Cannabis reduces headache and migraine pain by nearly half

November 25, 2019

Science Daily/Washington State University

Inhaled cannabis reduces self-reported headache severity by 47.3% and migraine severity by 49.6%, according to a recent study led by Carrie Cuttler, a Washington State University assistant professor of psychology.

The study, published online recently in the Journal of Pain, is the first to use big data from headache and migraine patients using cannabis in real time. Previous studies have asked patients to recall the effect of cannabis use in the past. There has been one clinical trial indicating that cannabis was better than ibuprofen in alleviating headache, but it used nabilone, a synthetic cannabinoid drug.

"We were motivated to do this study because a substantial number of people say they use cannabis for headache and migraine, but surprisingly few studies had addressed the topic," said Cuttler, the lead author on the paper.

In the WSU study, researchers analyzed archival data from the Strainprint app, which allows patients to track symptoms before and after using medical cannabis purchased from Canadian producers and distributors. The information was submitted by more than 1,300 patients who used the app over 12,200 times to track changes in headache from before to after cannabis use, and another 653 who used the app more than 7,400 times to track changes in migraine severity.

"We wanted to approach this in an ecologically valid way, which is to look at actual patients using whole plant cannabis to medicate in their own homes and environments," Cuttler said. "These are also very big data, so we can more appropriately and accurately generalize to the greater population of patients using cannabis to manage these conditions."

Cuttler and her colleagues saw no evidence that cannabis caused "overuse headache," a pitfall of more conventional treatments which can make patients' headaches worse over time. However, they did see patients using larger doses of cannabis over time, indicting they may be developing tolerance to the drug.

The study found a small gender difference with significantly more sessions involving headache reduction reported by men (90.0%) than by women (89.1%). The researchers also noted that cannabis concentrates, such as cannabis oil, produced a larger reduction in headache severity ratings than cannabis flower.

There was, however, no significant difference in pain reduction among cannabis strains that were higher or lower in levels of tetrahydrocannabinol (THC) and cannabidiol (CBD), two of the most commonly studied chemical constituents in cannabis, also known as cannabinoids. Since cannabis is made up of over 100 cannabinoids, this finding suggests that different cannabinoids or other constituents like terpenes may play the central role in headache and migraine relief.

More research is needed, and Cuttler acknowledges the limitations of the Strainprint study since it relies on a self-selected group of people who may already anticipate that cannabis will work to alleviate their symptoms, and it was not possible to employ a placebo control group.

"I suspect there are some slight overestimates of effectiveness," said Cuttler. "My hope is that this research will motivate researchers to take on the difficult work of conducting placebo-controlled trials. In the meantime, this at least gives medical cannabis patients and their doctors a little more information about what they might expect from using cannabis to manage these conditions."

https://www.sciencedaily.com/releases/2019/11/191125100353.htm

Chronic opioid therapy can disrupt sleep, increase risk of sleep disorders

Medical providers must be aware of adverse effects of opioid treatment

November 19, 2019

Science Daily/American Academy of Sleep Medicine

Patients and medical providers should be aware that chronic opioid use can interfere with sleep by reducing sleep efficiency and increasing the risk of sleep-disordered breathing, according to a position statement from the American Academy of Sleep Medicine.

Opioid use has boomed in the last decade, with nearly 92 million Americans using prescription opioids and 11.5 million people misusing them. In addition to understanding the risks of opioid addiction and abuse, it is important for health care providers to be aware that chronic opioid use is associated with changes in sleep architecture and an increased risk of respiratory depression during sleep.

"This statement increases awareness among health care providers of the important adverse events that can occur in patients on chronic opioid therapy," said co-author Dr. R. Nisha Aurora, Associate Professor of Medicine at Rutgers Robert Wood Johnson Medical School in New Jersey. "The paper also highlights the need for providers to recognize and diagnose sleep-related breathing disorders that are frequently seen with chronic opioid use."

The position statement was developed by the AASM board of directors and is published in the Nov. 15 issue of the Journal of Clinical Sleep Medicine.

Patients who have chronic pain often experience fatigue and disturbed sleep. Studies have shown that chronic opioid therapy has the potential to further disrupt sleep by reducing sleep efficiency, slow wave sleep, and rapid eye movement sleep. Another adverse effect of opioid use is respiratory depression, which can increase the risk of sleep-related breathing disorders such as sleep-related hypoventilation, central sleep apnea and obstructive sleep apnea.

If left untreated, sleep-related breathing disorders can be harmful to a patient's health. However, they can be diagnosed by a medical provider following an overnight sleep study in a sleep center. Effective treatments also are available, including several modalities of positive airway pressure therapy. Medical providers who care for patients on chronic opioid therapy need to be aware of the signs of disrupted sleep, such as snoring and excessive daytime sleepiness, in order to provide their patients with high quality care.

"Because of the complex relationship between pain, sleep, daytime functioning, and opioid therapy, a strong collaboration between pain specialists, sleep physicians, and primary care providers is needed to optimize patient benefit and minimize complications when opioids are part of chronic therapy," said Dr. Aurora.

While opioid therapy can contribute to sleep disruption and sleep disorders, it can be an effective treatment for patients with restless legs syndrome (RLS), a sleep disorder associated with disturbed sleep. Some patients with severe, refractory RLS, who are unresponsive or intolerant to other therapies, may find relief by using opioid medications at much lower doses than those used to treat chronic pain.

Dr. Aurora is currently collaborating with the Brain Health Institute at Rutgers to study sleep in those seeking therapy for opioid addiction.

https://www.sciencedaily.com/releases/2019/11/191119143240.htm

Daily cannabis use lowers odds of using illicit opioids among people who have chronic pain

Science Daily/University of British Columbia

For those using illicit opioids to manage their chronic pain, cannabis may be a beneficial -- and a less dangerous -- alternative, according to new research from the BC Centre on Substance Use (BCCSU).

Researchers from the BCCSU and University of British Columbia (UBC) interviewed more than 1,100 people at highest risk of opioid overdose in Vancouver between 2014 and 2017 who reported substance use and major or chronic pain. They found that daily cannabis use was associated with significantly lower odds of daily illicit opioid use, suggesting people are replacing opioids with cannabis to manage their pain.

The study was published today in a special issue of PLOS Medicine on substance dependence.

"These findings, in combination with past research, again demonstrate that people are using cannabis to help manage many different conditions, including pain. And in some cases, they're using cannabis in place of opioids," says senior author Dr. M-J Milloy, a research scientist at BCCSU and the Canopy Growth professor of cannabis science at UBC. "In the midst of an ongoing public health emergency caused by opioid overdose deaths, the results suggest that increasing access to cannabis for therapeutic purposes could help curb overdose risk associated with illicit opioid use."

Results from a statistical model showed that people who used cannabis every day had nearly 50 per cent lower odds of using illicit opioids every day compared to cannabis non-users, whereas people who reported occasional use of cannabis were neither more nor less likely than non-users to use illicit opioids on a daily basis.

Researchers further found that there may be an intentional therapeutic element associated with at least daily cannabis use. For instance, daily users were significantly more likely than occasional users to report a number of therapeutic uses of cannabis, including addressing pain, stress, nausea, mental health, and symptoms of HIV or side effects of HIV antiretroviral therapy, or improving sleep.

