Cannabis Appears Safe And Effective At Treating Chronic Pain, New Clinical Trial Shows
Cannabis appears to be a safe and potentially effective treatment for the chronic pain that afflicts people with sickle cell disease, according to a new clinical trial co-led by University of California, Irvine researcher Kalpna Gupta and Dr. Donald Abrams of UC San Francisco. The findings appear in JAMA Network Open.
“These trial results show that vaporized cannabis appears to be generally safe,” said Gupta, a professor of medicine on the faculty of UCI’s Center for the Study of Cannabis. “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.”
Opioids are currently the primary treatment for the chronic and acute pain caused by sickle cell disease. But the rise in opioid-associated deaths has prompted physicians to prescribe them less frequently, leaving sickle cell patients with fewer options.
The double-blind, placebo-controlled, randomized trial was the first to employ such gold-standard methods to assess cannabis’s potential for pain alleviation in people with sickle cell disease. The cannabis used in the trial was obtained from the National Institute on Drug Abuse – part of the National Institutes of Health – and contained equal parts of THC and CBD.
“Pain causes many people to turn to cannabis and is, in fact, the top reason that people cite for seeking cannabis from dispensaries,” Gupta said. “We don’t know if all forms of cannabis products will have a similar effect on chronic pain. Vaporized cannabis, which we employed, may be safer than other forms because lower amounts reach the body’s circulation. This trial opens the door for testing different forms of medical cannabis to treat chronic pain.”
Twenty-three patients with sickle cell disease-related pain completed the trial, inhaling vaporized cannabis or a vaporized placebo during two five-day inpatient sessions that were separated by at least 30 days. This allowed them to act as their own control group.
Researchers assessed participants’ pain levels throughout the treatment period and found that the effectiveness of cannabis appeared to increase over time. As the five-day study period progressed, subjects reported that pain interfered less and less with activities, including walking and sleeping, and there was a statistically significant drop in how much pain affected their mood. Although pain levels were generally lower in patients given cannabis than in those given the placebo, the difference was not statistically significant.
Bad eating habits may cause blindness, warn researchers
University of Bristol (UK), July 20, 2020
There’s no denying that eating junk food is bad for your health, as it’s linked to obesity and an increased risk of various health problems. A report in the Annals of Internal Medicine even found that a diet full of junk food could eventually cause vision loss.
Researchers from the University of Bristol in the U.K. looked at a particular case involving a teenager who was a “fussy eater” and didn’t eat anything except junk food. Several years of following an unhealthy diet eventually made him lose his eyesight.
This unusual and shocking case highlights the dangers of an unhealthy diet. It can cause obesity and increase your risk of developing heart disease and cancer. The report also found that consuming junk food may “permanently damage the nervous system, particularly vision.”
The adverse effects of poor eating habits
The teen first experienced problems when he was 14, and he consulted a doctor due to symptoms like tiredness. His blood tests then revealed that he had anemia.
Since the teenager had B12 deficiency, he was also treated with injections of the vitamin. His physician then told him to improve his eating habits.
When the teenager turned 15, he reported more issues like hearing loss and vision problems. His physicians were baffled because the results from an MRI and eye exam were all normal. (Related: Cut the junk: Eating junk food can give you food allergies.)
After two years, the teenager’s vision worsened. At 17, an eye test revealed that his vision was 20/200 in both eyes: The threshold for being considered “legally blind” in America. Results from other tests revealed that the teenager also suffered damage to his optic nerve, the bundle of nerve fibers that connects the back of the eye to the brain.
Despite being told to improve his eating habits when he was 14, the teenager still had a vitamin B12 deficiency. Worse, he also had low levels of copper, selenium and vitamin D. The physicians were alarmed at these deficiencies.
After questioning the teenager, they found out that he didn’t like eating “certain textures of food.” Since elementary school, the patient followed a limited diet that consisted only of foods such as:
- Chips
- Fries
- Processed ham slices
- Sausage
- White bread
Once the doctors ruled out other possible causes for his vision loss, the patient was diagnosed with nutritional optic neuropathy or damage to the optic nerve because of nutritional deficiencies. The researchers noted that “[purely] dietary causes are rare in developed countries.” Most of the time, nutritional optic neuropathy is caused by alcohol abuse, drugs, poor diet or the malabsorption of food.
