Marijuana concentrates spike THC levels but don't boost impairment

June 10, 2020

Science Daily/University of Colorado at Boulder

A study of 121 regular users of legal market cannabis found that higher potency does not necessarily mean greater intoxication. It also found that while balance and memory are impaired immediately after use, that impairment fades within in an hour.

Smoking high-potency marijuana concentrates boosts blood levels of THC more than twice as much as smoking conventional weed, but it doesn't necessarily get you higher, according to a new study of regular users published today by University of Colorado Boulder researchers.

"Surprisingly, we found that potency did not track with intoxication levels," said lead author Cinnamon Bidwell, an assistant professor in the Institute of Cognitive Science. "While we saw striking differences in blood levels between the two groups, they were similarly impaired."

The paper, published June 10 in JAMA Psychiatry, is the first to assess the acute impact of cannabis among real-world users of legal market products. It could inform everything from roadside sobriety tests to decisions about personal recreational or medicinal use.

But the study also raises concerns that using concentrates could unnecessarily put people at greater long-term risk of side-effects.

"It raises a lot of questions about how quickly the body builds up tolerance to cannabis and whether people might be able to achieve desired results at lower doses," said Bidwell.

While 33 states have legalized medicinal marijuana use, and 11 have legalized recreational use, both uses remain illegal at the federal level. Researchers are also prohibited from handling or administering marijuana. Some previous studies have used strains supplied by the government, but those strains contain far less THC than real-world products.

In order to study what people really use, Bidwell and her colleagues utilize two white Dodge Sprinter vans, also known as the "cannavans," as mobile laboratories. They drive the vans to the residences of study subjects who use cannabis they purchase on their own inside their homes and then walk out for tests.

"We cannot bring legal market cannabis into a university lab, but we can bring the mobile lab to the people," she said.

For the current study, the team assessed 121 regular cannabis users. Half typically used concentrates (oils and waxes that include the active ingredients without the leaves and stems). The other half typically used flower from the plant. Flower users purchased a product containing either 16% or 24% [tetrahydrocannabinol (THC)], the main psychoactive ingredient in marijuana. Concentrate users were assigned to a product containing either 70% or 90% THC.

On test day, researchers drew the subjects' blood, measured their mood and intoxication level and assessed their cognitive function and balance at three time points: before, directly after and one hour after they used.

Those who used concentrates had much higher THC levels at all three points, with levels spiking to 1,016 micrograms per milliliter in the few minutes after use, while flower users spiked at 455 micrograms per milliliter. (Previous studies have shown that THC levels hover around 160 to 380 micrograms per milliliter after marijuana use).

Regardless of what type or potency of cannabis participants used, their self-reports of intoxication, or "feeling high," were remarkably similar, as were their measures of balance and cognitive impairment.

"People in the high concentration group were much less compromised than we thought they were going to be," said coauthor Kent Hutchison, a professor of psychology and neuroscience at CU Boulder who also studies alcohol addiction. "If we gave people that high a concentration of alcohol it would have been a different story."

The study also found that, among all users, balance was about 11% worse after using cannabis, and memory was compromised. But within about an hour, that impairment faded.

"This could be used to develop a roadside test, or even to help people make personal decisions," said Bidwell.

The researchers aren't sure how the concentrate group could have such high THC levels without greater intoxication, but they suspect a few things are at play: Regular users of concentrates likely develop a tolerance over time. There may be genetic or biological differences that make some people metabolize THC more quickly. And it may be that once compounds in marijuana, called cannabinoids, fill receptors in the brain that spark intoxication, additional cannabinoids have little impact.

"Cannabinoid receptors may become saturated with THC at higher levels, beyond which there is a diminishing effect of additional THC," they write.

The authors caution that the study examined regular users who have learned to meter their use based on the desired effect, and does not apply to inexperienced users. Those users should still be extremely cautious with concentrates, said Hutchison.

Ultimately, the researchers hope to learn what, if any, long-term health risks concentrates truly pose.

"Does long-term, concentrated exposure mess with your cannabinoid receptors in a way that could have long-term repercussions? Does it make it harder to quit when you want to?" said Hutchison. "We just don't know yet."

https://www.sciencedaily.com/releases/2020/06/200610135016.htm

Cannabis temporarily relieves PTSD symptoms

June 9, 2020

Science Daily/Washington State University

People suffering from post-traumatic distress disorder report that cannabis reduces the severity of their symptoms by more than half, at least in the short term, according to a recent study led by Carrie Cuttler, a Washington State University assistant professor of psychology.

Cuttler and her colleagues analyzed data of more than 400 people who tracked changes in their PTSD symptoms before and after cannabis use with Strainprint, an app developed to help users learn what types of medical cannabis work best for their symptoms. The group collectively used the app more than 11,000 times over a 31-month period.

The study, recently published in Journal of Affective Disorders, shows cannabis reduced the severity of intrusions, returning thoughts of a traumatic event, by about 62%; flashbacks by 51%, irritability by 67%, and anxiety by 57%. The symptom reductions were not permanent, however.

"The study suggests that cannabis does reduce symptoms of PTSD acutely, but it might not have longer term beneficial effects on the underlying condition," said Cuttler. "Working with this model, it seems that cannabis will temporarily mask symptoms, acting as a bit of a band aid, but once the period of intoxication wears off, the symptoms can return."

PTSD is a disorder affecting people recovering from traumatic events and impacts women at about twice the rate as men with a 9.7% to 3.6% lifetime prevalence, respectively. While therapy is recommended as the primary treatment, Cuttler said there is growing evidence that many people with PTSD are self-medicating with cannabis.

"A lot of people with PTSD do seem to turn to cannabis, but the literature on its efficacy for managing symptoms is a little sparse," Cuttler said.

This study provides some insight into the effectiveness of cannabis on PTSD symptoms, but as the authors note, it is limited by reliance on a self-selected sample of people who self-identify as having PTSD. Also, it is not possible to compare the symptom reductions experienced by cannabis users to a control group using a placebo.

While some placebo-controlled clinical trials have been done with nabilone, a synthetic form of THC, few have examined the effects of the whole cannabis plant on PTSD.

In this study, Cuttler and her colleagues looked at a variety of variables but found no difference in the effect of cannabis with differing levels of tetrahydrocannabinol (THC) and cannabidiol (CBD), two of the most studied constituents of cannabis. The results imply that it is some combination of THC, CBD and perhaps some of the many other parts of the cannabis plant that create the therapeutic effect. Cannabis has many molecules that can create a biological effect, including up to 120 cannabinoids, 250 terpenes and around 50 flavonoids.

"We need more studies that look at whole plant cannabis because this is what people are using much more than the synthetic cannabinoids," said Cuttler. "It is difficult to do good placebo-controlled trials with whole plant cannabis, but they're still really needed."

https://www.sciencedaily.com/releases/2020/06/200609144458.htm

How psychedelic drug psilocybin works on brain

June 5, 2020

Science Daily/Johns Hopkins Medicine

To see how psychedelics impact the claustrum, a mysterious region of the brain believed to control the ego, researchers compared the brain scans of people after they took psilocybin with their scans after taking a placebo.

Perhaps no region of the brain is more fittingly named than the claustrum, taken from the Latin word for "hidden or shut away." The claustrum is an extremely thin sheet of neurons deep within the cortex, yet it reaches out to every other region of the brain. Its true purpose remains "hidden away" as well, with researchers speculating about many functions. For example, Francis Crick of DNA-discovery fame believed that the claustrum is the seat of consciousness, responsible for awareness and sense of self.

What is known is that this region contains a large number of receptors targeted by psychedelic drugs such as LSD or psilocybin ¾ the hallucinogenic chemical found in certain mushrooms. To see what happens in the claustrum when people are on psychedelics, Johns Hopkins Medicine researchers compared the brain scans of people after they took psilocybin with their scans after taking a placebo.

Their findings were published online on May 23, 2020, in the journal NeuroImage.

The scans after psilocybin use showed that the claustrum was less active, meaning the area of the brain believed responsible for setting attention and switching tasks is turned down when on the drug. The researchers say that this ties in with what people report as typical effects of psychedelic drugs, including feelings of being connected to everything and reduced senses of self or ego.

"Our findings move us one step closer to understanding mechanisms underlying how psilocybin works in the brain," says Frederick Barrett, Ph.D., assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine and a member of the school's Center for Psychedelic and Consciousness Research. "This will hopefully enable us to better understand why it's an effective therapy for certain psychiatric disorders, which might help us tailor therapies to help people more."

Because of its deep-rooted location in the brain, the claustrum has been difficult to access and study. Last year, Barrett and his colleagues at the University of Maryland, Baltimore, developed a method to detect brain activity in the claustrum using functional magnetic resonance imaging (fMRI).

For this new study, the researchers used fMRI with 15 people and observed the claustrum brain region after the participants took either psilocybin or a placebo. They found that psilocybin reduced neural activity in the claustrum by 15% to 30%. This lowered activity also appeared to be associated with stronger subjective effects of the drug, such as emotional and mystical experiences. The researchers also found that psilocybin changed the way that the claustrum communicated with brain regions involved in hearing, attention, decision-making and remembering.

