The 'inflammation' of opioid use
August 29, 2019
Science Daily/Thomas Jefferson University
Opioid dependence has become a national crisis with serious impact on economic and social welfare, and numerous casualties. A big goal of ongoing research in combating opioid use disorder is understanding drug withdrawal. The physical and emotional symptoms of withdrawal can be life threatening and make up a powerfully negative experience; the fear of these symptoms strongly motivates addiction.
Researchers in the lab of James Schwaber at the Daniel Baugh Institute for Functional Genomics and Computational Biology at Thomas Jefferson University are studying how inflammation contributes to drug withdrawal and dependence. Their study was published in Frontiers of Neuroscience on July 3.
Opioids can cause inflammation in the brain by inducing immune cells to release inflammatory molecules called cytokines. The main immune cells in the brain are microglia and astrocytes. Inflammatory responses induced by opioids have been observed in the central amygdala, a brain region that has been strongly implicated in opioid dependence because of its role in emotion and motivation. The central amygdala can also be affected by inflammation in other parts of the body, like the gut. In fact, the communication between the gut and the brain can shape a variety of motivated behaviors and emotional states, including those associated with drug dependence and withdrawal.
The researchers including first author Sean O'Sullivan in Dr. Schwaber's lab isolated single neurons, microglia, and astrocytes from the central amygdala and studied their genetic profiles in normal, opioid-dependent, and withdrawn rats. They were surprised to find that the profile of astrocytes changed the most, shifting genetic expression to a more activated state. This shift correlated strongly with opioid withdrawal. Furthermore, all three cell types showed a considerable increase in an inflammatory cytokine called TNF alpha in withdrawn animals.
In addition, the researchers also assayed different types of bacteria in the gut of rats and found that certain anti-inflammatory bacteria were suppressed in withdrawn animals, shifting the ratio of gut microbiota and causing a phenomenon called dysbiosis, which can cause inflammation in the digestive system. It is unclear how these changes influence opioid withdrawal, but the authors propose that the simultaneous inflammation in the gut and central amygdala may be linked to the negative emotional experience of withdrawal.
The findings underscore the highly complex relationship between the gut and the brain, and suggest that inflammation in the gut and brain may exacerbate symptoms associated with withdrawal. Targeting inflammation in these regions may alleviate the negative experience of drug withdrawal, and therefore prevent dependence.
https://www.sciencedaily.com/releases/2019/08/190829104621.htm
What we don't know about prenatal opioid exposure
Sparse data on how children fare after prenatal opioid exposure
August 28, 2019
Science Daily/University of Utah
'Will the baby be OK?' In cases of prenatal opioid exposure, the answer is unclear. Developmental psychologists collected and reviewed 52 publications to identify what's known so far about how prenatal opioid exposure affects childhood outcomes and development
Pregnancy can be a time of anxious uncertainty, particularly if there are any risks of complications. The question always arises, from parents, grandparents, friends and others: "Will the baby be OK?"
In cases where the baby has been exposed to opioids in the womb, the answer is unclear. As part of a National Institutes of Health initiative to study the effects of a child's environment on his or her life outcomes, University of Utah developmental psychologist Elisabeth Conradt and her colleagues collected and reviewed 52 publications to identify what's known so far about how prenatal opioid exposure affects childhood outcomes and development. The review is published in Pediatrics.
"Right now, the number one question mothers, fathers and clinicians have when they see that a mother is using opioids while pregnant is how will this opioid exposure affect the child's health?" Conradt says. "We cannot answer that question right now with the existing data that we have."
Effects at birth
For this review study, the researchers focused particularly on 11 studies of children diagnosed with neonatal opioid withdrawal syndrome, or NOWS. It's a condition diagnosed three to four days after birth and includes symptoms such as feeding problems, tremors and a high-pitched cry. Little is known about how a diagnosis of NOWS is connected to a child's neurological development throughout life.
The current question about babies exposed to opioids, Conradt says, echoes questions from the 1980s and '90s about babies exposed to crack cocaine in the womb. "What we actually found is that the effects of cocaine on these child outcomes were quite subtle," Conradt says. "Cocaine was probably a proxy for the type of environment in which the kids were raised."
The researchers found that studies of newborns with NOWS produced inconsistent results. Some showed differences in behavior between newborns exposed to buprenorphine versus those exposed to methadone. Both buprenorphine and methadone are given as treatments for opioid addiction in adults, with buprenorphine approved to treat addiction in pregnant women. Although some studies showed decreased NOWS symptoms in buprenorphine-exposed newborns, other studies found no significant differences between the two groups of newborns.
"Because the data were so tenuous and the findings were so inconsistent, we didn't feel comfortable drawing a conclusion," Conradt says. "So it's not clear what the effects of prenatal opioid exposure are at birth."
Infancy
The researchers found 21 studies looking at the development of children up to 2 years of age after prenatal opioid exposure. Conradt says that many of the studies had small numbers of children in the study, which makes it more difficult to tell whether the effects seen in the study are really due to opioid exposure or could be due to other confounding factors. One study had a sufficient size to control for confounding factors, Conradt says, with 131 children. That study found many null effects of opioid exposure on cognitive and behavioral outcomes. "We felt a little bit more comfortable saying that there may not be major effects of prenatal opioid exposure in infancy after controlling for these relevant confounders," Conradt says.
Two years and beyond
Conradt found some of the same inconsistent results in the 27 studies that looked at cognitive development beyond age 2, with some studies finding significant effects in IQ and language ability, and some finding no significant effects. But studies of behavior were more consistent. Children exposed to methadone had higher fear, aggression and anxiety, and a NOWS diagnosis was associated with lower attention. Conradt says it's not surprising that behavioral effects would emerge as children get older. "As children age, they're more challenged," she says. "They have to pay attention at school, they have to sit still, they have to control their behavior. It's not surprising that kids exposed to methadone in the womb may have a harder time with those skills."
