New Class of Chemicals Found to Use Marijuana-Like System in Brain
May 4, 2000
Science Daily/University of California, Irvine
Researchers at UC Irvine's College of Medicine have developed a chemical that could form the basis of a new class of drugs to treat a number of psychiatric disorders, including schizophrenia, Parkinson's disease, autism and attention-deficit hyperactivity disorder.
The chemical, which has been tested on rats, affects brain cells that use chemicals similar to marijuana to counteract the actions of a neurotransmitter called dopamine. Dopamine has been implicated in schizophrenia, Parkinson's disease, Tourette's syndrome and many other psychiatric disorders. The researchers' findings appear in the May issue of the Journal of Neuroscience.
Daniele Piomelli, professor of pharmacology, led a team that found that a chemical called AM404 reversed the normal inactivation of a naturally occurring chemical in the brain called anandamide, which is related to marijuana's active ingredient and opposes the actions of dopamine. By reversing the inactivation of anandamide, AM404 is able to gently curb the exaggerated movements and other disorders caused by too much dopamine activity in nerve cells.
"We were excited to find this action of AM404 in the brain. It's very encouraging to see it work in a very subtle and effective way to counteract the effects of too much dopamine-induced activity," said Piomelli. "With further testing, we hope this eventually will result in new treatments that don't have the side effects of many current psychiatric drugs."
Piomelli and his colleagues found that AM404 targeted nerves that produced unusually high levels of dopamine and caused exaggerated movements andother problems in rats. Instead of directly encouraging the production of dopamine-curbing anandamide, AM404 was found to discourage the disintegration of existing anandamide. More anandamide was then available to bind to receptors on nerve cells and reduce the stimulation of nerve cells by dopamine.
If further research proves successful, the chemical could be used to treat schizophrenia, Tourette's, Parkinson's, autism and attention-deficit disorder, all of which are currently treated by drugs that attack the dopamine system in the brain.
Piomelli warns that their research on cannabinoid receptors has shown consistently that smoking marijuana may actually make these disorders worse. "Although AM404 helps to manipulate cannabinoid receptors, we think that using marijuana directly creates too severe a reaction and can create adverse reactions among people suffering from these diseases," he said.
The researchers, who have been working for several years on detailing the cannabinoid nerve cell system in the brain, are now looking at how AM404 selects the nerve cells it affects in the brain.
"AM404's selection of nerve cells may mean that treatments may not have the side effects of many current drugs, which aren't as selective about the nerve cells they impact," Piomelli said. "Once we see how the drug actually works in the brain, we'll have a better idea of what disorders it may be most effective at treating. Using brain scans and analyzing the uptake of AM404 in rats and other animals, we can have a better idea of where it's working."
Piomelli's colleagues in this study were Massimo Beltramo and Andrea Giuffrida at UCI; Fernando Rodriguez de Fonseca, Miguel A. Gorriti and Miguel Navarro at the Complutense University, Madrid, Spain, and Antonio Calignano, Gerasimos Grammatikopoulos and Antonio G. Sadile at the University of Naples, Italy.
The researchers' work was supported by a grant from the National Institute of Drug Abuse.
https://www.sciencedaily.com/releases/2000/05/000503183344.htm
Cannabinoids' Role in Retinal Function Described
December 8, 1999
Science Daily/University of California, San Diego
A team led by scientists from the University of California, San Diego (UCSD) has demonstrated the prevalence of cannabinoid receptors in the retina, indicating an important role for cannabinoids—a family of compounds which includes the psychoactive components of marijuana and hashish—in retinal function and perhaps vision in general.
The UCSD researchers, in collaboration with colleagues from The Neurosciences Institute in San Diego and the University of Washington in Seattle, have described for the first time the specific distribution and effects on retinal function of the cellular receptor proteins activated by cannabinoids.
These findings, published in the December 7 issue of the Proceedings of the National Academy of Sciences (PNAS), may provide a missing link in efforts to unravel the complicated and fascinating machinery by which the retina turns light into meaningful information in the brain. The work also provides greater understanding of the effects of marijuana and hashish, drugs which have been used by man for millennia.
“The retina is incredibly complex, highly sensitive to shifts in light levels, and responsive to contrasts, colors and lines,” said Alex Straiker, principal author of the PNAS paper and a graduate student in UCSD's neuroscience program. “We understand very little about how the retina works. By demonstrating that this receptor system is present, we add another piece to the puzzle, opening one more window into how the eye works. It also suggests that marijuana affects vision because it plugs into an existing signaling system that is abundant in the retina.”
Cannabinoids are naturally occurring compounds in vertebrates, and are known to play an important role in intercellular signaling. The chemical THC found in marijuana is a cannabinoid, though different from the ones produced by the body. Two cannabinoid receptors, CB1 and CB2, were discovered only the last ten years. CB1 exists primarily in the central nervous system, while CB2 is found primarily in the peripheral nervous system.
The PNAS paper reports that the retinal cells of rhesus monkeys, chicks, salamanders, goldfish, mice and rats, all similar in many respects to the human eye, contain high levels of CB1. The researchers also found CB1 receptors localized in both rod and cone photoreceptors, the retinal structures that respond to light, processing colors and black and white images. The extensive and consistent localization of these receptors in the retinas of a variety of species suggests that they play a fundamental role in modulating the transmission of signals critical for visual perception.
“The fact that this system is so highly conserved in species separated by hundreds of millions of years of evolution suggests that it's important,” said Straiker. “Nature likes to tinker, so any time you see something this consistent, it raises eyebrows.” The paper also points to a functional role of cannabinoids in the inhibition of calcium channels involved in visual signaling.
“Two key players in the processing of light information in the retina are photoreceptors, which catch light and turn it into a signal that can be interpreted by other cells, and bipolar cells, which are next in line in the flow of information,” said Straiker. “Communication between the cells requires the release of a neurotransmitter called glutamate, triggered by calcium currents passing through a specific calcium channel. Cannabinoids are known to inhibit calcium channels. If you shut down the channel, you shut down the release of glutamate, and profoundly alter the cell's ability to signal.”
Some of the reported effects of the use of marijuana and hashish include the perception of a snowy visual field, increased light intensity and altered vision. In fact, Straiker said his interest in seeking CB1 receptors in the retina was sparked in part by accounts of dramatic alterations in visual perception following marijuana use.
These findings suggest that at least some of the visual effects of marijuana and hashish use occur at the earliest stage of visual processing, as the calcium channels critical for the normal processing of visual information are inhibited.
Co-authors of the paper are Harvey Karten, professor of neurosciences, and Greg Maguire, formerly assistant adjunct professor of ophthalmology, both of the UCSD School of Medicine; Nephi Stella and Daniele Piomelli, formerly at The Neurosciences Institute, and Ken Mackie of the University of Washington.
The research was supported by the National Institutes of Health, The Glaucoma Foundation, and the Neurosciences Institute, which receives major support from Novartis.
Straiker is a graduate student in the UCSD Graduate Program in Neurosciences, ranked as the premier neuroscience graduate program in the country by a National Research Council survey of the National Academy of Sciences. Straiker is presently continuing his work as a graduate student and researcher in the Molecular Neurobiology Laboratory at The Salk Institute, a participating institution.
https://www.sciencedaily.com/releases/1999/12/991208061213.htm
UC Irvine Researchers Demonstrate How Marijuana-Like Chemicals Work in the Brain
March 23, 1999
Science Daily/University of California, Irvine
Findings Could Lead to New Treatments for Schizophrenia, Parkinson's, Other Diseases
Researchers at UC Irvine's College of Medicine have discovered how chemicals in the brain that are related to the active ingredient of marijuana help regulate body movements and other motor activity in rats.
