Chili peppers and marijuana calm the gut
The active ingredients in both hot peppers and cannabis calm the gut's immune system
April 24, 2017
Science Daily/University of Connecticut
You wouldn't think chili peppers and marijuana have much in common. But when eaten, both interact with the same receptor in our stomachs, according to a paper by UConn researchers published in the April 24 issue of the journal Proceedings of the National Academy of Sciences. The research could lead to new therapies for diabetes and colitis, and opens up intriguing questions about the relationship between the immune system, the gut and the brain.
Touch a chili pepper to your mouth and you feel heat. And biochemically, you aren't wrong. The capsaicin chemical in the pepper binds to a receptor that triggers a nerve that fires off to your brain: hot! Those same receptors are found throughout the gastrointestinal tract, for reasons that have been mysterious.
Curious, UConn researchers fed capsaicin to mice, and found the mice fed with the spice had less inflammation in their guts. The researchers actually cured mice with Type 1 diabetes by feeding them chili pepper. When they looked carefully at what was happening at a molecular level, the researchers saw that the capsaicin was binding to a receptor called TRPV1, which is found on specialized cells throughout the gastrointestinal tract. When capsaicin binds to it, TRPV1 causes cells to make anandamide. Anandamide is a compound chemically akin to the cannabinoids in marijuana. It was the anandamide that caused the immune system to calm down. And the researchers found they could get the same gut-calming results by feeding the mice anandamide directly.
The brain also has receptors for anandamide. It's these receptors that react with the cannabinoids in marijuana to get people high. Scientists have long wondered why people even have receptors for cannabinoids in their brains. They don't seem to interact with vital bodily functions that way opiate receptors do, for example.
"This allows you to imagine ways the immune system and the brain might talk to each other. They share a common language," says Pramod Srivastava, Professor of Immunology and Medicine at UConn Health School of Medicine. And one word of that common language is anandamide.
Srivastava and his colleagues don't know how or why anandamide might relay messages between the immune system and the brain. But they have found out the details of how it heals the gut. The molecule reacts with both TRPV1 (to produce more anandamide) and another receptor to call in a type of macrophage, immune cells that subdue inflammation. The macrophage population and activity level increases when anandamide levels increase. The effects pervade the entire upper gut, including the esophagus, stomach and pancreas. They are still working with mice to see whether it also affects disorders in the bowels, such as colitis. And there are many other questions yet to be explored: what is the exact molecular pathway? Other receptors also react with anandamide; what do they do? How does ingesting weed affect the gut and the brain?
It's difficult to get federal license to experiment on people with marijuana, but the legalization of pot in certain states means there's a different way to see if regular ingestion of cannabinoids affects gut inflammation in humans.
"I'm hoping to work with the public health authority in Colorado to see if there has been an effect on the severity of colitis among regular users of edible weed," since pot became legal there in 2012, Srivastava says. If the epidemiological data shows a significant change, that would make a testable case that anandamide or other cannabinoids could be used as therapeutic drugs to treat certain disorders of the stomach, pancreas, intestines and colon.
It seems a little ironic that both chili peppers and marijuana could make the gut chill out. But how useful if it's true.
https://www.sciencedaily.com/releases/2017/04/170424152537.htm
Risk of psychosis from cannabis use lower than originally thought
April 20, 2017
Science Daily/University of York
The research, published in the journal, Addiction, also showed for the first time that there is sufficient evidence to demonstrate that for patients who already have schizophrenia, cannabis makes their symptoms worse.
More than two million people in England and Wales used cannabis in the past 12 months, but the latest research shows that banning the drug would have low impact on mental health.
In order to prevent just one case of psychosis, more than 20,000 people would have to stop using cannabis, as shown by a previous study led by the University of Bristol.
This means that at a population level, an increased risk of psychosis from cannabis use is low, and those vulnerable to developing serious mental health problems is relatively rare. The research highlights, however, that more reviews on the impact of high potency cannabis is needed in order to make a full assessment of the risks.
Ian Hamilton, lecturer in mental health at the University of York, said: "The link between cannabis and psychosis has been an ongoing research topic since the drug became popular in the 1960s. Most of the high profile studies that we have access to, however, are from a time when low potency cannabis was the norm, but today high potency is more common.
"High potency cannabis contains less of a chemical that is believed to protect against negative side-effects, such as psychosis, and a higher level of a chemical that can trigger psychosis. In this new study, we looked at both low and high potency, but it is clear that we need more evidence from high potency-related health cases to further investigate this link in modern-day users."
Despite this, the research was clear that the more high potency cannabis used, the higher the risk of developing mental health problems, even if they are relatively low in number. For those who already had schizophrenia cannabis exacerbated the symptoms.
The greatest risk to health, however, comes from cannabis users who combine the drug with tobacco. This exposes young people in particular to tobacco dependency at an early age, increasing the chances of cancers, infections, and other health-related issues.
Previous research at York showed that regulating cannabis use could result in more effective strategies aimed at helping drug users to access the right support and guidance. The policy report illustrated, however, that there is too much uncertainly around treatment regimes in an unregulated market to target the appropriate level of care.