But it's still difficult, Conradt says, to determine whether these behavior effects are directly due to opioid exposure, to the children's environment or interaction between the two over time.
Moving forward
One of the main takeaways from Conradt's study is that the existing body of work is hampered by small sample sizes and abundant confounding factors that could obscure the true effects of the opioid exposure. Conradt is part of a program that aims to resolve these issues. It's called the Environmental Influences on Child Health Outcome program, abbreviated ECHO, a nationwide research program supported by the NIH to enhance child health. It's a seven-year, 71-cohort study to examine what environmental factors before and after birth affect children's developmental outcomes.
"We have the opportunity to collect data on over 50,000 children across hundreds of different sites across the country, and tracking their outcomes in a systematic and rigorous manner," Conradt says. U researchers Joe Stanford, Christy Porucznik and Angelo Giardino are principal investigators of the NIH ECHO pediatric cohorts in Utah. In the future Conradt, an ECHO investigator, and others will utilize the data as it becomes available to continue working toward understanding what prenatal opioid exposure means for the future of a growing generation of children.
https://www.sciencedaily.com/releases/2019/08/190828080534.htm
Gene linked to autism undergoes changes in men's sperm after pot use
Further study is needed to determine if the altered gene contributes to autism in children
August 27, 2019
Science Daily/Duke University Medical Center
A specific gene associated with autism appears to undergo changes in the sperm of men who use marijuana, according to new research from Duke Health.
The gene change occurs through a process called DNA methylation, and it could potentially be passed along to offspring.
Publishing online Aug. 27 in the journal Epigenetics, the researchers said the findings do not establish a definitive link between cannabis use and autism, but the possible connection warrants further, urgent study, given efforts throughout the country to legalize marijuana for recreational and/or medicinal uses.
"This study is the first to demonstrate an association between a man's cannabis use and changes of a gene in sperm that has been implicated in autism," said senior author Susan Murphy, Ph.D., associate professor in the Department of Obstetrics & Gynecology at Duke University School of Medicine.
Murphy and colleagues, including lead author and Ph.D. student Rose Schrott, conducted studies using human biologics and animal models to analyze differences between the sperm of males who smoked or ingested marijuana compared to a control group with no such exposures.
In earlier work, published in December, the researchers noted several gene alterations in the sperm of men who smoke marijuana. The current study homed in on specific genes, notably one called Discs-Large Associated Protein 2, or DLGAP2. This gene is involved in transmitting neuron signals in the brain and has been strongly implicated in autism, as well as schizophrenia and post-traumatic stress disorder.
"We identified significant hypomethylation at DLGAP2 in the sperm of men who used marijuana compared to controls, as well as in the sperm of rats exposed to THC compared to controls," Schrott said. "This hypomethylated state was also detected in the forebrain region of rats born to fathers exposed to THC, supporting the potential for intergenerational inheritance of an altered sperm DNA methylation pattern."
The Duke team found that there was a sex-based difference in the relationship between DNA methylation and gene expression in human brain tissues. In both male and female brain tissues, increased DNA methylation was associated with decreased gene activity. This relationship was strongest in females, and seemed to be less well maintained in males, though the reason for this is unknown at this time. This anomaly was notable, because the ratio of boys to girls with autism is 4:1, and there are sex differences in the neurobehavioral symptoms.
"It's possible that the relationship between methylation and expression is modified if the methylation change we see in sperm is inherited by the offspring," Murphy said. "In any event, it's clear that the region of DNA methylation within DLGAP2 that is altered in association with cannabis use is functionally important in the brain."
Murphy said the study's sample size was small -- including 24 men, half who used marijuana and half who didn't -- and could not account for confounding factors such as diet, sleep and exercise, but the findings should prompt continued research.
"Given marijuana's increasing prevalence of use in the U.S. and the increasing numbers of states that have legalized its use, we need more studies to understand how this drug is affecting not only those who smoke it, but their unborn children," Murphy said. "There's a perception that marijuana is benign. More studies are needed to determine whether that is true."
https://www.sciencedaily.com/releases/2019/08/190827123515.htm
New breathalyzer can detect marijuana
August 27, 2019
Science Daily/University of Pittsburgh
A team has developed a breathalyzer device that can measure the amount of tetrahydrocannabinol (THC), the psychoactive compound in marijuana, in the user's breath. The breathalyzer was developed using carbon nanotubes, tiny tubes of carbon 100,000 times smaller than a human hair. Nanotechnology sensors can detect THC at levels comparable to or better than mass spectrometry, which is considered the gold standard for THC detection.
As recreational marijuana legalization becomes more widespread throughout the U.S., so has concern about what that means for enforcing DUI laws. Unlike a breathalyzer used to detect alcohol, police do not have a device that can be used in the field to determine if a driver is under the influence of marijuana. New research from the University of Pittsburgh is poised to change that.
An interdisciplinary team from the Department of Chemistry and the Swanson School of Engineering has developed a breathalyzer device that can measure the amount of tetrahydrocannabinol (THC), the psychoactive compound in marijuana, in the user's breath. Current drug testing methods rely on blood, urine or hair samples and therefore cannot be done in the field. They also only reveal that the user has recently inhaled the drug, not that they are currently under the influence.
The breathalyzer was developed using carbon nanotubes, tiny tubes of carbon 100,000 times smaller than a human hair. The THC molecule, along with other molecules in the breath, bind to the surface of the nanotubes and change their electrical properties. The speed at which the electrical currents recover then signals whether THC is present. Nanotechnology sensors can detect THC at levels comparable to or better than mass spectrometry, which is considered the gold standard for THC detection.