In the April issue of the journal Nature Neuroscience, the researchers also report finding a network of these chemicals within the brain that prevents the overactive motor behavior found in schizophrenia, Parkinson's disease and Tourette's syndrome. The discoveries ultimately could result in new treatments for these and other neurological diseases.
Daniele Piomelli, associate professor of pharmacology, and Andrea Giuffrida, a post-doctoral researcher, found that a marijuana-like chemical called anandamide (the Sanskrit word for "bliss") inhibits the effects of nerve cells that transmit dopamine, which is largely responsible for stimulating movement and other motor behavior in the brain. For years, scientists have linked the uncontrolled production of dopamine to schizophrenia, Tourette's syndrome (which causes severe "nervous tics") and Parkinson's disease.
"This shows for the first time how anandamides work in the brain to produce normal motor activity," Piomelli said. "Patients with schizophrenia and other diseases have reported that marijuana appears to relieve some of their symptoms, but scientists have never found a physiological reason why. By understanding how the anandamide system works similarly to marijuana, we can explore new ways to treat these diseases more effectively."
But Piomelli said his research group will not consider marijuana in future research aimed at developing new treatments, because its chemical activity doesn't produce the effects on dopamine that are useful for treating these diseases. "Marijuana doesn't provide the regulatory effects on dopamine in the brain that we're looking for," he said.
The researchers found that anandamide is part of a network of nerve cells in an area of the brain called the striatum, which coordinates all body movements and other motor behavior. In the striatum, the anandamide network inhibited dopamine's attempts to stimulate the body's motor nerves. Normally, nerve cells regulate this behavior by releasing anandamides at the same time they release dopamine. In order to temper the effects of dopamine, the anandamides bind to nerve cell sites called cannabinoid receptors, so-named because they are targets of tetrahydrocannabinol (marijuana's active ingredient) as well as related chemicals like anandamides. When anandamides were bound to these receptors, body movement in the rats decreased.
But when the researchers prevented the cannabinoid receptors from binding to anandamides, the blocked nerve cells could no longer inhibit dopamine's effects. In such a state, the rats experienced severe nervous tics and other uncontrolled motor activity. In humans, such exaggerated activity brought on by unregulated dopamine production can result in diseases such as schizophrenia, Tourette's and Parkinson's.
By enhancing the nerve cells' sensitivity to anandamide, new medicines could treat these diseases without the side effects of current medicines, Piomelli said. "Current drugs certainly halt the actions of dopamine, but the side effects, including sedation and dizziness, are very severe," he said. "Drugs that exploit the anandamide system can provide a gentler way of reducing the hyperactivity in the brain caused by too much dopamine."
But Piomelli said it will be many years before any drugs will be available on the market. "We're just beginning to map out where this system works in rats' brains. We still are a long way from knowing how anandamides work in humans, and any potential drugs would have to be tested rigorously for their effectiveness and safety."
Piomelli's research group discovered the existence of anandamides in the brain and has spent several years exploring how these chemicals and their nerve-cell receptors work in the central nervous system. Piomelli and Giuffrida were assisted in their research by Loren H. Parsons and Toni Kerr at the Scripps Research Institute, La Jolla, Calif., and Fernando Rodriguez de Fonseca and Miguel Navarro of the Universidad Complutense, Madrid.
https://www.sciencedaily.com/releases/1999/03/990323050735.htm
Insights on marijuana and opioid use in people with cancer
April 22, 2019
Science Daily/Wiley
A new study reveals that many people with cancer use marijuana, and rates of use in the U.S. have increased over time. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the study also found that patients with cancer are more likely to use prescription opioids than adults without cancer.
Pain is a common symptom of cancer, and many affected patients do not receive adequate pain relief. In light of rapidly evolving marijuana legislation and a growing opioid epidemic, a team led by Jona Hattangadi-Gluth, MD, and Kathryn Ries Tringale, MD, MAS, of the University of California, San Diego, examined trends in the self-disclosed use of marijuana and opioids among patients with cancer.
After analyzing data from the U.S. National Health and Nutrition Examination Survey between 2005 and 2014, the investigators matched 826 people with cancer to 1,652 controls without cancer. Among survey respondents who had cancer, 40.3 percent used marijuana within the past year, compared with 38.0 percent of respondents without cancer. Also, people with cancer were more likely to use prescription opioids than their demographically equivalent counterparts without cancer (13.9 percent versus 6.4 percent).
"Prospective clinical trials are needed to quantify the efficacy of marijuana in cancer-specific pain as well as the risk of opioid misuse in this patient population," said Dr. Tringale.
When looking at rates of marijuana and opioid use in more than 19,000 survey respondents with and without cancer over 10 years, the researchers found significantly increased use of marijuana over time -- likely reflecting increased availability due to legislative changes -- but they found stable rates of opioid use. A diagnosis of cancer did not significantly affect the odds of substance use over time from 2005 to 2014.
"Medical marijuana legalization has previously been associated with a reduction in hospitalizations related to opioid dependence or abuse, suggesting that if patients are in fact substituting marijuana for opioids, this may introduce an opportunity for reducing opioid-related morbidity and mortality," said Dr. Hattangadi-Gluth. "Of course, it will also be important to identify risks and adverse effects of marijuana, which has not previously been studied on large randomized clinical trials, given its scheduling as a class 1 controlled substance."
https://www.sciencedaily.com/releases/2019/04/190422100947.htm
Marijuana users weigh less, defying the munchies
April 19, 2019
Science Daily/Michigan State University
New evidence from Michigan State University suggests that those who smoke cannabis, or marijuana, weigh less compared to adults who don't.
The findings, published in the International Journal of Epidemiology, are contrary to the belief that marijuana users who have a serious case of the munchies will ultimately gain more weight.
"Over a three-year period, all participants showed a weight increase, but interestingly, those who used marijuana had less of an increase compared to those that never used," said Omayma Alshaarawy, lead author and an assistant professor of family medicine. "Our study builds on mounting evidence that this opposite effect occurs."
Results also suggest that new and persistent users are less likely to be overweight or obese, overall.
"We found that users, even those who just started, were more likely to be at a normal, healthier weight and stay at that weight," she said. "Only 15% of persistent users were considered obese compared to 20% of non-users."
Researchers used data from the National Epidemiologic Survey of Alcohol and Related Conditions and looked at the Body Mass Index, or BMI, of 33,000 participants, ages 18 and older, then compared the numbers.
While the actual weight difference among users and non-users was modest, around 2 pounds for a 5-foot-7-inch participant weighing about 200 pounds at the start of the study, the variance was prevalent among the entire sample size.
"An average 2-pound difference doesn't seem like much, but we found it in more than 30,000 people with all different kinds of behaviors and still got this result," Alshaarawy said.
So, what is it about marijuana that seems to affect weight? Alshaarawy indicated it's still relatively unknown but it could be several factors.
"It could be something that's more behavioral like someone becoming more conscious of their food intake as they worry about the munchies after cannabis use and gaining weight," she said. "Or it could be the cannabis use itself, which can modify how certain cells, or receptors, respond in the body and can ultimately affect weight gain. More research needs to be done."
Alshaarawy cautions, though, that marijuana should not be considered a diet aid.
