Providers show interest in prescribing therapeutic cannabinoids

December 10, 2018

Science Daily/George Washington University

The cannabis plant and its derivatives have been used in medicinal treatments for millennia. With the recent legalization of medical marijuana in 33 states across the country, as well as Washington, D.C., several specialties are weighing the possibilities of integrating cannabinoids into patient therapies, including dermatology.

 

Recent research has identified potential uses for cannabinoids, which are derived either from the resin of the cannabis plant or synthetically produced in the lab, in treatment for conditions such as psoriasis, atopic dermatitis, and wound healing.

 

A team from the George Washington University (GW) recently conducted a web-based survey to determine the perspectives of dermatology providers on the uses and potential benefits of cannabinoids as therapies in dermatology, as well as their knowledge about cannabinoids in general.

 

"Patients are enthusiastic about exploring the use of cannabinoids as part of their therapeutic armamentarium, and even initiate the conversation with their dermatologists," said Adam Friedman, MD, professor of dermatology at the GW School of Medicine and Health Sciences and senior author on the study.

 

Five hundred and thirty-one participants answered 19 multiple choice questions on demographics as well as perspectives on and knowledge of cannabinoids use in dermatology.

 

The survey revealed that, overall, dermatology providers are interested in learning more about and recommending cannabinoids to their patients. However, they are currently lacking in knowledge on cannabinoids and many posed concerns about the associated societal stigmas, limiting their pursuit of these active agents as potential treatments.

 

These results, the authors wrote, show the need for further education and research on the benefits and risks of cannabinoids in dermatology.

 

"The use of cannabis in medicine is a hot topic," Friedman said. "With the amount of mainstream coverage and the interest from patients, it's important that dermatology providers are able to make the right call when it comes to education and recommending cannabinoids to their patients."

https://www.sciencedaily.com/releases/2018/12/181210122857.htm

Vicious circle leads to loss of brain cells in old age

Researchers determine how dangerous inflammations in the brain are caused

Science Daily/August 31, 2018

University of Bonn

The so-called CB1 receptor is responsible for the intoxicating effect of cannabis. However, it appears to act also as a kind of "sensor" with which neurons measure and control the activity of certain immune cells in the brain. A recent study by the University of Bonn at least points in this direction. If the sensor fails, chronic inflammation may result -- probably the beginning of a dangerous vicious circle. The publication appears in the journal Frontiers in Molecular Neuroscience.

 

The activity of the so-called microglial cells plays an important role in brain aging. These cells are part of the brain's immune defense: For example, they detect and digest bacteria, but also eliminate diseased or defective nerve cells. They also use messenger substances to alert other defense cells and thus initiate a concerted campaign to protect the brain: an inflammation.

 

This protective mechanism has undesirable side effects; it can also cause damage to healthy brain tissue. Inflammations are therefore usually strictly controlled. "We know that so-called endocannabinoids play an important role in this," explains Dr. Andras Bilkei-Gorzo from the Institute of Molecular Psychiatry at the University of Bonn. "These are messenger substances produced by the body that act as a kind of brake signal: They prevent the inflammatory activity of the glial cells."

 

Endocannabinoids develop their effect by binding to special receptors. There are two different types, called CB1 and CB2. "However, microglial cells have virtually no CB1 and very low level of CB2 receptors," emphasizes Bilkei-Gorzo. "They are therefore deaf on the CB1 ear. And yet they react to the corresponding brake signals -- why this is the case, has been puzzling so far."

 

Neurons as "middlemen"

The scientists at the University of Bonn have now been able to shed light on this puzzle. Their findings indicate that the brake signals do not communicate directly with the glial cells, but via middlemen -- a certain group of neurons, because this group has a large number of CB1 receptors. "We have studied laboratory mice in which the receptor in these neurons was switched off," explains Bilkei-Gorzo. "The inflammatory activity of the microglial cells was permanently increased in these animals."

 

In contrast, in control mice with functional CB1 receptors, the brain's own defense forces were normally inactive. This only changed in the present of inflammatory stimulus. "Based on our results, we assume that CB1 receptors on neurons control the activity of microglial cells," said Bilkei-Gorzo. "However, we cannot yet say whether this is also the case in humans."

 

This is how it might work in mice: As soon as microglial cells detect a bacterial attack or neuronal damage, they switch to inflammation mode. They produce endocannabinoids, which activate the CB1 receptor of the neurons in their vicinity. This way, they inform the nerve cells about their presence and activity. The neurons may then be able to limit the immune response. The scientists were able to show that neurons similarly regulatory the other major glial cell type, the astroglial cells.

 

During ageing the production of cannabinoids declines reaching a low level in old individuals. This could lead to a kind of vicious circle, Bilkei-Gorzo suspects: "Since the neuronal CB1 receptors are no longer sufficiently activated, the glial cells are almost constantly in inflammatory mode. More regulatory neurons die as a result, so the immune response is less regulated and may become free-running."

 

It may be possible to break this vicious circle with drugs in the future. It is for instance hoped that cannabis will help slow the progression of dementia. Its ingredient, tetrahydrocannabinol (THC), is a powerful CB1 receptor activator -- even in low doses free from intoxicating effect. Last year, the researchers from Bonn and colleagues from Israel were able to demonstrate that cannabis can reverse the aging processes in the brains of mice. This result now suggest that an anti-inflammatory effect of THC may play a role in its positive effect on the ageing brain.

https://www.sciencedaily.com/releases/2018/08/180831130120.htm

Male tobacco smokers have brain-wide reduction of CB1 receptors

A study examines cannabinoid CB1 receptor binding in healthy male tobacco smokers

August 15, 2018

Science Daily/Elsevier

Chronic, frequent tobacco smokers have a decreased number of cannabinoid CB1 receptors, the "pot receptor," when compared with non-smokers, reports a study in Biological Psychiatry.

 

The study, the result of a collaboration of researchers affiliated with the National Institutes of Health, Maryland, supports that CB1 receptors play a role in smoking. The findings add to the group's previous studies that report the same finding in people who abuse cannabis or alcohol, suggesting that reduction of CB1 receptors is a common feature of addiction.

 

Of the 46 men who participated in the study all were considered healthy -- 18 of the participants were frequent cigarette smokers and 28 did not smoke. The researchers measured the number of receptors by using a brain imaging technique to detect a drug that binds to CB1 receptors.

 

The analysis indicated a nearly 20 percent reduction in CB1 receptors in the brains of smokers compared to non-smokers. The reduced receptor number was present throughout the brain (in all 18 regions examined in the study), with some regions more affected than others. The reduction in receptors was not exacerbated by more cigarettes smoked per day, or by starting before the age of 18.

 

"We think that the reduction of CB1 receptors may be unhealthy because these receptors are involved in many normal brain functions, such as memory and coping with stress," said Jussi Hirvonen, MD, PhD, of NIH and University of Turku, Finland. Dr. Hirvonen was co-first author of the study, along with Paolo Zanotti-Fregonara, MD, PhD, of NIH and Houston Methodist Research Institute, Texas.

 

A drug that blocks CB1 receptors, called rimonabant, has been tested in clinical trials for smoking cessation. Although the drug seemed to help people quit smoking, it caused problematic psychiatric side effects. "While rimonabant was associated with unacceptable risk for mood symptoms and suicidal ideation, other addiction treatments targeting cannabinoid signaling should be explored," said John Krystal, MD, Editor of Biological Psychiatry.