With the highly detailed imaging of the claustrum provided by fMRI, the researchers next hope to look at the mysterious brain region in people with certain psychiatric disorders such as depression and substance use disorder. The goal of these experiments will be to see what roles, if any, the claustrum plays in these conditions. The researchers also plan to observe the claustrum's activity when under the influence of other psychedelics, such as salvinorin A, a hallucinogen derived from a Mexican plant.

https://www.sciencedaily.com/releases/2020/06/200605121512.htm

Users of high-potency cannabis four times more likely to report associated problems

May 28, 2020

Science Daily/University of Bristol

Users of high-potency cannabis are four times more likely to report associated problems, and twice as likely to report anxiety disorder, than users of lower-potency strains, according to new research from the University of Bristol.

Published today on JAMA Psychiatry the research uses data from Children of the 90s, a long-term health study that recruited more than 14,000 pregnant women and their babies born in and around Bristol in the early 1990s and has been following their health and development ever since.

This is the first research of its kind to look at data from a general population sample, with previous research into the links between cannabis potency and mental health only looking at clinical and self-selecting samples of people who use drugs. Added to this, the nature of the data available from the Children of the 90s health study enabled the research team to take into account whether mental health symptoms were present before the individual started using cannabis.

Frequency of cannabis use, which is also often associated with increased mental health problems, was also taken into account in order to determine whether this would explain the relationship between higher-potency usage and mental health conditions.

Lead author Dr Lindsey Hines, Senior Research Associate from Bristol Medical School explained: "We know that people who use cannabis are more likely to report mental health problems than those who don't use cannabis, but we don't fully understand how recent increases in the strength and potency of cannabis affects this. This study gives us an estimate of the increased likelihood of mental health problems from use of high-potency cannabis, compared to use of lower-potency cannabis, and we are able to account for the effect that people's early adolescent mental health symptoms may have on this relationship."

The research looked at data collected from participants aged 24 years who had reported using cannabis in the previous year, of which 13 per cent reported use of high-potency cannabis. Participants were also asked about their usage, and those who self-reported two or more of the Cannabis Abuse Screening Test (CAST) items within the past year were classified as having recently experienced problems as a result of their cannabis use. Researchers were then able to compare this data to reported mental health symptoms at age 24 as well as early symptoms of mental health collected when participants were younger.

Dr Hines continued: "People who use cannabis are more likely to report mental health problems than those who don't use cannabis, but reducing the potency and regularity of their cannabis use may be effective for lessening likelihood of harms from use. In countries where cannabis is sold legally, limiting the availability of high-potency cannabis may reduce the number of individuals who develop cannabis use disorders, prevent cannabis use escalating to a regular behaviour, and reduce impacts on mental health. In countries like the UK, where we are not able to limit the availability of high-potency cannabis, we should make sure there is good treatment and support for those who develop problems from cannabis use."

https://www.sciencedaily.com/releases/2020/05/200528115817.htm

CBD improves arthritis symptoms in dogs

May 28, 2020

Baylor College of Medicine

This study shows that in dogs diagnosed with arthritis, CBD treatment significantly improved quality of life as documented by both owner and veterinarian assessments.

A team led by researchers at Baylor College of Medicine in collaboration with Medterra CBD conducted the first scientific studies to assess the potential therapeutic effects of cannabidiol (CBD) for arthritic pain in dogs, and the results could lead the way to studying its effect in humans. Researchers focused first on these animals because their condition closely mimics the characteristics of human arthritis, the leading cause of pain and disability in the U.S. for which there is no effective treatment.

Published in the journal PAIN, the study first showed both in laboratory tests and mouse models that CBD, a non-addictive product derived from hemp (cannabis), can significantly reduce the production of inflammatory molecules and immune cells associated with arthritis. Subsequently, the study showed that in dogs diagnosed with the condition, CBD treatment significantly improved quality of life as documented by both owner and veterinarian assessments. This work supports future scientific evaluation of CBD for human arthritis.

"CBD is rapidly increasing in popularity due to its anecdotal health benefits for a variety of conditions, from reducing anxiety to helping with movement disorders," said corresponding author Dr. Matthew Halpert, research faculty in the Department of Pathology and Immunology at Baylor. "In 2019, Medterra CBD approached Baylor to conduct independent scientific studies to determine the biological capabilities of several of its products."

In the current study, Halpert and his colleagues first measured the effect of CBD on immune responses associated with arthritis, both in human and murine cells grown in the lab and in mouse models. Using Medterra tinctures, they found that CBD treatment resulted in reduced production of both inflammatory molecules and immune cells linked to arthritis.

The researchers also determined that the effect was quicker and more effective when CBD was delivered encapsulated in liposomes than when it was administered 'naked.' Liposomes are artificially formed tiny spherical sacs that are used to deliver drugs and other substances into tissues at higher rates of absorption.

Halpert and colleagues next assessed the effect of naked and liposome-encapsulated CBD on the quality of life of dogs diagnosed with arthritis.

"We studied dogs because experimental evidence shows that spontaneous models of arthritis, particularly in domesticated canine models, are more appropriate for assessing human arthritis pain treatments than other animal models. The biological characteristics of arthritis in dogs closely resemble those of the human condition," Halpert said.

Arthritis is a common condition in dogs. According to the American Kennel Club, it affects one out of five dogs in the United States.

The 20 client-owned dogs enrolled in the study were seen at Sunset Animal Hospital in Houston. The dog owners were randomly provided with identical unidentified medication bottles that contained CBD, liposomal CBD, or a placebo. Neither the owners nor the veterinarian knew which treatment each dog received.

After four weeks of daily treatment, owners and veterinarians reported on the condition of the dogs, whether they observed changes in the animals' level of pain, such as changes related to running or gait. The dogs' cell blood count and blood indicators of liver and kidney function also were evaluated before and after the four weeks of treatment.

"We found encouraging results," Halpert said. "Nine of the 10 dogs on CBD showed benefits, which remained for two weeks after the treatment stopped. We did not detect alterations in the blood markers we measured, suggesting that, under the conditions of our study, the treatment seems to be safe."

The findings support conducting studies to evaluate CBD for the treatment of human arthritis.

https://www.sciencedaily.com/releases/2020/05/200528160611.htm

Minimum legal age for cannabis use should be 19

May 13, 2020

Science Daily/BMC (BioMed Central)

The optimal minimum legal age for non-medical cannabis use is 19 years of age, according to a study published in BMC Public Health.

A team of researchers at the Memorial University of Newfoundland, Canada, investigated how Canadians who started using cannabis at several young ages differed across important outcomes (educational attainment, cigarette smoking, self-reported general and mental health) in later-life.

Dr Hai Nguyen, lead author of the study said: "Prior to legalisation, the medical community recommended a minimum legal age of 21 or 25 for non-medical cannabis use in Canada. This recommendation was based on scientific evidence around the potential adverse impacts of cannabis on cognitive development. However, policymakers feared a high minimum legal age may lead to large underground markets, with those under the legal age continuing to use cannabis illegally. Ultimately, a lower legal age of 18 or 19 was decided across provinces, however there remains ongoing debate and calls to raise the legal age to 21."

To determine whether the age at which people begin to use cannabis may have an impact on later-life outcomes, the authors analysed data from nationally-representative Canadian Tobacco Use Monitoring Surveys (CTUMS) and Canadian Tobacco, Alcohol and Drugs Surveys (CTADS) conducted between 2004 and 2015, which annually interview up to 20,000 individuals aged 15 years and older.

The authors found different optimal minimum legal ages depending on the outcome of interest. For smoking, respondents who first used cannabis aged 19-20 were less likely to smoke cigarettes later in life than those who first used cannabis aged 18, but no significant difference was found in those who started using cannabis at an older age, indicating an optimum legal age of 19.

The number of respondents reporting a high level of completed education was 16% higher among those who first used cannabis between the ages of 21 and 24, relative to those who first used it before age 18, suggesting an optimal minimum legal age of 21.

General health was significantly better among those who started using cannabis aged 18, relative to those who started before age 18, but no significant difference was found among those who started at an older age, suggesting a minimum legal age of 18. However, mental health outcomes were found to be higher among those who first used cannabis aged 19-20 than before age 18, suggesting a minimum legal age of 19.

Dr Nguyen said: "The lower level of completed education reported in those who first used cannabis at an earlier age may reflect poor neurological development or a higher 'drop-out' rate from further education. It is also possible that those who initiate cannabis use early may use it as a gateway for further illicit drug use, resulting in poorer health in later life, which may explain the poor general or mental health scores recorded in the study."

Dr Nguyen said: "Taking into account all measured outcomes, our results indicate that, contrary to the Canadian federal government's recommendation of 18 and the medical community's support for 21 or 25, 19 is the optimal minimum legal age for non-medical cannabis use. Keeping the legal age below 21 may strike a balance between potential increases in underground markets and illegal use, and avoiding the adverse outcomes associated with starting to use cannabis at an earlier age."