The findings suggest that some people who use drugs and who are experiencing pain might be using cannabis as an ad-hoc, self-directed strategy to reduce the frequency of opioid use.

"These findings point to a need to design formal clinical evaluations of cannabis-based strategies for pain management, opioid use disorder treatment supports, and wider harm reduction initiatives," says Stephanie Lake, a PhD candidate at UBC's school of population and public health, and the lead author of the study.

Milloy is currently planning controlled trials to evaluate whether cannabis could help people with opioid use disorder stay on their treatment and serve as a substitute to opioid use.

https://www.sciencedaily.com/releases/2019/11/191119141233.htm

Ayahuasca compound changes brainwaves to vivid 'waking-dream' state

November 19, 2019

Science Daily/Imperial College London

Scientists have peered inside the brain to show how taking DMT affects human consciousness by significantly altering the brain's electrical activity.

DMT (or dimethyltryptamine) is one of the main psychoactive constituents in ayahuasca, the psychedelic brew traditionally made from vines and leaves of the Amazon rainforest. The drink is typically prepared as part of a shamanic ceremony and associated with unusual and vivid visions or hallucinations.

The latest study is the first to show how the potent psychedelic changes our waking brain waves -- with researchers comparing its powerful effects to 'dreaming while awake'.

The work, led by researchers from the Centre for Psychedelic Research at Imperial College London and published today in the journal Scientific Reports, may help to explain why people taking DMT and ayahuasca experience intense visual imagery and immersive 'waking-dream' like experiences.

DMT is a naturally occurring chemical found in miniscule amounts in the human brain but also in larger amounts in a number of plant species around the world.

Accounts from people who have taken DMT report intense visual hallucinations often accompanied by strong emotional experiences and even 'breakthroughs' into what users describe as an alternate reality or dimension.

But scientists are interested in using the powerful psychoactive compound for research as it produces relatively short but intense psychedelic experiences, providing a window for collecting data on brain activity when consciousness is profoundly altered.

In the latest study, the Imperial team captured EEG measures from healthy participants in a clinical setting, in a placebo-controlled design.

A total of 13 participants were given an intravenous infusion of DMT at the National Institute for Health Research (NIHR) Imperial Clinical Research Facility.

Volunteers were fitted with caps with electrodes to measure the brain's electrical activity, before, during and after their infusion, with the peak of the psychedelic experience lasting around 10 minutes.

Analysis revealed that DMT significantly altered electrical activity in the brain, characterised by a marked drop off in alpha waves -- the human brain's dominant electrical rhythm when we are awake. They also found a short-lived increase in brainwaves typically associated with dreaming, namely, theta waves.

In addition to changes in the types of brainwaves, they also found that, overall, brain activity became more chaotic and less predictable -- the opposite to what is seen in states of reduced consciousness, such as in deep sleep or under general anaesthesia.

"The changes in brain activity that accompany DMT are slightly different from what we see with other psychedelics, such as psilocybin or LSD, where we see mainly only reductions in brainwaves," said lead author Christopher Timmermann, from the Centre for Psychedelic Research.

"Here we saw an emergent rhythm that was present during the most intense part of the experience, suggesting an emerging order amidst the otherwise chaotic patterns of brain activity. From the altered brainwaves and participants' reports, it's clear these people are completely immersed in their experience -- it's like daydreaming only far more vivid and immersive, it's like dreaming but with your eyes open."

Mr Timmermann explains that while it's unclear as to whether DMT may have any clinical potential at this stage, the group hopes to take the work further by delivering a continuous infusion of DMT to extend the window of the psychedelic experience and collect more data.

The team says future studies could include more sophisticated measurements of brain activity, such as fMRI, to show which regions and networks of the brain are affected by DMT. They believe the visual cortex, the large area towards the back of the brain, is likely to be involved.

Dr Robin Carhart-Harris, head of Centre for Psychedelic Research, said: "DMT is a particularly intriguing psychedelic. The visual vividness and depth of immersion produced by high-doses of the substance seems to be on a scale above what is reported with more widely studied psychedelics such as psilocybin or 'magic mushrooms'.

"It's hard to capture and communicate what it is like for people experiencing DMT but likening it to dreaming while awake or a near-death experience is useful.

"Our sense it that research with DMT may yield important insights into the relationship between brain activity and consciousness, and this small study is a first step along that road."

https://www.sciencedaily.com/releases/2019/11/191119075305.htm

Cannabis use disorder is declining among young adolescents and young adults

October 31, 2019

Science Daily/Columbia University's Mailman School of Public Health

The prevalence of cannabis use disorder decreased in 2002 to 2016 among frequent users, according to a new study conducted at Columbia University Mailman School of Public Health. Changes in social attitudes and the traits of frequent users may explain the decline, according to researchers. This is one of the first studies to examine the general health profile of people using cannabis daily or almost daily and the trends in the prevalence of cannabis use disorder in this population. The findings are online in the journal Drug and Alcohol Dependence.

"Contrary to expectations, the frequency of cannabis use disorder among people reporting daily/almost daily use decreased significantly between 2002-2016, said Silvia Martins, MD, PhD, associate professor of Epidemiology at Columbia Mailman School. "The findings contradict the predominating hypothesis that the prevalence of DSM-IV CUD would be stable, or increase, among those using with this regularity."

Data from the National Survey on Drug Use and Health for 2002-2016 included 22,651 individuals using cannabis 300+ days in the past year. Cannabis use disorder was defined using DSM-IV criteria for cannabis abuse and/or dependence. Age categories included: 12-17, 18-25, and 26?and older.

From 2002-2016, the prevalence of cannabis use disorder among people reporting daily or almost daily use decreased across all age groups -- by 27 percent in adolescents, by 30 percent in ages 18-25, and by 37.5 percent for those age 26 and older.

"There could be several reasons behind these declining rates," noted Martins, who is also director, Substance Use Epidemiology Unit at Columbia. "First, the new national cannabis policy environment, with 33 states legalizing medical use and 10 states allowing recreational use of cannabis may have played a role in reducing stigma and perceptions of risk associated with cannabis use. "Secondly, increasing legalization may also be associated with changes in social attitudes resulting in fewer conflicts with relatives and friends around cannabis use."

For all age groups, there was no evidence of any significant reductions in the perceived need for mental health treatment among individuals using cannabis regularly (daily/near daily), or the prevalence of health problems as indicated by doctors.

The researchers also did not find evidence of significant reductions in prevalences of past-year health problems when examining health clusters separately including mental health, respiratory, digestive, cardiovascular, and infectious diseases health problems.

In contrast, there were significant decreases in self-reported driving under the influence of illegal drugs including alcohol across all age groups, ranging from a 26 percent, 29 percent and 38 percent change in adolescents, those 18-24 and age 26 and older, respectively.

https://www.sciencedaily.com/releases/2019/10/191031100512.htm

Insufficient evidence that medicinal cannabinoids improve mental health

October 28, 2019

Science Daily/The Lancet

The most comprehensive analysis of medicinal cannabinoids and their impact on six mental health disorders -- combining 83 studies including 3,000 people -- suggests that the use of cannabinoids for mental health conditions cannot be justified based on the current evidence. This is due to a lack of evidence for their effectiveness, and because of the known risks of cannabinoids.