"There's too many health concerns around cannabis that far outweigh the potential positive, yet modest, effects it has on weight gain," she said. "People shouldn't consider it as a way to maintain or even lose weight."
https://www.sciencedaily.com/releases/2019/04/190419094026.htm
Cannabidiol could help deliver medications to the brain
April 17, 2019
Science Daily/American Chemical Society
Cannabidiol (CBD), a non-psychoactive compound in cannabis, is being touted as beneficial for many health conditions, ranging from anxiety to epilepsy. Although much more research is needed to verify these claims, scientists have now shown that CBD could have a different use as a "Trojan horse": helping slip medications across the blood-brain barrier (BBB) and into mouse brains. The researchers report their results in the ACS journal Molecular Pharmaceutics.
The BBB consists of a layer of tightly linked cells that line capillaries in the brain, preventing substances from exiting the blood and entering the brain. However, the BBB does permit some molecules to pass, such as glucose and certain amino acids and neurotransmitters. For example, a class of neurotransmitters called endocannabinoids bind to proteins called cannabinoid receptors in the BBB, and the receptors help transport the molecules across the barrier and into the brain. Ana Torres-Suárez and colleagues wanted to make use of this system to sneak drug nanocarriers into the brains of mice.
To do so, the researchers attached CBD, which resembles endocannabinoids made by both mice and humans, to the outside surfaces of lipid nanocapsules. Instead of loading the nanocapsules with a medication, the researchers packaged them with a fluorescent molecule so they could track the particles. In experiments with human brain cells that mimic the BBB, the researchers showed that the CBD-displaying nanocarriers caused more of the fluorescent molecule to pass through the cells than nanocarriers of equal size that lacked CBD. Similarly, when injected into healthy mice, the CBD-nanocapsules targeted about 2.5 times more of the fluorescent molecule to the animals' brains.
https://www.sciencedaily.com/releases/2019/04/190417102739.htm
Mindful body awareness training during treatment for drug addiction helps prevent relapse
April 16, 2019
Science Daily/University of Washington
A novel type of body awareness training helps women recover from drug addiction, according to new research. People in the study made marked improvement, and many improvements lasted for a year.
It's the first time the mindfulness approach has been studied in a large randomized trial as an adjunct treatment. The training helps people better understand the physical and emotional signals in their body and how they can respond to these to help them better regulate and engage in self-care.
"We could teach this intervention successfully in eight weeks to a very distressed population, and participants not only really learned these skills, they maintained increases in body awareness and regulation over the yearlong study period," said Cynthia J. Price, a research associate professor in the UW School of Nursing and lead author of the study. "The majority of participants also reported consistent use of MABT skills, on a weekly basis, over the duration of the study."
And likely due to using the skills learned in the intervention, the women showed less relapse to drug and alcohol use compared to those who didn't receive the intervention, Price said. The findings were published in March in the journal Drug and Alcohol Dependence.
The training included one-on-one coaching in an outpatient setting, in addition to the substance use disorder treatment the women were already receiving. The intervention is called Mindful Awareness in Body-oriented Therapy (MABT) and combines manual, mindfulness and psycho-educational approaches to teach interoceptive awareness and related self-care skills. Interoceptive awareness is the ability to access and process sensory information from the body.
Researchers studied 187 women at three Seattle-area locations. The cohort, all women in treatment for substance use disorder (SUD), was split into three relatively equal groups. Every group continued with their regular SUD treatment. One group received SUD treatment only, another group was taught the mindfulness technique in addition to treatment, and the third group received a women's education curriculum in addition to treatment in order to test whether the additional time and attention explained any positive study outcomes.
Women were tested at the beginning, and at three, six and 12 months on a number of factors including substance use, distress craving, emotion regulation (self-report and psychophysiology), mindfulness skills and interoceptive awareness. There were lasting improvements in these areas for those who received the MABT intervention, but not for the other two study groups.
"Those who received MABT relapsed less," Price said. "By learning to attend to their bodies, they learned important skills for better self-care."
https://www.sciencedaily.com/releases/2019/04/190416141909.htm
Regular cannabis users require up to 220% higher dosage for sedation in medical procedures
Physicians concerned over possible rise in adverse side effects
April 15, 2019
Science Daily/American Osteopathic Association
Researchers in Colorado examined medical records of 250 patients who received endoscopic procedures after 2012, when the state legalized recreational cannabis. They found patients who smoked or ingested cannabis on a daily or weekly basis required 14% more fentanyl, 20% more midazolam, and 220% more propofol to achieve optimum sedation for routine procedures, including colonoscopy.
Patients who regularly use cannabis may require more than two times the usual level of sedation when undergoing medical procedures, according to a study published in The Journal of the American Osteopathic Association.
Researchers in Colorado examined medical records of 250 patients who received endoscopic procedures after 2012, when the state legalized recreational cannabis. They found patients who smoked or ingested cannabis on a daily or weekly basis required 14% more fentanyl, 20% more midazolam, and 220% more propofol to achieve optimum sedation for routine procedures, including colonoscopy.
"Some of the sedative medications have dose-dependent side effects, meaning the higher the dose, the greater likelihood for problems," says lead researcher Mark Twardowski, DO, an osteopathic internal medicine physician. "That becomes particularly dangerous when suppressed respiratory function is a known side effect."
A lack of research, due to cannabis's status as a schedule 1 drug, combined with its sudden widespread legalization, makes Dr. Twardowski concerned about other unforeseen issues.
"Cannabis has some metabolic effects we don't understand and patients need to know that their cannabis use might make other medications less effective. We're seeing some problematic trends anecdotally, and there is virtually no formal data to provide a sense of scale or suggest any evidence-based protocols," says Dr. Twardowski.
He says colleagues in nearby emergency departments have noticed more patients reporting with complaints of chronic nausea, a symptom that can occur from regular cannabis use. He also says that colleagues in anesthesiology have noted patients requiring much higher dosages for general anesthesia and higher rates of post-op seizures.
These types of recurring stories prompted Dr. Twardowski and his colleagues to gather real data.
Potential for more insight
Cannabis use in the United States increased 43% between 2007 and 2015. An estimated 13.5% of the adult population used cannabis during this period, with the greatest increase recorded among people 26 and older, according to the study.
As more states legalize medical and recreational cannabis, there is also greater potential for meaningful data collection. Not only are more patients using cannabis, but more are also now willing to admit cannabis use than in the past, which increases the likelihood that they will be forthcoming when questioned by a medical professional.
Adding specific questions regarding cannabis use to patient intake forms is the first step to acquiring useful information that influences patient care, according to researchers.
"This study really marks a small first step," says Dr. Twardowski. "We still don't understand the mechanism behind the need for higher dosages, which is important to finding better care management solutions."
Dr. Twardowski's team is developing a follow-up study on differences in requirements for sedation and anesthesia as well as post-procedure pain management for regular cannabis users versus non users.
https://www.sciencedaily.com/releases/2019/04/190415172147.htm
One-third of cancer patients use complementary and alternative medicine
April 11, 2019
Science Daily/UT Southwestern Medical Center
A stunning one-third of people with a cancer diagnosis use complementary and alternative medicines such as meditation, yoga, acupuncture, herbal medicine, and supplements.
UT Southwestern Medical Center's Dr. Nina Sanford made the discovery that's now drawing renewed attention to habits she said cancer patients must disclose during treatment. Dr. Sanford is an Assistant Professor of Radiation Oncology who specializes in and treats cancers of the gastrointestinal tract.