"The semiconductor carbon nanotubes that we are using weren't available even a few years ago," says Sean Hwang, lead author on the paper and a doctoral candidate in chemistry at Pitt. "We used machine learning to 'teach' the breathalyzer to recognize the presence of THC based on the electrical currents recovery time, even when there are other substances, like alcohol, present in the breath."
Hwang works in the Star Lab, led by Alexander Star, PhD, professor of chemistry with a secondary appointment in bioengineering. The group partnered with Ervin Sejdic, PhD, associate professor of electrical and computer engineering at the Swanson School of Engineering, to develop the prototype.
"Creating a prototype that would work in the field was a crucial step in making this technology applicable," says Dr. Sejdic. "It took a cross-disciplinary team to turn this idea into a usable device that's vital for keeping the roads safe."
The prototype looks similar to a breathalyzer for alcohol, with a plastic casing, protruding mouthpiece, and digital display. It was tested in the lab and was shown to be able to detect the THC in a breath sample that also contained components like carbon dioxide, water, ethanol, methanol, and acetone. The researchers will continue to test the prototype but hope it will soon move to manufacturing and be available for use.
"In legal states, you'll see road signs that say "Drive High, Get a DUI,' but there has not been a reliable and practical way to enforce that," says Dr. Star. "There are debates in the legal community about what levels of THC would amount to a DUI, but creating such a device is an important first step toward making sure people don't partake and drive."
https://www.sciencedaily.com/releases/2019/08/190827123239.htm
Chocolate muddles cannabis potency testing
August 25, 2019
Science Daily/American Chemical Society
In 2012, Washington and Colorado became the first states to legalize recreational marijuana. Since then, several other states have joined them, and cannabis-infused edibles, including gummy bears, cookies and chocolates, have flooded the market. But these sweet treats have created major headaches for the scientists trying to analyze them for potency and contaminants. Researchers now report that components in chocolate might be interfering with cannabis potency testing, leading to inaccurate results.
The researchers will present their results at the American Chemical Society (ACS) Fall 2019 National Meeting & Exposition.
"My research focuses on cannabis potency testing because of the high stakes associated with it," says David Dawson, Ph.D., the project's principal investigator. "If an edible cannabis product tests 10% below the amount on the label, California law states that is must be relabeled, with considerable time and expense. But it's even worse if a product tests 10% or more above the labeled amount -- then the entire batch must be destroyed."
Manufacturers add cannabis to a wide variety of foods, and the composition of these products, also known as the "matrix," can affect potency testing results. Dawson and his colleagues at CW Analytical Laboratories decided to focus on potency testing for cannabis-infused chocolates because they are a very common product. CW Analytical Laboratories is a cannabis testing lab in Oakland, California, where recreational marijuana became legal in 2018. "We also noticed, kind of anecdotally, some weird potency variations depending on how we prepared chocolate samples for testing," he says. So Dawson studied the effects of altering sample prep conditions, such as the amounts of chocolate and solvent, pH and type of chocolate, on the concentration of Δ9-tetrahydrocannabinol (Δ9-THC; the major psychoactive constituent of cannabis) measured by high-performance liquid chromatography (HPLC).
Their results were surprising. "When we had less cannabis-infused chocolate in the sample vial, say 1 gram, we got higher THC potencies and more precise values than when we had 2 grams of the same infused chocolate in the vial," Dawson says. "This goes against what I would consider basic statistical representation of samples, where one would assume that the more sample you have, the more representative it is of the whole." These results suggested that some other component of the chocolate -- a matrix effect -- was suppressing the signal for Δ9-THC.
"Simply changing how much sample is in the vial could determine whether a sample passes or fails, which could have a huge impact on the producer of the chocolate bars, as well as the customer who might be under- or overdosing because of this weird quirk of matrix effects," he notes.
Now Dawson is trying to figure out which ingredient of chocolate is responsible for the matrix effects. He has tried spiking a standard solution of Δ9-THC with varying amounts of chocolate bar, cocoa powder, baker's chocolate and white chocolate, all of which have different components, and observing how the HPLC signal changes. "Our best lead right now is that it has something to do with the fats, which makes sense considering that Δ9-THC is fat-soluble," Dawson says.
The team would like to extend their analyses to other cannabinoids, such as cannabidiol (CBD), a non-psychoactive substance that is cropping up in many edible products. Also, they plan to investigate other food matrices, such as chocolate chip cookies. Dawson says that he hopes the research will contribute toward developing standard methods for cannabis potency testing in a variety of edibles. "We owe this research to the scientific community, the producers and the consumers," he says. "We have to be able to provide highly accurate and precise testing across a wide swath of matrices."
https://www.sciencedaily.com/releases/2019/08/190825075930.htm
Cannabis flower is an effective mid-level analgesic medication for pain
Researchers use mobile app to measure how commercially available cannabis products affect pain intensity
August 21, 2019
Science Daily/University of New Mexico
Using the largest database of real-time recordings of the effects of common and commercially available cannabis products in the United States (U.S.), researchers at The University of New Mexico (UNM) found strong evidence that cannabis can significantly alleviate pain, with the average user experiencing a three-point drop in pain suffering on a 0-10 point scale immediately following cannabis consumption.
With a mounting opioid epidemic at full force and relatively few alternative pain medications available to the general public, scientists found conclusive support that cannabis is very effective at reducing pain caused by different types of health conditions, with relatively minimal negative side effects.
Chronic pain afflicts more than 20 percent of adults and is the most financially burdensome health condition that the U.S faces; exceeding, for example, the combined costs of treating heart disease and cancer.
"Our country has been flooded with an over-prescription of opioids medications, which then often leads to non-prescription opioid and heroin use for many people. This man-made disaster is killing our families and friends, regardless of socio-economic status, skin tone, and other superficial human differences" said Jacob Miguel Vigil, one of the lead investigators of the study, titled "The Effectiveness of Self-Directed Medical Cannabis Treatment for Pain," published in the journal Complementary Therapies in Medicine.