Meta-analysis finds inadequate evidence that cannabinoids relieve depression, anxiety disorders, attention-deficit hyperactivity disorder, Tourette syndrome, post-traumatic stress disorder, or psychosis.

The most comprehensive analysis of medicinal cannabinoids and their impact on six mental health disorders -- combining 83 studies including 3,000 people -- suggests that the use of cannabinoids for mental health conditions cannot be justified based on the current evidence. This is due to a lack of evidence for their effectiveness, and because of the known risks of cannabinoids.

The new findings, published in The Lancet Psychiatry journal, find insufficient evidence medicinal cannabinoids improve disorders overall or their symptoms, although there is a very low quality evidence that pharmaceutical tetrahydrocannabinol (THC) may lead to a small improvement in symptoms of anxiety in individuals with other medical conditions, such as chronic pain or multiple sclerosis.

Medicinal cannabinoids include medicinal cannabis and pharmaceutical cannabinoids, and their synthetic derivatives, THC and cannabidiol (CBD). Around the world, these are increasingly being made available for medicinal purposes (e.g. in the United States, Australia, and Canada), including for the treatment of mental health disorders. However, there are concerns around the adverse effects of this availability, as there is a large body of evidence indicating that non-medicinal cannabis use can increase the occurrence of depression, anxiety, and psychotic symptoms.

Professor Louisa Degenhardt of the National Drug and Alcohol Research Centre (NDARC) at UNSW Sydney, Australia, and lead author of the study says: "Our findings have important implications in countries where cannabis and cannabinoids are being made available for medical use. There is a notable absence of high-quality evidence to properly assess the effectiveness and safety of medicinal cannabinoids compared with placebo, and until evidence from randomised controlled trials is available, clinical guidelines cannot be drawn up around their use in mental health disorders."

She continues: "In countries where medicinal cannabinoids are already legal, doctors and patients must be aware of the limitations of existing evidence and the risks of cannabinoids. These must be weighed when considering use to treat symptoms of common mental health disorders. Those who decide to proceed should be carefully monitored for positive and negative mental health effects of using medicinal cannabinoids." 

This study follows The Lancet Series on Drug Use, which includes a paper on cannabis where the authors assess the current and possible future public health impacts of the legalisation of cannabis production, sale, and use in the Americas. They summarise the overall evidence on medicinal use of cannabinoids, regulation, and how medicinal use may have affected recreational use.

The authors set out to examine the available evidence for all types of medicinal cannabinoids. They included all study designs and investigated the impact on remission from and symptoms of six mental health disorders in adults: depression, anxiety, attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, post-traumatic stress disorder (PTSD), and psychosis.

They included published and unpublished studies between 1980 and 2018 and included 83 eligible studies, 40 of which were randomised controlled trials (RCTs) (the others were open-label trials, where participants knew which treatment they were taking). Of the 83 studies, 42 looked at depression (including 23 RCTs), 31 looked at anxiety (17 RCTs), eight looked at Tourette syndrome (two RCTs), three were on ADHD (one RCT), 12 were on PTSD (one RCT), and 11 were on psychosis (six RCTs).

In most RCTs examining depression and anxiety, the primary reason for cannabinoid use was for another medical condition such as chronic non-cancer pain or multiple sclerosis. In the studies looking at the other four disorders, the cannabinoid was used to treat the mental health disorder. Few randomised controlled trials examined the role of pharmaceutical CBD or medicinal cannabis; most looked at THC, with or without CBD.

The authors found that pharmaceutical THC (with or without CBD) improved anxiety symptoms among individuals with other medical conditions (seven studies of 252 people), though this may have been due to improvements in the primary medical condition. The authors suggest further research should explicitly study the effects of cannabinoids on anxiety and depression.

Pharmaceutical THC (with or without CBD) worsened negative symptoms of psychosis (one study, 24 people) and did not significantly affect any other primary outcomes for the mental health disorders examined. It also increased the number of people who had adverse events (ten studies; 1,495 people) and withdrawals due to adverse events (11 studies; 1,621 people) compared with placebo across all mental health disorders examined.

The study highlights the limited evidence and the low quality of the evidence that exists around using cannabinoids for treatment of mental health conditions. There is a need for high-quality research to understand the effects of different cannabinoids on a range of outcomes for people with mental health disorders.

Professor Degenhardt says: "Cannabinoids are often advocated as a treatment for various mental health conditions. Countries that allow medicinal cannabinoid use will probably see increased demand for such use. Clinicians and consumers need to be aware of the low quality and quantity of evidence for the effectiveness of medicinal cannabinoids in treating mental health disorders and the potential risk of adverse events. Given the likely interest but scant evidence to guide patient and clinician decisions around cannabinoids for mental health, there is an urgent need for randomised controlled trials to inform whether there are benefits of cannabinoids for these indications."

The authors highlight that their analysis and conclusions are limited by the small amount of available data, small study sizes, and the differences in findings between small studies. There is no recommended approach for addressing these issues in systematic reviews, but they tried to minimise them by keeping the focus of the review narrow. They also note that most studies are based on pharmaceutical cannabinoids, rather than medicinal cannabis, but plant products are most often used by those taking cannabinoids for medicinal purposes in the USA.

In a related Comment article, Professor Deepak Cyril D'Souza of Yale University School of Medicine, USA, says: "The process of drug development in modern medicine is to first demonstrate efficacy and safety in clinical trials before using the drug clinically. With cannabinoids, it seems that the cart (use) is before the horse (evidence). For cannabinoids to be used in the treatment of psychiatric disorders they should be tested in RCTs and subjected to the same regulatory approval process as other prescription medications."

https://www.sciencedaily.com/releases/2019/10/191028213912.htm

Teen marijuana use may have next-generation effects

October 28, 2019

Science Daily/University of Washington

A new study shows how a parent's use of marijuana, past or present, can influence their child's substance use and well-being.

Substance use at any age has consequences. Studies frequently cite the negative impacts -- and occasionally tout some benefits of limited consumption -- of alcohol and marijuana.

What is less known is how patterns of alcohol or marijuana use in one phase of life can affect the next generation, even long after an individual has stopped using.

A new study by the University of Washington's Social Development Research Group shows how a parent's use of marijuana, past or present, can influence their child's substance use and well-being.

"The really important takeaway is that parent history of marijuana use is an important risk factor for kids," said Marina Epstein, lead author of the study and a project director at the SDRG, which is part of the UW School of Social Work.

The study, published online Sept. 9 in the journal Psychology of Addictive Behaviors, builds off previous work that had grouped participants according to whether, when and how often they used, and examined impacts to their health and behavior. That study found four distinct patterns: "nonusers"; "adolescent-limited" (confined to only that period of life); "late onset" (starting in their late teens, early 20s); and "chronic" (ongoing and frequent). This study is based on a subset of the original participants who have become parents, and has linked parents' past use of marijuana to their children's use of and attitudes toward alcohol and marijuana, other problem behavior, and school achievement.

The original investigation involving parents began in the 1980s when the now-adults were in fifth grade at several Seattle elementary schools. Researchers have followed the participants ever since. In 2002, when the participants were 27, SDRG recruited those who had become parents and began interviewing their children about alcohol beginning at age 6, and marijuana starting at age 10. To date, 360 children completed interviews between the ages of 10 and 20.