Herbal supplements were the most common alternative medicine and chiropractic, or osteopathic manipulation, was the second most common, according to Dr. Sanford's analysis of data from the Centers for Disease Control and Prevention's National Health Interview Survey. Her findings were published in the journal JAMA Oncology.
"Younger patients are more likely to use complementary and alternative medicines and women were more likely to, but I would have thought more people would tell their doctors," Dr. Sanford said, referring to the finding that 29 percent of people who use complementary and alternative medicine did not tell their physicians. Many survey respondents said they did not say anything because their doctors did not ask, or they did not think their doctors needed to know.
Dr. Sanford and other cancer specialists agree this is concerning, especially in the case of herbal supplements.
"You don't know what's in them," Dr. Sanford said. "Some of these supplements are kind of a mishmash of different things. Unless we know what's in them, I would recommend patients avoid using them during radiation because there's likely not data on certain supplements, which could interfere with treatment. With radiation specifically, there is concern that very high levels of antioxidants could make radiation less effective."
Dr. David Gerber, a lung cancer specialist and a Professor of Internal Medicine and Population and Data Sciences at UTSW, said physicians need to know if their patients use herbal supplements because they can completely throw off traditional cancer treatments.
"They may interact with the medicines we're giving them, and through that interaction it could alter the level of the medicine in the patient," he said. "If the levels get too high, then toxicities increase, and if the levels get too low, the efficacy would drop."
Nancy Myers wanted to use supplements during her 2015-2017 cancer treatments, but she ran it by her doctors first.
"I would ask the physician, 'Could I?' and everyone said, 'No, we don't know how that interacts with your conventional medicine,' so I respected that," the 47-year-old mother of four said. Only after treatment did she start taking turmeric, omega-3, vitamin D, and vitamin B6.
"I have plenty of friends in this cancer journey who I've met who take supplements. A lady I met recently takes 75 supplements a day. It takes her two hours to package her supplements every week," she said.
Ms. Myers said every person in her cancer support group uses some kind of alternative medicine. In addition to supplements, she practices meditation and yoga with guidance from a smartphone app.
"It's what we can control. We can't control the whole cancer," she said. "It helps because it takes your mind off just thinking about it."
She said she knows of some people with cancer who use only alternative medicine -- and no traditional medical treatments. Dr. Sanford said this is a dangerous approach that could be fatal. The most famous case of this was Apple founder Steve Jobs, who reportedly used special diets, acupuncture, and other alternatives after receiving a diagnosis of pancreatic cancer. He turned to traditional medicine late in his battle with cancer and died in 2011.
While doctors are highly cautious about the use of herbs and other supplements during treatment, they are much more open to meditation and yoga as practices that can help patients cope with the shock of a cancer diagnosis and the stress of chemotherapy, radiation, and surgery.
"We strongly advise patients to stay active and engage in exercise during treatment," Dr. Sanford said. "A common side effect of radiation is fatigue. I let the patients know that the patients who feel the most fatigue are the ones who are the most sedentary and that those who are doing exercise are the ones who frequently have the most energy."
Belindy Sarembock, 53, of Dallas, said she practiced yoga during her treatments for breast cancer. She started the classes with skepticism and quickly became convinced of the benefits.
"I was one who would have laughed at yoga before breast cancer, but now it just helps me so much," she said. "It's just so relaxing, I just feel so good after I leave. It's just so peaceful. For your body, I can't think of anything better than that."
She said she had neuropathy or nerve damage from chemotherapy, and yoga almost immediately took the pain away.
"I couldn't get onto my toes. After the second time of going to yoga, I was able to go onto my toes," she said. "I wish I would have known about the yoga earlier. It was just such a benefit and helped me so much. I highly recommend it to anyone."
https://www.sciencedaily.com/releases/2019/04/190411172529.htm
Woman with novel gene mutation lives almost pain-free
March 27, 2019
Science Daily/University College London
A woman in Scotland can feel virtually no pain due to a mutation in a previously-unidentified gene, according to a research paper co-led by UCL.
She also experiences very little anxiety and fear, and may have enhanced wound healing due to the mutation, which the researchers say could help guide new treatments for a range of conditions, they report in the British Journal of Anaesthesia.
"We found this woman has a particular genotype that reduces activity of a gene already considered to be a possible target for pain and anxiety treatments," said one of the study's lead researchers, Dr James Cox (UCL Medicine).
"Now that we are uncovering how this newly-identified gene works, we hope to make further progress on new treatment targets."
At age 65, the woman sought treatment for an issue with her hip, which turned out to involve severe joint degeneration despite her experiencing no pain. At age 66, she underwent surgery on her hand, which is normally very painful, and yet she reported no pain after the surgery. Her pain insensitivity was diagnosed by Dr Devjit Srivastava, Consultant in Anaesthesia and Pain Medicine at an NHS hospital in the north of Scotland and co-lead author of the paper.
The woman tells researchers she has never needed painkillers after surgery such as dental procedures.
She was referred to pain geneticists at UCL and the University of Oxford, who conducted genetic analyses and found two notable mutations. One was a microdeletion in a pseudogene, previously only briefly annotated in medical literature, which the researchers have described for the first time and dubbed FAAH-OUT. She also had a mutation in the neighbouring gene that controls the FAAH enzyme.
Further tests by collaborators at the University of Calgary, Canada, revealed elevated blood levels of neurotransmitters that are normally degraded by FAAH, further evidence for a loss of FAAH function.
The FAAH gene is well-known to pain researchers, as it is involved in endocannabinoid signalling central to pain sensation, mood and memory. The gene now called FAAH-OUT was previously assumed to be a 'junk' gene that was not functional. The researchers found there was more to it than previously believed, as it likely mediates FAAH expression.
Mice that do not have the FAAH gene have reduced pain sensation, accelerated wound healing, enhanced fear-extinction memory and reduced anxiety.
The woman in Scotland experiences similar traits. She notes that in her lifelong history of cuts and burns (sometimes unnoticed until she can smell burning flesh), the injuries tend to heal very quickly. She is an optimist who was given the lowest score on a common anxiety scale, and reports never panicking even in dangerous situations such as a recent traffic incident. She also reports memory lapses throughout life such as forgetting words or keys, which has previously been associated with enhanced endocannabinoid signalling.
The researchers say that it's possible there are more people with the same mutation, given that this woman was unaware of her condition until her 60s.
"People with rare insensitivity to pain can be valuable to medical research as we learn how their genetic mutations impact how they experience pain, so we would encourage anyone who does not experience pain to come forward," said Dr Cox.
The research team is continuing to work with the woman in Scotland, and are conducting further tests in cell samples, in order to better understand the novel pseudogene.
"We hope that with time, our findings might contribute to clinical research for post-operative pain and anxiety, and potentially chronic pain, PTSD and wound healing, perhaps involving gene therapy techniques," said Dr Cox.
"The implications for these findings are immense," said Dr Srivastava.
"One out of two patients after surgery today still experiences moderate to severe pain, despite all advances in pain killer medications and techniques since the use of ether in 1846 to first 'annul' the pain of surgery. There have already been unsuccessful clinical trials targeting the FAAH protein -- while we hope the FAAH-OUT gene could change things particularly for post-surgical pain, it remains to be seen if any new treatments could be developed based on our findings."
"The findings point towards a novel pain killer discovery that could potentially offer post-surgical pain relief and also accelerate wound healing. We hope this could help the 330 million patients who undergo surgery globally every year," Dr Srivastava said.
"I would be elated if any research into my own genetics could help other people who are suffering," the woman in Scotland commented.