Mr Hamilton said: "Regulation could help reduce the risks to health that cannabis use poses, as a regulated cannabis market would introduce some quality control.
"This would provide users with information about the strength of cannabis on offer, something they usually only discover after exposure in the current unregulated market.
"The public health message about the link between cannabis and psychosis has been a difficult one to communicate, but the evidence still points to the benefits of regulations that seek to advise on the greatest potential health risks, which currently arise due to tobacco use."
https://www.sciencedaily.com/releases/2017/04/170420132334.htm
Natural chemical helps brain adapt to stress
March 29, 2017
Science Daily/Vanderbilt University Medical Center
A natural signaling molecule that activates cannabinoid receptors in the brain plays a critical role in stress-resilience -- the ability to adapt to repeated and acute exposures to traumatic stress, according to researchers at Vanderbilt University Medical Center.
The findings in a mouse model could have broad implications for the potential treatment and prevention of mood and anxiety disorders, including major depression and post-traumatic stress disorder (PTSD), they reported in the journal Nature Communications.
"The study suggests that deficiencies in natural cannabinoids could result in a predisposition to developing PTSD and depression," said Sachin Patel, M.D., Ph.D., director of the Division of Addiction Psychiatry at Vanderbilt University School of Medicine and the paper's corresponding author.
"Boosting this signaling system could represent a new treatment approach for these stress-linked disorders," he said.
Patel, the James G. Blakemore Professor of Psychiatry, received a Presidential Early Career Award for Scientists and Engineers last year for his pioneering studies of the endocannabinoid family of signaling molecules that activate the CB1 and CB2 cannabinoid receptors in the brain.
Tetrahydrocannabinol (THC), the active compound in marijuana, binds the CB1 receptor, which may explain why relief of tension and anxiety is the most common reason cited by people who use marijuana chronically.
Patel and his colleagues previously have found CB1 receptors in the amygdala, a key emotional hub in the brain involved in regulating anxiety and the fight-or-flight response. They also showed in animal models that anxiety increases when the CB1 receptor is blocked by a drug or its gene is deleted.
More recently they reported anxiety-like and depressive behaviors in genetically modified mice that had an impaired ability to produce 2-arachidonoylglycerol (2-AG), the most abundant endocannabinoid. When the supply of 2-AG was increased by blocking an enzyme that normally breaks it down, the behaviors were reversed.
In the current study, the researchers tested the effects of increasing or depleting the supply of 2-AG in the amygdala in two populations of mice: one previously determined to be susceptible to the adverse consequences of acute stress, and the other which exhibited stress-resilience.
Augmenting the 2-AG supply increased the proportion of stress-resilient mice overall and promoted resilience in mice that were previously susceptible to stress, whereas depleting 2-AG rendered previously stress-resilient mice susceptible to developing anxiety-like behaviors after exposure to acute stress.
Taken together, these results suggest that 2-AG signaling through the CB1 receptor in the amygdala promotes resilience to the adverse effects of acute traumatic stress exposure, and support previous findings in animal models and humans suggesting that 2-AG deficiency could contribute to development of stress-related psychiatric disorders.
Marijuana use is highly cited by patients with PTSD as a way to control symptoms. Similarly, the Vanderbilt researchers found that THC promoted stress-resilience in previously susceptible mice.
However, marijuana use in psychiatric disorders has obvious drawbacks including possible addiction and cognitive side effects, among others. The Vanderbilt study suggests that increasing production of natural cannabinoids may be an alternative strategy to harness the therapeutic potential of this signaling system.
If further research finds that some people with stress-related mood and anxiety disorders have low levels of 2-AG, replenishing the supply of this endocannabinoid could represent a novel treatment approach and might enable some of them to stop using marijuana, the researchers concluded.
https://www.sciencedaily.com/releases/2017/03/170329140945.htm
Aggression disorder linked to greater risk of substance abuse
February 28, 2017
Science Daily/University of Chicago Medical Center
People with intermittent explosive disorder (IED) -- a condition marked by frequent physical or verbal outbursts -- are at five times greater risk for abusing substances such as alcohol, tobacco and marijuana than those who don't display frequent aggressive behavior, according to a new study by researchers from the University of Chicago.
In the study, published Feb. 28, 2017 in the Journal of Clinical Psychiatry, Emil Coccaro, MD, and colleagues analyzed data from more than 9,200 subjects in the National Comorbidity Survey, a national survey of mental health in the United States. They found that as the severity of aggressive behavior increased, so did levels of daily and weekly substance use. The findings suggest that a history of frequent, aggressive behavior is a risk factor for later substance abuse, and effective treatment of aggression could delay or even prevent substance abuse in young people.
IED affects as many as 16 million Americans, more than bipolar disorder and schizophrenia combined. It is often first diagnosed in adolescents, some of whom are as young as 11, years before substance abuse problems usually develop. IED runs in families and is thought to have a significant genetic component, although Coccaro said people tend to treat it as a social-behavioral issue instead of as a true neurobiological disorder.