The authors caution that as the study used self-reported data, respondents may not have accurately recalled the age at which they first used cannabis. Data was also collected prior to legalization of non-medical cannabis in Canada and the authors were unable to predict the impact of cannabis use after legalization. They suggest that further research is needed to establish potential causal effects between the age at which cannabis is first used and the outcomes measured in the study, and could also focus on additional outcomes such as driving behaviours and street drug use.

https://www.sciencedaily.com/releases/2020/05/200513200400.htm

Early exposure to cannabis boosts young brains' sensitivity to cocaine

April 20, 2020

Science Daily/The Zuckerman Institute at Columbia University

Cannabis use makes young brains more sensitive to the first exposure to cocaine, according to a new study on rodents led by scientists at Columbia University and the University of Cagliari in Italy. By monitoring the brains of both adolescent and adult rats after giving them synthetic psychoactive cannabinoids followed by cocaine, the research team identified key molecular and epigenetic changes that occurred in the brains of adolescents -- but not adults. This discovery reveals a new interplay between the two drugs that had never previously been directly observed in biological detail.

These findings, reported this week in the Proceedings of the National Academy of Sciences, provide new understanding of how the abuse of cannabis during teenage years may enhance the first experience with cocaine and lead to continued use among vulnerable individuals.

"We know from human epidemiological studies that individuals who abuse cocaine have a history of early cannabis use, and that a person's initial response to a drug can have a large impact on whether they continue to use it. But many questions remain on how early cannabis exposure affects the brain," said epidemiologist Denise Kandel, PhD, who is a professor of Sociomedical Sciences in Psychiatry at Columbia's Vagelos College of Physicians and Surgeons and co-senior author of today's paper.

"Our study in rats is the first to map the detailed molecular and epigenetic mechanisms by which cocaine interacts with brains already exposed to cannabinoids, providing much-needed clarity to the biological mechanisms that may increase the risk for drug abuse and addiction," added co-author and Nobel laureate Eric Kandel, MD, codirector of Columbia's Mortimer B. Zuckerman Mind Brain Behavior Institute and Senior Investigator of the Howard Hughes Medical Institute.

Previous research had revealed key differences in how cannabis and cocaine affect brain chemistry. "Studies on the addictive properties of cocaine have traditionally focused on the mesolimbic dopaminergic pathway, a brain system that underlies our motivation to pursue pleasurable experiences," said Philippe Melas, PhD, who was an associate research scientist in Eric Kandel's lab at Columbia's Zuckerman Institute and is the paper's co-senior author. "While cannabis enhances mesolimbic dopaminergic activity similarly to cocaine, it also affects an entirely different neurochemical system that is widespread in the brain called the endocannabinoid system. This system is essential for brain development -- a process that is still ongoing in adolescence."

Besides the dopaminergic system, both cannabis and cocaine appear to share some additional features. Recent studies have suggested that the development of cocaine craving is dependent on the brain's glutamatergic system. This system uses glutamate, a brain molecule that acts as a synaptic transmitter in the brain, enhancing the transmission of signals between the brain's neurons. According to previous research, as well as findings presented in today's new study, using cannabis during adolescence may also affect this glutamatergic signaling process.

To delve deeper into a potential link between the two drugs, Dr. Melas and the husband-and-wife team of Drs. Eric and Denise Kandel partnered with Paola Fadda, PhD, Maria Scherma, PhD, and Walter Fratta, PhD, researchers in the Department of Biomedical Sciences, at the University of Cagliari in Italy. The group examined the behavioral, molecular and epigenetic changes that occur when both adolescent and adult rats are first exposed to WIN, a synthetic cannabinoid with psychoactive properties similar to those of THC found in cannabis, and then are subsequently exposed to cocaine.

"We found that adolescent rats that had been pre-exposed to WIN had an enhanced reaction to their initial exposure to cocaine. Notably, we observed this effect in adolescent but not in adult rats," said Dr. Melas, who is now a junior researcher in the Department of Clinical Neuroscience at the Karolinska Institutet in Sweden.

Upon further examination, the team found that, when preceded by a history of psychoactive cannabinoid use in adolescence, exposure to cocaine sets off a battery of unique molecular reactions in the rat brain. These reactions included not only changes in the aforementioned glutamate receptors but also key epigenetic modifications. Epigenetic modifications are distinct, in that they affect the way genes are switched on or off but do not affect the sequence of the genes themselves.

The Columbia team had previously found similar epigenetic mechanisms in adult animals in response to nicotine and alcohol in the brain's reward center, known as the nucleus accumbens. In the present study, however, the epigenetic effects of cannabinoids were found to be specific to adolescents and to target the brain's prefrontal cortex. The prefrontal cortex, which plays a role in various executive functions, including long-term planning and self-control, is one of the last regions of the brain to reach maturity, a fact that has long been linked to adolescents' propensity for risky behavior.

Moreover, aberrant prefrontal cortex activity is often observed in patients suffering from addiction. Efforts to enhance the function of the prefrontal cortex are currently being evaluated in the treatment of addiction through the use of brain stimulation and other methodologies.

"Our findings suggest that exposure to psychoactive cannabinoids during adolescence primes the animals' prefrontal cortex, so that it responds differently to cocaine compared to animals who had been given cocaine without having previously experienced cannabis," said Dr. Melas.

These results in rats offer important clues to the biological mechanisms that may underlie the way that different classes of drugs can reinforce each other in humans. The results also support the notion that cannabis abuse during adolescence can enhance a person's initial positive experience with a different drug, such as cocaine, which in turn can have an effect on whether that person chooses to continue, or expand, their initial use of cocaine.

"This study suggests that teenagers who use cannabis may have a favorable initial reaction to cocaine, which will increase their likelihood of engaging in its repeated use so that they eventually become addicted, especially if they carry additional environmental or genetic vulnerabilities," said Dr. Denise Kandel.

Most research involving rodents and addiction has traditionally focused on adult animals. It has also largely been limited to studying one substance of abuse at a time, without taking into consideration a history of drug exposure in adolescence.

"These and other experiments are key to understanding the molecular changes to the brain that occur during drug use," said Dr. Eric Kandel, who is also University Professor and Kavli Professor of Brain Science at Columbia. "This knowledge will be crucial for developing effective treatments that curb addiction by targeting the disease's underlying mechanisms."

https://www.sciencedaily.com/releases/2020/04/200420165718.htm

Frequent cannabis users are way too high ... in their estimates of cannabinoids

In study at Hash Bash, frequent users reported low knowledge of, and substantially overestimated, cannabinoid content

April 15, 2020

Science Daily/University at Buffalo

Researchers surveyed nearly 500 Hash Bash attendees, asking them to fill out a 24-item questionnaire. Participants were asked to fill in, in milligrams, the amounts they considered to be effective doses of THC and CBD. They were way off.

One would think that cannabis enthusiasts attending a marijuana advocacy event would be knowledgeable about cannabinoids.

Not necessarily, according to the findings of a study by researchers from the University at Buffalo and the University of Michigan, who surveyed frequent cannabis users at an annual marijuana advocacy event held on the University of Michigan campus.

The surprisingly low level of knowledge about tetrahydrocannabinol (THC) and cannabidiol (CBD) content, and effective dosages, demonstrated by Hash Bash participants highlights the need for additional public health education and research, according to Daniel Kruger, PhD, the lead author of the study, published online ahead of print today in the journal Drugs: Education, Prevention and Policy.

"Even the people who are most enthusiastic have very poor knowledge of cannabinoid content. They greatly overestimated how much THC and how much CBD was in various strains, and what the effective dosages were," said Kruger, a research associate professor of community health and health behavior in the UB's School of Public Health and Health Professions. He is also a research investigator with the Population Studies Center at the University of Michigan.

Researchers surveyed nearly 500 Hash Bash attendees, asking them to fill out a 24-item questionnaire. Two-thirds of participants reported using cannabis every day, and most said it was for health or medical purposes. More than three-quarters of survey-takers said their knowledge of cannabis came from their own experiences.

The study survey asked participants to fill in, in milligrams, the amounts they considered to be effective doses of THC and CBD. (THC is the principal psychoactive compound and the one largely responsible for the high experienced by users. CBD does not have the same psychoactivity, but has other effects, such as reduction of anxiety.) Participants could also check the box for "I don't know."

The majority reported they didn't know. Other participants gave average estimates of 91 milligrams for THC and 177 milligrams for CBD. In other words, they were way off.

"The average estimate for an effective dose of THC would actually be fatal in humans," Kruger said.

One participant even said 1 million milligrams was the effective dose for THC. "That's a kilogram of THC. That's enough to fill an entire football stadium full of people and get them all high," Kruger said.

Participants also were asked to fill in what they thought were the percentages for high and low THC strains, and high and low CBD strains. The majority (58%) believed that a low-THC strain of cannabis was 20% THC or higher -- a level that would actually be considered a high-THC strain. In addition, 22% believed that a low-THC strain of cannabis was 40% THC or higher, which exceeds the levels of anything available now.

For CBD, 86% felt that a low strain of cannabis was 10% CBD or higher, a level considered representative of a high-CBD strain of cannabis. Nearly half believed that a low strain was 30% CBD or higher, which exceeds the CBD level of any existing strain.