"I had no idea until a few years ago that there was anything that unusual about how little pain I feel -- I just thought it was normal. Learning about it now fascinates me as much as it does anyone else."
Lead funding for the study came from the Medical Research Council and Wellcome.
https://www.sciencedaily.com/releases/2019/03/190327203450.htm
Ketamine reverses neural changes underlying depression-related behaviors in mice
Study sheds light on the neural mechanisms underlying remission of depression
April 11, 2019
Science Daily/NIH/National Institute of Mental Health
Researchers have identified ketamine-induced brain-related changes that are responsible for maintaining the remission of behaviors related to depression in mice -- findings that may help researchers develop interventions that promote lasting remission of depression in humans. The study, funded by the National Institute of Mental Health (NIMH), part of the National Institutes of Health, appears in the journal Science.
Major depression is one of the most common mental disorders in the United States, with approximately 17.3 million adults experienced a major depressive episode in 2017. However, many of the neural changes underlying the transitions between active depression, remission, and depression re-occurrence remain unknown. Ketamine, a fast-acting antidepressant which relieves depressive symptoms in hours instead of weeks or longer, provides an opportunity for researchers to investigate the short- and long-term biological changes underlying these transitions.
"Ketamine is a potentially transformative treatment for depression, but one of the major challenges associated with this drug is sustaining recovery after the initial treatment," said study author Conor Liston, M.D., Ph.D., of Weill Cornell Medicine, New York City.
To understand mechanisms underlying the transition from active depression to remission in humans, the researchers examined behaviors related to depression in mice. Researchers took high-resolution images of dendritic spines in the prefrontal cortex of mice before and after they experienced a stressor. Dendritic spines are protrusions in the part of neurons that receive communication input from other neurons. The researchers found that mice displaying behaviors related to depression had increased elimination of, and decreased formation of, dendritic spines in their prefrontal cortex compared with mice not exposed to a stressor. This finding replicates prior studies linking the emergence of behaviors related to depression in mice with dendritic spine loss.
In addition to the effects on dendritic spines, stress reduced the functional connectivity and simultaneous activity of neurons in the prefrontal cortex of mice. This reduction in connectivity and activity was associated with behaviors related to depression in response to stressors. Liston's group then found that ketamine treatment rapidly restored functional connectivity and ensemble activity of neurons and eliminated behaviors related to depression. Twenty-four hours after receiving a single dose of ketamine, mice exposed to stress showed a reversal of behaviors related to depression and an increase in dendritic spine formation when compared to stressed mice that had not received ketamine. These new dendritic spines were functional, creating working connections with other neurons.
The researchers found that while behavioral changes and changes in neural activity in mice happened quickly (three hours after ketamine treatment), dendritic spine formation happened more slowly (12-24 after hours after ketamine treatment). While further research is needed, the authors suggest these findings might indicate that dendritic spine regrowth may be a consequence of ketamine-induced rescue of prefrontal cortex circuit activity.
Although dendritic spines were not found to underly the fast-acting effects of ketamine on behaviors related to depression in mice, they were found to play an important role in maintaining the remission of those behaviors. Using a new technology developed by Haruo Kasai, Ph.D., and Haruhiko Bito, Ph.D., collaborators at the University of Tokyo, the researchers found that selectively deleting these newly formed dendritic spines led to the re-emergence of behaviors related to depression.
"Our results suggest that interventions aimed at enhancing synapse formation and prolonging their survival could be useful for maintaining the antidepressant effects of ketamine in the days and weeks after treatment," said Dr. Liston.
"Ketamine is the first new anti-depressant medication with a novel mechanism of action since the 1980s. Its ability to rapidly decrease suicidal thoughts is already a fundamental breakthrough," said Janine Simmons, M.D., Ph.D., chief of the NIMH Social and Affective Neuroscience Program. "Additional insights into ketamine's longer-term effects on brain circuits could guide future advances in the management of mood disorders."
https://www.sciencedaily.com/releases/2019/04/190411145105.htm
Marijuana for morning sickness? It's not great for baby's brain
Study pinpoints how pot exposure during pregnancy can lead to problems with behavior and memory
April 9, 2019
Science Daily/Experimental Biology
With a growing number of states legalizing recreational or medical marijuana, more women are using the drug during pregnancy, in part due to its reported ability to relieve morning sickness. A new study, conducted in rats, sheds light on how cannabis exposure affects the brain of a developing fetus.
Previous research has shown children born to mothers who used marijuana during pregnancy are more likely to develop behavioral problems as well as learning and memory impairments. The new research offers further confirmation on those findings and pinpoints how the drug alters the intricate connections in nerves in the hippocampus, the brain's center for learning and memory. Understanding exactly how marijuana affects these brain connections could one day lead to interventions to reduce the damage, researchers say.
"The findings from this study will serve as an excellent premise for future interventions to restore memory in children exposed to cannabis during pregnancy, and for the first time, identify a specific mechanism by which learning and memory impairment occurs and how this impairment can be ameliorated," said Priyanka Das Pinky, a graduate student in the laboratory of Vishnu Suppiramaniam, PhD, acting associate dean for research and graduate programs at Auburn University.
Pinky will present the research at the American Society for Pharmacology and Experimental Therapeutics annual meeting during the 2019 Experimental Biology meeting, held April 6-9 in Orlando, Fla.
According to one previous analysis, the use of marijuana during pregnancy increased by 62 percent between 2002 and 2014, paralleling the rising popularity of marijuana in the adult U.S. population as a whole.
"Based on our research and the previous existing findings in the field, it can be said that using marijuana during pregnancy would not be a wise choice," said Pinky. "However, it is also notable that the observed effect in the offspring can vary according to their age and according to the trimester during which they were exposed to the drug as well as dose and route of administration of the drug."
The research team raised several groups of rats and exposed some of the females to a synthetic chemical that activates the same proteins as cannabis while they were pregnant. They used a dose equivalent to moderate-to-heavy marijuana use in humans. Examining the brains of the baby rats, they found the connections, or synapses, between the nerves in the hippocampus were reduced in those exposed to the synthetic cannabis.
Upon further examination, they found evidence that the root of the problem was a reduction in neural cell adhesion molecules (NCAM), a protein important for maintaining proper neural connection and synaptic strength. The finding suggests it may be possible to counteract marijuana's effects by increasing the NCAM, though more research is needed to understand the mechanisms involved and determine whether the findings, from studies in animals, would translate to human babies.
"It is still very early to come up with a conclusion about the possible safe use of marijuana during pregnancy," Pinky said. "More research is needed to evaluate the exact mechanism by which NCAM and/or its active form is modulating cellular effects while focusing on target specific drug development for amelioration of the observed cognitive deficits."
https://www.sciencedaily.com/releases/2019/04/190409135933.htm
Combining opioids and marijuana may be advantageous for pain sufferers
Study suggests using the two drugs together could reduce risk of dependency without causing cognitive problems
April 9, 2019
Science Daily/Experimental Biology
Researchers report combining cannabinoids with morphine did not significantly increase impulsivity or memory impairment in a study conducted in rhesus monkeys. The findings suggest using opioids and marijuana together could offer a safe way to cut opioid dosage among patients suffering from pain and thereby reduce their risk of becoming addicted to opioids.
"These data provide additional evidence supporting the notion that opioid-cannabinoid mixtures that are effective for treating pain do not have greater, and in some cases have less, adverse effects compared with larger doses of each drug alone," said Vanessa Minervini, PhD, a postdoctoral fellow at the University of Texas Health Science Center at San Antonio.