"People don't see this as a medical problem. They think of it as simply bad behavior they have developed over the course of their lives, but it isn't. It has significant biology and neuroscience behind it," said Coccaro, who is the Ellen C. Manning Professor of Psychiatry and Behavioral Neuroscience at UChicago.
Previous research has implied that aggressive behavior in IED is due to the presence of other psychiatric disorders, such as anxiety or depression. But the new UChicago study found no such relationship. While substance abuse, like excessive drinking, can clearly make aggressive behavior worse, the onset of IED almost always precedes the development of chronic substance abuse. Coccaro and his team found that IED preceded substance abuse in 92.5 percent of the cases where subjects developed both disorders.
Coccaro emphasized that early psychological intervention, medication and cognitive therapy are the most effective treatments to prevent, or at least delay, substance abuse problems in adolescents diagnosed with IED.
"What you're really treating is the emotional dysregulation that leads to aggression," Coccaro said. "The earlier you treat this dysregulation, the more likely you are to offset other disorders that come later down the road."
https://www.sciencedaily.com/releases/2017/02/170228222829.htm
Researchers discover how the brain turns chronic stress into pathological anxiety
February 13, 2017
Science Daily/Scripps Research Institute
n a new study, researchers at The Scripps Research Institute (TSRI) have described how two important molecules in the brain work together to trigger intense anxiety.
The new findings in animal models point to a novel interaction in the regulation of the brain's stress response that may underlie the pathological anxiety related to symptoms of post-traumatic stress disorder (PTSD).
"Anxiety and stress disorders affect millions of people worldwide," explained study leader Marisa Roberto, a professor at TSRI. "Understanding the mechanisms underlying these disorders is important for identifying potential new targets for therapeutic use."
The researchers focused on the endogenous cannabinoid (endocannabinoid or eCB) system, which include natural lipid signaling molecules that bind to cannabinoid receptors in the brain. Cannabinoid (type 1) receptors control stress-mediating circuits by inhibiting neurotransmitter release -- a sort of gating mechanism to keep anxiety in check.
In contrast to the stress-reducing properties of endocannabinoids, a peptide molecule called corticotropin-releasing factor (CRF) activates the stress response and promotes increased sensitivity to stress and anxiety when activated over and over again.
In the new study, published in the journal Biological Psychiatry, the researchers investigated the interaction between the stress-promoting (CRF) and stress-constraining (eCBs) mechanisms in the central nucleus of the amygdala, a critical brain region involved in mediating emotional reactions. The findings suggest that overactive CRF signaling in this region produces a wide range of effects that override the stress-reducing capabilities of a major eCB called N-arachidonoylethanolamine (anandamide), turning chronic stress into unchecked, or pathological, anxiety.
"Anxiety is something that everyone experiences on a day-to-day basis," said study first author Luis A. Natividad, a research associate in the Roberto lab. "But it is unclear what changes this otherwise natural process into something debilitating."
To answer this question, Roberto's lab teamed up with Roberto Ciccocioppo's lab at the University of Camerino, Italy, and the lab of TSRI Professor Loren ("Larry") Parsons, a leader in the fields of endocannabinoid signaling, stress and drug addiction who passed away in 2016.
The researchers studied rats that were genetically selected for higher alcohol drinking and also display an anxiety-like phenotype. These rats exhibit a mutation in a gene called Crhr1 that increases CRF (type 1) receptor signaling.
Using behavioral, neurochemical and electrophysiological approaches, the researchers found that increased CRF signaling led to elevated activity of the anandamide clearance enzyme fatty acid amide hydrolase (FAAH). Increased CRF was also associated with drops in anandamide levels in the central nucleus of the amygdala. Together, increased FAAH activity and decreased anandamide signaling reduce inhibitory control of excitatory neurotransmission in this critical region, and lower the brain's ability to regulate stress and anxiety.
The researchers concluded that long-term dysregulation of CRF-FAAH mechanisms in the amygdala keeps anandamide from doing its job. Without anandamide to balance out the system, the brain is primed to react to stress.
Follow-up experiments showed that inhibiting FAAH could blunt CRF's effects and reduce signs of anxiety in the rats.
Roberto said the next step will be to further study this rat model to better understand relationships between high anxiety and alcoholism. She added that the rat model could also be useful for studying PTSD, where high anxiety is connected to a higher risk of developing alcoholism.
"The results of our study may be useful, not only in understanding the neurobiological basis of alcoholism, anxiety and possibly PTSD, but also in developing more efficacious pharmacotherapies to treat these disorders," added Ciccocioppo.
The researchers dedicated this study to Parsons. Natividad added a note on Parson's influence on the research and on the TSRI campus:
"Larry's guidance throughout the study was critical in bringing together a cohesive story exploring the relevance of endocannabinoid signaling with downstream neural processing in a way that is unique to the field and has translational relevance to the human condition. He serves as a role model for me not only as a scientist, but also in terms of being a good colleague, mentor and friend to those around him. I feel privileged to have been part of his lab, his teachings and mentorship. He will be dearly missed."
https://www.sciencedaily.com/releases/2017/02/170213131201.htm
Cannabis: Non-addictive pathway to pain relief?