 

The findings have important and immediate implications for research examining the role of the brain's cannabinoid system in the cause of neuropsychiatric disorders. Because smoking is so common in people with neuropsychiatric disorders, clinical studies will have to carefully consider smoking habits in patients that could interfere with cannabinoid receptor measurements.

https://www.sciencedaily.com/releases/2018/08/180815105316.htm

Cannabinoid improves survival rates of mice with pancreatic cancer

July 30, 2018

Science Daily/Queen Mary University of London

Mice with pancreatic cancer that were treated with a naturally occurring constituent of medicinal cannabis alongside chemotherapy, survived almost three times longer than those treated with chemotherapy alone, a new study reports.

 

The study is published in the journal Oncogene and was led by Queen Mary University of London and Curtin University, Australia. It tested the impact of the cannabinoid Cannabidiol (CBD) on the use of the commonly used chemotherapy medication Gemcitabine as a treatment for pancreatic cancer in mice.

 

Each year around 9,800 people in the UK are diagnosed with pancreatic cancer. The disease is particularly aggressive and has one of the lowest survival rate of all cancers.

 

Lead researcher Professor Marco Falasca from Queen Mary University of London said: "This is a remarkable result. We found that mice with pancreatic cancer survived nearly three times longer if a constituent of medicinal cannabis was added to their chemotherapy treatment.

 

"Cannabidiol is already approved for use in clinics, which means we can quickly go on to test this in human clinical trials. If we can reproduce these effects in humans, cannabidiol could be in use in cancer clinics almost immediately, compared to having to wait for authorities to approve a new drug.

 

"The life expectancy for pancreatic cancer patients has barely changed in the last 40 years because there are very few, and mostly only palliative care, treatments available. Given the five-year survival rate for people with pancreatic cancer is less than seven per cent, the discovery of new treatments and therapeutic strategies is urgently needed."

 

The cannabinoid CBD does not cause psychoactive effects, as opposed to tetrahydrocannabinol (THC) -- the cannabinoid known to cause the psychoactive effects in cannabis. As such, CBD is already cleared for use in the clinic, and does not face the same challenges as products including cannabis oil, which contain controlled substances such as THC.

 

The researchers add that CBD is also known to improve the side effects of chemotherapy, including nausea, diarrhea, vomiting, meaning it could also improve the quality of life of patients undergoing chemotherapy.

 

The research was supported by the UK charity Pancreatic Cancer Research Fund and the Avner Pancreatic Cancer Foundation and also involved researchers from The Beatson Institute for Cancer Research in Scotland.

 

The study only looked at the effect of this treatment in mice, and clinical trials in humans are needed to confirm whether or not CBD improves survival rates of pancreatic cancer patients.

https://www.sciencedaily.com/releases/2018/07/180730160618.htm

Cannabis does not improve breathlessness during exercise in patients with advanced COPD

July 28, 2018

Science Daily/American Thoracic Society

Inhaled vaporized cannabis does not appear to improve or worsen exercise performance and activity-related breathlessness in patients with advanced chronic obstructive pulmonary disease (COPD), according to a randomized controlled trial published online in the Annals of the American Thoracic Society.

 

In "Effect of Vaporized Cannabis on Exertional Breathlessness and Exercise Endurance in Advanced COPD: A Randomized Controlled Trial," Sara J. Abdallah, a PhD candidate in exercise physiology at McGill University, and co-authors report that the trial did not find a difference between vaporized cannabis and placebo on lung volumes or heart rate at rest or during exercise. Nor did the study find that cannabis affected cognitive function, mood or psycho-activity.

 

The burden of breathlessness in patients with COPD is high. Even when on optimal medication for their lung disease, many patients with COPD continue to suffer from disabling breathlessness at rest and while performing basic activities of daily living.

 

"We first became aware of the therapeutic potential of cannabis in managing COPD symptoms from patients themselves," Ms. Abdallah said. "We decided to pursue this study because patients were reporting symptomatic relief of their COPD symptoms after cannabis use."

 

In the 1970s, controlled studies reported that smoking cannabis opened the airways of adults with and without asthma. More recently, a large observational study found a positive association between cannabis use and forced expiratory volume (the amount of air that can be forcefully exhaled in one second) and forced vital capacity (the total amount of air that can be exhaled after taking a deep breath).

 

In the current crossover study of 16 patients with advanced COPD, all the patients were taking optimal medication for their lung disease: dual or triple inhalation therapy (long-acting muscarinic antagonist and long-acting beta2-agonist bronchodilator with or without an inhaled corticosteroid).

 

Participants were randomly selected to inhale a single dose of vaporized cannabis or a placebo before exercising on a stationary bike. Participants then "crossed over" to the other arm of the trial. Neither the researchers nor the patients knew when they were receiving the vaporized cannabis or the placebo.

 

Although the study did not find a clinically meaningful negative or positive effect of vaporized cannabis on breathlessness during exercise or on exercise performance, the researchers noted variability in responsiveness to the cannabis.

 

After inhaling vaporized cannabis, breathlessness during exercise improved in 4 of the 16 patients. In the remaining 12 patients, breathlessness during exercise did not change, or worsened.

 

Senior study author Dennis Jensen, PhD, associate professor of kinesiology and physical education and a scientist in the Translational Research in Respiratory Diseases Program at McGill University, said that trial results may not be generalizable because the number of participants was small and represented a relatively homogenous group of patients with stable, but advanced, COPD.

 

In addition to the fact that all the participants were on optimal COPD therapy, Dr. Jensen, who is also director of the McGill Research Centre for Physical Activity and Health, suggested a number of factors that may have limited the therapeutic benefit of cannabis in the study, including the dose of cannabis used, that it was inhaled rather than taken orally and that it was administered only once and not repeated.

 

"Future clinical trials are warranted and should evaluate the therapeutic potential of various doses of vaporized and oral cannabis, including oils and pills, administered over longer periods of time in patients with mild to moderate COPD," he said.

https://www.sciencedaily.com/releases/2018/07/180728084133.htm

How cannabis and cannabis-based drugs harm your brain

July 23, 2018

Science Daily/Lancaster University

Long-term use of either cannabis or cannabis-based drugs impairs memory say researchers.

 

The study has implications for both recreational users and people who use the drug to combat epilepsy, multiple sclerosis and chronic pain.

 

They found that mice exposed to the drug long-term had "significant ... memory impairments" and could not even discriminate between a familiar and novel object.

 

There is little understanding of the potential negative side effects of long-term cannabinoid exposure, though it is already known that heavy, regular cannabis use increases the risk of developing mental health problems including psychosis and schizophrenia.

 

More and more people are using the drug long-term due to its legalisation in several countries, while more potent varieties are available for recreational users.

 

Researchers from Lancaster and Lisbon Universities studied the effects of the cannabinoid drug WIN 55,212-2 in mice and found that:

·     Long-term exposure impairs learning and memory in the animals

·     Brain imaging studies showed that the drug impairs function in key brain regions involved in learning and memory

·     Long-term exposure to the drug impairs the ability of brain regions involved in learning and memory to communicate with each other, suggesting that this underlies the negative effects of the drug on memory

Dr Neil Dawson, the lead researcher from Lancaster University said "This work offers valuable new insight into the way in which long-term cannabinoid exposure negatively impacts on the brain. Understanding these mechanisms is central to understanding how long-term cannabinoid exposure increases the risk of developing mental health issues and memory problems."

 

He also highlighted the relevance of the work to those using cannabinoid-based therapies to treat medical conditions.

 

"Cannabis-based therapies can be very effective at treating the symptoms of chronic diseases such as epilepsy and multiple sclerosis, and dramatically increase the quality of life for people living with these conditions. We need to understand the side effects that these people may experience so that we can develop new interventions to minimise these side effects."