Children and teens of chronic users were most likely to use alcohol and marijuana themselves, as researchers had predicted. But what came as more of a surprise was the behavior of children whose parents had primarily used during adolescence: Compared to the children of nonusers, children of adults in the "adolescent-limited" group were more than 2.5 times as likely to use marijuana and 1.8 times as likely to use alcohol. This was true even after parents' current marijuana use was accounted for.

In comparison, children of chronic users were nearly 4.5 times as likely to use marijuana, and 2.75 times as likely to use alcohol, as children of nonusers.

Children in the "late-onset" group, as it turned out, were least likely to use marijuana, as were children of nonusers. They did, however, have lower grades.

"Using marijuana in adolescence is associated with a host of other problems in the present and later into adulthood," said Epstein, who was the lead author on the earlier paper that established the marijuana usage patterns. "Now we see that echoing through to their children."

According to that prior study, people who used marijuana during their teen years tended to have poorer functioning during the period in which they were actively using, and, by their early 30s, to have lower academic and economic outcomes than people who started using as adults, or who never used.

Chronic users had the worst outcomes in terms of health and quality of life, Epstein added: Poor mental health, lower academic outcomes, less financial stability and greater tendency of criminal and/or risky behaviors were associated with frequent, lifetime marijuana use.

The researchers need additional studies to uncover reasons for the relatively high usage patterns among children in the adolescent-limited group. There may be a connection between a parent's use during adolescence, for example, and their subsequent attitudes toward substance use among teenagers in general, Epstein said.

Today, 33 states have legalized marijuana in some form, often for medical purposes, and of those, 11 states -- including Washington -- have legalized it for recreational use. Those developments have implications for how parents talk to their children about marijuana and how health care providers talk to patients. Even a routine review of a child's health history could include a question about a parent's history of marijuana use -- just to consider the potential impact on the child, Epstein said.

"Now that marijuana is legal, we have to be able to talk to parents about how they're using, and to be more specific -- how much, how often, whether this is lifelong pattern," said Epstein. "The landscape of marijuana is changing, and we have to be mindful of it."

https://www.sciencedaily.com/releases/2019/10/191028164418.htm

The frostier the flower, the more potent the cannabis

Advanced microscopy reveals internal structures of cannabis biochemical factories

October 28, 2019

Science Daily/University of British Columbia

Cannabis flowers with the most mushroom-shaped hairs pack the biggest cannabinoid and fragrance punch, according to new research from the University of British Columbia.

While the cannabis leaf is iconic, it's the chemicals produced by the tiny, frostlike hairs on cannabis flowers that give the plant its psychoactive and medicinal properties and distinctive smell.

In a study published in The Plant Journal, UBC researchers have revealed the unique structures and chemical outputs of the different types of hairs, or glandular trichomes, for the first time.

Their findings confirm what many cannabis connoisseurs have long suspected: that the largest, mushroom-shaped stalked glandular trichomes are the richest source of THC- and CBD-forming metabolites and fragrance-giving terpenes.

"Despite its high economic value, our understanding of the biology of the cannabis plant is still in its infancy due to restricted legal access," said co-lead author Teagen Quilichini, a postdoctoral fellow at UBC botany and Anandia Laboratories Inc. "Trichomes are the biochemical factories of the cannabis plant and this study is the foundation for understanding how they make and store their valuable products."

Previous research had identified three types of glandular trichomes based on their appearance -- bulbous, sessile and stalked -- but their relative contributions to the chemical production of cannabis flowers were unknown.

For this study, the UBC researchers used a combination of advanced microscope techniques and chemical profiling to examine the internal structures and development of individual trichomes in a fast-flowering hemp variety of Cannabis sativa called 'Finola.'

They found that under ultraviolet light, the stalked trichomes emitted a bright blue colour and contained a large, distinctive pie-shaped disc of cells. The smaller sessile trichomes, which do not have a stalk, emitted a red colour, had smaller secretory discs, and produced fewer fragrant terpenes.

"We saw that stalked glandular trichomes have expanded "cellular factories" to make more cannabinoids and fragrant terpenes," said co-lead author Sam Livingston, a PhD candidate at UBC botany. "We also found that they grow from sessile-like precursors and undergo a dramatic shift during development that can be visualized using new microscopy tools.

As a result, Livingston explains, UV light could be used to monitor trichome maturity on flowers and inform optimal harvest times.

The researchers also conducted a gene expression analysis to investigate how instructions in trichome DNA are converted into the plant's biochemical products. They found that the stalked trichomes in Finola were strongly geared towards making cannabidiolic acid (CBDA) and terpenes.

"We found a treasure trove of genes that support the production of cannabinoids and terpenes," said principal investigator Anne Lacey Samuels, a botany professor at UBC. "With further investigation, this could be used to produce desirable traits like more productive marijuana strains or strains with specific cannabinoid and terpene profiles using molecular genetics and conventional breeding techniques."

Next, the researchers will investigate how trichomes export and store the metabolites they produce.

"Trichomes store the metabolites in their cell walls," said Livingston. "And what's really astounding is that such high levels of product should be toxic to the cells, so we want to understand how they manage this."

The research was funded by the Natural Science and Engineering Research Council of Canada (NSERC) and a MITACS Elevate postdoctoral fellowship, in partnership with Anandia Laboratories.

https://www.sciencedaily.com/releases/2019/10/191028092408.htm

Years of education may impact drinking behavior and risk of alcohol dependence

October 25, 2019

Science Daily/Springer

Higher educational attainment -- spending more years in education -- may impact people's drinking behaviour and reduce their risk of alcohol dependence, according to a study published in Molecular Psychiatry.

Alcohol consumption is a major risk factor for death and disability worldwide. Identifying factors associated with how much, how often and what people drink may be important for developing and improving intervention and treatment strategies. Previous studies have suggested that educational attainment may influence drinking, but with conflicting results.

To assess the possible effects of educational attainment on alcohol use behaviours and alcohol dependence, a team of researchers at the National Institutes of Health, USA used two -sample Mendelian randomisation statistical methods. The authors used genetic data generated by international genomics consortiums and examined a set of 53 genetic variants previously associated with differences in educational attainment, and their links with certain alcohol use behaviours. They tested which of the 53 variants associated with educational attainment in one study were present in the DNA of people who reported different alcohol use behaviours in the other study.

Dr Falk Lohoff, the corresponding author said: "Using data from a total of approximately 780,000 study participants, we found that genetic variants associated with an additional 3.61 years of schooling were associated with an approximately 50% reduced risk of alcohol dependence. The presence of genetic variants associated with educational attainment also affected the pattern of alcohol use and type of alcoholic beverage people consumed."

The authors showed that genetic variants associated with higher educational attainment were not associated with the total amount of alcohol people drank in a week, but with a reduced frequency of binge drinking (consuming six or more units of alcohol per session), frequency of memory loss due to drinking, total drinks consumed per drinking day and weekly intake of distilled spirits, beer and cider. The association with drinking fewer spirits was more pronounced in women than it was in men, while decreased average weekly beer plus cider intake was more pronounced in men than women.