Medicinal properties of cannabis examined
January 12, 2017
Science Daily/Oregon Health & Science University
OHSU research suggests an avenue for developing treatments for chronic pain that harness the medicinal properties of cannabis while minimizing the threat of addiction.
The study, conducted in a rodent model, provides additional rationale for the development of therapeutics using cannabinoid receptors to treat chronic pain, which afflicts about 30 percent of the U.S. population. OHSU investigators studied the function of two forms of cell membrane receptors that bind cannabinoids that occur naturally within the body, called endocannabinoids.
"It may be an avenue where we can get better pain medications that are not addictive," said senior author Susan Ingram, Ph.D., an associate professor of neurosurgery in the OHSU School of Medicine.
Ingram and colleagues report the treatment of chronic pain has challenged the medical system, with medications that are ineffective or create serious side effects: "However, emerging data indicate that drugs that target the endocannabinoid system might produce analgesia with fewer side effects compared with opioids."
The body's endocannabinoid system comprises receptors, endocannabinoid molecules and enzymes that make and degrade the endocannabinoids located in the brain and throughout the central and peripheral nervous system. The research team focused on two cannabinoid receptors, known as CB1 and CB2, in the rostral ventromedial medulla -- a group of neurons located in the brainstem known to modulate pain. The study is the first to examine CB1 and CB2 receptor function at the membrane level in late adolescent and adult neurons.
The researchers observed that chronic inflammatory pain increased activity of CB2 receptors and decreased CB1 activity. Cannabis activates both CB1 and CB2 receptors equally. The study suggests that selective activation of CB2 receptors contributes to the medicinal benefit of cannabis while minimizing the propensity of the other cannabinoid receptor, CB1, to induce tolerance and withdrawal. Ingram said the next phase of the research will further explore this area of brain circuitry, which ultimately could lead to the development of a new class of pain medications.
Co-authors include lead author Ming-Hua Li, Ph.D., and Katherine L. Suchland, both with the Department of Neurological Surgery, OHSU School of Medicine.
The study was funded by grants from the National Institutes of Health (DA035316 and R56NS093894) and American Heart Association (13SDG14590005, MH.L.).
https://www.sciencedaily.com/releases/2017/01/170112130145.htm
How a Western diet leads to overeating and obesity
Peripheral endocannabinoid signaling identified as a pharmaceutical target for overeating associated with diet-induced obesity
January 11, 2017
Science Daily/University of California - Riverside
More than two in three adults in the United States are considered overweight or obese, with substantial biomedical and clinical evidence suggesting that chronic overconsumption of a "western diet" -- foods consisting high levels of sugars and fats -- is a major cause of this epidemic.
New research by scientists at the University of California, Riverside now shows that chronic consumption of a western diet leads to overeating and obesity due to elevations in "peripheral endocannabinoid signaling."
The endocannabinoid system is located throughout the mammalian body, including the brain and all peripheral organs, and participates in the control of many physiological functions in the body, including food intake, energy balance, and reward. It is comprised of lipid signaling molecules called endocannabinoids -- which can be thought of as the body's own "natural cannabis" -- that bind to cannabinoid receptors located on cells throughout the body.
"Our research shows that targeting cannabinoid receptors in the periphery with pharmacological inhibitors that do not reach the brain holds promise as a safe therapeutic approach for the treatment of overeating and diet-induced obesity," said Nicholas V. DiPatrizio, an assistant professor of biomedical sciences in the School of Medicine, who led the research project. "This therapeutic approach to targeting the periphery has substantial advantages over traditional drugs that interact with the brain and cause psychiatric side-effects."
The work describes for the first time that overeating associated with chronic consumption of a western diet is driven by an enhancement in endocannabinoid signals generated in peripheral organs.
Study results appear in the journal Physiology & Behavior.
To examine the role for endocannabinoids generated in peripheral organs in controlling the overeating of western diet, DiPatrizio and coauthor Donovan A. Argueta, a bioengineering Ph.D. student in his lab, used a mouse model of western diet-induced obesity (chronic exposure to high levels of sugars and fats).
They found that when compared to mice fed a standard low-fat/low-sugar diet, mice fed a western diet for 60 days rapidly gained body weight and became obese, and displayed "hyperphagia," that is, they consumed significantly more calories, and consumed significantly larger meals at a much higher rate of intake (calories per minute).
"These hyperphagic responses to western diet were met with greatly elevated levels of endocannabinoids in the small intestine and circulation," DiPatrizio said. "Importantly, we found that blocking the actions of the endocannabinoids with pharmacological inhibitors of cannabinoid receptors in the periphery completely normalized food intake and meal patterns in western diet-induced obese mice to levels found in control lean mice fed standard chow."
DiPatrizio and Argueta caution that further research is necessary to identify whether similar mechanisms drive obesity in humans.
"Importantly, however, other research groups have reported elevations in circulating levels of endocannabinoids in obese human subjects, which suggests that this system may also be overactive in human obesity," DiPatrizio said.
He explained that rimonabant, a drug which blocked endocannabinoid signaling at cannabinoid receptors, was on the market in Europe for the treatment of human obesity.