 

Professor Ana Sebastiao, lead researcher at the University of Lisbon, said: "Importantly, our work clearly shows that prolonged cannabinoid intake, when not used for medical reasons, does have a negative impact in brain function and memory. It is important to understand that the same medicine may re-establish an equilibrium under certain diseased conditions, such as in epilepsy or MS, but could cause marked imbalances in healthy individuals. "As for all medicines, cannabinoid based therapies have not only beneficial disease-related actions, but also negative side effects. It is for the medical doctor to weight the advantages of the therapy, taking into consideration quality of life and diseases progression, against the potential side effects."

 

The research was published in the Journal of Neurochemistry and was conducted as part of the European Commission Horizon 2020 funded SynaNET project.

https://www.sciencedaily.com/releases/2018/07/180723132251.htm

Products of omega-3 fatty acid metabolism may have anticancer effects

July 13, 2018

Science Daily/University of Illinois at Urbana-Champaign

A class of molecules formed when the body metabolizes omega-3 fatty acids could inhibit cancer's growth and spread, University of Illinois researchers report in a new study in mice. The molecules, called endocannabinoids, are made naturally by the body and have similar properties to cannabinoids found in marijuana -- but without the psychotropic effects.

 

In mice with tumors of osteosarcoma -- a bone cancer that is notoriously painful and difficult to treat -- endocannabinoids slowed the growth of tumors and blood vessels, inhibited the cancer cells from migrating and caused cancer cell death. The results were published in the Journal of Medicinal Chemistry.

 

"We have a built-in endocannabinoid system which is anti-inflammatory and pain-reducing. Now we see it is also anti-cancer, stopping the cells from proliferating or migrating," said study leader Aditi Das, a professor of comparative biosciences and an affiliate of biochemistry at Illinois. "These molecules could address multiple problems: cancer, inflammation and pain."

 

In 2017, the Illinois team identified a new group of omega-3 fatty-acid metabolites called endocannabinoid epoxides, or EDP-EAs. They found that these molecules had anti-inflammatory properties and targeted the same receptor in the body that cannabis does.

 

Since cannabis has been shown to have some anti-cancer properties, in the new study the researchers investigated whether EDP-EAs also affect cancer cells. They found that in mice with osteosarcoma tumors that metastasized to their lungs, there was an 80 percent increase in naturally occurring EDP-EAs in cancerous lung tissues over the lungs of healthy mice.

 

"The dramatic increase indicated that these molecules were doing something to the cancer -- but we didn't know if it was harmful or good," Das said. "We asked, are they trying to stop the cancer, or facilitating it? So we studied the individual properties and saw that they are working against the cancer in several ways."

 

The researchers found that in higher concentrations, EDP-EAs did kill cancer cells, but not as effectively as other chemotherapeutic drugs on the market. However, the compounds also combated the osteosarcoma in other ways: They slowed tumor growth by inhibiting new blood vessels from forming to supply the tumor with nutrients, they prevented interactions between the cells, and most significantly, they appeared to stop cancerous cells from migrating.

 

"The major cause of death from cancer is driven by the spread of tumor cells, which requires migration of cells," said study coauthor Timothy Fan, a professor of veterinary clinical medicine and veterinary oncology. "As such, therapies that have the potential to impede cell migration also could be useful for slowing down or inhibiting metastases."

 

The researchers isolated the most potent of the molecules and are working to develop derivatives that bind better to the cannabinoid receptor, which is plentiful on the surface on cancer cells.

 

"Dietary consumption of omega-3 fatty acids can lead to the formation of these substances in the body and may have some beneficial effects. However, if you have cancer, you want something concentrated and fast acting," Das said. "That's where the endocannabinoid epoxide derivatives come into play -- you could make a concentrated dose of the exact compound that's most effective against the cancer. You could also mix this with other drugs such as chemotherapies."

 

Next, the researchers plan to perform preclinical studies in dogs, since dogs develop osteosarcoma spontaneously, similarly to humans. They also plan to study the effects of EDP-EAs derived from omega-3 fatty acids in other cancer types.

 

"Particular cancers that might be most interesting to study would be solid tumors or carcinomas, which tend to spread and cause pain within the skeleton. Some of the most common tumors that behave this way are breast, prostate, and lung carcinomas, and we can certainly explore these tumors in the future," said Fan, who is also a member of the Carle Illinois College of Medicine, the Cancer Center at Illinois and the Carl R. Woese Institute for Genomic Biology.

https://www.sciencedaily.com/releases/2018/07/180713220137.htm

Overdose risk factors in youth with substance use disorders

More than a quarter of young people seeking treatment had history of at least one overdose

April 24, 2018

Science Daily/Massachusetts General Hospital

A team of Massachusetts General Hospital (MGH) investigators has identified factors that may increase the risk of drug overdose in adolescents and young adults. In their report published online in the Journal of Clinical Psychiatry, the researchers describe finding that more than a quarter of those seeking treatment at Addiction Recovery Management Service, an MGH-based outpatient substance-use-disorder treatment program for youth ages 14 to 26, had a history of at least one overdose. Factors associated with increased overdose risk were disorders involving the use of alcohol, cocaine or amphetamines and histories of depression, anxiety or eating disorders.

 

"Very little research exists on risk factors associated with overdose in young people presenting for substance use disorder treatment," says lead and corresponding author Amy Yule, MD, of Addiction Recovery Management Service and the MGH Division of Child Psychiatry. "In addition to screening for substance-specific risk factors, it is important that providers systematically screen young patients for overdose histories and for psychiatric factors that may increase overdose risk."

 

Most studies of overdose risk among individuals with substance use disorders have focused on adults, and the few that specifically studied young people only assessed substance-related risk factors and not psychiatric symptoms. Yule notes that, since substance use patterns are known to differ between youth and adults, and since brain regions important to decision making do not fully mature until the 20s, it is important to investigate whether risk factors differ between the two age groups.

 

The research team conducted a retrospective analysis of deidentified data from intake assessments conducted at Addiction Recovery Management Service from January 2012 through June 2013. These comprehensive assessments include details of both substance use and psychiatric histories and are conducted by social workers, psychologists and psychiatrists with additional training in addiction medicine.

 

Of the 200 patients whose data were collected, 58 had a history of at least one overdose -- defined as substance use associated with significant impairment in the level of consciousness or an ingestion of any substance with the intent of self-harm that was reported as a suicide attempt. Among those with an overdose history, 62 percent (36 patients) had unintentional overdoses only, 31 percent (18 patients) had intentional overdose only, and 7 percent (4 patients) had a history of both intentional and unintentional overdose; 24 patients had histories of more than one overdose.

 

Patients with two or more substance use disorders were more than three times as likely to have a history of overdose, compared to patients with a single substance use disorder. The best substance-associated predictors of an overdose were alcohol use disorder, cocaine use disorder and amphetamine use disorder; psychiatric conditions associated with overdose history were eating disorders, depression and anxiety disorders. Patients with a history of intentional overdose were more likely than those with unintentional overdose to have a history of self-harming behavior and inpatient psychiatric treatment.

 

Yule notes that, since the association of eating disorders with overdose risk has never been reported previously, it needs to be replicated in future studies, but assessing for eating disorders and other psychiatric risk factors in youth with substance use disorders is essential. The lack of an association between opioid use and overdose history in this study could reflect the fact that opioid use usually begins at later ages than does use of substances such as cannabis and alcohol, which are more common among adolescents. In addition, she adds, the presence of fentanyl, which significantly increases overdose risk, was much lower in Massachusetts at the time this study's data were collected.