Early detection can potentially reverse vision loss due to nutritional optic neuropathy. But unfortunately for the teenager, by the time his condition was diagnosed, his vision loss was permanent.
Dr. Denize Atan, a senior lecturer in ophthalmology at Bristol Medical School and a co-author of the study, explained that eyeglasses wouldn’t help the patient’s vision since any damage to the optic nerve can’t be addressed with lenses. To prevent his vision loss from worsening, physicians prescribed the teenager nutritional supplements.
Avoidant-restrictive food intake disorder and mental health
The doctors involved in the patient’s case also referred him to mental health services for an eating disorder because there seemed to be more to his unusual diet. Unlike kids who were simply picky eaters, the teenager’s diet “was very restrictive and caused multiple nutritional deficiencies.”
They believe that the teenager might have a condition called “avoidant-restrictive food intake disorder” (ARFID). This relatively new diagnosis, previously called “selective eating disorder,” may cause a lack of interest in food or avoidance of foods with certain colors, textures or other factors without links to the patient’s body weight or shape.
Other symptoms of ARFID include:
- Abdominal pain, cold intolerance, constipation, lethargy or excess energy
- Dramatic restriction in amount or types of food eaten
- Dramatic weight loss
- Eating only certain textures of food
- Eating a limited range of preferred foods that becomes narrower over time or picky eating that worsens with time
- Fears of choking or vomiting
- Inconsistent and vague gastrointestinal issues, like an upset stomach, around mealtimes with no known cause
- No body image disturbance or fear of weight gain
ARFID often manifests in childhood, and patients tend to have a normal body mass index (BMI) like the teenaged boy, concluded the study authors.
Chronic inflammation alters the evolution of cells in the colon, study finds
Researchers have compared diseased colon with healthy tissue to better understand how inflammatory bowel disease (IBD) is linked to an increased risk of colorectal cancers
Cambridge University and Wellcome Sanger Institute, July 21, 2020
In a new study, researchers have compared diseased colon with healthy tissue to better understand how inflammatory bowel disease (IBD) is linked to an increased risk of colorectal cancers, at a molecular level. Researchers from the Wellcome Sanger Institute and Cambridge University Hospitals found that the rate of DNA change within colon cells affected by IBD was more than double that in healthy colon, increasing the likelihood of these cells gaining DNA changes that could lead to cancer.
The study, published today (21 July) in Cell, also found that chronic inflammation associated with IBD disrupts the tissue structure of the colon, allowing cells to expand over an abnormally wide area. The results provide valuable insights into evolution within the body, and the development of IBD and colorectal cancers.
IBD primarily refers to ulcerative colitis and Crohn's disease, chronic illnesses characterised by inflammation of the digestive system that can be highly disruptive to a patient's quality of life. Between 1990 and 2017, the number of IBD cases worldwide rose from 3.7 million to 6.8 million*. The causes of the disease remain unknown, though it is thought that inflammation occurs as a result of an inappropriate immune response to gut microbes.
People suffering from IBD are at an increased risk of developing gastrointestinal cancers compared to the general population. Patients will undergo regular surveillance for this and may, in some cases, opt to undergo surgery to remove their entire colon in order to mitigate this risk.
In this new study, clinicians at Addenbrooke's Hospital, Cambridge provided colon tissue samples donated by 46 IBD patients, along with anonymised information about their medical history and treatment. Researchers at the Wellcome Sanger Institute then used laser-capture microdissection to cut out 446 individual crypts, the tiny cavities that make up colon tissue, so they could be whole-genome sequenced.
These sequences were analysed to discover the mutation rate in the tissue, the genetic relationship between crypts and any genes that were more mutated than normal. They were then compared to sequences from 412 crypts from 41 individuals without IBD, so that the effects of chronic inflammation on the DNA sequence could be observed.
The team found that there were more than twice as many DNA changes in the diseased tissue than in normal, and the longer the duration of the disease, the greater this excess.