"Our results suggest the need for broad-based cannabis education programs to help advocates and the general public to better understand and manage their use of the drug," said study co-author, R. Lorraine Collins, PhD, associate dean for research in UB's School of Public Health and Health Professions.

The current paper is the latest in a series of studies Kruger and his UB colleagues have published in recent years, based on data collected at Hash Bash. Their findings have shown how little many cannabis users know about the drug. The researchers also have highlighted the lackluster public health efforts to promote an effective harm reduction approach to marijuana use, especially during an era when cannabis is being deregulated in many states.

The stakes are higher with an increasing percentage of Americans using cannabis for a variety of recreational and medical reasons, as well as increasing cannabis potency, researchers say.

"Cannabis strains are 20 times as potent today as they were during the Summer of Love," said study co-author Jessica Kruger, PhD, clinical assistant professor of community health and health behavior in UB's School of Public Health and Health Professions.

The main message: "We really have to educate people. This has very real consequences, because these compounds have differential effects," Daniel Kruger said.

"Most Americans now live in a state where cannabis is legal, at least for medical purposes, but the information channels aren't there regarding safe and effective cannabis use."

https://www.sciencedaily.com/releases/2020/04/200415133416.htm

Whether marijuana helps with pain is unclear

Daily users with severe pain report worsening health

April 8, 2020

Science Daily/Ohio State University

Medical marijuana users who say they have high levels of pain are more likely than those with low pain to say they use cannabis three or more times a day, a new study finds.

However, daily marijuana users with severe pain also reported their health had become worse in the past year.

The results don't necessarily mean that marijuana is not effective in treating at least some kinds of pain, according to the researchers. But it suggests more research is needed before marijuana is accepted as an effective treatment for severe pain.

"It's not clear if marijuana is helping or not," said Bridget Freisthler, co-author of the study and professor of social work at The Ohio State University.

"The benefits aren't as clear-cut as some people assume."

The study was published recently in the International Journal of Drug Policy.

One issue is the complex relationship between pain, marijuana use and self-reported health, said Alexis Cooke, lead author of the study and postdoctoral scholar in psychiatry at the University of California, San Francisco.

"Having high chronic pain is related to poorer health, so it may be that people who are using marijuana more often already had worse health to begin with," Cooke said.

"There are still a lot of questions to answer."

The study involved a survey of 295 medical marijuana dispensary patients in Los Angeles. The surveys were conducted in 2013, when California allowed marijuana use only for medical purposes.

All participants were asked how often they used marijuana; rated how their current health compared to one year ago (on a five-point scale from "much better" to "much worse"); and were asked two questions about their pain levels. Based on their answers, the researchers rated participants' pain as low, moderate or high.

Among those surveyed, 31 percent reported high pain, 24 percent moderate pain, and 44 percent were in the low-pain category.

Daily marijuana use was reported by 45 percent of the sample, and 48 percent said they used three or more times per day.

The percentage of participants who used marijuana every day did not differ by pain categories. But about 60 percent of those who reported high pain used the drug three or more times a day, compared to 51 percent of those with moderate pain and 39 percent of those in the low-pain group.

Findings showed no association between daily marijuana use and change in health status among those with low levels of pain. But daily marijuana use was linked to worsening health status among those reporting high levels of pain.

However, strangely, there was no association between how often participants used marijuana per day and changes in health status. There's no easy explanation for this, Freisthler said.

"It shows how little we know about marijuana as medicine, how people are using it, the dosages they are receiving and its long-term effects," she said.

People use marijuana for a variety of different types of pain, including cancer, joint pain, HIV and nerve pain. Researchers don't know if marijuana has different effects on different causes of pain, Cooke said.

"Chronic pain is also associated with depression and anxiety. Marijuana may help with these problems for some people, even if it doesn't help with the pain," she said.

In addition, marijuana use seems to help people who have lost their appetite due to pain or nausea caused by cancer drugs.

"It may not be the pain that patients are trying to address," Cooke said.

The results do suggest we need to know more about the link between marijuana and pain relief, Freisthler said.

"Particularly since the opioid crisis, some people have been touting marijuana as a good substitute for opioids for people in pain," she said.

"But our study suggests we don't know that marijuana is helping to address pain needs."

https://www.sciencedaily.com/releases/2020/04/200408145805.htm

Marijuana may impair female fertility

April 2, 2020

Science Daily/The Endocrine Society

Female eggs exposed to THC, the psychoactive ingredient in marijuana, have an impaired ability to produce viable embryos, and are significantly less likely to result in a viable pregnancy, according to an animal study accepted for presentation at ENDO 2020, the Endocrine Society's annual meeting.

Marijuana, or cannabis, is the most commonly used recreational drug by people of reproductive age. The rise in marijuana use has occurred at the same time that THC percentages in the drug have increased. "Currently, patients seeking infertility treatments are advised against cannabis use, but the scientific evidence backing this statement is weak," said Master student Megan Misner, part of the research laboratory led by Laura Favetta, Ph.D., in the Department of Biomedical Sciences at the University of Guelph in Canada. "This makes it difficult for physicians to properly advise patients undergoing in vitro fertilization."

In the new study, researchers treated cow oocytes, or female eggs, with concentrations of THC equivalent to therapeutic and recreational doses. The oocytes were collected and matured into five groups: untreated, control, low THC, mid THC and high THC.

The eggs' developmental rates and gene expression were measured. The researchers evaluated the ability of embryos to reach critical stages of development at specific time points. With higher concentrations of THC, they found a significant decrease and delay in the ability of the treated oocytes to reach these checkpoints. "This is a key indicator in determining the quality and developmental potential of the egg," Misner said.

THC exposure led to a significant decrease in the expression of genes called connexins, which are present at increased levels in higher quality oocytes. Poorer quality oocytes, with lower connexin expression levels, have been shown to lead to a poorer embryo development. "This embryo would be less likely to proceed past the first week of development, and thus lead to infertility," Misner said.

Preliminary data also showed THC affected the activity of a total of 62 genes in the treatment groups compared with the non-treated groups. "This implies lower quality and lower fertilization capability, therefore lower fertility in the end," she said.

https://www.sciencedaily.com/releases/2020/04/200402134628.htm

Artisanal CBD not as effective as pharmaceutical CBD for reducing seizures

February 27, 2020

Science Daily/American Academy of Neurology

Children and teens with epilepsy who were treated with pharmaceutical cannabidiol (CBD) had much better seizure control than those who were treated with artisanal CBD, according to a preliminary study to be presented at the American Academy of Neurology's 72nd Annual Meeting in Toronto, Canada, April 25 to May 1, 2020.

CBD is a cannabis component that relieves stress and anxiety and has anti-seizure properties. It does not produce a "high" like another cannabis component called tetrahydrocannabinol (THC). Pharmaceutical CBD for epilepsy does not have THC. It is FDA approved for use in two severe forms of childhood epilepsy, Dravet syndrome and Lennox-Gastaut syndrome, which do not respond well to other medications. Artisanal CBD is manufactured using varying techniques and contains variable amounts of CBD and THC.

"The use of medical cannabis to treat various medical conditions has grown in recent years. While not always legal, artisanal CBD has been available longer, so some people have been using it to treat epilepsy for years," said study author Nathan T. Cohen, M.D., of Children's National Hospital in Washington D.C., and a member of the American Academy of Neurology. "They may want to reconsider because our research indicates that pharmaceutical CBD may indeed be more effective than artisanal CBD."

For the study, researchers reviewed the medical charts of 31 children and teens with an average age of 10 who were followed for an average age of one year. All had some form of epilepsy including 32% with Lennox-Gastaut syndrome and 6% with Dravet syndrome. Of the group, 22 were taking pharmaceutical CBD and nine were taking artisanal CBD. Researchers recorded medication doses, levels of CBD in the blood, seizure history and reduction in seizures with medication and side effects.

Those taking artisanal CBD had an average level of CBD in the blood of 31 nanograms per milliliter (ng/mL) compared to 124 ng/mL for those taking pharmaceutical CBD.

Researchers found children and teens taking artisanal CBD had a 70% increase in seizures during the study. Those taking prescription CBD had a 39% reduction in seizures.

However, 11 participants reported side effects. All were taking pharmaceutical CBD. Side effects included sleepiness, low appetite, nausea and diarrhea. Six of those participants stopped taking pharmaceutical CBD due to side effects.

"The difference in seizure control is dramatic and is definitely of concern since many people continue to use artisanal CBD," said Cohen. "However, a limitation of our study is that it was small. More research is needed to see if similar results are found in larger groups of people."

Another limitation of the study was that it was a look back at medical records. It did not involve participants who were given either pharmaceutical or artisanal CBD and then followed over time.

https://www.sciencedaily.com/releases/2020/02/200227160545.htm

Preliminary study suggests tuberculosis vaccine may be limiting COVID-19 deaths

July 10, 2020

Science Daily/Virginia Tech

One of the emerging questions about the coronavirus that scientists are working to understand is why developing countries are showing markedly lower rates of mortality in COVID-19 cases than expected.