 

"It's going to be helpful to assess overdose risk among young people with substance use disorders over a longer period of time and to examine whether treatment mitigates the risk for subsequent overdose," says Yule, an instructor in Psychiatry at Harvard Medical School (HMS). "While the opioid epidemic has raised public awareness of the importance of increased access to evidence-based treatment for substance use disorders, our findings support the importance of considering all substances of misuse -- both opioids and non-opioids -- when assessing overdose risk."

 

Study senior author Timothy Wilens, MD, chief of Child and Adolescent Psychiatry at MGH and associate professor of Psychiatry at HMS adds, "The striking prevalence of overdose history in treatment-seeking young people reflects how common overdose unfortunately is among those with substance use disorders, no matter the age."

https://www.sciencedaily.com/releases/2018/04/180424141140.htm

Scientists identify connection between dopamine and behavior related to pain and fear

New research illuminates crucial links between avoidance behavior and key brain chemicals

April 19, 2018

Science Daily/University of Maryland School of Medicine

Scientists at the University of Maryland School of Medicine have for the first time found direct causal links between the neurotransmitter dopamine and avoidance -- behavior related to pain and fear.

 

Researchers have long known that dopamine plays a key role in driving behavior related to pleasurable goals, such as food, sex and social interaction. In general, increasing dopamine boosts the drive toward these stimuli. But dopamine's role in allowing organisms to avoid negative events has remained mysterious.

 

The new study establishes for the first time that dopamine is central in causing behavior related to the avoidance of specific threats. The work was published today in the journal Current Biology.

 

"This study really advances what we know about how dopamine affects aversively motivated behaviors," said Joseph F. Cheer PhD, a professor in the UMSOM Department of Anatomy & Neurobiology and the study's corresponding author. "In the past, we thought of dopamine as a neurotransmitter involved in actions associated with the pursuit of rewards. With this new information we can delve into how dopamine affects so many more kinds of motivated behavior."

 

To better understand the role that dopamine plays in this process, Dr. Cheer and his colleagues, including principal author Jennifer Wenzel, PhD, a fellow in Dr. Cheer's laboratory, studied rats, focusing on a particular brain area, the nucleus accumbens. This brain region plays a crucial role in linking the need or desire for a given reward -- food, sex, etc. -- with the motor response to actually obtain that reward.

 

To study the animals under natural conditions, they used optogenetics, a relatively new technique in which specific groups of neurons can be controlled by exposure to light. In this case, Dr. Cheer's group used a blue laser to stimulate genetically modified rats whose dopamine neurons could be controlled to send out more or less dopamine. In this way, they were able to see how dopamine levels affected the animals' behavior. The principal advantage of this approach: he could control dopamine levels even as the animals moved freely in their environment.

 

The researchers subjected the animals to small electric shocks, but also taught the animals how to escape the shocks by pressing a small lever. Using optogenetics, they controlled the amount of dopamine released by neurons in the nucleus accumbens. Animals with high levels of dopamine in this brain region learned to avoid a shock more quickly and more often than animals that had a lower level of dopamine in this region.

 

Dr. Cheer says that this indicates that dopamine causally drives animals to avoid unpleasant or painful situations and stimuli. The results greatly expand the role that dopamine plays in driving behavior.

 

The researchers also examined the role that endocannabinoids play in this process. Endocannabinoids, brain chemicals that resemble the active ingredients in marijuana, play key roles in many brain processes. Here, Dr. Cheer and his colleagues found that endocannabinoids essentially open the gate that allows the dopamine neurons to fire. When the researchers reduced the level of endocannabinoids, the animals were much less likely to move to avoid shocks.

 

Dr. Cheer argues that the research sheds light on brain disorders such as post-traumatic stress disorder and depression. In depression, patients feel unable to avoid a sense of helplessness in the face of problems, and tend to ruminate rather than act to improve their situation. In PTSD, patients are unable to avoid an overwhelming sense of fear and anxiety in the face of seemingly low-stress situations. Both disorders, he says, may involve abnormally low levels of dopamine, and may be seen on some level as a failure of the avoidance system.

 

In both depression and PTSD, doctors already sometimes treat patients with medicine to increase dopamine and there are now clinical trials testing use of endocannabinoid drugs to treat these conditions. Dr. Cheer suggests that this approach may need to be used more often, and should certainly be studied in more detail.

https://www.sciencedaily.com/releases/2018/04/180419131108.htm

Medical cannabis significantly safer for elderly with chronic pain than Opioids

February 13, 2018

Science Daily/American Associates, Ben-Gurion University of the Negev

A new study found cannabis therapy is safe and efficacious for elderly patients who are seeking to address cancer symptoms, Parkinson's disease, post-traumatic stress disorder, ulcerative colitis, Crohn's disease, multiple sclerosis, and other medical issues. After six months, more than 18 percent of patients surveyed had stopped using opioid analgesics or had reduced their dosage.

 

Medical cannabis therapy can significantly reduce chronic pain in patients age 65 and older without adverse effects, according to researchers at Ben-Gurion University of the Negev (BGU) and the Cannabis Clinical Research Institute at Soroka University Medical Center.

 

The new study, published in The European Journal of Internal Medicine, found cannabis therapy is safe and efficacious for elderly patients who are seeking to address cancer symptoms, Parkinson's disease, post-traumatic stress disorder, ulcerative colitis, Crohn's disease, multiple sclerosis, and other medical issues.

 

"While older patients represent a large and growing population of medical cannabis users, few studies have addressed how it affects this particular group, which also suffers from dementia, frequent falls, mobility problems, and hearing and visual impairments," says Prof. Victor Novack, M.D., a professor of medicine in the BGU Faculty of Health Sciences (FOHS), and head of the Soroka Cannabis Clinical Research Institute. Novack is also the BGU Gussie Krupp Chair in Internal Medicine.

 

"After monitoring patients 65 and older for six months, we found medical cannabis treatment significantly relieves pain and improves quality of life for seniors with minimal side effects reported."

 

This older population represents a growing segment of medical cannabis users, ranging from approximately seven percent to more than 33 percent, depending on the country. Recent U.S. polls indicate Americans over 65 represent 14 percent of the total population and use more than 30 percent of all prescription drugs, including highly addictive painkillers.

 

BGU researchers surveyed 2,736 patients 65 years and older who received medical cannabis through "Tikun Olam," the largest Israeli medical cannabis supplier. More than 60 percent were prescribed medical cannabis due to the pain, particularly pain associated with cancer. After six months of treatment, more than 93 percent of 901 respondents reported their pain dropped from a median of eight to four on a 10-point scale. Close to 60 percent of patients who originally reported "bad" or "very bad" quality of life upgraded to "good" or "very good" after six months. More than 70 percent of patients surveyed reported moderate to significant improvement in their condition.

 

The most commonly reported adverse effects were dizziness (9.7 percent) and dry mouth (7.1 percent). After six months, more than 18 percent of patients surveyed had stopped using opioid analgesics or had reduced their dosage.

 

All patients received a prescription after consulting with a doctor who prescribed treatment. More than 33 percent of patients used cannabis-infused oil; approximately 24 percent inhaled therapy by smoking, and approximately six percent used vaporization.

 

While the researchers state their findings to date indicate cannabis may decrease dependence on prescription medicines, including opioids, more evidence-based data from this special, aging population is imperative.

https://www.sciencedaily.com/releases/2018/02/180213111508.htm

Pre-clinical study suggests path toward non-addictive painkillers

Researchers use a compound with a novel mechanism to treat pain in mice without tolerance or physical dependence

Science Daily/October 25, 2017

Indiana University

A pre-clinical study led by Indiana University scientists reports a promising step forward in the search for pain relief methods without the addictive side effects behind the country's current opioid addiction crisis.