Vigil explains, "Cannabis offers the average patient an effective alternative to using opioids for general use in the treatment of pain with very minimal negative side effects for most people."
The researchers relied on information collected with Releaf App, a mobile software program developed by co-authors Franco Brockelman, Keenan Keeling and Branden Hall. The app. enables cannabis users to monitor the real-time effects of the breadth of available cannabis-based products, which are always variable, of course, given the complexity of the Cannabis plant from which these products are obtained.
Since its release in 2016, the commercially developed Releaf App has been the only publicly available, incentive-free app for educating patients on how different types of products (e.g., flower or concentrate), combustion methods, cannabis subspecies (Indica, Sativa, and hybrid), and major cannabinoid contents (THC and CBD) affect their symptom severity levels, providing the user invaluable feedback on their health status, medication choices, and the clinical outcomes of those choices as measured by symptom relief and side effects.
Scientifically, software like the Releaf App enables researchers to overcome the inherent limitations of government-funded clinical trials on the real-time effects of Cannabis, which are rare in general, but also often limited by onerous federal regulations, including its Schedule I status (no accepted medical use and a high abuse potential) and the mandate that investigators use the notoriously poor quality and low potency cannabis products supplied by the National Institute of Drug Abuse.
"Even just rescheduling cannabis just from Schedule I to Schedule II, i.e., classifying it with fentanyl, oxycodone, and cocaine rather than heroin and ecstasy, could dramatically improve our ability to conduct research and only would require that the DEA recognizes that accepted medical uses for cannabis exist, as clearly evidenced by our results and the flourishing medical cannabis programs in the majority of U.S. states," pointed out co-author Sarah Stith.
Among the study's findings the greatest analgesic responses were reported by people that used whole dried cannabis flower, or 'buds,' and particularly cannabis with relatively high levels of tetrahydrocannabinol, otherwise known as THC. The more recently popularized cannabinoid, cannabidiol or CBD, in contrast, showed little association with the momentary changes in pain intensity, based on the massive database explored in the study.
"Cannabis likely has numerous constituents that possess analgesic properties beyond THC, including terpenes and flavonoids, which likely act synergistically for people that use whole dried cannabis flower," said Vigil, "Our results confirm that cannabis use is a relatively safe and effective medication for alleviating pain, and that is the most important message to learn from our results. It can only benefit the public for people to be able to responsibly weigh the true risks and benefits of their pain medication choices, and when given this opportunity, I've seen numerous chronic pain patients substitute away from opioid use, among many other classes of medications, in favor of medical cannabis."
"Perhaps the most surprising result is just how widespread relief was with symptom relief reported in about 95 percent of cannabis administration sessions and across a wide variety of different types of pain," added lead author of the study, Xiaoxue Li.
The authors do caution that cannabis use does carry the risks of addiction and short-term impairments in cognitive and behavioral functioning, and may not be effective for everyone. However, there are multiple mechanisms by which cannabis alleviates pain suffering. In addition to its anti-inflammatory properties, cannabis activates receptors that are colocalized with opioid receptors in the brain. "Cannabis with high THC also causes mood elevation and adjusts attentional demands, likely distracting patients from the aversive sensations that people refer to "pain," explains Vigil.
"When compared to the negative health risks associated with opioid use, which currently takes the lives of over 115 Americans a day, cannabis may be an obvious value to patients. Chronic opioid use is associated with poorer quality of life, social isolation, lower immune functioning and early morbidity. In contrast, my own ongoing research increasingly suggests that cannabis use is associated with a reversal of each of these potential outcomes," said Vigil
https://www.sciencedaily.com/releases/2019/08/190821125525.htm
Cannabis-related poison control calls for Massachusetts kids doubled after medical pot legalized
August 16, 2019
Science Daily/University of Massachusetts at Amherst
After medical marijuana became legal in Massachusetts, cannabis-related poison control calls involving the commonwealth's children and teenagers doubled, according to a public health investigation led by University of Massachusetts Amherst injury prevention researcher Jennifer Whitehill.
The increase in calls to the Regional Center for Poison Control and Prevention at Boston Children's Hospital occurred despite legislative mandates for childproof packaging and warning labels, and before the recreational use of marijuana was legalized for adults.
"As states across the country enact more permissive marijuana policies, we need to do more to promote safe storage in households with children," says Whitehill, assistant professor of health promotion and policy and lead author of the research published in JAMA Network Open.
Whitehill and former UMass Amherst graduate student Calla Harrington analyzed data from the poison control center in collaboration with staff from the center, including medical director Dr. Michele Burns and clinical fellow Dr. Michael Chary. The research team reviewed the center's data from 2009 through 2016 -- four years before and four years after medical marijuana was legalized in Massachusetts.
During the study period, the poison control center received 218 calls from Massachusetts involving cannabis exposure in children and teens, from infancy to age 19, including 98 single-substance calls and 120 polysubstance calls. Those calls represented 0.15 percent of all poison control calls during that time period for that age group.
"While we're pleased to see that the incidence is relatively low, we feel these cases are preventable, and the issue needs to be on the radar of policymakers and parents, particularly now that dispensaries are open for adult-use sales," Whitehill says.
Some highlights of the findings:
· The incidence of calls for single-substance cannabis exposure increased 140 percent during the study period -- from 0.4 per 100,000 population before medical marijuana was legalized to 1.1 per 100,000 population after legalization.
· Nearly 80 percent of the calls to the poison control center came from healthcare facilities, and, in terms of medical outcomes, most of the exposures resulted in moderate and minor effects. Four cases with major effects and no deaths were reported.
· A little more than a quarter of the cases were reported as unintentional, with 19.4 percent of calls involving children from infancy through age 4.