"It worked quite well at reducing body weight and improving metabolic profiles; however, this drug was not restricted to the periphery and thus, led to severe psychiatric side effects and was not given FDA approval in the United States," DiPatrizio said. "Peripherally restricted inhibitors of cannabinoid receptors, such as AM6545 used in our experiments, however, would be devoid of these side effects given that they do not reach the brain."
DiPatrizio and Argueta were surprised to find that inhibiting peripheral endocannabinoid signaling with inhibitors like AM6545 completely normalized intake to that found in lean mice maintained on a standard chow.
"This suggests that these elevations in peripheral endocannabinoid signaling are critical in driving hyperphagia associated with a western diet," said Argueta, the first author of the research paper.
Next, the researchers plan to identify critical upstream and downstream mechanisms of endocannabinoid signaling in western diet-induced obesity, as well as the possible specific dietary constituents in western diet (e.g., sucrose) that drive overeating as a result of elevated peripheral endocannbinoid levels.
"In addition, we aim to translate our work in rodents to similar studies in humans," DiPatrizio said.
https://www.sciencedaily.com/releases/2017/01/170111184359.htm
Pain relief without the high
January 4, 2017
Science Daily/Leiden, Universiteit
Researchers at Leiden University led by Mario van der Stelt (Leiden Institute for Chemistry) have set ‘gold standards’ for developing new painkillers based on the medicinal effects of cannabis.
Medicinal marijuana
Medicinal marijuana is in frequent use as a painkiller, but its psycho-active side-effects are a major disadvantage. The pharmaceutical industry is desperately seeking a synthetic form of cannabis that inhibits inflammation and pain, but without the high. Leiden researchers have now brought the development of such drugs a step closer. In an article in Nature Communications they set out 'gold standards' for the use of reference substances, to improve trials with synthetic cannabis.
Many of the clinical trials carried out to date with with synthetic cannabis have failed, with no measurable effect being recorded in patients. One of the causes of these failures can be found in the pre-clinical lab, during testing with animals. Substances are often used in these tests whose biochemical and molecular-pharmaceutical effects have never been properly characterised. As a result, there have been a lot of contradictory publications on research findings, the results of which cannot be reproduced. This is having a major effect on the allocation of research funding, the use of animal testing and the exposure of patients to non-active substances.
International and public-private collaboration
Marjolein Soethoudt, a PhD candidate in Van der Stelt's research group, studied together with 12 international academic groups, the National Institute of Health (US) and pharmaceuticals concern Hoffman-LaRoche (Switzerland), the 18 most commonly used reference substances, including the psychoactive ingredient in marijuana, Δ9-THC. They carried out their studies under standardised conditions in 36 different tests, to analyse the molecular pharmacological characteristics of the substances. They hoped to be able to identify the most suitable reference sustances for the research on synthetic cannabis. The research led to three 'gold standards' that should make it possible to give an impetus to the development of new painkillers and anti-inflammatories.
Cannabinoid CB2 receptor
Δ9-THC binds to two types of proteins in the human body: the cannabinoid CB1 receptor in the brain and the cannabinoid CB2 receptor in the immune system. Activating the CB1 receptor in the brain makes you high, while activating the CB2 receptor has an anti-inflammatory effect. The three 'gold standards' are molecules that are highly selective in activating only the CB2 receptor and ignoring the CB1 receptor. These three gold standards also appeared to cause the fewest side-effects, nor did they give the mice a high. Earlier studies have shown that these substances do have an analgesic and anti-inflammatory effect. The researchers advise that these three gold standards should be used in future in research on new medicines that rely on the activation of the cannabinoid CB2 receptor for their effectiveness.
This is your brain on (legal) cannabis: Researchers seek answers
For those suffering depression or anxiety, using cannabis for relief may not be the long-term answer
December 16, 2016
Science Daily/Colorado State University
For those suffering depression or anxiety, using cannabis for relief may not be the long-term answer.
That's according to new research from a team at Colorado State University seeking scientific clarity on how cannabis -- particularly chronic, heavy use -- affects neurological activity, including the processing of emotions.
Researchers led by Lucy Troup, assistant professor in the Department of Psychology, have published a study in PeerJ describing their findings from an in-depth, questionnaire-based analysis of 178 college-aged, legal users of cannabis. Recreational cannabis became legal in Colorado in 2014. Since then, seven other states have enacted legalization for recreational use, while many others allow medical use.
"One thing we wanted to focus on was the significance of Colorado, the first state to legalize recreational cannabis, and its own unique population and use that occurs here," Troup said.
Through the study, which was based solely upon self-reported use of the drug, the researchers sought to draw correlations between depressive or anxious symptoms and cannabis consumption.
They found that those respondents categorized with subclinical depression, who reported using the drug to treat their depressive symptoms, scored lower on their anxiety symptoms than on their depressive symptoms - so, they were actually more depressed than they were anxious. The same was true for self-reported anxiety sufferers: they were found to be more anxious than they were depressed.