 

The research, which appears in the journal Biological Psychiatry, finds that the use of compounds called positive allosteric modulators, or PAMs, enhances the effect of pain-relief chemicals naturally produced by the body in response to stress or injury. This study also significantly strengthens preliminary evidence about the effectiveness of these compounds first reported at the 2016 Society for Neuroscience Conference in San Diego, California.

 

"Our study shows that a PAM enhances the effects of these pain-killing chemicals without producing tolerance or decreased effectiveness over time, both of which contribute to addiction in people who use opioid-based pain medications," said Andrea G. Hohmann, a Linda and Jack Gill Chair of Neuroscience and professor in the IU Bloomington College of Arts and Sciences' Department of Psychological and Brain Sciences, who led the study. "We see this research as an important step forward in the search for new, non-addictive methods to reduce pain."

 

Over 97 million Americans took prescription painkillers in 2015, with over 2 million reporting problems with the drugs. Drug overdoses are the No. 1 cause of death for Americans under 50, outranking guns and car accidents and outpacing the HIV epidemic at its peak.

 

Medical researchers are increasingly studying positive allosteric modulators because they target secondary drug receptor sites in the body. By contrast, "orthosteric" drugs -- including cannabinoids such as delta-9-tetrahydrocannabinol (THC) and opioids such as morphine -- influence primary binding sites, which means their effects may "spill over" to other processes in the body, causing dangerous or unwanted side effects. Rather than acting as an on/off switch, PAMs act like an amplifier, enhancing only the effects of the brain's own natural painkillers, thereby selectively altering biological processes in the body that naturally suppress pain.

 

The PAM used in the IU-led study worked by amplifying two brain compounds -- anandamide and 2-arachidonoylglycerol -- commonly called "endocannabinoids" because they act upon the CB1 receptor in the brain that responds to THC, the major psychoactive ingredient in cannabis.

 

Although the PAM compound enhanced the effects of the endocannabinoids the study found that it did not cause unwanted side effects associated with cannabis -- such as impaired motor functions or lowered body temperature -- because its effect is highly targeted in the brain. The pain relief was also stronger and longer-lasting than drugs that block an enzyme that breaks down and metabolizes the brain's own cannabis-like compounds. The PAM alone causes the natural painkillers to target only the right part of the brain at the right time, as opposed to drugs that bind to every receptor site throughout the body.

 

The PAMs also presented strong advantages over the other alternative pain-relief compounds tested in the study: a synthetic cannabinoid and a metabolic inhibitor. The analysis' results suggested these other compounds' remained likely to produce addiction or diminish in effectiveness over time.

 

While the IU-led research was conducted in mice, Hohmann said it's been shown that endocannabinoids are also released by the human body in response to inflammation or pain due to nerve injury. The compounds may also play a role in the temporary pain relief that occurs after a major injury.

 

"These results are exciting because you don't need a whole cocktail of other drugs to fully reverse the pathological pain in the animals," Hohmann said. "We also don't see unwanted signs of physical dependence or tolerance found with delta-9-tetrahydrocannabinol or opioid-based drugs. If these effects could be replicated in people, it would be a major step forward in the search for new, non-addictive forms of pain relief."

 

The PAM used in the study was GAT211, a molecule designed and synthesized by Ganesh Thakur at Northeastern University, who is a co-author on the study. The lead author on the study was Richard A. Slivicki, a graduate student in Hohmann's lab in the IU Program in Neuroscience and Department of Psychological and Brain Sciences. Additional authors on the study are Zhili Xu, an IU research fellow; Ken Mackie, IU professor and director of the Gill Center; Pushkar M. Kulkarni at Northeastern University; and Roger G. Pertwee at the University of Aberdeen, Scotland.

 

This study was supported in part by the National Institutes of Health.

https://www.sciencedaily.com/releases/2017/10/171025105038.htm

Muted stress response linked to long-term cannabis use

July 31, 2017

Science Daily/Washington State University

A new study by Washington State University psychology researchers reveals a dampened physiological response to stress in chronic cannabis users.

 

Using a nationally recognized procedure designed to provoke elevated levels of stress, Carrie Cuttler, clinical assistant professor of psychology, Ryan McLaughlin, assistant professor of integrative physiology and neuroscience, and colleagues in the WSU Department of Psychology examined levels of the stress hormone cortisol in both chronic cannabis users and non-users.

 

"To the best of our knowledge, this is the first study to examine the effects of acute stress on salivary cortisol levels in chronic cannabis users compared to non-users," Cuttler said. "While we are not at a point where we are comfortable saying whether this muted stress response is a good thing or a bad thing, our work is an important first step in investigating potential therapeutic benefits of cannabis at a time when its use is spreading faster than ever before."

 

The WSU researchers found virtually no difference in the salivary cortisol levels of two groups of heavy cannabis users confronted with either a psychologically and physiologically stressful situation or a non-stressful one.

 

In contrast, cortisol levels among non-users of cannabis who experienced the same simulated stressful situation were found to be much greater than the cortisol level of non-users in the no-stress scenario.

 

The findings are consistent with a growing body of literature that indicates chronic cannabis use is associated with dulled adrenal and emotional reactivity. The study was published recently in the journal Psychopharmacology.

 

The stress test

Research participants self-identified as either a chronic cannabis consumer, with daily or nearly daily use for the previous year, or as a non-user who had consumed cannabis 10 or fewer times in their life and not at all within the previous year. Forty daily cannabis users and 42 non-users participated in the study. All were required to abstain from consuming cannabis on the day of testing.

 

Upon arrival at the lab, participants provided a saliva sample and were asked to rate their current level of stress. The chronic cannabis users and non-users were randomly assigned to experience either the high-stress or no-stress version of the Maastricht Acute Stress Test. Known by its acronym MAST, it is a commonly used procedure for stress-related research which combines elements of physical, psychosocial and unpredictable types of stress.

 

The no-stress version was simple: participants placed one hand in lukewarm water for 45-90 seconds and then were asked to count from 1 to 25.

 

The high-stress version upped the stakes significantly. Participants placed their hand in ice cold water for 45-90 seconds. They were then asked to count backwards from 2043 by 17 and were given negative verbal feedback when they made a mistake. On top of this, subjects were monitored by a web camera and the video feed was displayed on a screen directly in front of the participants so they couldn't help but see themselves.

 

Immediately following the stress manipulation, all participants once again provided a saliva sample and were asked to rate their current level of stress. Before departing the testing facility, participants also provided a urine sample so researchers could corroborate self-reported use with bodily THC levels.

 

Interpreting the results

Cuttler and her colleagues' work suggests cannabis may have benefits in conferring resilience to stress, particularly in individuals who already have heightened emotional reactivity to stressful situations.

 

However, the researchers emphasized the release of cortisol typically serves an adaptive purpose, allowing an individual to mobilize energy stores and respond appropriately to threats in the environment.

 

"Thus, an inability to mount a proper hormonal response to stress could also have detrimental effects that could potentially be harmful to the individual," Cuttler said. "Research on cannabis is really just now ramping up because of legalization and our work going forward will play an important role in investigating both the short-term benefits and potential long-term consequences of chronic cannabis use."

 

Next steps in the research will include investigating various factors, such as the presence of residual THC, which may be influencing the muted stress response in cannabis users.

https://www.sciencedaily.com/releases/2017/07/170731090828.htm

Depression among young teens linked to cannabis use at 18

Seattle-focused study suggests earlier intervention with depressed youths could reduce rate of cannabis-use disorder

July 17, 2017

Science Daily/University of Washington Health Sciences/UW Medicine

A study looking at the cumulative effects of depression in youth, found that young people with chronic or severe forms of depression were at elevated risk for developing a problem with cannabis in later adolescence.