· Calls involving edible cannabis products increased for most age groups, including ages 15-19. Because other research has found that the proportion of teens using marijuana is remaining about the same even as marijuana laws are loosening, this finding suggests that teenagers may be caught off guard by the potentially potent effects of edibles and concentrated extracts, Whitehill says.
The paper concludes, "This study suggests that states liberalizing marijuana policies should consider strengthening regulations to prevent unintentional exposure among young children and enhancing efforts to prevent use by teenagers, with particular attention to edible cannabis products and concentrated extracts."
Whitehill says the next step is to study the impact of marijuana's legalization for adult use, which went into effect in late 2016. Two years later, in November 2018, marijuana retail stores began opening.
"Given what we've seen here," Whitehill says, "I would expect the calls to the poison control center to increase even more."
https://www.sciencedaily.com/releases/2019/08/190816123234.htm
High fat foods can increase oral cannabidiol absorption into the body
August 13, 2019
Science Daily/University of Minnesota
While oral cannabidiol (CBD) capsules were approved by the U.S. Food and Drug Administration (FDA) for use in patients with seizures in 2018, very little was known about the effect of food on CBD absorption.
A University of Minnesota study, published in Epilepsia, examined whether eating high-fat foods after taking CBD increased the body's absorption of CBD. The study tested whether fasting or a high fat meal has an effect when cannabidiol oral capsules were taken by patients.
To find out what effect a fatty meal would have on CBD absorption, the research group measured CBD concentrations in epilepsy patients at the MINCEP Epilepsy Care clinic who were taking 99 percent pure CBD capsules. Concentrations from patients who took CBD on an empty stomach and a standardized fatty breakfast (i.e. breakfast burrito) were compared.
"The type of food can make a large difference in the amount of CBD that gets absorbed into the body. Although fatty foods can increase the absorption of CBD, it can also increase the variability as not all meals contain the same amount of fat," said Angela Birnbaum, a professor in the College of Pharmacy and study co-author.
"Increases in the amount of the CBD dose being absorbed into the body can also lead to lower medication costs," said Ilo Leppik, study co-author, a professor in the College of Pharmacy and an adjunct professor at the Medical School.
The study found:
· CBD exposure is vastly increased when CBD is taken with high fatty foods;
· when compared to fasting, taking CBD with food increased the amount of CBD in the body by four-times and the maximum amount recorded in the participants' blood by 14-times;
· no cognitive differences were identified, which is consistent with previous studies.
"For epilepsy patients, a goal is to maintain consistent blood concentrations of drug," said Birnbaum. "This study shows that CBD concentrations could vary significantly if patients take it differently, sometimes with or without food. Variations in blood concentrations could leave a patient more susceptible to seizures."
https://www.sciencedaily.com/releases/2019/08/190813130426.htm
Marijuana may boost risky effects of drinking alcohol
August 13, 2019
Science Daily/Penn State
Compared to people who only drank alcohol, those who used alcohol and marijuana simultaneously were more likely to drink heavier and more often, according to researchers. They were also more likely to experience alcohol-related problems -- like impulsive actions they later regretted.
As the legalization of medical marijuana and marijuana use are both on the rise in the United States, people are not necessarily using alcohol less and may be unaware of the risks of combining alcohol and marijuana, according to researchers.
A new study from Penn State found that compared to people who only drank alcohol, those who used alcohol and marijuana simultaneously were more likely to drink heavier and more often. They were also more likely to experience alcohol-related problems -- like impulsive actions they later regretted.
"The results suggest that individuals who simultaneously use alcohol and marijuana are at a disproportionately higher risk for heavy, frequent, and problematic substance use," said Ashley Linden-Carmichael, assistant research professor at the Edna Bennett Pierce Prevention Research Center at Penn State.
The researchers said the findings -- recently published in the journal Substance Use and Misuse -- also suggest that prevention and intervention programs should take into account not just alcohol, but also if people are using additional substances, as well.
"Right now, a lot of campus programs focus on whether students are drinking, and while sometimes they are asked about other substances, it's not necessarily whether they're using these substances simultaneously," Linden-Carmichael said. "I think we do need to be asking about whether they're drinking in combination with other drugs and educating students about how that exacerbates their risk."
According to the researchers, marijuana use is at an all-time high among young adults in the U.S., possibly leading to people using marijuana and alcohol simultaneously.
"The problem with simultaneous use is that it can affect people cognitively and perceptually, and also have an impact on motor impairment," Linden-Carmichael said. "There is a burgeoning area of research that is examining why people are using marijuana and alcohol together and what those effects are."
In the study, Linden-Carmichael said she and the other researchers were interested in learning more about how people use marijuana and alcohol together. They also wanted to explore whether personality traits -- like the tendency to pursue new and exciting experiences, or "sensation seeking" -- were associated with higher odds of using alcohol and marijuana at the same time.
The researchers recruited 1,017 participants from 49 states in the U.S. between the ages of 18 and 25 for the study. The participants provided information about how often they used alcohol, marijuana and the two substances simultaneously. They also filled out questionnaires that measured their experiences with alcohol-related problems, whether they had a sensation-seeking personality, and how they perceived the drinking habits of their friends.
Linden-Carmichael said that across the board, individuals who used alcohol and marijuana simultaneously were at a greater risk than individuals using alcohol alone.
"Even after controlling for the number of drinks a person typically consumed, people who used alcohol and marijuana at the same time were at a greater risk for problems like blacking out, getting in an argument, or other concerns," Linden-Carmichael said. "Additionally, 70 percent of those who engaged in simultaneous use reported using at least weekly."
The researchers found that among people who used alcohol and marijuana simultaneously, those who used more frequently were more likely to drink more alcohol, more often, and for longer periods of time. They were also associated with using more marijuana more often.