Genetic variants associated with increased educational attainment were also associated with more frequent drinking in both men and women, with drinking alcohol with meals, especially in men, and with higher consumption of wine. Dr Lohoff said: "It is important to understand that while these genetic variants allow us to investigate the possible effect of educational attainment on alcohol consumption and alcohol dependence, this doesn't mean that educational attainment can't be modified. The possible effect of educational attainment on drinking that we show in this study, suggests that increasing educational attainment may be a useful target for prevention programs against problematic alcohol use, alcohol dependence, and their consequences."

The authors caution that as the genetic data examined in this study was obtained from people from Anglophone countries, the applicability of the findings to other countries may be limited. Replication of the findings using data from different countries and ethnicities is necessary.

As educational attainment only measures completed years of schooling, determining how various aspects of education differently impact alcohol consumption was not possible, but should be investigated in future studies, the authors add.

https://www.sciencedaily.com/releases/2019/10/191025075838.htm

Even short-term 'vaping' causes inflammation in non-smokers

October 16, 2019

Science Daily/Ohio State University Wexner Medical Center

E-cigarette (e-cig) use is rising at concerning levels among both smokers and non-smokers, and new research data suggests that even short-term e-cig use can cause cellular inflammation in never-smoker adults.

Researchers at The Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James) report the first evidence of biological changes correlated with e-cig use in never-smokers in the journal Cancer Prevention Research on Oct. 16.

Using a procedure called bronchoscopy to test for inflammation and smoking-related effects, researchers report a measurable increase in inflammation after four weeks of e-cig use (without nicotine or flavors). Although the magnitude of change was small compared with a control group, the pilot data suggests that even short-term usage can result in inflammatory changes at a cellular level. Inflammation from smoking is an important driver of lung cancer and other respiratory disease development.

Peter Shields, MD, senior author of the study and deputy director of the OSUCCC -- James, says any level of cellular inflammation correlated with e-cig use is concerning because the biological and health effects of e-cig constituents such as propylene glycol and vegetable glycerine -- while "generally regarded as safe" by the U.S. Food and Drug Administration (FDA) when used in foods and cosmetics -- are unknown when heated and inhaled with e-cigs. Researchers note that even in this small study, there were observable effects.

"The implication of this study is that longer term use, increased daily use and the addition of flavors and nicotine may promote additional inflammation," says Shields. "The general perception among the public is that e-cigs are 'safer' than cigarettes. The reality is the industry is changing so fast ¬- and with minimal regulation -- that usage is outpacing the rate of our scientific understanding. It's becoming a public health crisis we should all take very seriously from a general pulmonary health, cancer risk and addiction perspective. E-cigs may be safer than smoking, but that is not the same as safe, and we need to know how unsafe they are."

With the recent reports of lung disease and deaths associated with vaping, the effects of vaping nicotine and marijuana oils makes this research more critical.

For this pilot study, OSUCCC -- James researchers recruited 30 healthy, non-smoking volunteers to directly assess the impact of tobacco and e-cig use on the lungs through bronchoscopy, an outpatient test in which a doctor inserts a thin tube through the nose or mouth to view the airways. A small sample of lung cells is collected from fluid in the lungs. Participants were randomized to a four-week intervention with e-cigs containing only 50% propylene glycol (PG) or 50% vegetable glycerine (VG) without nicotine or flavors. (PG and VG are used in e-cig devices.) Results from these tests were then compared to a separate control group of never-smokers. Researchers did not see levels of inflammation higher than the controls, but there was an increase in inflammation among the users who inhaled more of the e-cigs.

In August 2016, the FDA was granted regulatory authority over e-cig product design. Data about e-cig toxicity in humans is urgently needed to establish scientific evidence-based regulatory policies.

"Human clinical trials can provide valuable information regarding actual toxicant exposure and risk for disease. Through the randomized clinical trial of healthy never-smokers over a month, we found that an increase in urinary propylene glycol, a marker of inhalation-e-cig intake, was significantly correlated with increased inflammatory response in the lung," says Min-Ae Song, first author of the manuscript and environmental health researcher at the Ohio State College of Public Health. "Future studies could be of longer duration, include an assessment of flavors, the effect by varying ratios of propylene glycol and vegetable glycerine, and examine randomization of smokers to e-cigs."

https://www.sciencedaily.com/releases/2019/10/191016104252.htm

Potential therapy to treat detrimental effects of marijuana

October 15, 2019

Science Daily/University of Maryland School of Medicine

A new study using a preclinical animal model suggests that prenatal exposure to THC, the psychoactive component of cannabis, makes the brain's dopamine neurons (an integral component of the reward system) hyperactive and increases sensitivity to the behavioral effects of THC during pre-adolescence.

As a growing number of U.S. states legalize the medicinal and recreational use of marijuana, an increasing number of American women are using cannabis before becoming pregnant and during early pregnancy often to treat morning sickness, anxiety, and lower back pain. Although emerging evidence indicates that this may have long-term consequences for their babies' brain development, how this occurs remains unclear.

A University of Maryland School of Medicine study using a preclinical animal model suggests that prenatal exposure to THC, the psychoactive component of cannabis, makes the brain's dopamine neurons (an integral component of the reward system) hyperactive and increases sensitivity to the behavioral effects of THC during pre-adolescence. This may contribute to the increased risk of psychiatric disorders like schizophrenia and other forms of psychosis later in adolescence that previous research has linked to prenatal cannabis use, according to the study published today in journal Nature Neuroscience.

The team of researchers, from UMSOM, the University of Cagliari (Italy) and the Hungarian Academy of Sciences (Hungary), found that exposure to THC in the womb increased susceptibility to THC in offspring on several behavioral tasks that mirrors the effects observed in many psychiatric diseases. These behavioral effects were caused, at least in part, by hyperactivity of dopamine neurons in a brain region called the ventral tegmental area (VTA), which regulates motivated behaviors.

More importantly, the researchers were able to correct these behavioral problems and brain abnormalities by treating experimental animals with pregnenolone, an FDA-approved drug currently under investigation in clinical trials for cannabis use disorder, schizophrenia, autism, and bipolar disorder.

"This is an exciting finding that suggests a therapeutic approach for children born to mothers who used cannabis during pregnancy," said Joseph Cheer, PhD, a Professor of Anatomy & Neurobiology and Psychiatry at the University of Maryland School of Medicine. "It also raises important questions that need to be addressed such as how does pregnenolone exert its effects and how can we improve its efficacy? Do these detrimental effects persist into adulthood, and if so, could they also be treated in a similar way?"

The researchers concluded that as physicians caution pregnant women against alcohol and cocaine intake because of their detrimental effects to the fetus, they should also, based on these new findings, advise them on the potential negative consequences of using cannabis 

Vaping-associated lung injury may be caused by toxic chemical fumes

October 2, 2019

Science Daily/Mayo Clinic

Research into the pathology of vaping-associated lung injury is in its early stages, but a Mayo Clinic study published in The New England Journal of Medicine finds that lung injuries from vaping most likely are caused by direct toxicity or tissue damage from noxious chemical fumes.

Researchers reviewed lung biopsies from 17 patients, all of whom had vaped and were suspected to have vaping-associated lung injury. The study was the first to examine a group of biopsies from patients with lung injury due to vaping. Researchers found no evidence of tissue injury caused by accumulation of lipids -- fatty substances such as mineral oils -- which has been suspected as a possible cause of the lung injuries associated with vaping.