Minervini will present the research at the American Society for Pharmacology and Experimental Therapeutics annual meeting during the 2019 Experimental Biology meeting, held April 6-9 in Orlando, Fla.
Previous studies have suggested the cannabinoids in marijuana enhance some of the pain-relieving effects of opioid drugs but do not enhance effects related to addiction and overdose. However, both drugs individually are known to slightly impair cognition, leading to a concern that such side effects could be amplified if opioids and marijuana are used together. Researchers say the new study offers encouraging evidence this is not the case.
The research comes amid a national opioid abuse crisis in which many addictions start with opioids prescribed for pain. At the same time, marijuana use is on the rise as more states legalize the drug for medical or recreational use.
"The current opioid epidemic underscores the need for safe and effective pharmacotherapies for treating pain," said Minervini. "Combining opioid receptor agonists with drugs that relieve pain through actions at non-opioid mechanisms (for example, cannabinoid receptors) could be a useful strategy for reducing the dose of opioid needed to achieve pain relief."
The researchers gave several monkeys moderate doses of morphine and CP55940, a synthetic drug that mimics the activity of the tetrahydrocannabinol (THC) naturally found in marijuana. They assessed impulsivity and memory with tests involving touchscreens and treats. The results showed each drug impeded performance and that giving the monkeys both drugs together had a lower effect on performance than either drug alone.
While clinical trials would need to be conducted to confirm whether these results translate to humans, monkeys tend to process drugs similarly to humans and are considered a good model for cognition.
https://www.sciencedaily.com/releases/2019/04/190409135930.htm
Performance-enhancing drugs may increase risk of teen cocaine abuse, impair fertility
Exposure to anabolic steroids increased psychoactive effects of cocaine in rat study
April 8, 2019
Science Daily/American Physiological Society
Performance-enhancing steroid use could increase the risk of cocaine use and addiction in teens, according to a new rodent study. The combination of these drugs could also impair fertility in young women. The research will be presented today at the American Physiological Society's (APS) annual meeting at Experimental Biology 2019 in Orlando, Fla.
Athletes sometimes use anabolic steroids to boost performance. In addition to building muscle, performance-enhancing drugs have been found to affect mood and behavior, including risk-taking behavior. Previous research has shown that approximately one-third of young adults who use anabolic steroids also use cocaine. This rate is substantially higher than the roughly 5 percent of young adults who use cocaine but do not take anabolic steroids. Although there appears to be a link between anabolic steroid use and the tendency to use other addiction-forming drugs in adults, it has not been well-studied in adolescents.
Researchers from the University of Puerto Rico studied female rats, half of which were exposed to nandrolone, one of the anabolic steroids most commonly used by young adults. After 10 days of steroid exposure, the animals were divided into four groups:
· One group was exposed to nandrolone only.
· One group was exposed to nandrolone and cocaine.
· One group was exposed to cocaine only.
· A control group was exposed to neither nandrolone nor cocaine.
The researchers observed that the group exposed to nandrolone showed increased sensitivity to cocaine -- called locomotor sensitization -- than the other groups. The researchers also saw a reduction in ovary weight and the development of ovarian cysts -- which can compromise fertility -- in the nandrolone groups. The animals exposed to cocaine alone did not show the same level of drug-induced locomotor sensitization.
Exposure to androgens during adolescence "modifies the brain circuitry that regulates addictive behaviors, increasing the psychoactive properties of cocaine," the researchers wrote. In addition, anabolic steroids are also detrimental to the female reproductive system and may reduce fertility. A similar outcome in humans could significantly increase the risk of cocaine addiction and negatively affect fertility in teen athletes who use performance-enhancing steroids.
https://www.sciencedaily.com/releases/2019/04/190408113944.htm
Fresh guidance to fill 'information vacuum' on new cannabis products for medicinal use
April 7, 2019
Science Daily/University of Bath
A clinical review, published today (Saturday 6 April 2019) for the BMJ, provides new interim advice for doctors and clinicians in prescribing cannabis-based products and cannabinoids to treat certain conditions.
Since a policy change in November 2018, specialist doctors registered with the General Medical Council (GMC), have been permitted to prescribe new medicines which derive from cannabis. Yet, research into these products has, to date, been limited creating an 'information vacuum' about these medicines, their benefits or harms.
A new review authored by leading scientists and clinicians from the University of Bath and University College London (UCL) points to the array of different cannabis-based products and cannabinoids available, and a clear need to educate both patients and clinicians into what these different products do and how they might help.
In particular, it points to important differences between products containing THC (the main psychoactive and intoxicating constituent of cannabis) versus CBD (the non-intoxicating element). Although in certain medicines CBD and THC are combined for clinical benefit, in others these components can work independently, playing different roles in improving certain symptoms.
For example, several studies have found that a combination of THC and CBD can alleviate symptoms of chronic pain, while CBD alone may be effective for treatment-resistant epilepsy. By contrast THC alone may be effective for treating nausea and vomiting caused by chemotherapy. THC and CBD are both 'cannabinoids' that act in different ways on the body's endogenous cannabinoid system.
The cannabis plant produces over 144 different cannabinoids such as THC or CBD. Some medicinal products contain THC and/or CBD derived from the cannabis plant, while others contain synthetically produced cannabinoids. CBD is also available in non-medicinal products such as oils and tinctures.
Lead author, Dr Tom Freeman of the University of Bath's Addiction and Mental Health Group explains: "In this complex and rapidly evolving field, there are several different cannabis-based and cannabinoid medicinal products. These differ in their THC and CBD content, who can prescribe them, and the conditions they may be used to treat. Here we provide an update for clinicians in advance of forthcoming NICE guidelines.
"A key message is that CBD products widely sold online and in health food shops lack quality standards and should not be treated as medicinal products."
Research on cannabis was previously restricted because it was listed in Schedule 1, implying that it had no medical value. Cannabis was recently moved to Schedule 2 in the UK.
Dr Freeman adds: "Research on unlicensed cannabis products has been limited to date. The rescheduling of cannabis and allocation of dedicated UK research funding will improve the evidence we have to guide clinical decision-making."
Co-author, Dr Michael Bloomfield Head of Translational Psychiatry at University College London (UCL) added: "There have been leaps and bounds in our scientific knowledge in recent years, which combined with confusing claims about the medicinal uses of these drugs can be potentially perplexing for doctors and patients. We hope that our new guidance is helpful to doctors and patients worldwide. Much more research is needed into this new class of medicine."
Co-author Dr Chandni Hindocha of the Clinical Psychopharmacology Unit at UCL added: "Resources must be made available to update and educate clinicians about cannabis and cannabinoid based medicines. We would like to encourage doctors to maintain a compassionate and evidence-based approach when engaging with their patients in this rapidly developing field, in order to provide the best standard of care."
https://www.sciencedaily.com/releases/2019/04/190407144234.htm
Severe psychological distress and daily cannabis use: Implications for mental health?
April 4, 2019
Science Daily/Columbia University's Mailman School of Public Health
Daily cannabis use increased significantly from 2008 to 2016 among those with and without past-month serious psychological distress (SPD) and use among those with SPD was persistently higher compared to those without SPD. Research at Columbia Mailman School and CUNY shows that in 2016, past-month daily cannabis use was about three times higher for SPD (8%) compared to those without SPD (2.7%). The findings are online in the journal Drug and Alcohol Dependence.