Additionally, they found that people who used alcohol and marijuana together were more likely to have higher levels of sensation-seeking characteristics and think their friends were drinking larger amounts of alcohol.
https://www.sciencedaily.com/releases/2019/08/190813143853.htm
Adults who mix cannabis with opioids for pain report higher anxiety, depression
They have more mental health issues than those who use opioids alone
Science Daily/August 12, 2019
University of Houston
A researcher from the University of Houston has found that adults who take prescription opioids for severe pain are more likely to have increased anxiety, depression and substance abuse issues if they also use marijuana.
"Given the fact that cannabis potentially has analgesic properties, some people are turning to it to potentially manage their pain," Andrew Rogers, said in describing the work published in the Journal of Addiction Medicine. Rogers focuses on the intersection of chronic pain and opioid use, and identifying the underlying psychological mechanisms, such as anxiety sensitivity, emotion regulation, pain-related anxiety, of these relationships. Rogers is a doctoral student in clinical psychology who works in the UH Anxiety and Health Research Laboratory and its Substance Use Treatment Clinic.
Under the guidance of advisor Michael Zvolensky, Hugh Roy and Lillie Cranz Cullen Distinguished University Professor of psychology and director of the lab and clinic, Rogers surveyed 450 adults throughout the United States who had experienced moderate to severe pain for more than three months. The study revealed not only elevated anxiety and depression symptoms, but also tobacco, alcohol, cocaine and sedative use among those who added the cannabis, compared with those who used opioids alone. No increased pain reduction was reported.
Importantly, said Rogers, while the co-use of substances generally is associated with poorer outcomes than single substance use, little work has examined the impact of mixing opioids and cannabis.
Opioid misuse constitutes a significant public health problem and is associated with a host of negative outcomes. Despite efforts to curb this increasing epidemic, opioids remain the most widely prescribed class of medications. Prescription opioids are often used to treat chronic pain, despite the risks, and chronic pain remains an important factor in understanding this epidemic.
Cannabis is another substance that has recently garnered attention in the chronic pain literature, as increasing numbers of people use it to manage chronic pain.
"There's been a lot of buzz that maybe cannabis is the new or safer alternative to opioid, so that's something we wanted to investigate," said Rogers, who said the idea for the study evolved from a conversation with Zvolensky. Rogers was studying opioid use and pain management when they began discussing the role of cannabis in managing pain.
"The findings highlight a vulnerable population of polysubstance users with chronic pain and indicates the need for more comprehensive assessment and treatment of chronic pain," said Rogers.
https://www.sciencedaily.com/releases/2019/08/190812130840.htm
Marijuana legalization reduces opioid deaths
August 7, 2019
Science Daily/Wiley
A new Economic Inquiry study finds that marijuana access leads to reductions in opioid-related deaths.
The study examined how the changing legal status of marijuana has impacted mortality in the United States over the past two decades. Investigators found that legalization and access to recreational marijuana reduced annual opioid mortality in the range of 20% to 35%, with particularly pronounced effects for synthetic opioids.
The research extends prior findings that medical marijuana laws reduce opioid mortality rates. The findings are timely given the scale of the opioid epidemic in the United States and growing calls for marijuana legalization throughout North America.
"Recreational marijuana laws affect a much larger population than medical marijuana laws, yet we know relatively little about their effects." said co-author Nathan W. Chan, PhD, of University of Massachusetts Amherst. "Focusing on the recent wave of recreational marijuana laws in the U.S., we find that opioid mortality rates drop when recreational marijuana becomes widely available via dispensaries."
https://www.sciencedaily.com/releases/2019/08/190807092350.htm
Cannabis' effects on brain neurochemistry
August 7, 2019
Science Daily/Wiley
A new Addiction Biology study provides the first evidence of a blunted response to stress-induced dopamine signaling in the brain's prefrontal cortex in individuals at high risk for psychosis who regularly used cannabis.
Little is known about the effects of cannabis on brain neurochemistry, and specifically about its impact on dopamine signaling. Of note, a recent analysis found a dose-response relationship between higher cannabis use and increased risk for schizophrenia, a condition associated with abnormal dopamine synthesis and release in the brain.
This latest study's results are important given the global trend to legalize cannabis and the growing evidence of the increased risks for psychosis in vulnerable youth.
"Regular cannabis use has a profound effect on cortical dopamine function, in particular in relation to the stress response, which is critical for young adults at risk for psychosis," said senior author Romina Mizrahi, MD, PhD, of the Centre for Addiction and Mental Health, in Toronto. "These results highlight the need for further research on the impact of cannabis on brain neurochemistry, especially in populations at risk for psychosis."
https://www.sciencedaily.com/releases/2019/08/190807092348.htm
Antioxidant compound from soybeans may prevent marijuana-induced blood vessel damage
July 30, 2019
Science Daily/American Heart Association
Marijuana exposure damages cells of the inner lining of blood vessels throughout the heart and vascular system. In studies with human cells and arteries from mice, a compound found in soybeans blocked the damage and may have potential in preventing cardiovascular side effects of marijuana use.
In laboratory tests, a compound found in soybeans blocked damage to the lining of blood vessels in the heart and circulatory system and may someday provide a way to prevent the cardiovascular side effects of recreational and medical marijuana use, according to preliminary research presented at the American Heart Association's Basic Cardiovascular Sciences 2019 Scientific Sessions.
Marijuana is the most widely used illicit drug worldwide and is increasingly being made legal for recreational and medicinal purposes. However, there have been studies that link marijuana smoking to an increased risk of heart attack and stroke.
There can also be cardiovascular side effects, including changes in heart rate and blood pressure, when people take FDA-approved medications containing a synthetic version of delta-9-tetrahydrocannabinol (THC) -- the main compound in marijuana that gives the sensation of being high.