Research by Assistant Professor Luis Escobar of the College of Natural Resources and Environment and two colleagues at the National Institutes of Health suggests that Bacille Calmette-Guérin (BCG), a tuberculosis vaccine routinely given to children in countries with high rates of tuberculosis infection, might play a significant role in mitigating mortality rates from COVID-19. Their findings have been published in the Proceedings of the National Academy of Sciences.

"In our initial research, we found that countries with high rates of BCG vaccinations had lower rates of mortality," explained Escobar, a faculty member in the Department of Fish and Wildlife Conservation and an affiliate of the Global Change Center housed in the Fralin Life Sciences Institute. "But all countries are different: Guatemala has a younger population than, say, Italy, so we had to make adjustments to the data to accommodate those differences."

Escobar, working with NIH researchers Alvaro Molina-Cruz and Carolina Barillas-Mury, collected coronavirus mortality data from around the world. From that data, the team adjusted for variables, such as income, access to education and health services, population size and densities, and age distribution. Through all of the variables, a correlation held showing that countries with higher rates of BCG vaccinations had lower peak mortality rates from COVID-19.

One sample that stood out was Germany, which had different vaccine plans prior to the country's unification in 1990. While West Germany provided BCG vaccines to infants from 1961 to 1998, East Germany started their BCG vaccinations a decade earlier, but stopped in 1975. This means that older Germans -- the population most at risk from COVID-19 -- in the country's eastern states would have more protection from the current pandemic than their peers in western German states. Recent data shows this to be the case: western German states have experienced mortality rates that are 2.9 times higher than those in eastern Germany.

"The purpose of using the BCG vaccine to protect from severe COVID-19 would be to stimulate a broad, innate, rapid-response immunity," said Escobar, who noted that the BCG vaccines have already been shown to provide broad cross-protections for a number of viral respiratory illnesses in addition to tuberculosis.

Escobar stresses that the team's findings are preliminary, and that further research is needed to support their results and determine what the next steps should be for researchers. The World Health Organization noted that there is no current evidence that the BCG vaccine can protect people from COVID-19 infections, and stated that it does not currently recommend BCG vaccinations for the prevention of COVID-19. There are currently clinical trials underway to establish whether BCG vaccination in adults confers protection from severe COVID-19.

"We're not looking to advise policy with this paper," Escobar said. "This is, instead, a call for more research. We need to see if we can replicate this in experiments and, potentially, in clinical trials. We also need to come back to the data as we get more information, so we can reevaluate our understanding of the coronavirus pandemic."

Barillas-Mury, a chief researcher who specializes in mosquito-borne disease vectors, noted that establishing a link between BCG vaccines and COVID-19 case severity could result in attempts to stockpile doses of the BCG vaccine, placing countries with high tuberculosis rates at risk.

"If the BCG vaccine is protective, production would have to increase to meet the sudden spike in vaccine demand in order to prevent a delay in distribution to countries that very much need it to fight tuberculosis," she said.

While a direct correlation between BCG vaccinations and a reduction in coronavirus mortalities still needs to be understood more fully, researchers hold hope that the BCG vaccine might be able to provide at least short-term protections against severe COVID-19, particularly for front-line medical workers or high-risk patients. And, if BCG does provide short-term protection, there are longer term considerations about how countries could best utilize BCG vaccines to reduce mortality rates for future viral outbreaks that target the human respiratory system.

https://www.sciencedaily.com/releases/2020/07/200708121433.htm

Socio-economic, environmental impacts of COVID-19 quantified

Holistic study charts effects of the coronavirus on sectors and regions globally

July 10, 2020

Science Daily/University of Sydney

The first comprehensive study of the pandemic shows consumption losses amount to more than US$3.8 trillion, triggering full-time equivalent job losses of 147 million and the biggest-ever drop in greenhouse gas emissions.

The international group of researchers, using a global and highly detailed model, found that most directly hit was the travel sector and regions of Asia, Europe, the United States, with cascading multiplier effects across the entire world economy because of globalisation.

The loss of connectivity imposed to prevent the virus spreading triggers an economic 'contagion', causing major disruptions to trade, tourism, energy and finance sectors, while easing environmental pressures most in some of the hardest-hit areas.

This study focuses on 'live' data to 22 May (with the exception of air travel, for which only a 12-month forecast exists), differing from most assessments of the economic impacts of the pandemic based on scenario analyses and/or projections -- and it is the first to provide an overview of the combined economic, social and environmental impacts, including indirect effects, of the coronavirus.

The findings publish today in the international scientific journal PLOS ONE.

Key Reductions

• Consumption: US$3.8 trillion (4.2 percent ~ GDP of Germany)

• Jobs: 147m (4.2 percent of the global workforce)

• Income from wages and salaries: $2.1 trillion (6 percent)

• Most directly hit: US, China (mainland), air transport and related tourism

• Greenhouse gas emissions: 2.5Gt (4.6 percent) -- larger than any drop in human history*

• Other atmospheric emissions -- PM2.5: Dangerously fine particulate matter emissions fall 0.6 Mt (3.8 percent); SO2 & NOx: Sulfur dioxide emissions from burning fossil fuels -- which has been linked to asthma and chest tightness -- and emissions from nitrogen oxide -- from fuel combustion, for example, driving cars -- fall 5.1 Mt (2.9 percent).

Corresponding author Dr Arunima Malik, from Integrated Sustainability Analysis (ISA) and University of Sydney Business School, said the experience of previous financial shocks showed that, without structural change, environmental gains were unlikely to be sustained during economic recovery.

"We are experiencing the worst economic shock since the Great Depression, while at the same time we have experienced the greatest drop in greenhouse gas emissions since the burning of fossil fuels began," Dr Malik said.

"In addition to the sudden drop in climate-change inducing greenhouse gasses, prevented deaths from air pollution are of major significance.

"The contrast between the socio-economic and the environmental variables reveals the dilemma of the global socio-economic system -- our study highlights the interconnected nature of international supply chains, with observable global spillover effects across a range of industry sectors, such as manufacturing, tourism and transport."

The University of Sydney Vice-Chancellor Dr Michael Spence said it was wonderful to see significant applications come to life through a collaborative platform seeded a decade ago with University of Sydney funding.

"Thanks to pioneering work here at Sydney in collaboration with other world leaders in footprinting, it's now possible to simulate the world economy quickly and accurately to see how society and the environment are impacted by changes in our consumption," Dr Spence said.

"This research was conducted in the cloud-based Global MRIO Lab and it is these sorts of global, multidisciplinary collaborations that will help us tackle the complex issues of our time."

Research Using the Global MRIO Lab

To chart the world economy and post-disaster impacts using global multi-regional input-output (MRIO) analysis or GMRIO, researchers worked in the open-source Global MRIO Lab. This customisable database is an extension of the Australian Industrial Ecology Lab (IE Lab) led by the University of Sydney.

The advancement of GMRIO has underpinned the increasing popularity and uptake of so-called consumption-based accounting, or footprinting, which avoids loopholes such as 'carbon leakage' where pollution is externalised to the producers, rather than consumers of goods and services. The Global MRIO Lab includes data from statistical agencies, including National Accounts and Eurostat and international trade data such as UN Comtrade. The lab is powered by supercomputers calculating the impacts of international trade along billions of supply chains extending to 221 countries.

Input-output (I-O) models were developed in the 1930s by Nobel Prize Laureate Wassily Leontief to analyse the relationships between consumption and production in the economy; I-O or multi-regional input-output (MRIO) models take account of actual data, from I-O records worldwide. Global MRIO or GMRIO models now not only extend to global value chains (GVCs) incorporating all orders of production but are also able to answer flexible and complex questions to a high degree of accuracy within a relatively short time lag. Once assembled, tables can be quickly updated, limited only by the timeliness of the data to hand.

Lead author Professor Manfred Lenzen, also from ISA and a recent co-author of the "Scientists' warning on affluence," said that the Australian-funded and University of Sydney-led innovation of the IO Labs had really catalysed new research efficiency in Australia. "Whilst the Labs were initially developed by a dedicated team from eight Universities and the CSIRO, supported by the Australian Bureau of Statistics, there are now hundreds of users, answering questions ranging from building sustainable cities, avoiding food waste, and carbon-footprinting tourism, to hedging against major disasters such as tropical cyclones," said Professor Lenzen.

For this study into COVID-19, 38 regions in the world were analysed and 26 sectors. In order to incorporate as much information as possible, co-authors were allocated countries with which they had language skills and familiarity, with data translated from sources in 12 languages ranging from Arabic to Hindi and Spanish.

The international team of researchers are from: University of Sydney; Edinburgh Napier University; University of Queensland; UNSW Sydney; Ministry of Finance of the Republic of Indonesia; National Institute for Environmental Studies & Research Institute for Humanity and Nature, Japan; Yachay Tech University, Ecuador; Duke University; Beijing Normal University.

https://www.sciencedaily.com/releases/2020/07/200709141538.htm

Study links abnormally high blood sugar with higher risk of death in COVID-19 patients not previously diagnosed with diabetes

July 10, 2020

Science Daily/Diabetologia

New research from Wuhan, China shows that, in patients with COVID-19 but without a previous diagnosis of diabetes, abnormally high blood sugar is associated with more than double the risk of death and also an increased risk of severe complications. The study is by Dr Yang Jin, Union Hospital and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China, and colleagues. The study is published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]).

