americans. The vulnerable cells have a shorter lifespan than normal cells and thus, there is a decreased amount of oxygen being transported through the body. As these cells tend to clog smaller blood vessels as well, they can result in acute or chronic pain, infection, and serious cardiovascular complications.

Currently, the Centers for Disease Control and Prevention recommend over-the-counter analgesics for the treatment of mild pain in cases of sickle cell disease. In more severe cases, clinicians often prescribe opioid medications, such as morphine, which come with serious and potentially fatal side effects. As such, there has been a growing number of research efforts into pain management methods for patients with sickle cell disease that mitigate adverse health outcomes.

Previous research has found that cannabis-based interventions can be effective at mitigating chronic pain, inflammation, and other unwanted symptoms. Emerging evidence published in JAMA Network Open explores the potential benefit of cannabis as an intervention for successful and safe pain management. The proof of principle study found that cannabis was a relatively safe intervention and could improve mood levels in patients who experience chronic pain from sickle cell disease.

Cannabis-Based Interventions

The medicinal indications of cannabis – now legal in 33 states – continue to expand as cannabis becomes increasingly popular as an analgesic within the scientific community. In the latest study, using cannabis as an analgesic was found to have the best evidence base compared to that of other interventions; however, authors of the study note that few human studies have explored the use of cannabis as a treatment for chronic pain in the case of chronic health conditions thus far.

Researchers conducted a double-blind, placebo-controlled, randomized proof of principle study aiming to test the hypothesis that cannabis can be an efficacious pain reliever in adults with sickle cell disease compared with placebo interventions. Participants of the study had all been diagnosed with sickle cell disease and were being treated with opioid analgesics at the time. They were required to have prior experience smoking cannabis to ensure they would administer the medication properly and be able to recognize its effects. Individuals currently using cannabis were asked to discontinue use for a week prior to the initiation of the trial. Out of the 27 total participants, 23 completed the full study and were included in the final analysis.

As part of the study, participants completed two 5-day trips to an inpatient research center – visits were at least 30 days apart – at which they inhaled either vaporized cannabis or vaporized placebo three times per day. Throughout their stay, researchers assessed participants’ pain levels, the interference of pain in a range of daily activities, mood, as well as associated side effects.

Reduced Impact on Mood

The study’s authors report that inhaled, vaporized cannabis did not significantly improve the intensity of pain compared with placebo interventions, however, they found that when participants inhaled cannabis, pain interfered less with their mood. Additionally, the effects were noted without significant adverse side effects implicating the relative safety of the intervention.

Co-author Dr. Kalpna Gupta from the University of California Irvine’s Center for the Study of Cannabis explained in a Medical News Today article: “These trial results show that vaporized cannabis appears to be generally safe. They also suggest that sickle cell patients may be able to mitigate their pain with cannabis — and that cannabis might help society address the public health crisis related to opioids. Of course, we still need larger studies with more participants to give us a better picture of how cannabis could benefit people with chronic pain.”

The latest research paves the way for future studies that are needed to verify these initial findings although, its findings are promising for quality of life improvement in sickle cell disease patients. However, the trial had limitations as a proof of principle design; the cohort was small and larger scale studies are necessary to validate its results. Furthermore, the short treatment duration and follow-up period limits the generalizability of the data as participants only ingested vaporized cannabis three times a day during the study; this may not be reflective of actual use patterns of medicinal cannabis for pain relief. Nonetheless, the latest evidence shows promise for the development of future novel treatments and cannabis-based interventions for chronic pain management and mood improvement.

Reversing Age-Related Impairment and Immunity

While the average life-expectancy for humans continues to increase, a longer life span has been tied to an uptick in age-related disease and impairment across the globe. As a result of a declining immune system, the growing elderly population is more prone to infectious diseases – including influenza and COVID-19. Additionally, this group is commonly affected by age-related frailty, which has a significant negative impact on quality of life. The high level of care and involvement required to maintain the health of these patients has the potential to bear a growing burden on the healthcare system which is part of the reason underlying research efforts in the field of human longevity.

The current body of knowledge suggests the role of chronic low-grade inflammation in the biological aging process and development of age-related diseases; scientific evidence implicates that the presence of inflammation in the body accelerates aging. Hoping to uncover more information about additional factors that may contribute to an accelerated process and potential methods of reversing them, a team of researchers from the Department for BioMedical Research at the University of Bern conducted a study with findings published in Nature Metabolism.

Age-Related Frailty and Immunity

Under Bernese guidance, Dr. Mario Noti and Dr. Alexander Eggel aimed to identify new approaches to improving health-span in an ever-increasing aging population by focusing on adipose tissue eosinophils (ATEs) present in humans and mice. These immune cells found in visceral adipose tissue, otherwise known as belly fat, play an essential role in regulating inflammation and could be used to reverse aging processes; these cells are important in the control of obesity-related inflammation and metabolic disease as they are responsible for maintaining local immune homeostasis. Increasing age is tied to a decrease in eosinophils in adipose tissue and an increase in pro-inflammatory macrophages – turning belly fat into a source of pro-inflammatory activity.

Role of Eosinophils in Chronic Inflammation

The study’s authors demonstrated that visceral adipose tissue contributed to the development of chronic low-grade inflammation. They found that ATEs undergo major age-related changes in distribution and function associated with impaired adipose tissue homeostasis and systemic low-grade inflammation in human subjects as well as mice. However, exposure to a young systemic environment  was able to partially restore ATE distribution in aged subjects by reducing adipose tissue inflammation.