In other words, "if they were using cannabis for self-medication, it wasn't doing what they thought it was doing," explained co-author Jacob Braunwalder, a recently graduated student researcher in Troup's lab.
Study co-author Jeremy Andrzejewski led the development of the questionnaire, called R-CUE (Recreational Cannabis Use Evaluation), that took a deep dive into users' habits, including questions about whether users smoked the drug, or consumed stronger products like hash oils or edibles. The researchers are particularly motivated to study biochemical and neurological reactions from higher-tetrahydracannabinol (THC) products available in the legal market, which can be up to 80-90 percent THC.
The researchers are quick to point out that their analysis does not say that cannabis causes depression or anxiety, nor that it cures it. But it underscores the need for further study around how the brain is affected by the drug, in light of legalization, and by some accounts, more widespread use in Colorado since legalization.
For example, said Andrzejewski, "there is a common perception that cannabis relieves anxiety." Yet research has yet to support this claim fully, he said.
Graduate student and co-author Robert Torrence pointed to past research that shows that chronic use reduces naturally occurring endocannabinoids in the brain, which are known to play a role physiological processes including mood and memory.
"There is research to suggest that cannabis can help with anxiety and depression in the beginning, but it has the reverse effect later on," said Torrence, a U.S. Army veteran who is especially interested in studying cannabis' effectiveness in treating post-traumatic stress disorders.
Due to the federal government's stringent regulations around researching cannabis, which is a schedule I drug, the general public's perception of how it affects the brain is often based in "mythos," Braunwalder said. "We want to add more information to the entire body of research."
There are currently no CSU research labs that administer cannabis to study participants, as administration of the drug for research would require special licensing and security.
Moving forward, the researchers want to refine their results and concentrate on respondents' level and length of exposure to legally available high-THC products like concentrates and hash oils, around which there has been little scientific inquiry.
"It is important not to demonize cannabis, but also not to glorify it," Troup said. "What we want to do is study it, and understand what it does. That's what drives us."
https://www.sciencedaily.com/releases/2016/12/161216115555.htm
Baby boomers on dope: Recreational marijuana use is on the rise among adults over 50
Study seeks to understand prevalence of use in older adults
December 5, 2016
Science Daily/New York University
The recent legalization of recreational marijuana (cannabis) use in California, Colorado, and Washington reflect the sweeping changes in the attitudes and perceptions towards marijuana use in the United States. Eight states have voted in favor of legal recreational marijuana and 26 states in total allow medicinal marijuana.
There is a common misperception that widespread marijuana use is limited to younger generations. However, the Baby Boomer generation has reported higher rates of substance use than any preceding generation.
"Given the unprecedented aging of the U.S. population, we are facing a never before seen cohort of older adults who use recreational drugs," says Benjamin Han, MD, MPH, a geriatrician and health services researcher at the Center for Drug Use and HIV Research (CDUHR) and in the Division of Geriatric Medicine and Palliative Care at NYU Langone Medical Center (NYULMC).
"With the increased availability of legalized marijuana, there is an urgent need to understand the prevalence of its use and also its effects among older generations," continued Dr. Han. "The paucity of knowledge in this area constrains the care for a changing demographic of older adults with higher rates of substance use."
To address this, Dr. Han and his team led a study, "Demographic Trends among Older Cannabis Users in the United States, 2006-2013." Published in Addiction, the study sought to determine the trends in the prevalence and patterns of cannabis use, attitudes towards cannabis use, and determine correlates of use among adults over the age of 50.
The researchers evaluated responses from 47,140 adults aged 50 and older in the United States through a secondary analysis of the National Survey on Drug Use and Health (NSDUH) from 2006 to 2013. The NSDUH provides national data on the use of tobacco, alcohol, illicit drugs and mental health in the United States.
The authors found a 71% increase in marijuana use among adults aged 50 and older between 2006 and 2013. Adults ages 65 and older had a significantly lower prevalence of marijuana use compared to those ages 50-64, but prevalence of use increased two and a half times over eight years. Overall, prevalence was higher among men than women through all years.
"We found only five percent of these older adults felt using marijuana once or twice a week was a great risk to their health" said Joseph J. Palamar, PhD, MPH, a CDUHR affiliated researcher and an assistant professor of Population Health at NYULMC.
"I thought the perception of low risk was fascinating because, typically, we think of older generations as drug-adverse, and perceiving most drugs to be risky," said Dr. Palamar. "But apparently very few Baby Boomers consider marijuana use risky. But after all, this was the generation who was there, in the late 1960s, when the counterculture revolution exploded marijuana into mainstream popularity."
The researchers note that the majority of self-reported marijuana users indicated they first started using before the age of 18. This means that most of the current users either continued use or have begun using again more recently. Research is needed to determine whether this is related to changes in local, state, and national acceptance.
"Personally, I don't think we need to be very alarmed about most older people who are using marijuana," notes Dr. Palamar, "as our results suggest that only 4% started use after age 35. It is probable that most older users are at least somewhat experienced and are hopefully at reasonably low risk of harming themselves or others after use."