The study also uncovered evidence of an evolutionary process whereby mutations in particular genes are under positive selection. Some of these positively-selected mutations were enriched in genes associated with colorectal cancers, shedding light on the link between IBD and certain cancers. The researchers also detected evidence of positive selection of mutations in genes associated with immune system regulation in the gut and the ability of the cells to fend off the bacteria resident in the colon.
Sigurgeir Olafsson, first author of the study from the Wellcome Sanger Institute, said: "How our bodies continue to evolve during our lifetime is a fundamental part of our biology. It has been fascinating to study the effect of a chronic disease on this process and uncover evidence that changes in the genetic sequence of gut cells could have a direct role in the onset of inflammatory bowel disease."
Dr Tim Raine, clinical lead for the inflammatory bowel disease (IBD) service at Addenbrooke's Hospital, Cambridge and Honorary Faculty member at the Wellcome Sanger Institute, said: "Colorectal cancer is one of the main clinical concerns when treating patients with IBD. In this study, we found that normal mutational processes that are operative in us all are accelerated in the IBD affected gut, leading to a more than two-fold increase in the rate at which some gut cells acquire mutations, and this underpins the increased cancer risk in IBD."
Dr Peter Campbell, an author on the study from the Wellcome Sanger Institute, said: "The role of somatic mutations in cancer susceptibility has long been appreciated. It is exciting to see the methods that we and others have used to understand cancers now being applied to other common diseases. These approaches have given us unique insights into the effects of inflammatory bowel disease on the DNA sequence of the inflamed tissue."
A previously unexplained observation in IBD is that repeated flares of inflammation tend to affect the same patch of tissue, suggesting some permanent alterations to the colon. These findings highlight genetic mutations as a possible explanation, with some positively-selected mutations in immune regulation genes occurring in the same regions of the bowel affected by chronic inflammation.
Dr Carl Anderson, lead author of the study from the Wellcome Sanger Institute, said: "We know that DNA changes contribute to the development of cancer, but their role in common non-cancerous diseases like inflammatory bowel disease (IBD) has not been extensively studied. Our study revealed that somatic changes in the DNA sequence of the cells that line our gut may contribute to the development of IBD. I strongly believe that studying somatic mutations in all common diseases, not just IBD and cancers, has the potential to provide novel insights into disease biology and highlight potential drug targets."
Studies suggest a fasting diet could boost breast cancer therapy
A USC-led team of international scientists found that a one-two punch of a fasting diet with hormone therapy may enhance the effects of breast cancer treatment
University of Southern California, July 22, 2020
A USC-led team of scientists has found that a fasting-mimicking diet combined with hormone therapy has the potential to help treat breast cancer, according to newly published animal studies and small clinical trials in humans.
In studies on mice and in two small breast cancer clinical trials, researchers at USC and the IFOM Cancer Institute in Milan -- in collaboration with the University of Genova -- found that the fasting-mimicking diet reduces blood insulin, insulin-like growth factor 1 (IGF1) and leptin. In mice, these effects appear to increase the power of the cancer hormone drugs tamoxifen and fulvestrant and delay any resistance to them. The results from 36 women treated with the hormone therapy and fasting-mimicking diet are promising, but researchers say it is still too early to determine whether the effects will be confirmed in large-scale clinical trials.
The research was published in the journal Nature.
"Our new study suggests that a fasting-mimicking diet together with endocrine therapy for breast cancer has the potential to not only shrink tumors but also reverse resistant tumors in mice," said Valter Longo, the study's co-senior author and the director of the Longevity Institute at the USC Leonard Davis School of Gerontology and professor of biological sciences at the USC Dornsife College of Letters, Arts and Sciences. "We have data that for the first time suggests that a fasting-mimicking diet works by changing at least three different factors: IGF1, leptin and insulin."
The researchers say the two small clinical trials are feasibility studies that showed promising results, but they are in no way conclusive. They believe the results support further clinical studies of a fasting-mimicking diet used in combination with endocrine therapy in hormone-receptor-positive breast cancer.
The scientists also contributed to a recent clinical study of 129 breast cancer patients conducted with the University of Leiden. The results, published last month in Nature Communications, appeared to show increased efficacy of chemotherapy in patients receiving a combination of chemotherapy and a fasting-mimicking diet.