 

The study led by UW Medicine researchers interviewed 521 students recruited from four Seattle public middle schools. Researchers used data from annual assessments when students were ages 12-15 and then again when they were 18. The results were published in the journal Addiction.

 

"The findings suggest that if we can prevent or reduce chronic depression during early adolescence, we may reduce the prevalence of cannabis use disorder," said lead author Isaac Rhew, research assistant professor of psychiatry and behavioral sciences at the University of Washington School of Medicine.

 

What researchers called "a 1 standard deviation increase" in cumulative depression during early adolescence was associated with a 50 percent higher likelihood of cannabis-use disorder.

 

According to researchers, during the past decade cannabis has surpassed tobacco with respect to prevalence of use among adolescents. Cannabis and alcohol are the two most commonly used substances among youth in the United States. They pointed to one national study showing increases in prevalence of cannabis use disorder and alcohol use disorder in the United States, especially among young adults.

 

Longitudinal studies looking at the link between depression and later use of alcohol and cannabis, however, have been mixed. Some show a link. Others don't. But most studies have assessed adolescent depression at a single point in time -- not cumulatively, said the researchers. Further, there have been differences in how substance use has been measured ranging from the initiation of any use to heavier problematic forms of use.

 

The study oversampled for students with depressive and/or conduct problems. The researchers were surprised to see that the prevalence of cannabis and alcohol use disorder in this study was notably higher than national estimates with 21 percent meeting criteria for cannabis use disorder and 20 percent meeting criteria for alcohol use disorder at age 18.

 

What effect the easing of marijuana laws in Washington state had on the youth is unclear. Researchers said it would be informative to conduct a similar study in a state with more strict marijuana laws to understand whether the relationship between depression and cannabis misuse would still hold in areas where marijuana may be less accessible.

 

The age 18 substance abuse assessments occurred between 2007-2010. Washington state legalized medical cannabis in 1998 and its medical cannabis market expanded greatly after 2009 when the federal justice department issued a ruling known as the Ogden Memo. And in 2003, the city of Seattle made cannabis offenses the lowest enforcement priority for police and the city attorney.

https://www.sciencedaily.com/releases/2017/07/170717151031.htm

Why does prenatal alcohol exposure increase the likelihood of addiction?

July 7, 2017

Science Daily/University at Buffalo

One of the many negative consequences when fetuses are exposed to alcohol in the womb is an increased risk for drug addiction later in life. Neuroscientists in the University at Buffalo Research Institute on Addictions are discovering why.

 

Through a research grant from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) of the National Institutes of Health (NIH), Senior Research Scientist Roh-Yu Shen, PhD, is studying how prenatal alcohol exposure alters the reward system in the brain and how this change continues through adulthood.

 

The key appears to lie with endocannibinoids, cannabis-like chemicals that are produced by the brain itself.

 

"By understanding the role endocannibinoids play in increasing the brain's susceptibility to addiction, we can start developing drug therapies or other interventions to combat that effect and, perhaps, other negative consequences of prenatal alcohol exposure," Shen says.

 

Prenatal alcohol exposure is the leading preventable cause of birth defects and neurodevelopmental abnormalities in the United States. Fetal Alcohol Spectrum Disorders (FASD) cause cognitive and behavioral problems. In addition to increased vulnerability of alcohol and other substance use disorders, FASD can lead to other mental health issues including Attention Deficit Hyperactivity Disorder (ADHD), depression, anxiety and problems with impulse control.

 

"After the prenatal brain is exposed to alcohol, the endocannibinoids have a different effect on certain dopamine neurons which are involved in addicted behaviors than when brain is not exposed to alcohol," Shen says. "The end result is that the dopamine neurons in the brain become more sensitive to a drug of abuse's effect. So, later in life, a person needs much less drug use to become addicted."

 

Specifically, in the ventral tegmental area (VTA) of the brain, endocannibinoids play a significant role in weakening the excitatory synapses onto dopamine neurons. The VTA is the part of the brain implicated in addiction, attention and reward processes. However, in a brain prenatally exposed to alcohol, the effect of the endocannabinoids is reduced due to a decreased function of endocannabinoid receptors. As a result, the excitatory synapses lose the ability to be weakened and continue to strengthen, which Shen believes is a critical brain mechanism for increased addiction risk.

https://www.sciencedaily.com/releases/2017/07/170707211125.htm

New approach to combatting anxiety states, pain and inflammation

June 6, 2017

Science Daily/University of Bern

Endogenous cannabinoids (endocannabinoids) play an important role in the brain and immune system. Bern researchers from the National Centre of Competence in Research (NCCR) "TransCure" have now found a new way to influence the endocannabinoid system. Anti-inflammatory, analgesic as well as anxiolytic effects could be achieved in an animal model.

 

Endocannabinoids are substances similar to fatty acids which are produced by the body. They activate specific cannabinoid receptors and among other things can exert anti-inflammatory or analgesic effects. Cannabis or tetrahydrocannabinol (THC) exhibit similar therapeutic effects in clinical use, but they are fraught with adverse effects. In contrast, endogenous cannabinoids are only produced in the cells when the body needs them, and therefore cannot be overdosed. The endocannabinoid system is considered promising as it uncovers new therapeutic options, for instance for disorders of the nervous system. For years, the research team led by Jürg Gertsch from the Institute of Biochemistry and Molecular Medicine at the University of Bern has been exploring the possibility to selectively activate endocannabinoids in the brain in order to treat neuropsychiatric disorders -- for example, anxiety states -- within the scope of the NCCR "TransCure" financed by the Swiss National Science Foundation (SNSF).

 

In cooperation with an international research team, the Bern research group led by Gertsch has now succeeded in blocking the transport route or endocannabinoids in the brain of mice for the first time by means of innovative inhibitors. This led to positive effects on the stress behaviour and immune system of mice. Anti-inflammatory, analgesic as well as anxiolytic effects have been observed. Although for several years it has been assumed that there is an endocannabinoid transport system in nerve cells and immune cells, this could now be shown for the first time. "I am convinced that in addition to the administration of exogenous cannabinoids, the endocannabinoid system will be specifically activated for therapeutic purposes in the future," says Gertsch. The study was published in the journal "Proceedings of the National Academy of Sciences (PNAS)."

 

Endocannabinoid Transport blocked

In cooperation with chemists from the Swiss Federal Institute of Technology/ETH Zurich (research group led by Prof. Karl-Heinz Altmann) and the industry, hundreds of endocannabinoid transport inhibitors were synthesised in order to develop ideal pharmacological properties. The researchers were inspired for these inhibitors by a natural substance from the purple coneflower (Echinacea purpurea), a medicinal plant which is frequently utilised for colds and partially has an effect on the endocannabinoid system. The newly developed inhibitors block the uptake of endocannabinoids through the membrane of cells. As a result, cannabinoid receptors on nerve and immune cells are activated, which leads to a "brake" in the brain and in the immune system upon stress and in inflammatory disorders, restoring the physiological equilibrium.

 

New perspectives for new medicines

Andrea Chicca, lead author of the study from the group led by Prof. Gertsch, is confident that the molecular mechanism of endocannabinoid transporter can be elucidated in the coming years: "Then nothing stands in the way for the development of new medicines." Thanks to the new findings from the study, already now substances can be made which differ from previous drugs as they specifically activate the endogenous cannabinoids in the brain. The researchers see great potential in the field of stress-related disorders, because endocannabinoids regulate important stress hormones and restore the equilibrium in the brain.

https://www.sciencedaily.com/releases/2017/06/170606090806.htm

Prenatal cocaine exposure increases risk of higher teen drug use

May 3, 2017

Science Daily/Case Western Reserve University

While the crack cocaine epidemic peaked in the late 1980's, its effects are still causing harm to an estimated 3 million teenagers and young adults exposed to the stimulant in the womb.

