Insight into the proteins in the brain that detect cannabis
April 30, 2019
Science Daily/University of Bristol
Researchers at the University of Bristol have made new progress in understanding how cannabinoid receptors (CB1Rs), the proteins that detect the active components of marijuana, are controlled in the brain.
The brain contains about 100 billion nerve cells that are constantly communicating with one another at specialised junctions called synapses. Nerve cells possess extensions called axons, which send signals to synapses, and dendrites, which receive information from synapses.
At the synapse, the electrical 'firing' of a nerve cell causes the release of chemicals called neurotransmitters from the presynaptic terminals of its axon. These neurotransmitters cross the synapse and pass on the signal by binding to receptors at postsynaptic sites on the dendrites of the next nerve cell.
CB1Rs help control information flow in the brain by binding molecules made in the brain called endocannabinoids, which influence brain functions such as pain, appetite, mood and memory. Unusually, endocannabinoid signalling goes in the reverse direction compared to most other neurotransmitters. The 'receiving' CB1Rs are located at presynaptic sites on axons, whereas the release sites are at postsynaptic sites on dendrites.
This reverse or 'retrograde' signalling that activates presynaptic CB1Rs 'dampens down' presynaptic release of other neurotransmitters resulting in a slowing of brain activity. Moreover, the active components of cannabis bind to CB1Rs in a similar manner to endocannabinoids, resulting in the 'mellow' sensation caused by the recreational use of cannabis.
For CB1Rs to regulate brain function properly, it is essential that they are sent to the right place on the surface of the axon. However, very little is known about exactly how this occurs. The research published today [Tuesday 30 April] in eLife investigated how this process happens.
The Bristol group showed that a specific part of the CB1R protein plays a key role in the getting CB1R into axons. The research team tracked newly made CB1Rs in nerve cells grown in a dish and found that a short region of CB1R is crucial for sending CB1R to the axon and preventing it from going to the dendrites. They also discovered that this region stabilises CB1R at the surface of the axon, making it more available to receive signals from endocannabinoids.
Jeremy Henley, Professor of Molecular Neuroscience in Bristol's School of Biochemistry, said: "In recent years there has been tremendous interest in -- and controversy about -- activation of CB1R by medical marijuana. It is becoming increasingly apparent that activation of CB1Rs could be therapeutically useful for a wide range of diseases such as chronic pain, epilepsy, or multiple sclerosis. Understanding the fundamental properties of CB1R is an important basis for future studies exploring the efficacy and optimisation of these targeted approaches."
It is hoped that this increased understanding of how CB1Rs behave in nerve cells will pave the way for future studies aimed at examining the possible medical uses of marijuana, or other drugs that target CB1Rs, in treating a wide range of disorders.
https://www.sciencedaily.com/releases/2019/04/190430103457.htm
One in 7 Washington State drivers with children in the car recently used marijuana
April 25, 2019
Science Daily/Journal of Studies on Alcohol and Drugs
According to a roadside survey conducted in Washington State, 14.1% of drivers with children in the car -- nearly one in seven -- tested positive for THC, the principal psychoactive compound in marijuana. The results are published in the latest issue of the Journal of Studies on Alcohol and Drugs.
Because detecting THC in blood or saliva does not correspond to impairment as does a positive alcohol test, it's unclear if these drivers were actively impaired by THC. Nonetheless, the study sheds light on the potential for increased impaired driving, and the risks for children, for states considering legalizing marijuana, and the need for better roadside testing for THC.
"Currently, there are a number of different tests being developed and validated to detect whether drugs are present, including saliva and even breath tests for THC," according to study coauthor Angela Eichelberger, Ph.D., from the Insurance Institute for Highway Safety. "However, there is still a need for reliable, valid measures of impairment."
For their research, the group, which was led by Eduardo Romano, Ph.D., of the Pacific Institute for Research and Evaluation, analyzed data from a roadside survey of more than 2,000 drivers age 21 and older conducted in Washington State in 2014 and 2015, after the legalization of recreational marijuana sales there.