"While we can't discount the potential role of lipids, we have not seen anything to suggest this is a problem caused by lipid accumulation in the lungs. Instead, it seems to be some kind of direct chemical injury, similar to what one might see with exposures to toxic chemical fumes, poisonous gases and toxic agents," says Brandon Larsen, M.D., Ph.D., a surgical pathologist at Mayo Clinic Arizona, and a national expert in lung pathology.

The Centers for Disease Control and Prevention (CDC) has reported more than 800 lung injury cases that are associated with electronic cigarette use, or vaping, over the past few months. Twelve deaths have been confirmed in 10 states, and investigative findings suggest that products containing THC -- the principal psychoactive compound in marijuana -- or other cannabis oils, such as cannabidiol or CBD, may play a role in the outbreak.

Some states have imposed a temporary ban on the sale of e-cigarettes or flavored liquids used in them while researchers investigate health-related issues. The Food and Drug Administration is considering a ban on all nontobacco flavors of vaping liquids. The CDC recommends that e-cigarettes should not be used by children, young adults, pregnant women or adults who don't already use tobacco products. The American Lung Association has warned that e-cigarettes are not safe and can cause irreversible lung damage and disease.

Of the 17 biopsies that were examined, two were from Mayo Clinic patients. The others were from hospitals around the country that were sent to Mayo Clinic for further investigation. All of the patients had vaped, and 71% had vaped with marijuana or cannabis oils. All showed acute lung injury, including pneumonitis, and two of the patients died.

"We were not surprised by what we found, regarding toxicity," says Dr. Larsen, senior author of the study. "We have seen a handful of cases, scattered individual cases, over the past two years where we've observed the same thing, and now we are seeing a sudden spike in cases. Our study offers the first detailed review of the abnormalities that may be seen in lung biopsies to help clinicians and pathologists make a diagnosis in an appropriate clinical context."

Vaping-associated lung injury can be difficult to diagnose, unless clinicians and pathologists are armed with information beforehand, Dr. Larsen says.

"This is a public health crisis, and a lot of people are working frantically around the clock to find out what the culprit or culprits could be -- and what chemicals may be responsible," Dr. Larsen says. "Based on what we have seen in our study, we suspect that most cases involve chemical contaminants, toxic byproducts or other noxious agents within vape liquids."

In the meantime, the public should heed what leading medical organizations and public health agencies are saying about the dangers of vaping.

"Everyone should recognize that vaping is not without potential risks, including life-threatening risks, and I think our research supports that," he says. "It would seem prudent based on our observations to explore ways to better regulate the industry and better educate the public, especially our youth, about the risks associated with vaping."

https://www.sciencedaily.com/releases/2019/10/191002181133.htm

Cannabis study reveals how CBD offsets the psychiatric side-effects of THC

September 30, 2019

Science Daily/University of Western Ontario

Researchers at Western University have shown for the first time the molecular mechanisms at work that cause cannabidiol, or CBD, to block the psychiatric side-effects caused by tetrahydrocannabinol (THC), the main psychoactive chemical in cannabis.

It has been previously shown that strains of cannabis with high levels of THC and low levels of CBD can cause increased psychiatric effects, including paranoia, anxiety and addictive-behaviours, but why that was occurring was not fully understood.

Steven Laviolette, PhD, and his research team used rats to investigate the role of a molecule in the brain's hippocampus called extracellular-signal regulated kinase (ERK) which triggers the neuropsychiatric effects of THC.

"For years we have known that strains of cannabis high in THC and low in CBD were more likely to cause psychiatric side-effects," said Laviolette, a professor at Western's Schulich School of Medicine & Dentistry. "Our findings identify for the first time the molecular mechanisms by which CBD may actually block these THC-related side-effects."

The research, published in the Journal of Neuroscience demonstrates that rats that were given THC had higher levels of activated ERK, showed more anxiety behaviours and were more sensitive to fear-based learning. Rats that were given both CBD and THC acted like the control rats: they had normal levels of activated ERK, less anxiety behaviours, and were less sensitive to fear-based learning.

Based on these results, the research team proposes that CBD blocks the ability of THC to overstimulate the ERK pathway in the hippocampus and thus prevent its negative side-effects.

"Our findings have important implications for prescribing cannabis and long-term cannabis use. For example, for individuals more prone to cannabis-related side-effects, it is critical to limit use to strains with high CBD and low THC content," said Laviolette. "More importantly, this discovery opens up a new molecular frontier for developing more effective and safer THC formulations."

PhD Candidate and Vanier Scholar Roger Hudson, lead author on the study, says another interesting finding was that CBD alone had no effect on the ERK pathway. "CBD by itself had no effect," he said. "However, by co-administering CBD and THC, we completely reversed the direction of the change on a molecular level. CBD was also able to reverse the anxiety-like behaviour and addictive-like behaviour caused by the THC."

Laviolette says they will be following up these studies by continuing to identify the specific features of this molecular mechanism. The research team will examine ways to formulate THC with fewer side effects and to improve the efficacy of CBD-derived therapies.

https://www.sciencedaily.com/releases/2019/09/190930131115.htm

Older adults with COPD more likely to use synthetic cannabinoids

September 23, 2019

Science Daily/St. Michael's Hospital

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that's often associated with a variety of health problems, including chronic muscle pain and insomnia. Psychoactive drug classes, like cannabinoids, are often prescribed to help reduce pain, promote sleep and decrease breathlessness. A study has found that older adults with COPD were twice as likely to use prescription synthetic oral cannabinoids compared to older adults without COPD, raising safety concerns.

A study published today in Drugs & Aging found that older adults in Ontario with chronic obstructive pulmonary disease (COPD) were twice as likely to use prescription synthetic oral cannabinoids compared to older adults without COPD.

Using provincial health administrative databases, researchers found that while synthetic oral cannabinoid use was relatively low among adults over the age of 66 with COPD (0.6 per cent), this group was twice as likely to be using these drugs compared to adults of the same age without COPD (0.3 per cent).

The research led by St. Michael's Hospital in Toronto and the not-for-profit research institute ICES raises concerns about the use of synthetic cannabinoids, human-made versions of tetrahydrocannabinol (THC) -- a key chemical in marijuana. When ingested, THC activates receptors in the central nervous system, producing a variety of potential effects including sedation, anxiety, muscle weakness and pain relief.

COPD is a progressive lung disease that causes breathing difficulty, but it can be associated with a variety of other problems too, like chronic muscle pain and insomnia. Psychoactive drug classes, like cannabinoids, are often prescribed to help reduce pain, promote sleep and decrease difficult-to-control breathlessness.

"Our study showed that patients and clinicians are turning to cannabinoids more frequently to manage the symptoms associated with COPD, but little is known about the potential dangers associated with this medication class," said Dr. Nicholas Vozoris, lead author, a respirologist at St. Michael's and an associate scientist at the hospital's Li Ka Shing Knowledge Institute and ICES.

"Previous studies by our team found that other psychoactive drugs, like opioids and benzodiazepines, are frequently used in COPD. We wanted to find out if this was the case too for synthetic oral cannabinoids."

Researchers also found that synthetic oral cannabinoids were used more frequently in subgroups of older adults with COPD at heightened risk for adverse events, such as those with psychiatric disease and those receiving other sedating psychoactive medications.