The results, however, give the researchers reason to believe the population may be at a particularly high risk for adverse health outcomes, as the concurrent use of multiple substances (marijuana, prescribed prescription drug, and even self-prescribed illicit drugs) all used in combination may make older adults further vulnerable to poor physical and mental health outcomes and certainly can impact their care.
Dr. Palamar notes that as a public health researcher, "for years we've been worried about the potential effects of marijuana on the developing brains of teens, but now we may need a bit more focus on their grandparents, who are increasingly more likely to be current users."
"Older people may use marijuana for a variety of reasons -- including medical reasons -- however we need to make sure they are not using in a hazardous manner since older adults may be vulnerable to its possible adverse effects. One particular concern for older users is the risk of falls while using marijuana, however this has not yet been studied," Dr. Han added.
This study underscores the need for further research on marijuana use and its effects in this population. More importantly, the research dispels the myth that older adults do not use recreational drugs. It is the researchers' hope that their study encourages cannabis use questions to become a part of older adults' care plan screenings.
https://www.sciencedaily.com/releases/2016/12/161205091216.htm
Highest-resolution model to date of brain receptor behind marijuana's high
UT Southwestern Medical Center. "Highest-resolution model to date of brain receptor behind marijuana's high”.
November 16, 2016
Science Daily/UT Southwestern Medical Center
Researchers at UT Southwestern Medical Center report the most detailed 3-D structure to date of the brain receptor that binds and responds to the chemical at the root of marijuana's high.
Their high-resolution structure of the human cannabinoid receptor 1 (CB1) and its binding site for the chemical tetrahydrocannabinol (THC) should lead to a better understanding of how marijuana affects the brain. The research also could aid discovery of new treatments for conditions that target the receptor, said Dr. Daniel Rosenbaum, Assistant Professor of Biophysics and Biochemistry at UT Southwestern.
"What is most exciting from a therapeutic standpoint is that the same receptor pocket that binds THC also binds cannabinoid inhibitors that have been studied as possible treatments for conditions such as obesity," said Dr. Rosenbaum, senior author of the study published online by Nature. "The structure is an important step toward explaining how cannabinoids initiate signals in the brain that affect the release of neurotransmitters that relay messages between the brain's neurons," Dr. Rosenbaum said. "This 3-D structure provides high-resolution details of the binding pocket in the CB1 receptor, where plant cannabinoids like THC, cannabinoids made in the body, and synthetic cannabinoid inhibitors all work to modulate receptor function and physiology." He said the CB1 receptor is the target for cannabinoid inhibitor drugs now under study as possible treatments for epilepsy, pain control, obesity, and other conditions.
In a competing study released last month by the journal Cell, a U.S.-Chinese team of researchers reported a 3-D structure of the CB1 receptor at a resolution of 2.8 angstroms. The UT Southwestern study reports a higher resolution of 2.6 angstroms. (One angstrom is equivalent to one hundred-millionth of a centimeter.) The higher the resolution, the finer the details of the relationship between atoms of the protein.
"The resolution is very important. Our structure shows a different and better resolved structure at the important binding pocket that is of interest to scientists involved in drug development," Dr. Rosenbaum said. "Overall, these two structures are complementary, but we believe our structure may provide a better framework for understanding how cannabinoids and inhibitors bind to the receptor."
The Cell study examined the CB1 receptor bound to a synthetic chemical created to stabilize the receptor. In contrast, the UT Southwestern research team successfully imaged the receptor bound to the drug taranabant, which was tested as a possible anti-obesity treatment in clinical trials. Those trials ended due to side effects such as anxiety and depression, Dr. Rosenbaum said.
CB1 and the related CB2, which still lacks a high-resolution structural solution, are both members of the human G protein-coupled receptor family. Members of that receptor family control signaling pathways involving hormones, neurotransmitters, and sensory stimuli such as light and odors.
The team's success depended on overcoming the receptor protein's resistance to crystallization, which is required for the diffraction measurements used in X-ray crystallography. The researchers also conducted computer simulations of how THC might bind to the CB1 receptor, he said.
The next step is to obtain structures of CB1 actually bound to THC, he said.
https://www.sciencedaily.com/releases/2016/11/161116131935.htm
Marijuana use may be linked to temporarily weakened heart muscle
November 13, 2016
Science Daily/American Heart Association
Active marijuana use may double the risk of stress cardiomyopathy, an uncommon heart muscle malfunction that can mimic heart attack symptoms, according to research presented at the American Heart Association's Scientific Sessions 2016.
The researchers found that marijuana users were almost twice as likely to develop stress cardiomyopathy compared to non-users, even after taking other cardiovascular risk factors into consideration. Active marijuana use was identified either by information provided by the patient in their medical history, or by a marker in the patient's urine.
"The effects of marijuana, especially on the cardiovascular system, are not well known yet. With its increasing availability and legalization in some states, people need to know that marijuana may be harmful to the heart and blood vessels in some people," said Amitoj Singh, M.D. study co-author and chief cardiology fellow at St. Luke's University Health Network in Bethlehem, Pennsylvania.
Stress cardiomyopathy is a sudden, usually temporary, weakening of the heart muscle that reduces the heart's ability to pump, leading to chest pain, shortness of breath, dizziness and sometimes fainting.