During both daytime and nighttime hours, researchers asked drivers at stop lights and stop signs if they wanted to volunteer for the study. They obtained breath samples as well as blood and saliva samples from the volunteers and noted if children were present in the car, and surveyed the drivers about their attitudes regarding substance use.
Whether drivers had a child in the car seemed to affect their choice to drive while impaired by alcohol (that is, have a breath alcohol concentration over .08%).
"Encouragingly, we . . . found that among those with children [in the car], most did not drink and drive," the authors write. No study volunteers had breath alcohol concentrations above .08% if they had a child in the vehicle. But nearly 1% of those without children in the car were above this legal limit. Further, only 0.2% of drivers of children had any alcohol in their system compared with 4.5% of drivers with no children present.
However, having a child in the car did not affect whether drivers had THC in their system. More than 14% of drivers with a child in the car tested positive for THC, but so did 17.7% of drivers without a child in the car, not a statistically significant difference.
The authors also found that most of those surveyed said marijuana was "very likely" to affect driving. Still, some drivers did not recognize the risk of impairment, and those who thought marijuana was not likely to impair driving were more likely to test positive for THC than were other drivers. Among drivers with children who thought marijuana was not impairing, 40.6% tested positive for THC. Eichelberger notes that her previous research has shown that people tend to think that marijuana is less likely to impair driving than is alcohol.
"States need to consider multiple factors when legalizing marijuana," concludes coauthor Tara Kelley-Baker, Ph.D., of the AAA Foundation for Traffic Safety in Washington, DC. "Although there are legal age limits for purchasing and using, we know from previous research examining child endangerment issues that very young children are really vulnerable to driver impairment. States' policies protecting young children from alcohol-impaired drivers are ineffective. Now we are legalizing another drug which may further increase risk to the most vulnerable group."
https://www.sciencedaily.com/releases/2019/04/190425073640.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
Clues to brain differences between males and females
How male sex steroids play a key role in understanding behavioral development
March 1, 2019
Science Daily/University of Maryland School of Medicine
Researchers at the University of Maryland School of Medicine have discovered a mechanism for how androgens -- male sex steroids -- sculpt brain development. The research, conducted by Margaret M. McCarthy, Ph.D., who Chairs the Department of Pharmacology, could ultimately help researchers understand behavioral development differences between males and females.
The research, published in Neuron, discovered a mechanism for how androgens, male sex steroids, sculpt the brains of male rats to produce behavioral differences, such as more aggression and rougher play behavior. "We already knew that the brains of males and females are different and that testosterone produced during the second trimester in humans and late gestation in rodents contributes to the differences but we did not know how testosterone has these effects" said Dr. McCarthy.
Jonathan Van Ryzin, PhD, a Postdoctoral Fellow, was lead author on this research conducted in Dr. McCarthy's lab.
A key contributor to the differences in play behavior between males and females is a sex-based difference in the number of newborn cells in the part of the brain called the amygdala, which controls emotions and social behaviors. The research showed that males have fewer of these newborn cells, because they are actively eliminated by immune cells.
In females, the newborn cells differentiated into a type of glial cell, the most abundant type of cell in the central nervous system. In males however, testosterone increased signaling at receptors in the brain which bind endocannabinoids, causing immune cells to be activated. The endocannabinoids prompted the immune cells to effectively eliminate the newborn cells in males. Females rats in the study were unaffected, suggesting that the activation of the immune cells by the increased endocannabinoids in males was necessary for cell elimination. In this respect, this research shows that cannabis use, which stimulates endocannabinoids in the brain and nervous system, could impact brain development of the fetus and this impact could differ between male and female fetuses.
This study provides a mechanism for sex-based differences in social behaviors and suggests that differences in androgen and endocannabinoid signaling may contribute to individual differences in brain development and thus behavioral differences among people.
"These discoveries into brain development are critical as we work to tackle brain disorders as early in life as possible, even in pregnancy," said UMSOM Dean E. Albert Reece, MD, PhD, MBA, who is also the Executive Vice President for Medical Affairs, University of Maryland, and the John Z. and Akiko K. Bowers Distinguished Professor.
https://www.sciencedaily.com/releases/2019/03/190301160901.htm