"These medications are prescribed to reduce the nausea and vomiting induced by chemotherapy and to increase appetite in certain people with acquired immune deficiency syndrome," said Tzu-Tan "Thomas" Wei, Ph.D., the study's lead author and assistant professor of pharmacology in the College of Medicine at National Taiwan University in Taipei City. "The goal of our studies is to investigate the mechanisms of marijuana-induced damage and discover new drugs to prevent those side effects."
The effects of THC occur after it binds to one of two cannabinoid receptors (CB1 and CB2) that are found throughout the brain and body and are also acted on by naturally occurring cannabinoids.
In the current study, the researchers used endothelial cells (like those that line blood vessels) derived from the stem cells of five healthy people. Exposing the cells to THC, they found that:
THC exposure induced inflammation and oxidative stress, which are known to affect the inner linings of blood vessels and are associated with the development of heart disease.
Lab techniques that block access to the CB1 receptor by THC eliminated the effects of THC exposure on endothelial cells.
Treatment with JW-1, an antioxidant compound found in soybeans, eliminated the effects of THC exposure.
In addition, the researchers used a laboratory technique called wire myography to examine the response of mouse arteries to THC, finding that JW-1 blocked THC's negative effects on the function of the inner lining.
An earlier attempt to gain health benefits from blocking the CB1 receptor proved problematic.
"Previously, a drug that blocked CB1 was approved in Europe for the treatment of obesity, but it had to be withdrawn because of severe psychiatric side effects," Wei said. "In contrast, as an antioxidant, JW-1 may have neuroprotective effects. Discovering a new way to protect blood vessels without psychiatric side effects would be clinically important with the rapid growth of cannabis use worldwide."
The researchers are currently extending their research by testing cells derived from regular marijuana users and those who smoke both cigarettes and marijuana. In addition, they are looking at the impact of THC along with the other main component of marijuana, cannabidiol.
"Meanwhile, if you have heart disease, talk to your doctor before you use marijuana or one of the synthetic THC-containing medications," Wei said. "Marijuana may cause more severe effects on the cardiovascular system in those with pre-existing heart disease."
https://www.sciencedaily.com/releases/2019/07/190730182430.htm
People are more likely to try drugs for the first time during the summer
July 23, 2019
Science Daily/NYU Langone Health / NYU School of Medicine
American teenagers and adults are more likely to try illegal or recreational drugs for the first time in the summer, a new study shows.
Led by researchers at NYU School of Medicine, the study found that over a third (34 percent) of recent LSD initiates first used the drug in the summer. In addition, 30 percent of marijuana, 30 percent of ecstasy (also known as MDMA or Molly), and 28 percent of cocaine use was found to begin in summer months.
"First-time users may be unfamiliar with the effects of various drugs, so it is important to first understand when people are most likely to start these behaviors," says study senior investigator Joseph J. Palamar, MPH, PhD, an associate professor in the Department of Population Health at NYU School of Medicine.
In 2017, according to the U.S. Substance Abuse and Mental Health Services Administration, more than 3 million people in the United States tried LSD, marijuana, cocaine, or ecstasy for the first time.
Publishing online July 23 in the Journal of General Internal Medicine, the study used data collected from the National Survey on Drug Use and Health between 2011 and 2017 involving about 394,415 people ages 12 and older. Participants were surveyed about their use of various drugs through a computer-assisted interview. New users were asked to recall the month and year when they initiated use.
The investigators suggest that the results could be explained, in part, by people having extra recreational time during the summer, as well as the growing popularity of outdoor activities, such as music festivals, at which recreational drug use is common.
"Parents and educators who are concerned about their kids need to educate them year-round about potential risks associated with drug use, but special emphasis appears to be needed before or during summer months when rates of initiation increase," says Palamar, who is also a researcher in the Center for Drug Use and HIV/HCV Research at NYU College of Global Public Health.
Palamar recommends that potential users become educated about the drugs they are going to use and their side effects. He further recommends, based on previous research, having the company of trusted friends when taking drugs for the first time, drinking enough fluids, and getting enough rest to avoid dehydration, exhaustion, or more serious outcomes such as heat stroke.
The investigators stress that further research is needed to determine the particular situations -- especially in the summer -- when people are most likely to use drugs for the first time and to determine the extent to which use is planned or unplanned.
https://www.sciencedaily.com/releases/2019/07/190723085951.htm
More women using cannabis daily before and during pregnancy
Current advice is to avoid cannabis exposure during pregnancy
July 19, 2019
Science Daily/Kaiser Permanente
The number of women using cannabis in the year before they get pregnant and early in their pregnancies is increasing, and their frequency of use is also rising, according to new data from Kaiser Permanente.
The research, published July 19, 2019, in JAMA Network Open, examined self-reported cannabis use among 276,991 pregnant women (representing 367,403 pregnancies) in Northern California over 9 years and found that cannabis use has increased over time.
From 2009 to 2017, the adjusted prevalence of self-reported cannabis use in the year before pregnancy increased from 6.8% to 12.5%, and the adjusted prevalence of self-reported cannabis use during pregnancy increased from 1.9% to 3.4% (rates were adjusted for demographics). Annual rates of change in self-reported daily, weekly, and monthly-or-less cannabis use increased significantly, though daily use increased most rapidly.
Among women who self-reported cannabis use during the year before pregnancy, the proportion who were daily users increased from 17% to 25%, and weekly users increased from 20% to 22%, while monthly-or-less users decreased from 63% to 53% during the study period. Similarly, among women who self-reported cannabis use during pregnancy, the proportion who were daily users increased from 15% to 21%, and weekly users from 25% to 27%, while monthly users decreased from 60% to 52%.
"These findings should alert women's health clinicians to be aware of potential increases in daily and weekly cannabis use among their patients," said lead author Kelly Young-Wolff, PhD, MPH, a research scientist with the Kaiser Permanente Division of Research. "The actual numbers are likely higher, as women may be unwilling to disclose their substance use to a medical professional."