 

They are twice as likely to use tobacco and marijuana at age 15 and develop a substance use disorder at 17 than teens who weren't exposed to the drug in utero, according to researchers at Case Western Reserve University.

 

They are also more likely to handle stress in negative ways, especially if mistreated as a child, using fewer problem-solving skills and having less control over their emotions. They're also more likely to become distracted or disengaged.

 

These poor coping strategies are typically associated with acting out behaviors: Teens in the study were likely to break rules, fight, show aggression, steal and use drugs, tobacco and alcohol.

 

At 15 years old, more than 36 percent of these teens had used a drug within the past month; at 17, it was 43 percent, significantly higher than their peers who were not exposed to cocaine in utero.

 

"Children exposed to cocaine in the womb are more susceptible to addiction themselves because they are more likely to have trouble controlling their behaviors and emotions, which can lead to using substances more often and at earlier ages," said Sonia Minnes, an associate professor at the Jack, Joseph and Morton Mandel School of Applied Social Sciences at Case Western Reserve.

 

As lead researcher of Project Newborn, a National Institutes of Health (NIH)-funded study that began in 1994, Minnes and her research team have followed babies with prenatal cocaine-exposure from birth into emerging adulthood.

 

While researchers are in the midst of a four-year, $2.5 million NIH grant to report on the group at age 21, the latest results come from two studies published in Drug and Alcohol Dependence that focus on the children at ages 15 and 17.

 

Cocaine, in any form, is toxic to a fetal brain, by restricting blood flow and altering the expression of genes, which can affect executive functioning, language and other types of development.

 

Many of the teens in the study were raised in chaotic caregiving environments; more than 30 percent reported maltreatment, including physical and emotional abuse and neglect.

 

These teens were more likely to use denial as a coping strategy and less likely to override initial impulses to calm themselves down, redirect thoughts positively or forego gratification when they also experienced childhood maltreatment.

 

"Prenatal cocaine exposure may predispose children to a lower threshold for activating 'stress circuits' and may increase their vulnerability to the harmful effects of environmental stress such as childhood maltreatment," said Meeyoung O. Min, a research associate professor at the Mandel School and a researcher with Project Newborn.

 

Many of the mothers in the study also used other substances during pregnancy including tobacco, alcohol and marijuana.

 

"Given the many challenges presented to these children, they are doing better than expected as they enter adulthood," Minnes said. "They are a testament to the benefits of providing a positive environment for a child who was put at higher risk due to drug exposure."

 

Project Newborn data suggests that specialized drug use prevention programs could benefit such high-risk children as they develop. In addition, the project's findings may provide insights into addressing similar public health crises, such as prenatal exposure to opiates.

 

"You want to prevent the next generation from using drugs while pregnant, and this is powerful data that helps make this case," Minnes said. "This project helps us better understand the many factors and pitfalls facing children whose mothers used drugs."

https://www.sciencedaily.com/releases/2017/05/170503080213.htm

Cannabis use in adolescence linked to schizophrenia

Psychoactive compound in cannabis may trigger the brain disorder, researchers say

April 26, 2017

Science Daily/American Friends of Tel Aviv University

Scientists believe that schizophrenia, a disorder caused by an imbalance in the brain's chemical reactions, is triggered by a genetic interaction with environmental factors. A new Tel Aviv University study published in Human Molecular Genetics now points to cannabis as a trigger for schizophrenia.

 

The research, conducted by Dr. Ran Barzilay and led by Prof. Dani Offen, both of TAU's Sackler School of Medicine, finds that smoking pot or using cannabis in other ways during adolescence may serve as a catalyst for schizophrenia in individuals already susceptible to the disorder.

 

"Our research demonstrates that cannabis has a differential risk on susceptible versus non-susceptible individuals," said Dr. Barzilay, principal investigator of the study. "In other words, young people with a genetic susceptibility to schizophrenia -- those who have psychiatric disorders in their families -- should bear in mind that they're playing with fire if they smoke pot during adolescence."

 

The research team included Prof. Inna Slutsky and Hadar Segal-Gavish, both of TAU's Sackler School of Medicine, and Prof. Abraham Weizman of Geha Medical Health Center and Prof. Akira Sawa of Johns Hopkins Medical Center.

 

Clinical picture of mouse models mimics human adolescence

 

Researchers exposed mouse models with a genetic susceptibility to schizophrenia -- the mutant DISC-1 gene -- to THC, the psychoactive compound in cannabis. During a time period similar to that of human adolescence, the susceptible mice were found to be at a far higher risk for lasting brain defects associated with the onset of schizophrenia.

 

Four categories of mice were used in the experiment: Genetically susceptible and exposed to cannabis; genetically susceptible and not exposed to cannabis; genetically intact and exposed to cannabis; and, finally, genetically intact and not exposed to cannabis. Only the genetically susceptible mice developed behavioral and biochemical brain pathologies related to schizophrenia after being exposed to cannabis, behavioral tests and neurological biochemical analyses revealed.

 

"The study was conducted on mice but it mimics a clinical picture of 'first episode' schizophrenia, which presents during adolescence in proximity to robust cannabis use," said Dr. Barzilay, a child and adolescent psychiatrist.

 

The researchers also discovered the mechanism through which the cannabis and the specific gene interact.

 

"A protective mechanism was observed in the non-susceptible mice," said Prof. Offen. "This mechanism involves the upregulation of a protective neurotrophic factor, BDNF, in the hippocampus. We showed in the study that if we artificially deliver BDNF to the genetically susceptible mice, they could be protected from the deleterious effect of THC during adolescence.

 

"This research clearly has implications in terms of public health," Prof. Offen concluded. "The novel protective mechanism identified in the study may serve as a basis for the future development of compounds capable of attenuating the deleterious effect of cannabis on brain development. However, until that time, it is important that young people at risk for psychiatric disorders (i.e., have psychiatric disorders in their family or have reacted strongly to drugs in the past) should be particularly cautious with cannabis use during adolescence."

https://www.sciencedaily.com/releases/2017/04/170426124305.htm

Chili peppers and marijuana calm the gut

The active ingredients in both hot peppers and cannabis calm the gut's immune system

April 24, 2017

Science Daily/University of Connecticut

You wouldn't think chili peppers and marijuana have much in common. But when eaten, both interact with the same receptor in our stomachs, according to a paper by UConn researchers published in the April 24 issue of the journal Proceedings of the National Academy of Sciences. The research could lead to new therapies for diabetes and colitis, and opens up intriguing questions about the relationship between the immune system, the gut and the brain.

 

Touch a chili pepper to your mouth and you feel heat. And biochemically, you aren't wrong. The capsaicin chemical in the pepper binds to a receptor that triggers a nerve that fires off to your brain: hot! Those same receptors are found throughout the gastrointestinal tract, for reasons that have been mysterious.

 

Curious, UConn researchers fed capsaicin to mice, and found the mice fed with the spice had less inflammation in their guts. The researchers actually cured mice with Type 1 diabetes by feeding them chili pepper. When they looked carefully at what was happening at a molecular level, the researchers saw that the capsaicin was binding to a receptor called TRPV1, which is found on specialized cells throughout the gastrointestinal tract. When capsaicin binds to it, TRPV1 causes cells to make anandamide. Anandamide is a compound chemically akin to the cannabinoids in marijuana. It was the anandamide that caused the immune system to calm down. And the researchers found they could get the same gut-calming results by feeding the mice anandamide directly.