"Our research found that persons with SPD reported higher daily cannabis prevalence each study year," said senior author Renee Goodwin, PhD, Department of Epidemiology. "Therefore, it is important to consider potential consequences of this increased use for those with mental health vulnerabilities."
Data were drawn from adults age 18 and older in the 2008-2016 National Survey on Drug Use and Health, a sample of 356,413 and measured by the Kessler Psychological Distress Scale.
Non-Hispanic Black respondents were the only demographic group where daily cannabis use did not significantly differ among persons with and without SPD.
"With the rapid legalization of medicinal and recreational use of cannabis in the U.S. and liberalization of social norms, more research is needed to understand the impact of these changes on vulnerable groups," said Goodwin. "A better understanding of whether some subgroups need tailored clinical efforts to reduce (daily and/or heavy) cannabis use, especially among those with SPD, will also provide a clearer picture of what is needed next."
https://www.sciencedaily.com/releases/2019/04/190404132532.htm
Psychedelic drug MDMA may reawaken 'critical period' in brain to help treat PTSD
April 4, 2019
Science Daily/Johns Hopkins Medicine
Johns Hopkins neuroscientists have found that the psychedelic drug MDMA reopens a kind of window, called a "critical period," when the brain is sensitive to learning the reward value of social behaviors. The findings, reported April 3 in Nature, may explain why MDMA may be helpful in treating people with post-traumatic stress disorder (PTSD).
Critical periods were first described in the 1930s in snow geese. About 24 hours after a gosling hatches, if mother goose is nowhere to be found, the hatchling will bond with an object, including non-living ones. Yet, if mother goose disappears 48 hours after her gosling hatches, the critical period is over, and the hatchling won't bond to an object.
There is evidence for critical periods that smooth the way for development of language, touch and vision.
For the current study, neuroscientist Gül Dölen says, "We wanted to know if there was a critical period for learning social reward behaviors, and if so could we reopen it using MDMA, since this drug is well-known to have prosocial effects."
Dölen and her team studied groups of mice in enclosures with different bedding. They put several mice together in one enclosure with one type of bedding for 24 hours and, in the next 24 hours, put the same mice by themselves in another enclosure with a different type of bedding. The mice began to associate certain types of bedding with isolation or companionship. Then, they let the mice wander between enclosures with the two types of bedding and tracked how long the mice spent in each enclosure. The more time the mice spent in the bedding linked to their companions indicated more social reward learning.
"It's why people gather around the water cooler," says Dölen, assistant professor of neuroscience at the Johns Hopkins University School of Medicine. People are conditioned to know that the water cooler is an optimal place to chitchat with companions.
In their experiments, Dölen and her colleagues found that the critical period for social reward learning in mice is around puberty and wanes once they become mature adults. To determine if they could reopen the critical period, the scientists gave MDMA to mature mice, waited 48 hours for the drug to be washed out of their system, and observed how the mice explored their enclosure and behaved with other mice in the enclosure. Following the treatment with MDMA, most of the animals responded to social interactions the same way as juveniles, by forming a positive association between social interactions and the bedding. This effect lasted for at least two weeks after the MDMA treatment, and it was not observed in mice given saline injections.
"This suggests that we've reopened a critical period in mice, giving them the ability to learn social reward behaviors at a time when they are less inclined to engage in these behaviors," says Dölen.
Dölen and her postdoctoral student and first author of the current study, Romain Nardou, also observed that MDMA works to reopen the critical period only if the drug is given to mice when they are with other mice, not if it is given to mice while they are alone. This suggests that reopening the critical period using MDMA may depend on whether the animals are in a social setting, say the scientists.
The mice maintained their ability to learn the rewards of social behavior for up to two weeks from the time they were given MDMA. During this time, Dölen and her colleagues also found that the brains of the mice had corresponding responses to oxytocin, known as the "love hormone," which is made in the hypothalamus and acts in the brain as a signal between neurons that encode information about social rewards. They found these responses by looking more closely at synapses, the spaces between brain cells called neurons. Their experiments showed that, in mature mice given MDMA, oxytocin triggers signaling in the synapses that encodes learning and memory, which does not typically happen in mature mice.
Dölen says that opening the critical window for social reward behavior may also have implications for treating psychiatric conditions. A strong bond between a psychotherapist and patient is well-known to be important for successful treatment. If MDMA reopens the critical period for social reward learning in humans in the same way it does for mice, then it could explain why the drug has been successful in treating people with PTSD, perhaps by strengthening the psychotherapist-patient bond.
MDMA has been designated by the U.S. Food and Drug Administration as a "breakthrough therapy" for PTSD, meaning that the agency will fast-track the development and review of clinical trials to test it. However, the researchers caution that MDMA may not work for every psychiatric condition linked to social behaviors.
"As we develop new therapies or determine when to give these therapies, it's critical to know the biological mechanism on which they act," says Dölen.
Funding for the study was provided by the Kinship Foundation, Hartwell Foundation, Klingenstein-Simons Foundation, the National Institutes of Health (MH115177, 1R01NS075421), the New York Stem Cell Foundation-Robertson Award and the National Institutes of Health Director's Pioneer Award (1DP1NS087724).
In addition to Dölen and Nardou, other contributors to the study include Eastman M. Lewis and Rebecca Rothhaas from Johns Hopkins and Ran Xu, Aimei Yang and Edward Boyden from MIT.
https://www.sciencedaily.com/releases/2019/04/190404094832.htm
Psychostimulants play a major role in fatal strokes among young adults
April 3, 2019
Science Daily/Wiley
An estimated 76 million people use psychostimulants, which include illicit drugs such as methamphetamine, cocaine, and 3,4-methylenedioxymethamphetamine, as well as prescription stimulants. A new Journal of Forensic Sciences study from Australia is the first to present national data of psychostimulant use in young adults who experienced a fatal stroke.
Investigators found that from 2009-2016, psychostimulant users constituted nearly a fifth of the 279 cases of fatal stroke in adults aged 15-44 years, the majority of which had evidence of consumption immediately prior to the fatal stroke.
Methamphetamine was overwhelmingly the drug implicated. The median methamphetamine concentration was similar to that reported for all methamphetamine-related deaths in Australia but less than half that of deaths attributed solely to methamphetamine toxicity. This suggests that high concentrations are not essential to cause a methamphetamine-related stroke.
Cases of haemorrhagic stroke were also documented involving other illicit and licit psychostimulants. In no cases were medications for attention deficit hyperactivity disorder identified.
"This is the first study to show the major role that psychostimulants play in causing fatal strokes amongst young adults," said lead author Prof. Shane Darke, of the University of New South Wales, in Australia. "All of these deaths were preventable. Users of these drugs, however, appear to be largely unaware of the risk. Psychostimulant users, and those treating them, need to be aware of their elevated stroke risk, which may have devastating consequences.
https://www.sciencedaily.com/releases/2019/04/190403080504.htm
Brain growth inhibited by heavy alcohol use
April 1, 2019
Science Daily/Oregon Health & Science University
New research in nonhuman primates shows that heavy use of alcohol can actually slow the rate of growth in developing brains. The study, to be published April 1, in the journal eNeuro, shows that heavy alcohol use reduced the rate of brain growth by 0.25 milliliters per year for every gram of alcohol consumed per kilogram of body weight. In human terms, that's the equivalent of four beers per day.
Heavy use of alcohol among adolescents and young adults is not only dangerous in its own right, but new research in nonhuman primates shows that it can actually slow the rate of growth in developing brains.