Previous studies have established that hyperglycaemia (abnormally high blood sugar) is associated with an elevated risk of mortality in community-acquired pneumonia, stroke, heart attacks, trauma and surgery, among other conditions. A number of studies have also shown links between diabetes and poor outcomes in COVID-19 patients. However, direct correlation between fasting blood glucose (FBG) level at admission to hospital and clinical outcomes of COVID-19 patients without diagnosed diabetes has not been well established. In this new study the authors examined the association between FBG on admission and the 28-day mortality of COVID-19 patients without previously diagnosed diabetes in two hospitals.

The retrospective study assessed all consecutive COVID-19 patients with a known outcome at 28-days and FBG measurement at admission from 24 January 2020 to 10 February 2020 in two hospitals based in Wuhan, China. Demographic and clinical data, 28-day outcomes, in-hospital complications and CRB-65 scores of COVID-19 patients in the two hospitals were analysed. The CRB-65 score is an effective measure for assessing the severity of pneumonia and is based on four indicators: level of confusion, respiratory rate (over 30 breaths per min), systolic blood pressure (90 mmHg or less) or diastolic blood pressure (60 mmHg or less), and age (65 years or over).

A total of 605 COVID-19 patients were enrolled, including 114 who died in hospital. The median age of participants was 59 years and 322 (53.2%) were men. A total of 208 (34%) had one or more underlying conditions (but not diagnosed diabetes), of which high blood pressure was the most common. Almost one third (29%) of patients fell into the highest category of FBG on admission (7.0 mmol/L) which if found consistently would result in a diagnosis of type 2 diabetes. A further 17% were in the range that would be considered pre-diabetic (6.1-6.9 mmol/L), while more than half (54%) were in the 'normal' FBG range of 6.0 mmol/L or below.

The results showed that patients in the highest FBG group were 2.3 times more likely to die than those in the lowest, a statistically significant result. Those in the middle (pre-diabetic) FBG group were 71% more likely to die than those in the lowest group, although this result only had borderline statistical significance. The data also showed that men were 75% more likely to die than women; and that patients with higher CRB65 scores (and thus worse pneumonia) were also at higher risk of death: those with a score of 3-4 were more than 5 times more likely to die than those with a score of 0, while for those with a score of 1-2 there was a 2.7 times increased risk.

When looking at FBG and CRB65 scores together, the patients in the highest FBG group had an increased risk of death compared to the lowest, regardless of whether or not the CRB65 score was zero or higher, further underlining that FBG independently increases the risk of death in COVID-19 patients. However, the increased risk of death for the highest FBG group was lower in patients with CRB65 scores of above zero compared with those with a CRB65 score of zero. The risk of complications was also found to be 4 times higher in the highest FBG group compared to the lowest, and 2.6 times higher in the middle (pre-diabetic) group compared to the lowest.

The authors say: "This study shows, for the first time, that elevated FBG (?7.0 mmol/l) at admission is independently associated with increased 28-day mortality and percentages of in-hospital complications in COVID-19 patients without previous diagnosis of diabetes... we have also shown that FBG of 7.0 mmol/l or higher is associated with increased mortality, regardless of whether the patient has pneumonia that is more or less severe."

They add: "These results indicate that our study included both undiagnosed diabetic patients and non-diabetic patients with hyperglycaemia caused by an acute blood-glucose disorder, since the 29% found in the highest FBG group is much higher than the estimated prevalence of diabetes in the Chinese population at 12%. Similarly to what was found in a previous study, COVID-19 patients might suffer from high blood sugar brought about by other conditions, and critically ill patients may develop acute insulin resistance, manifested by high levels of blood sugar and insulin levels. Patients with conditions not related to diabetes, such as severe sepsis, systemic inflammatory response syndrome (SIRS) and traumatic brain injury tend to have abnormally high blood sugar."

The authors note several limitations with their study. First, this was a retrospective study. Second, they did not analyse glycated haemoglobin (HbA1c), a long-term blood sugar control indicator that helps distinguish patients with poor long-term blood sugar control from those with stress hyperglycaemia. Also, they did not have sufficient data to study the effect of glucose-lowering treatment (e.g. insulin, metformin) on the outcome of the patients in their study. However, they believe that acute hyperglycaemia is more important than long-term glycaemic control in predicting the prognosis of hospitalised COVID-19 patients.

The authors suggest that possible mechanisms for this increased mortality include hyperglycaemia-induced changes in coagulation (clotting), worsening of endothelial function (the function of the walls of blood vessels), and overproduction of inflammatory cytokines produced by the immune system (the so-called cytokine storm).

The authors conclude: "In conclusion, a fasting blood glucose level of 7.0 mmol/l or higher at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes. Blood sugar testing and control should be recommended to all COVID-19 patients even if they do not have pre-existing diabetes, as most COVID-19 patients are prone to glucose metabolic disorders. During a pandemic of COVID-19, measuring fasting blood glucose can facilitate the assessment of prognosis and early intervention of hyperglycaemia to help improve the overall outcomes in treatment of COVID-19."

https://www.sciencedaily.com/releases/2020/07/200710212247.htm

Physicians give first comprehensive review of COVID-19's effects outside the lung

July 10, 2020

Science Daily/Columbia University Irving Medical Center

After only a few days caring for critically ill COVID-19 patients at the start of the outbreak in New York City, Aakriti Gupta, MD, realized that this was much more than a respiratory disease.

"I was on the front lines right from the beginning. I observed that patients were clotting a lot, they had high blood sugars even if they did not have diabetes, and many were experiencing injury to their hearts and kidneys," says Gupta, one of the first Columbia cardiology fellows to be deployed to the COVID intensive care units at Columbia University Irving Medical Center.

In early March, there wasn't much clinical guidance on the non-respiratory effects of COVID-19, so Gupta decided to coalesce findings from studies that were just beginning to appear in the literature with what the physicians were learning from experience.

Gupta, along with senior author Donald Landry, MD, PhD, chair of medicine at Columbia University Vagelos College of Physicians and Surgeons, organized senior co-authors, and Gupta, along with two other colleagues, Mahesh Madhavan, MD, a cardiology fellow at CUIMC, and Kartik Sehgal, MD, a hematology/oncology fellow at Beth Israel Deaconess Medical Center/Harvard Medical School, mobilized clinicians at Columbia, Harvard, Yale, and Mount Sinai Hospital, among other institutions, to review the latest findings on COVID-19's effect on organ systems outside the lungs and provide clinical guidance for physicians.

Their review -- the first extensive review of COVID-19's effects on all affected organs outside the lungs -- was published today in Nature Medicine.

"Physicians need to think of COVID-19 as a multisystem disease," Gupta says. "There's a lot of news about clotting but it's also important to understand that a substantial proportion of these patients suffer kidney, heart, and brain damage, and physicians need to treat those conditions along with the respiratory disease."

Blood Clots, Inflammation, and an Immune System in Overdrive

"In just the first few weeks of the pandemic, we were seeing a lot of thrombotic complications, more than what we would have anticipated from experience with other viral illnesses," says Sehgal, "and they can have profound consequences on the patient."

Scientists think these clotting complications may stem from the virus's attack on cells that line the blood vessels. When the virus attacks blood vessel cells, inflammation increases, and blood begins to form clots, big and small. These blood clots can travel all over the body and wreak havoc on organs, perpetuating a vicious cycle of thromboinflammation.

To combat clotting and its damaging effects, clinicians at Columbia, many of whom are co-authors on this review, are conducting a randomized clinical trial to investigate the optimal dose and timing of anticoagulation drugs in critically ill patients with COVID-19.

The untempered inflammation can also overstimulate the immune system, and though doctors initially shied away from using steroids to globally suppress the immune system, a recent clinical trial has found that at least one steroid, dexamethasone, reduced deaths in ventilated patients by one-third. Randomized clinical trials are underway to target specific components of thromboinflammation and the immune system, such as interleukin-6 signaling.

"Scientists all over the world are working at an unprecedented rate towards understanding how this virus specifically hijacks the normally protective biological mechanisms. We hope that this would help in the development of more effective, precise, and safer treatments for COVID-19 in the near future," says Sehgal.

Straight to the Heart

Clots can cause heart attacks, but the virus attacks the heart in other ways, one author says.

"The mechanism of heart damage is currently unclear, as the virus has not been frequently isolated from the heart tissue in autopsy cases," says Gupta.

The heart muscle may be damaged by systemic inflammation and the accompanying cytokine release, a flood of immune cells that normally clears up infected cells but can spiral out of control in severe COVID-19 cases.

Despite the degree of heart damage, physicians were not able to utilize the diagnostic and therapeutic strategies, including heart biopsies and cardiac catheterizations, that they would normally use during the early stages of the pandemic given the need to protect personnel and patients from viral transmission. This has changed as the disease prevalence has gone down in New York CIty.

Kidney Failure

Another surprising finding was the high proportion of COVID-19 patients in the ICU with acute kidney damage.