In addition, the prevalence of daily and weekly cannabis use may have risen even further in the past year and a half following legalization of cannabis for recreational use in California in 2018, Young-Wolff said.
The data come from women's initial prenatal visits at Kaiser Permanente in Northern California, which usually take place at around 8 weeks gestation, and do not reflect continued use throughout pregnancy. Investigators were unable to differentiate whether self-reported cannabis use during pregnancy occurred before or after women were aware that they were pregnant.
While the current findings are based on women's self-reporting, the results are supported by the Kaiser Permanente research team's December 2017 JAMA Research Letter showing an increase in prenatal cannabis use via urine toxicology testing. In this newer study, the authors focus on trends in frequency of use in the year before and during pregnancy.
Some women may use cannabis during pregnancy to manage morning sickness, the authors noted. The authors' previous work published in JAMA Internal Medicine in 2018 found women with severe nausea and vomiting in pregnancy were nearly 4 times more likely to use cannabis during the first trimester of pregnancy.
Women may get the impression from cannabis product marketing and online media that cannabis use is safe during pregnancy, said Young-Wolff. However, there is substantial evidence that exposure to cannabis in pregnancy is associated with having a low-birthweight baby, and the American College of Obstetricians and Gynecologists recommends women who are pregnant or contemplating pregnancy discontinue cannabis use because of concerns about impaired neurodevelopment and exposure to the adverse effects of smoking.
"There is still much that is unknown on the topic, including what type of cannabis products pregnant women are using and whether the health consequences differ based on mode of cannabis administration and frequency of prenatal cannabis use," Young-Wolff noted.
More research is needed to offer women better, specific advice, said study senior author Nancy Goler, MD, an obstetrician/gynecologist and associate executive director of The Permanente Medical Group.
"There is an urgent need to better understand the effects of prenatal cannabis exposure as cannabis becomes legalized in more states and more widely accepted and used," Dr. Goler said. "Until such time as we fully understand the specific health risks cannabis poses for pregnant women and their fetuses, we are recommending stopping all cannabis use prior to conceiving and certainly once a woman knows she is pregnant."
The study was supported by a grant from the National Institute on Drug Abuse.
Young-Wolff and Kaiser Permanente Division of Research colleague Lindsay Avalos, PhD, MPH, have received a new 5-year grant from NIDA to support further research on maternal cannabis use during pregnancy. They plan to study whether prenatal cannabis use is associated with increased risk of adverse maternal, fetal, and neonatal outcomes using data from urine toxicology testing, self-reported frequency of prenatal cannabis use, and mode of cannabis administration. They will also test whether legalization of cannabis for recreational use in 2018 and local regulatory practices (such as retailer bans) are associated with variation in prenatal cannabis use.
https://www.sciencedaily.com/releases/2019/07/190719173602.htm
Marijuana use may not make parents more 'chill'
Pot linked to more use of all kinds of discipline
July 17, 2019
Science Daily/Ohio State University
Sorry, marijuana moms and dads: Using pot may not make you a more relaxed parent, at least when it comes to how you discipline your children.
A study of California parents found that current marijuana users administered more discipline techniques of all kinds to their children on average than did non-users. That includes everything from timeouts to, in some cases, physical abuse.
"The acceptability of marijuana is growing in the United States and with that, more parents feel free to use the drug, sometimes even in front of their children," said Bridget Freisthler, co-author of the study and professor of social work at The Ohio State University.
"Some parents claim it makes them a better, more relaxed parent, but that may not be the case."
The effect of marijuana use on parenting is a relevant concern: A 2017 survey from Yahoo News and Marist College found that 54 percent of adults who use marijuana in the United States are parents. A majority of those parents have children under the age of 18. Some groups of "marijuana moms" claim that use makes them better parents.
The results of this new study suggest that marijuana users -- who are nearly always (92 percent of the time) also alcohol users -- are trying to control their kids more than non-users, Freisthler said.
"It appears that users may be quicker than other parents to react to minor misbehavior," she said.
"We can't tell from this study, but it may be that parents who use marijuana or alcohol don't want their children to spoil the buzz they have, or bother them when they have a hangover."
Freisthler conducted the study with Nancy Jo Kepple of the University of Kansas. Their results were published online this week in the Journal of Social Work Practice in the Addictions.
The researchers interviewed 3,023 randomly selected California parents of children 12 years old or younger by telephone in 2009. They asked participants about their recent use (in the past year) and past use (a year or more ago) of alcohol, marijuana, methamphetamine and other drugs.
They also asked how often the parents used non-violent discipline (such as timeouts or taking away privileges), corporal punishment (such as spanking) and physical abuse (such as hitting a child with a fist).
This is one of the first studies to look at how use of specific types of substances are related to a variety of parental discipline practices in the general population, Freisthler said.
The findings revealed that parents who used marijuana in the past year tended to use more of all types of discipline compared to non-users, even after taking into account a variety of other factors that could impact use of discipline, such as parental stress and depression and child and parent demographics. The same was true of alcohol users.
Parents who had used alcohol or marijuana in the past, but were not at the time of the research interview, also applied most types of discipline more often than did non-users.
And the more substances that parents used, the more often they disciplined their children in all types of ways, according to the study. For example, parents who reported using the most substances practiced physical abuse at a rate about 1.45 times greater than those who used only one substance.
Results showed that the annual frequency of physical abuse was 0.5 times higher among parents who used both alcohol and marijuana in the past year, compared to those who consumed only alcohol.
"The use of several different kinds of substances certainly is a warning sign that parents may be relying more heavily on discipline to control their children," she said.
Freisthler said this study shows that while marijuana use has become more mainstream and is legal in more states, there is still need for caution.
"Marijuana use is not risk-free. It affects a lot of behaviors, including parenting."
https://www.sciencedaily.com/releases/2019/07/190717084343.htm