In the two new small clinical trials -- one of which was directed by the study co-corresponding author Alessio Nencioni -- patients with hormone-receptor-positive breast cancer receiving estrogen therapy along with cycles of a fasting-mimicking diet seemed to experience metabolic changes similar to those observed in mice. These changes included a reduction in insulin, leptin and IGF1 levels, with the last two remaining low for extended periods. In mice, these long-lasting effects are associated with long-term anti-cancer activity, so further studies in humans is needed.
"Some patients followed monthly cycles of the fasting-mimicking diet for almost two years without any problems, suggesting that it is a well-tolerated intervention," Nencioni said. "We hope this means that this nutritional program that mimics fasting could one day represent a weapon to better fight cancer in patients receiving hormone therapy without serious side effects."
"The results in mice are very promising. And the early clinical results show potential as well, but now we need to see it work in a 300- to 400-patient trial," Longo explained.
The data also suggest that in mice, the fasting-mimicking diet appears to prevent tamoxifen-induced endometrial hyperplasia, a condition in which the endometrium (or the lining of the uterus) becomes abnormally thick. The study authors believe this potential use of the fasting diet should be explored further, given the prevalence of this side effect of tamoxifen and the limited options for preventing it.
Approximately 80% of all breast cancers express estrogen and/or progesterone receptors. The most common forms of hormone therapy for these breast cancers work by blocking hormones from attaching to receptors on cancer cells or by decreasing the body's hormone production. Endocrine therapy is frequently effective in these hormone-receptor-positive tumors, but the long-term benefits are often hindered by treatment resistance.
Several clinical trials, including one at USC on breast cancer and prostate patients, are now investigating the effects of the fasting-mimicking diets in combination with different cancer-fighting drugs.
"I like to call it the nontoxic wildcard for cancer treatment," Longo said. "These clinical studies we have just published -- together with the many animal studies published in the past 12 years -- suggest that cycles of the fasting-mimicking diet has the potential to make standard therapy more effective against different cancers, each time by changing a different factor or nutrient important for cancer cell survival."
Scientists identify 10 risk factors for Alzheimer disease
Fudan University (China), July 17, 2020
Alzheimer’s disease may be preventable by keeping an eye on key factors including weight gain, blood pressure and avoiding stress, experts say.
Researchers said many risk factors are modifiable in the fight to prevent dementia, which affects around 850,000 people in the UK, two-thirds of whom have Alzheimer’s.
Their review of existing studies found 10 risk factors had strong evidence of a link with Alzheimer’s, and people could take action to avoid them.
These included ensuring good education in early life, keeping the brain active through activities such as reading, and not being overweight or obese in later life.
People should also avoid depression, stress, high blood pressure, head trauma and diabetes to reduce their risk, they said.
Other factors had weaker links that could be adjusted, including not being obese in midlife, taking exercise, getting enough sleep, including vitamin C in the diet and not smoking.
The study, published in the Journal of Neurology, Neurosurgery & Psychiatry, was led by Professor Jin-Tai Yu at Fudan University in China.
The researchers gathered 395 studies and came up with a list of factors that could be used by doctors to try to prevent Alzheimer’s disease.
They said research into preventing dementia should continue but their report offered “clinicians and stakeholders an evidence-based guideline for Alzheimer’s disease prevention”.
Fiona Carragher, director of research and influencing at the Alzheimer’s Society, said: “In recent years, research has suggested that nearly a third of dementia cases may be preventable and this review builds on this idea, specifically in relation to Alzheimer’s disease and how certain risk factors, many of which are associated with cardiovascular health, may be within our control.
“We need a deeper dive into each of these risk factors to understand how they work together on an individual level and how best to support people to manage them.
“This review demonstrates that, while observational studies are useful to help identify potential risk factors, we need to see many more interventional trials to understand what the best approaches are to preventing Alzheimer’s disease developing in the first place.
“We don’t have all the answers yet, but we do know that small steps to improving your physical and mental health can make a big difference, like walking to your local shop for milk instead of jumping in the car.”