The ACE2 receptor used by the virus to gain entry into the cells is found in high concentrations in the kidney and could likely be responsible for the renal damage. Studies in China reported renal complications, but in New York City, clinicians saw renal failure in up to 50% of patients in the ICU.

"About 5 to 10% of patients needed dialysis. That's a very high number," Gupta says.

Data regarding long-term renal damage are currently lacking, but a significant proportion of patients will likely go on to require permanent dialysis.

"Future studies following patients who experienced complications during hospitalizations for COVID-19 will be crucial," notes Madhavan.

Neurological Effects

Neurological symptoms, including headache, dizziness, fatigue, and loss of smell, may occur in about a third of patients.

More concerning, strokes caused by blood clots occur in up to 6% of severe cases and delirium in 8% to 9%.

"COVID-19 patients can be intubated for two to three weeks; a quarter require ventilators for 30 or more days," Gupta says.

"These are very prolonged intubations, and patients need a lot of sedation. 'ICU delirium' was a well known condition before COVID, and the hallucinations may be less an effect of the virus and more an effect of the prolonged sedation."

"This virus is unusual and it's hard not to take a step back and not be impressed by how many manifestations it has on the human body," says Madhavan.

"Despite subspecialty training as internists, it's our job to keep all organ systems in mind when caring for the patients in front of us. We hope that our review, observations, and recommendations can help other clinicians where cases are now surging."

https://www.sciencedaily.com/releases/2020/07/200710212240.htm

Global COVID-19 registry finds strokes associated with COVID-19 are more severe, have worse outcomes and higher mortality

July 10, 2020

Science Daily/American Heart Association

Patients with COVID-19 who have an acute ischemic stroke (AIS) experience more severe strokes, have worse functional outcomes and are more likely to die of stroke than AIS patients who do not have COVID-19. The wide range of complications associated with COVID-19 likely explain the worse outcomes.

Acute ischemic strokes (AIS) associated with COVID-19 are more severe, lead to worse functional outcomes and are associated with higher mortality , according to new research published yesterday in Stroke, a journal of the American Stroke Association, a division of the American Heart Association.

In "Characteristics and Outcomes in Patients with COVID-19 and Acute Ischemic Stroke: The Global COVID-19 Stroke Registry," researchers analyzed data on patients with COVID-19 and AIS treated at 28 health care centers in 16 countries this year and compared them to patients without COVID-19 from the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) Registry, from 2003 to 2019. Researchers sought to determine the clinical characteristics and outcomes of patients with COVID-19 and AIS.

Between January 27, 2020 to May 19, 2020, there were 174 patients hospitalized with COVID-19 and AIS. Each COVID-19 patient with AIS was matched and compared to a non-COVID-19 AIS patient based on a set of pre-specified factors including age, gender and stroke risk factors (hypertension, diabetes, atrial fibrillation, coronary artery disease, heart failure, cancer, previous stroke, smoking, obesity and dyslipidemia). The final analysis included 330 patients total.

In both patient groups, stroke severity was estimated with the National Institute of Health Stroke Scale (NIHSS), and stroke outcome was assessed by the modified Rankin score (mRS). When AIS patients with COVID-19 were compared to non-COVID-19 patients:

• COVID-19 patients had more severe strokes (median NIHSS score of 10 vs. 6, respectively);

• COVID-19 patients had higher risk for severe disability following stroke (median mRS score 4 vs. 2, respectively); and

• COVID-19 patients were more likely to die of AIS.

The researchers noted there are several potential explanations for the relationship between COVID-19-associated strokes and increased stroke severity: "The increased stroke severity at admission in COVID-19-associated stroke patients compared to the non-COVID-19 cohort may explain the worse outcomes. The broad, multi-system complications of COVID-19, including acute respiratory distress syndrome, cardiac arrhythmias, acute cardiac injury, shock, pulmonary embolism, cytokine release syndrome and secondary infection, probably contribute further to the worse outcomes including higher mortality in these patients. ... The association highlights the urgent need for studies aiming to uncover the underlying mechanisms and is relevant for prehospital stroke awareness and in-hospital acute stroke pathways during the current and future pandemics."

https://www.sciencedaily.com/releases/2020/07/200710131516.htm

About half of health care workers positive for COVID-19 by serology have no symptoms

July 9, 2020

Science Daily/Vanderbilt University Medical Center

The IVY Research Network has completed initial studies evaluating the epidemiology of COVID-19 in health care workers and patients.

Among 249 front-line health care workers who cared for COVID-19 patients during the first month of the pandemic in Tennessee, 8% tested positive for COVID-19 antibodies by serology testing, suggesting they had contracted COVID-19 in the first several weeks of taking care of COVID-19 patients. Among these health care workers with positive serology results, 42% reported no symptoms of a respiratory illness in the prior two months. This suggests that front-line health care workers are at high risk for COVID-19 and that many health care workers with the virus may not have typical symptoms of a respiratory infection. These results were published in the journal Clinical Infectious Diseases on July 6.

"Our results suggest that screening health care workers for COVID-19 even when they don't have any symptoms could be important to prevent the spread of the virus within hospitals," said Wesley Self, MD, associate professor of Emergency Medicine at Vanderbilt University Medical Center and lead investigator for the IVY Network.

Investigator Bo Stubblefield, MD, instructor of Emergency Medicine, added, "We are continuing to study COVID-19 in front-line health care workers across the country to better understand what may be done to decrease their risk of infection, such as using specific types of personal protective equipment."

In a separate study, the IVY investigators studied 350 patients across 11 medical centers in the U.S. who tested positive for COVID-19; 54% of these patients reported no close contact with another person known to have COVID-19 in the two weeks before getting sick.

"With over half of COVID-19 patients not identifying a clear source of their infection, this study reinforces the need for practical measures to reduce the spread of the virus, such as social distancing and the use of face coverings when out in public," Self said.

Additionally, 40% of COVID-19 patients in the study remained symptomatic two weeks after a positive COVID-19 test, showing that patients with COVID-19 tend to remain ill longer than with other respiratory infections, such as influenza. The results were published by the journal Morbidity and Mortality Weekly Report on June 30.

The IVY Network is a collaborative research group of multiple medical centers in the U.S led by Vanderbilt University Medical Center. It is funded by Centers of Disease Control and Prevention (CDC) to conduct research on severe respiratory infections, including COVID-19 and influenza.

https://www.sciencedaily.com/releases/2020/07/200709113509.htm

Black individuals at higher risk for contracting COVID-19, according to new research

July 9, 2020

Science Daily/American Thoracic Society

Results of an analysis published in the Annals of the American Thoracic Society found that Black individuals were twice as likely as White individuals to test positive for COVID-19. The average age of all participants in the study was 46. However, those infected were on average 52 years old, compared to those who tested negative, who were 45 years old on average.

"Association of Black Race with Outcomes in COVID-19 Disease: A Retrospective Cohort Study" is not the first to examine race. However, it provides further evidence that, while anyone can get COVID-19, race is indeed a factor in the extent to which some populations are affected. Of the 4413 individuals tested, 17.8 percent tested positive. Of those who tested positive, 78.9 percent were Black while 9.6 percent were White.

Study author Ayodeji Adegunsoye, MD, MS, assistant professor of medicine at the University of Chicago, sees logic in the results of the analysis as it relates to the infection rates along racial lines: "I think this really amplifies how pre-existing socioeconomic and health care disparities affect outcomes in the population. We already know that the common comorbidities that have been associated with COVID such as hypertension and diabetes disproportionately affect the Black community. So, it wasn't too surprising that COVID-19 seemed to more commonly affect Black individuals as well."

In addition, noted Dr. Adegunsoye, given that Black individuals are overly represented in the service industry, and therefore more likely to be essential workers, their risk of exposure to COVID-19 is greater: "Even during precautionary lockdowns to reduce spread, these jobs were often deemed essential services, and included jobs such as bus drivers, janitors, city sanitation workers, hospital food production personnel, security guards, etc. so it wasn't too surprising that Black people were disproportionately infected and subsequently hospitalized with the virus."

The results showing that the individuals who tested positive were older than their counterparts who tested negative is consistent with reports of infection rates in the U.S. and elsewhere. "We have observed that for various reasons, older individuals are more likely to develop severe symptoms when they get infected and therefore they are more likely to get tested for COVID-19," said Dr. Adegunsoye.

"It's a vicious cycle of sorts, as older people are more likely to have hypertension and other comorbid diseases, which further increase the risk for hospitalization with COVID. Even after accounting for their older age, Black patients were still at significantly increased risk of COVID-19 infection and hospitalization."

In addressing the disparity in COVID-19 infection rates, Dr. Adegunsoye proposes making COVID-19 screening free and widely accessible. He hopes that there will be an increase in policy decisions that result in increased funding for community-led prevention efforts as well as "improved public enlightenment campaigns targeted at minorities to reduce the risk of developing hypertension and diabetes."