 

The brain also has receptors for anandamide. It's these receptors that react with the cannabinoids in marijuana to get people high. Scientists have long wondered why people even have receptors for cannabinoids in their brains. They don't seem to interact with vital bodily functions that way opiate receptors do, for example.

 

"This allows you to imagine ways the immune system and the brain might talk to each other. They share a common language," says Pramod Srivastava, Professor of Immunology and Medicine at UConn Health School of Medicine. And one word of that common language is anandamide.

 

Srivastava and his colleagues don't know how or why anandamide might relay messages between the immune system and the brain. But they have found out the details of how it heals the gut. The molecule reacts with both TRPV1 (to produce more anandamide) and another receptor to call in a type of macrophage, immune cells that subdue inflammation. The macrophage population and activity level increases when anandamide levels increase. The effects pervade the entire upper gut, including the esophagus, stomach and pancreas. They are still working with mice to see whether it also affects disorders in the bowels, such as colitis. And there are many other questions yet to be explored: what is the exact molecular pathway? Other receptors also react with anandamide; what do they do? How does ingesting weed affect the gut and the brain?

 

It's difficult to get federal license to experiment on people with marijuana, but the legalization of pot in certain states means there's a different way to see if regular ingestion of cannabinoids affects gut inflammation in humans.

 

"I'm hoping to work with the public health authority in Colorado to see if there has been an effect on the severity of colitis among regular users of edible weed," since pot became legal there in 2012, Srivastava says. If the epidemiological data shows a significant change, that would make a testable case that anandamide or other cannabinoids could be used as therapeutic drugs to treat certain disorders of the stomach, pancreas, intestines and colon.

 

It seems a little ironic that both chili peppers and marijuana could make the gut chill out. But how useful if it's true.

https://www.sciencedaily.com/releases/2017/04/170424152537.htm

Risk of psychosis from cannabis use lower than originally thought

April 20, 2017

Science Daily/University of York

The research, published in the journal, Addiction, also showed for the first time that there is sufficient evidence to demonstrate that for patients who already have schizophrenia, cannabis makes their symptoms worse.

 

More than two million people in England and Wales used cannabis in the past 12 months, but the latest research shows that banning the drug would have low impact on mental health.

 

In order to prevent just one case of psychosis, more than 20,000 people would have to stop using cannabis, as shown by a previous study led by the University of Bristol.

 

This means that at a population level, an increased risk of psychosis from cannabis use is low, and those vulnerable to developing serious mental health problems is relatively rare. The research highlights, however, that more reviews on the impact of high potency cannabis is needed in order to make a full assessment of the risks.

 

Ian Hamilton, lecturer in mental health at the University of York, said: "The link between cannabis and psychosis has been an ongoing research topic since the drug became popular in the 1960s. Most of the high profile studies that we have access to, however, are from a time when low potency cannabis was the norm, but today high potency is more common.

 

"High potency cannabis contains less of a chemical that is believed to protect against negative side-effects, such as psychosis, and a higher level of a chemical that can trigger psychosis. In this new study, we looked at both low and high potency, but it is clear that we need more evidence from high potency-related health cases to further investigate this link in modern-day users."

 

Despite this, the research was clear that the more high potency cannabis used, the higher the risk of developing mental health problems, even if they are relatively low in number. For those who already had schizophrenia cannabis exacerbated the symptoms.

 

The greatest risk to health, however, comes from cannabis users who combine the drug with tobacco. This exposes young people in particular to tobacco dependency at an early age, increasing the chances of cancers, infections, and other health-related issues.

 

Previous research at York showed that regulating cannabis use could result in more effective strategies aimed at helping drug users to access the right support and guidance. The policy report illustrated, however, that there is too much uncertainly around treatment regimes in an unregulated market to target the appropriate level of care.

 

Mr Hamilton said: "Regulation could help reduce the risks to health that cannabis use poses, as a regulated cannabis market would introduce some quality control.

 

"This would provide users with information about the strength of cannabis on offer, something they usually only discover after exposure in the current unregulated market.

 

"The public health message about the link between cannabis and psychosis has been a difficult one to communicate, but the evidence still points to the benefits of regulations that seek to advise on the greatest potential health risks, which currently arise due to tobacco use."

https://www.sciencedaily.com/releases/2017/04/170420132334.htm

Natural chemical helps brain adapt to stress

March 29, 2017

Science Daily/Vanderbilt University Medical Center

A natural signaling molecule that activates cannabinoid receptors in the brain plays a critical role in stress-resilience -- the ability to adapt to repeated and acute exposures to traumatic stress, according to researchers at Vanderbilt University Medical Center.

 

The findings in a mouse model could have broad implications for the potential treatment and prevention of mood and anxiety disorders, including major depression and post-traumatic stress disorder (PTSD), they reported in the journal Nature Communications.

 

"The study suggests that deficiencies in natural cannabinoids could result in a predisposition to developing PTSD and depression," said Sachin Patel, M.D., Ph.D., director of the Division of Addiction Psychiatry at Vanderbilt University School of Medicine and the paper's corresponding author.

 

"Boosting this signaling system could represent a new treatment approach for these stress-linked disorders," he said.

 

Patel, the James G. Blakemore Professor of Psychiatry, received a Presidential Early Career Award for Scientists and Engineers last year for his pioneering studies of the endocannabinoid family of signaling molecules that activate the CB1 and CB2 cannabinoid receptors in the brain.

 

Tetrahydrocannabinol (THC), the active compound in marijuana, binds the CB1 receptor, which may explain why relief of tension and anxiety is the most common reason cited by people who use marijuana chronically.

 

Patel and his colleagues previously have found CB1 receptors in the amygdala, a key emotional hub in the brain involved in regulating anxiety and the fight-or-flight response. They also showed in animal models that anxiety increases when the CB1 receptor is blocked by a drug or its gene is deleted.

 

More recently they reported anxiety-like and depressive behaviors in genetically modified mice that had an impaired ability to produce 2-arachidonoylglycerol (2-AG), the most abundant endocannabinoid. When the supply of 2-AG was increased by blocking an enzyme that normally breaks it down, the behaviors were reversed.

 

In the current study, the researchers tested the effects of increasing or depleting the supply of 2-AG in the amygdala in two populations of mice: one previously determined to be susceptible to the adverse consequences of acute stress, and the other which exhibited stress-resilience.

 

Augmenting the 2-AG supply increased the proportion of stress-resilient mice overall and promoted resilience in mice that were previously susceptible to stress, whereas depleting 2-AG rendered previously stress-resilient mice susceptible to developing anxiety-like behaviors after exposure to acute stress.

 

Taken together, these results suggest that 2-AG signaling through the CB1 receptor in the amygdala promotes resilience to the adverse effects of acute traumatic stress exposure, and support previous findings in animal models and humans suggesting that 2-AG deficiency could contribute to development of stress-related psychiatric disorders.

 

Marijuana use is highly cited by patients with PTSD as a way to control symptoms. Similarly, the Vanderbilt researchers found that THC promoted stress-resilience in previously susceptible mice.

 

However, marijuana use in psychiatric disorders has obvious drawbacks including possible addiction and cognitive side effects, among others. The Vanderbilt study suggests that increasing production of natural cannabinoids may be an alternative strategy to harness the therapeutic potential of this signaling system.

 

If further research finds that some people with stress-related mood and anxiety disorders have low levels of 2-AG, replenishing the supply of this endocannabinoid could represent a novel treatment approach and might enable some of them to stop using marijuana, the researchers concluded.

https://www.sciencedaily.com/releases/2017/03/170329140945.htm

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