"Safety recommendations provided for these medications advise against prescribing cannabinoids in these groups," said Dr. Vozoris. "And yet these individuals with COPD are being exposed at greater rates."

The team also found that synthetic oral cannabinoids were used more often in potentially concerning ways among older adults with COPD, including more frequently at higher doses and for longer durations of time.

"Though the use of these drugs isn't too frequent today, without careful monitoring of the way they're being prescribed and used now, we could end up with larger problems in the future," Dr. Vozoris said.

As one of the first studies to describe the use of this drug class in individuals with COPD, Dr. Vozoris said these results provide a basis for future research to examine the effects of oral synthetic cannabinoid use on respiratory outcomes among individuals with COPD.

The results also provide a foundation for clinicians to make more informed decisions regarding the use of this drug class.

"We hope that clinicians read our paper and walk away with a better understanding of this drug class," said Dr. Vozoris. "We'd like them to reflect on their own prescribing practices and ensure cannabinoid drugs are used and prescribed with vigilance."

https://www.sciencedaily.com/releases/2019/09/190923130929.htm

CBD may alleviate seizures, benefit behaviors in people with neurodevelopmental conditions

September 18, 2019

Science Daily/University of North Carolina Health Care

A marijuana plant extract, also known as cannabidiol (CBD), is being commonly used to improve anxiety, sleep problems, pain, and many other neurological conditions. Now UNC School of Medicine researchers show it may alleviate seizures and normalize brain rhythms in Angelman syndrome, a rare neurodevelopmental condition.

Published in the Journal of Clinical Investigation, the research conducted using Angelman syndrome animal models shows that CBD could benefit kids and adults with this serious condition, which is characterized by intellectual disability, lack of speech, brain rhythm dysfunction, and deleterious and often drug-resistant epilepsy.

"There is an unmet need for better treatments for kids with Angelman syndrome to help them live fuller lives and to aid their families and caregivers," said Ben Philpot, PhD, Kenan Distinguished Professor of Cell Biology and Physiology and associate director of the UNC Neuroscience Center. "Our results show CBD could help the medical community safely meet this need."

CBD, which is a major phytocannabinoid constituent of cannabis, has already shown to have anti-epileptic, anti-anxiety, and anti-psychotic effects. And in 2018, the FDA approved CBD for the treatment of seizures associated with two rare forms of epilepsy, but little is known about the potential anti-seizure and behavioral effects of CBD on Angelman symptom.

The Philpot lab is a leader in the creation of genetically modified mouse models of neurodevelopmental disorders, and they use these models to identify new treatments for various diseases, such as Rett, Pitt-Hopkins, and Angelman syndromes.

In experiments led by first author Bin Gu, PhD, a postdoctoral fellow in the Philpot lab, the UNC-Chapel Hill researchers systematically tested the beneficial effects of CBD on seizures, motor deficits, and brain activity abnormalities -- as measured by EEG -- in mice that genetically model Angelman syndrome, with the expectation that this information could guide eventual clinical use.

The researchers found that a single injection of CBD substantially lessened seizure severity in mice when the seizures were experimentally triggered by elevated body temperature or loud sounds. A typical anti-convulsant dose of CBD (100 mg/kg) caused mild sedation in mice but had little effect on motor coordination or balance. CBD also restored the normal brain rhythms which are commonly impaired in Angelman syndrome.

"We're confident our study provides the preclinical framework necessary to better guide the rational development of CBD as a therapy to help lessen seizures associated with Angelman syndrome and other neurodevelopmental disorders," Gu said.

Philpot and Gu added that patients and families should always seek advice from their physician before taking any CBD products, and that a human clinical trial is needed to fully understand its efficacy and safety.

https://www.sciencedaily.com/releases/2019/09/190918105631.htm

Scientists find psychiatric drugs affect gut contents

September 9, 2019

Science Daily/European College of Neuropsychopharmacology

Scientists have found that antidepressants and other psychiatric drugs can change the quantity and composition of gut bacteria in rats. These results raise questions about the specificity of psychoactive drug action, and if confirmed in humans whether psychiatrists might need to consider the effects on the body before prescribing. The research team is currently carrying out a large-scale human observational study which aims to answer the questions posed by these findings. This work is presented at the ECNP Conference in Copenhagen following part-publication in a peer-review journal (see Notes for Editors).

Scientists are increasingly finding that the microbiome -- the bacterial content of the digestive system -- has effects on other functions in the body, and vice versa. A group of Irish-based scientists has given 7 groups of rats (8 animals in each group) normal or slightly elevated levels of individual psychopharmaceuticals, including Lithium, valproate, and the antidepressants fluoxetine (Prozac) and escitalopram. After 4 weeks of treatment, the scientists examined the gut bacteria -- the microbiome -- to see what the effects the drugs had (see abstract for experimental details).

They found that some drugs consistently increased the number of certain bacteria in the gut. For example, lithium and valproate (both used for bipolar disorder) increased the numbers of Clostridium and other bacteria. In contrast, the (SSRI) antidepressants escitalopram and fluoxetine significantly inhibited growth of bacterial isolated strains such as E.coli.

Describing the work, lead researcher, Ms Sofia Cussotto (University College, Cork) said:

"We found that certain drugs, including the mood stabiliser lithium and the antidepressant fluoxetine, influenced the composition and richness of the gut microbiota. Although some psychotropic drugs have been previously investigated in in vitro settings, this is the first evidence in an animal model.

There are several implications of this work. First of all, some studies have shown that depressed or schizophrenic patients can have altered microbiota composition, therefore psychotropic drugs might work on intestinal microbes as part of their mechanisms of action. Of course, this has to be proved. Given that antidepressants, for example work on some people but not others, making an allowance for microbiome may change an individual's response to antidepressants. On the other hand, microbiome-targeting effects might be responsible for the side effects associated with these medications. All these hypotheses have to be tested in preclinical models and in humans, and this is our next step."

Commenting, Professor Serguei Fetissov from Rouen University, France said:

"These early data are intriguing, and worthy of further investigation. At the moment it would be premature to ascribe a direct role of gut bacteria in the action of antidepressant drugs until this work can be reproduced in humans, which is what the authors now hope to do. The composition of gut microbiota is very sensitive to the metabolic processes of the body and can change naturally, through drug-induced metabolic shifts in the brain and other organs. Some of the changes reported here, for example increased Christensenella, can be indeed beneficial, but overall significance of drug-induced changes of bacterial composition on the metabolic and mental health needs further research.

https://www.sciencedaily.com/releases/2019/09/190909095019.htm

Medical marijuana laws impact use among sexual minorities differently than heterosexuals

Daily marijuana use is seven times higher among bisexual women than heterosexual women

September 4, 2019

Science Daily/Columbia University's Mailman School of Public Health

Bisexual women had higher rates of past-year and daily marijuana use compared to heterosexual women, according to a study just published at Columbia University Mailman School of Public Health. Gay/lesbian women were also more likely to report daily marijuana use and past year medical marijuana use than heterosexual women. While previous research has explored the association between state-level medical marijuana laws (MMLs) and marijuana use (MU) and MU disorder (MUD) among the general U.S. population, this is the first to explore this relationship for lesbian, gay and bisexual (LGB) individuals, including gender differences. The findings are online in the journal Drug and Alcohol Dependence.