The study, published today in the journal eNeuro, shows that heavy alcohol use reduced the rate of brain growth by 0.25 milliliters per year for every gram of alcohol consumed per kilogram of body weight. In human terms, that's the equivalent of four beers per day. The research involved rhesus macaque monkeys at the Oregon National Primate Research Center.
"Chronic alcohol self-intoxication reduced the growth rate of brain, cerebral white matter and subcortical thalamus," the researchers write.
Researchers measured brain growth through magnetic resonance imaging of 71 rhesus macaques that voluntarily consumed ethanol or beverage alcohol. Scientists precisely measured intake, diet, daily schedules and health care, thus ruling out other factors that tend to confound results in observational studies involving people. The findings in the study help validate previous research examining the effect of alcohol use on brain development in people.
"Human studies are based on self-reporting of underage drinkers," said co-author Christopher Kroenke, Ph.D., an associate professor in the Division of Neuroscience at the primate center. "Our measures pinpoint alcohol drinking with the impaired brain growth."
The new study is the first to characterize normal brain growth of 1 milliliter per 1.87 years in rhesus macaques in late adolescence and early adulthood. And it further reveals a decrease in the volume of distinct brain areas due to voluntary consumption of ethanol.
Lead author Tatiana Shnitko, Ph.D., a research assistant professor in the Division of Neuroscience at the primate center, said previous research has shown the brain has a capacity to recover at least in part following the cessation of alcohol intake. However, it's not clear whether there would be long-term effects on mental functions as the adolescent and young adult brain ends its growth phase. The next stage of research will explore that question.
"This is the age range when the brain is being fine-tuned to fit adult responsibilities," Shnitko said. "The question is, does alcohol exposure during this age range alter the lifetime learning ability of individuals?"
This study was funded by the National Institute on Alcohol Abuse and Alcoholism (U01 AA013510, P60 AA013510 and U24 AA025473.
https://www.sciencedaily.com/releases/2019/04/190401133019.htm
Cannabis during pregnancy bumps psychosis risk in offspring
With marijuana use rising among pregnant women, study raises new concerns
March 27, 2019
Science Daily/Washington University in St. Louis
Pregnant women who use cannabis may slightly increase the risk their unborn child will develop psychosis later in life, suggests new research from Washington University in St. Louis.
"Our research shows that prenatal marijuana exposure after maternal knowledge of pregnancy is associated with a small increase in psychosis proneness during middle childhood or about age 10," said Jeremy Fine, an undergraduate majoring in psychological & brain sciences in Arts & Sciences at Washington University and the study's lead author.
The findings come on the heels of several national studies documenting a dramatic increase in marijuana usage by pregnant women, including a 2018 study from Washington University School of Medicine in St. Louis that found past-month marijuana use among pregnant mothers in the United States increased by 75 percent between 2002 (2.85 percent) and 2016 (4.98 percent).
As more states legalize medicinal and recreational use of cannabis, other reports suggest that many marijuana dispensaries commonly suggest cannabis as a natural cure for pregnancy related nausea.
This latest study, published March 27 in the journal JAMA Psychiatry, suggests that pregnant women should be discouraged from using cannabis at any time in their pregnancy because so little is yet known about its health effects.
But its findings also raise new concerns that prenatal exposure to cannabis may pose a greater risk after the fetal brain begins to develop a receptor system for endocannabinoids, which are part of the naturally occurring neurotransmitter network through which cannabis affects the brain.
"One possible explanation for the finding of increased psychosis risk for marijuana use following, but not before, knowledge of pregnancy is that the endocannabinoid receptor system may not be in place during the early weeks of pregnancy," said Ryan Bogdan, associate professor of psychological & brain sciences and senior author of the paper. "Prenatal cannabis exposure may be associated with later psychosis proneness in offspring only when there is sufficient fetal endocannabinoid type 1 receptor expression, which may not occur until after many mothers learn they are pregnant."
Bogdan, who directs the Washington University BRAIN Lab where the research took place, said these latest findings build on other basic research suggesting that endocannabinoid signaling may contribute to processes, such as neurogenesis and neural migration, that play important roles in early development of brain structure and connections.
"This study raises the intriguing possibility there may be developmental windows during which cannabis exposure may be more likely to increase psychosis risk," he said.
Tetrahydrocannabinol (THC), which is the principal psychoactive component of marijuana, mimics our body's endocannabinoids and binds to endocannabinoid receptors to exert its effects. Various studies have confirmed that THC crosses the placental barrier to gain access to the developing fetus.
"Data from rodent studies suggest that the endocannabinoid type 1 receptor, through which the psychoactive effects of THC largely arise, is not expressed until the equivalent of 5-6 weeks of human gestation," Fine said. "Given that mothers in our study on average learned of their pregnancy at 7.7 weeks, it is plausible that any impact of THC on psychosis risk would not arise until sufficient endocannabinoid type 1 receptors are expressed."
The BRAIN Lab findings are based on data from the Adolescent Brain Cognitive Development (ABCD) study, an ongoing longitudinal study of child health and brain development with data collection sites throughout the nation. They used data from the initial ABCD baseline data release which included survey responses from 3,774 mothers about marijuana usage during 3,926 pregnancies. Risk of psychosis in the 4,361 children born from these pregnancies between 2005 and 2008 was measured using a questionnaire administered to the children between ages 8.9 and 11 years.
Among the 4,361 children sampled in this study, 201 (4.61 percent) were reported to have been exposed to marijuana before birth. Of these, 138 were exposed only before mothers knew they were pregnant; two were exposed only after the mother knew she was pregnant.
Bogdan and his co-authors acknowledge that the study has many limitations, including the small sample of prenatal cannabis-exposed offspring; potential maternal underreporting of use during pregnancy; imprecise data on timing, amount, frequency and potency of cannabis exposure; absence of data on whether childhood psychosis proneness is associated with conversion to psychosis; and lack of data on some potential confounders, such as maternal stress and genetic risk of psychosis among parents.
"Our research is correlational and as such cannot draw causal conclusions," said Allison Moreau, study co-author and a graduate student in psycholody at Washington University. "However, that the relationship between prenatal marijuana exposure following maternal knowledge of pregnancy was associated with offspring psychosis proneness after accounting for potentially confounding variables -- such as maternal education, prenatal vitamin usage, prenatal alcohol and nicotine use, child substance use, and so on -- increases the plausibility that prenatal cannabis exposure may contribute to a small risk of increased psychosis liability in children."
The study provides further evidence that expectant mothers should think twice before considering cannabis usage during pregnancy.
"Given increasing cannabis accessibility and potency, as well as growing public perceptions that it's safe to use, it is critical for additional research to understand the potential adverse consequences and benefits of cannabis throughout development and how these associations may arise." Bogdan said. "In the meantime, evidence that prenatal marijuana use is associated with a small increase in offspring psychosis proneness suggests that marijuana use during pregnancy should be discouraged until more is known."
Other Washington University co-authors include Nicole Karcher, post-doctoral research scholar; Arpana Agrawal, professor of psychiatry; and Cynthia Rogers, assistant professor of child psychiatry, all in the Department of Psychiatry in the School of Medicine; and Deanna Barch, chair of the Department of Psychological & Brain Sciences in Arts & Sciences and the Gregory B. Couch Professor of Psychiatry at the School of Medicine.
Funding for this study was provided by the Adolescent Brain Cognitive Development (ABCD) study, which was funded by awards from the National Institutes of Health and additional federal partners.
https://www.sciencedaily.com/releases/2019/03/190327112617.htm