These measures, together with renewed strategic focus on reducing health inequities, will improve the lives of all Americans.

https://www.sciencedaily.com/releases/2020/07/200709085329.htm

Our itch to share helps spread COVID-19 misinformation

Study finds social media sharing affects news judgment, but a quick exercise reduces the problem

July 9, 2020

Science Daily/Massachusetts Institute of Technology

To stay current about the Covid-19 pandemic, people need to process health information when they read the news. Inevitably, that means people will be exposed to health misinformation, too, in the form of false content, often found online, about the illness.

Now a study co-authored by MIT scholars contains bad news and good news about Covid-19 misinformation -- and a new insight that may help reduce the problem.

The bad news is that when people are consuming news on social media, their inclination to share that news with others interferes with their ability to assess its accuracy. The study presented the same false news headlines about Covid-19 to two groups of people: One group was asked if they would share those stories on social media, and the other evaluated their accuracy. The participants were 32.4 percent more likely to say they would share the headlines than they were to say those headlines were accurate.

"There does appear to be a disconnect between accuracy judgments and sharing intentions," says MIT professor David Rand, co-author of a new paper detailing the findings. "People are much more discerning when you ask them to judge the accuracy, compared to when you ask them whether they would share something or not."

The good news: A little bit of reflection can go a long way. Participants who were more likely to think critically, or who had more scientific knowledge, were less likely to share misinformation. And when asked directly about accuracy, most participants did reasonably well at telling true news headlines from false ones.

Moreover, the study offers a solution for over-sharing: When participants were asked to rate the accuracy of a single non-Covid-19 story at the start of their news-viewing sessions, the quality of the Covid-19 news they shared increased significantly.

"The idea is, if you nudge them about accuracy at the outset, people are more likely to be thinking about the concept of accuracy when they later choose what to share. So then they take accuracy into account more when they make their sharing decisions," explains Rand, who is the Erwin H. Schell Associate Professor with joint appointments at the MIT Sloan School of Management and the Department of Brain and Cognitive Sciences.

The paper, "Fighting COVID-19 misinformation on social media: Experimental evidence for a scalable accuracy nudge intervention," appears in Psychological Science. Besides Rand, the authors are Gordon Pennycook, an assistant professor of behavioral science at the University of Regina; Jonathan McPhetres, a postdoc at MIT and the University of Regina who is starting a position in August as an assistant professor of psychology at Durham University; Yunhao Zhang, a PhD student at MIT Sloan; and Jackson G. Lu, the Mitsui Career Development Assistant Professor at MIT Sloan.

Thinking, fast and slow

To conduct the study, the researchers conducted two online experiments in March, with a total of roughly 1,700 U.S. participants between them, using the survey platform Lucid. Participants matched the nation's distribution of age, gender, ethnicity, and geographic region.

The first experiment had 853 participants, and used 15 true and 15 false news headlines about Covid-19, in the style of Facebook posts, with a headline, photo, and initial sentence from a story. The participants were split into two groups. One group was asked if the headlines were accurate; the second group was asked if they would consider sharing the posts on platforms such as Facebook and Twitter.

The first group correctly judged the stories' accuracy about two-thirds of the time. The second group might therefore be expected to share the stories at a similar rate. However, the participants in the second group shared about half of the true stories, and just under half of the false stories -- meaning their judgment about which stories to share was almost random in regard to accuracy.

The second study, with 856 participants, used the same group of headlines and again split the participants into two groups. The first group simply looked at the headlines and decided whether or not they would share them on social media.

But the second group of participants were asked to evaluate a non-Covid-19 headline before they made decisions about sharing the larger group of Covid-19 headlines. (Both studies were focused on headlines and the single sentence of text, since most people only read headlines on social media.) That extra step, of evaluating one non-Covid-19 headline, made a substantial difference. The "discernment" score of the second group -- the gap between the number of accurate and inaccurate stories they shared -- was almost three times larger than that of the first group.

The researchers evaluated additional factors that might explain tendencies in the responses of the participants. They gave all participants a six-item Cognitive Reflection Test (CRT), to evaluate their propensity to analyze information, rather than relying on gut instincts; evaluated how much scientific knowledge participants had; and looked at whether respondents were located close to Covid-19 outbreaks, among other things. They found that participants who scored higher on the CRT, and knew more about science, rated headlines more accurately and shared fewer false headlines.

Those findings suggest that the way people assess news stories has less to do with, say, preset partisan views about the news, and a bit more to do with their broader cognitive habits.

"A lot of people have a very cynical take on social media and our moment in history, that we're post-truth and no one cares about the truth any more," Pennycook says. "Our evidence suggests it's not that people don't care; it's more that they're distracted."

Something systemic about social media

The study follows others Rand and Pennycook have conducted about explicitly political news, which similarly suggest that cognitive habits, more so than partisan views, influence the way people judge the accuracy of news stories and lead to the sharing of misinformation. In this study, the scholars wanted to see if readers analyzed Covid-19 stories, and health information, differently than political information. But the results were generally similar to the political-news experiments the researchers have conducted.

"Our results suggest that the life-and-death stakes of Covid-19 do not make people suddenly take accuracy into [greater] account when they're deciding what to share," Lu says.

Indeed, Rand suggests, the very importance of Covid-19 as a subject may interfere with readers' ability to analyze it.

"Part of the issue with health and this pandemic is that it's very anxiety-inducing," Rand says. "Being emotionally aroused is another thing that makes you less likely to stop and think carefully."

Still, the central explanation, the scholars think, is simply the structure of social media, which encourages rapid browsing of news headlines, elevates splashy news items, and rewards users who post eye-catching news, by tending to give them more followers and retweets, even if those stories happen to be untrue.

"There is just something more systemic and fundamental about the social media context that distracts people from accuracy," Rand says. "I think part of it is that you're getting this instantaneous social feedback all the time. Every time you post something, you immediately get to see how many people liked it. And that really focuses your attention on: How many people are going to like this? Which is different from: How true is this?"

The research was supported by the Ethics and Governance of Artificial Intelligence Initiative of the Miami Foundation; the William and Flora Hewlett Foundation; the Omidyar Network; the John Templeton Foundation; the Canadian Institute of Health Research; and the Social Sciences and Humanities Research Council of Canada.

https://www.sciencedaily.com/releases/2020/07/200709121232.htm

Contracting COVID-19: lifestyle and social connections may play a role

July 9, 2020

Science Daily/Association for Psychological Science

Unhealthy lifestyle choices, like smoking and avoiding exercise, are known risk factors for certain cancers and cardiovascular disease. A growing body of research reveals that these risk factors and a lack of supportive social connections can also increase the risk of developing respiratory infections, like the common cold and influenza.

A new article published in the journal Perspectives on Psychological Science explores how lifestyle, social, and psychological factors also may increase the risk of contracting COVID-19.

"We know little about why some of the people exposed to the coronavirus that causes COVID-19 are more likely to develop the disease than others," said Sheldon Cohen, a professor of psychology at Carnegie Mellon University and one of the authors on the paper. "Our research on psychological factors that predict susceptibility to other respiratory viruses may provide clues to help identify factors that matter for COVID-19."

Through a series of studies spanning more than 30 years, Cohen and his team examined how lifestyle, social, and psychological factors affect whether or not healthy adults exposed to respiratory viruses become ill. This work focused on eight viral strains that cause the common cold and two that cause influenza.

"In our work, we intentionally exposed people to cold and influenza viruses and studied whether psychological and social factors predict how effective the immune system is in suppressing infection, or preventing or mitigating the severity of illness," said Cohen. "We found a strong correlation between social and psychological stressors and increased susceptibility."

Intriguingly, the researchers also found that social integration and social support offer a protective shield against respiratory infection and illness.

Until now, the only tactics to slow the spread of coronavirus have been behavioral changes that reduce the probability of being exposed to the virus, such as stay-at-home measures and social-distancing requirements. These same behaviors, however, are often associated with interpersonal stressors, like loneliness, loss of employment, and familial conflict. According to the researchers, these stressors may be powerful predictors of how a person will respond if exposed to coronavirus because of the stressors' direct physiological effects on immunity and their psychological factors, which are thought to have their influence through the mind-body connection.

Cohen's work demonstrates that psychological and social stressors are associated with an overproduction of proinflammatory chemicals known as cytokines in response to cold and influenza viruses. In turn, this excess of inflammation was associated with an increased risk of becoming ill.

Similarly, research on COVID-19 has shown that producing an excess of proinflammatory cytokines is associated with more severe COVID-19 infections, suggesting that a stress-triggered excessive cytokine response might also contribute to excessive inflammation and symptoms in COVID-19 patients.

Cohen and his colleagues acknowledge that, as of now, there are no firmly established links between behavioral and psychological factors and the risk for disease and death in persons exposed to the corona virus that causes COVID-19. However, their prior body of research may be relevant to the current pandemic because, they note, the most potent predictors of disease, interpersonal and economic stressors, are the types of stressors that are commonly experienced among those who are isolated or in quarantine.

"If you have a diverse social network (social integration), you tend to take better care of yourself (no smoking, moderate drinking, more sleep and exercise)," said Cohen. "Also if people perceive that those in their social network will help them during a period of stress or adversity (social support) then it attenuates the effect of the stressor and is less impactful on their health."

https://www.sciencedaily.com/releases/2020/07/200709113521.htm