"Our work builds on the Institute of Medicine report highlighting the importance of conducting additional research on LGB populations across the life course," said Morgan Philbin, PhD, assistant professor of Sociomedical Sciences at Columbia's Mailman School. ""While research has explored how LGB discrimination polices may impact substance use, less work has explored how substance use policies may impact LGB men and women differently than heterosexuals."

The researchers analyzed data from 126,463 adults 18 and older in the 2015-2017 National Survey on Drug Use and Health to study the odds of past-year marijuana use, any past-year medical marijuana use, daily/near-daily marijuana use, and marijuana use disorder. They also tested the interaction between residence in a state with medical marijuana laws and sexual identity.

When the researchers examined the relationship between state MML status and MU outcomes they found that gay/lesbian women in MML states had higher daily/near-daily (300+ days/year) MU than gay/lesbian women in non-MML states while bisexual women in MML states had higher past-year use than bisexual women in non-MML states; both lesbian/gay and bisexual women in MML states had higher medical MU than those in non-MML states.

"We further extended these findings to estimate daily/near-daily MU prevalence, which was seven times higher among bisexual women than heterosexual women and 2.3 times as high for bisexual men compared to heterosexual men," noted Silvia Martins, MD, PhD, associate professor of Epidemiology and senior author.

Past-year marijuana use was 10 percent among heterosexual women, 26 percent among gay/lesbian women and 40 percent among bisexual women. Daily use was lower among heterosexual women (1.5 percent) compared to lesbians (6 percent) and bisexual women (10 percent). Similar patterns emerged for past-year marijuana use disorder.

Past-year marijuana use for medical reasons was reported by slightly more than one percent of heterosexual women, 5 percent of lesbian/gay women and 5.5 percent of bisexual women.

Compared to heterosexual men (17 percent), past-year use marijuana was higher among bisexual men, (30 percent) and gay men (29 percent). Daily marijuana use among men was highest among bisexual men (9 percent) followed by gay (7 percent) and heterosexual men (4 percent). Any past-year medical marijuana use was 2 percent among heterosexual men, 5 percent among gay men and 4 percent among bisexual men.

Rates of daily marijuana use or marijuana use disorder for gay men did not differ significantly in states that had passed medical marijuana laws compared to states that had not passed these laws.

While beyond the scope of these analysis, the difference in policy effects of medical marijuana laws for bisexual women compared to heterosexual women may be a result of the high levels of stigma faced by bisexual women, according to the researchers. This could result in self-medication with medical marijuana even in states without MMLs if LGB adults are in part using marijuana to alleviate sexual minority stress.

"Our results support existing literature by demonstrating that bisexual women have higher marijuana use disorder compared to heterosexual women. This is part of a larger health burden, as bisexual women are twice as likely to have co-occurring mental health and substance use disorders yet often have little contact with service providers," observed Philbin.

"This study represents an important contribution to the literature on the structural determinants of substance use for LGB individuals and demonstrates the need to allocate resources that target sexual minority women, especially as medical marijuana laws and recreational marijuana laws continue to change at the state level," said Martins. "Future surveys that capture how individuals identify will help us pinpoint how state-level marijuana policies may differentially impact specific sub-populations, ultimately advancing the development of more health-promoting policies for all."

https://www.sciencedaily.com/releases/2019/09/190904113222.htm

Cannabis may hold promise to treat PTSD but evidence lags behind use

September 3, 2019

Science Daily/University College London

As growing numbers of people are using cannabis to treat post-traumatic stress disorder (PTSD), a new UCL study reports that prescriptions are not backed up by adequate evidence.

The systematic review, published in the Journal of Dual Diagnosis, finds that the active components of cannabis, called cannabinoids, may hold promise as a treatment for PTSD, particularly for reducing nightmares and helping people sleep, but more research is needed to determine whether these drugs should be used in routine clinical practice.

"There has been a recent surge of interest in the use of cannabinoids to treat PTSD, particularly from military veterans, many of whom are already self-medicating or obtaining prescriptions in some American states," said the study's lead author, Dr Chandni Hindocha (UCL Clinical Psychopharmacology Unit).

"The lack of evidence supporting cannabis as a PTSD treatment is striking given the vast interest in it, and the large unmet need for better PTSD treatments," she said.

PTSD is a potentially debilitating condition affecting roughly 1% of the UK population, typically consisting of re-experiencing a traumatic event through intrusive memories, flashbacks or nightmares, and often involves hyper-reactivity (a state of constant vigilance) and insomnia.

Psychotherapies (talking therapies) including trauma-focussed cognitive-behavioural therapy have been shown to be effective for PTSD. However, not everyone can access talking therapies and they do not work for everyone, so many people still need to take prescribed medications. Existing drugs approved for PTSD do not work for everyone, and can have side effects, so researchers say there is an urgent need to identify new treatments.

A growing number of people have turned to cannabinoids, which is an approved treatment for PTSD in most states in the USA that permit medical cannabis.

Cannabinoids, the active ingredients of cannabis, which include tetrahydrocannabinol (THC) and cannabidiol (CBD), may be helpful at treating PTSD as they can change how the brain processes memories. The cannabinoids act on the brain's in-built endocannabinoid system which also regulates other brain functions that are affected by PTSD.

The research team conducted a systematic review of all studies where someone with a PTSD diagnosis has been using a cannabinoid to reduce their symptoms, and they assessed the quality of each study.

They found 10 studies that met their criteria, which cover a range of products including smoked cannabis, THC or CBD separately in oil or pill form, and a synthetic cannabinoid called nabilone.

Every study had medium to high risk of bias and all were assessed as low in quality due to limitations such as small sample size, retrospective study design, lack of a control group or placebo, short follow-up periods, and not reporting other medication use or addiction. Only one study was a randomised controlled trial, investigating nabilone, but it was in a small sample over a relatively short period of time.

The researchers say there are still many unanswered questions about the safety and efficacy of cannabis-based medications for PTSD, and potential long-term effects such as addiction or a risk of psychosis.

The existing evidence shows promise, however, as some studies showed that cannabis products appeared to reduce PTSD symptoms such as insomnia and nightmares.

"Based on the evidence, we cannot yet make any clinical recommendations about using cannabinoids to treat PTSD. Current prescribing of cannabinoids for PTSD is not backed up by high quality evidence, but the findings certainly highlight the need for more research, particularly long-term clinical trials," said the study's senior author, Dr Michael Bloomfield (UCL Psychiatry and the Traumatic Stress Clinic, St Pancras Hospital).

"Many of these studies have been conducted in military veterans, but we also need to be looking at other groups, as PTSD can vary depending on the nature of the trauma so different approaches may benefit different groups," he added.

Dr Hindocha added: "Unfortunately, medicinal uses of cannabis have historically been difficult to study due to legal restrictions, so it could take a long time before there is enough evidence to support clinical recommendations. New approaches are needed to make the most of existing evidence in the meantime."

The study was conducted by researchers at UCL and the University of Amsterdam, and was supported by the National Institute for Health Research UCLH Biomedical Research Centre.

https://www.sciencedaily.com/releases/2019/09/190903194249.htm

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