“In different experimental approaches, we were able to show that transfers of eosinophils from young mice into aged recipients resolved not only local but also systemic low-grade inflammation,” the researchers told ScienceDaily. ”In these experiments, we observed that transferred eosinophils were selectively homing into adipose tissue.”

Using an adoptive transfer or eosinophils from young mice to aged subjects, researchers were able to restore ATE distribution and sufficiently mitigate age-related local and systemic low-grade inflammation. As a result of the transfer, youthful systemic environments were restored and systemic rejuvenation took place in aged mice. Changes were both physical – assessed by endurance and grip strength tests – and immune-related – manifested in improved vaccination responses.

Dr. Noti and Dr. Eggel’s findings support the critical function of adipose tissue as a source contributing to accelerated aging and uncover the new role of eosinophils in sustaining adipose tissue homeostasis and thus, promoting healthy aging.

Because the age-related changes in adipose immune cell distribution were confirmed in human subjects, the latest study may have significant positive implications for the anti-aging medicine field when translated into clinical practice. Age-related frailty and immune decline may be halted and potentially even reversed as a result of this novel cell-based therapeutic approach.

“Our results indicate that the biological processes of aging and the associated functional impairments are more plastic than previously assumed,” Dr. Noti stated. “A future direction of our research will be to now leverage the gained knowledge for the establishment of targeted therapeutic approaches to promote and sustain healthy aging in humans,” his research partner Dr. Eggel concluded.

 

Natural Compound Promotes Healthy Aging

The seven human sirtuins (SIRT 1-7), or NAD-dependent deacetylases, have been strongly correlated with human longevity due to their connection with metabolic function, aging, and the development of age-related diseases. In recent years, the protein SIRT1 has received the most attention due to its influence on gene regulation, genomic stability, and energy metabolism, garnering interest among the scientific community as a potentially viable pharmacologic therapy for the prevention of several health conditions, including type 2 diabetes, obesity, cancer, as well as cardiovascular and neurodegenerative diseases.

Several compounds have been found to impact the activation of sirtuins, including resveratrol which can be found in red wine, peanuts, pistachios, certain fruits, and cocoa. In small amounts, resveratrol may be able to replicate the health benefits of the steroid hormone estrogen, known for regulating reproduction, protecting against certain age-related diseases such as metabolic syndrome and Alzheimer’s disease.

A new study conducted in the United Kingdom aimed to uncover the mechanisms underlying resveratrol’s health benefits, its association with sirtuin proteins, and its ability to protect against age-related diseases; the latest findings were published in Scientific Reports.

Resveratrol and Healthy Aging

Small amounts of resveratrol – commonly found in red wine, berries, and chocolate – may be able to replicate the beneficial effects of estrogen in preventing metabolic diseases and cognitive decline. Larger amounts, on the other hand, may have the opposite effect, according to the study’s authors.

By activating estrogen receptors, the compound in turn activates sirtuin proteins to exert its physiological effects. Sirtuin proteins play a significant role in the healthy aging process as they control mitochondrial biogenesis, promote DNA repair, and help regulate metabolic function. They are believed to protect the body against several age-related diseases and are thought to have excellent potential drug targets according to the scientific community; however, clinical applications of the proteins remain unclear. Even still, there remains a lack of understanding of how sirtuin signaling translates to increased healthspan in human beings.

Studying Sirtuin-Activating Compounds

Led by Dr. Henry Bayele, molecular biologist at the University College London, researchers conducted an in vitro study of human liver cells which exposed them to a variety of dietary compounds aimed at activating sirtuin proteins. Collectively known as dietary sirtuin-activating compounds (dSTACs),  resveratrol and isoflavones, such as daidzein, are natural activators in comparison with other synthetic compounds developed to spur sirtuin signaling. Researchers found that at low doses, resveratrol increased sirtuin signaling in cells by mimicking estrogen although, at high doses it actively reduced signaling.

“Numerous studies in animals have suggested that these proteins could prolong healthy lifespan by preventing or slowing disease onset,” Dr. Bayele told Medical News Today. “But developing effective drugs or dietary interventions has been frustrated by a lack of a common understanding of how exactly they work in the body’s cells.”

The study’s findings support the notion that small amounts of red wine can promote healthy aging as can other dietary components; Dr. Bayele reported that the compound present in licorice, isoliquiritigenin, is even more effective at activating sirtuins. His research supports the claim that dSTACs can be viewed as “plant estrogens”, benefiting human health by performing functions that estrogen would typically be responsible for.

Implications for Anti-Aging

Emerging evidence supportive of resveratrol’s benefits could lead to the development of alternatives to hormone replacement therapy – which can increase the risk of cardiometabolic disease – for menopause patients. However, further clinical studies are required to confirm whether individuals using dSTACs as estrogen substitutes to promote healthy aging display positive results.

“Regular low doses of resveratrol, such as through moderate consumption of red wine as part of a healthy diet, may be able to provide the benefits of estrogen,” Dr. Bayele explained. “This would apply to both men and women of all ages, but postmenopausal women may feel these benefits the most because they have lower estrogen reserves than men of a similar age.”

Dr. Bayele and his colleagues caution that the effects of dSTACs on cells in vitro found in their study may not reflect their effects in human subjects. For instance, the body may digest resveratrol compounds in the gut or metabolize them in the intestinal microbiota. If they do survive digestion intact, the absorption of the compounds into the bloodstream may be poor or the liver may break them down during digestion. Hence why additional study is needed to develop novel strategies for effectively delivering resveratrol for maximum benefit.