Data from the Nationwide Inpatient Sample identified 33,343 people who were hospitalized with stress cardiomyopathy between 2003-2011 in the United States. Of those, 210 (less than one percent) were also identified as marijuana users.
Compared with non-users, researchers found that marijuana users were more likely to be younger, male with fewer cardiovascular risk factors, including less high blood pressure, diabetes and high cholesterol.
However, despite being younger and with fewer cardiovascular risk factors than non-users, during stress cardiomyopathy the marijuana users were significantly more likely to go into cardiac arrest (2.4 percent vs. 0.8 percent) and to require an implanted defibrillator to detect and correct dangerously abnormal heart rhythms (2.4 percent vs. 0.6 percent).
"This development of stress cardiomyopathy in younger patients who used marijuana suggests a possible link that needs to be further investigated," said Sahil Agrawal, M.D., co-author of the paper and also a chief cardiology fellow at St. Luke's.
Marijuana users were more likely than non-users to have a history of depression (32.9 percent vs. 14.5 percent), psychosis (11.9 percent vs. 3.8 percent), anxiety disorder (28.4 percent vs. 16.2 percent), alcoholism (13.3 percent vs. 2.8 percent), tobacco use (73.3 percent vs. 28.6 percent) and multiple substance abuse (11.4 percent vs. 0.3 percent). Because some of these can increase the risk of stress cardiomyopathy, the researchers adjusted for known risk factors to investigate the association between marijuana use and stress cardiomyopathy.
"If you are using marijuana and develop symptoms such as chest pain and shortness of breath, you should be evaluated by a healthcare provider to make sure you aren't having stress cardiomyopathy or another heart problem," Singh said.
The study has some limitations. Because this was a retrospective study, the researchers could not determine how frequently the marijuana users were using marijuana, or what the timeframe was between the use of marijuana and occurrence of stress cardiomyopathy. Observational studies are not designed to prove cause and effect; therefore, it cannot be said that marijuana is or is not a direct cause of stress cardiomyopathy. In addition, because the database the researchers used reports regional but not state-by-state statistics, the researchers could not analyze whether possibly marijuana-related heart problems are increasing where use is legal.
https://www.sciencedaily.com/releases/2016/11/161113160447.htm
First atomic-level image of the human 'marijuana receptor' unveiled
October 20, 2016
Science Daily/Scripps Research Institute
In a discovery that advances the understanding of how marijuana works in the human body, an international group of scientists, including those from the Florida campus of The Scripps Research Institute (TSRI), have for the first time created a three-dimensional atomic-level image of the molecular structure activated by tetrahydrocannabinol (THC), the active chemical in marijuana.
The new insights into the human cannabinoid receptor 1 (CB1) will provide an essential tool for understanding why some molecules related to THC have unexpectedly complex and sometimes harmful effects. The findings also have the potential to guide drug design for pain, inflammation, obesity, fibrosis and other indications.
The new study, published by the journal Cell, was led by a quartet of scientists: TSRI's Laura Bohn, Northeastern University's Alexandros Makriyannis, Shanghai Tech University's Zhi-Jie Liu and Raymond C. Stevens (also of the University of Southern California).
At the beginning of the study, the team struggled to produce a crystal form -- needed to obtain data to recreate the high-resolution structure -- of the receptor bound with AM6538, a stabilizing a molecule that blocks the receptor's action.
"The CB1 receptor proved as challenging for crystallization as it did for understanding its functional regulation and signaling," said Bohn, who is a professor in TSRI's Department of Molecular Therapeutics.
When the scientists succeeded in crystalizing the receptor and collecting the data, the structure of the cannabinoid receptor complex revealed an expansive and complicated binding pocket network consisting of multiple sub-pockets and channels to various regions of the receptor.
Cannabinoid receptors are part of a large class of receptors known as G protein-coupled receptors (GPCR), which account for about 40 percent of all prescription pharmaceuticals on the market, and play key roles in many physiological functions. When an outside substance binds to a GPCR, it activates a G protein inside the cell to release components and create a specific cellular response.
AM6538, is an antagonist/inverse agonist that binds tightly to the receptor; it has a long half-life, making it potentially useful as a treatment of addiction disorders.
"As marijuana continues to become more common in society, it is critical that we understand how it works in the human body," said Liu, who is professor and deputy director of the iHuman Institute of Shanghai Tech and is also affiliated with the Chinese Academy of Sciences.
https://www.sciencedaily.com/releases/2016/10/161020223928.htm
Cannabis reduces creativity, but user generally not aware
October 4, 2016
Science Daily/Leiden, Universiteit
Regular users of cannabis are less aware of their own mistakes, and they are not good at creative thinking. This is the conclusion drawn by psychologist Mikael Kowal from his research on the effects of cannabis. PhD defence 6 October.
Dopamine
Kowal conducted experiments on 40 regular users of cannabis. The control group of 20 non-users were given a placebo. Kowal studied the direct and chronic effects of cannabis on dopamine-related functions, such as creative thinking and the ability to recognise one's own mistakes. The brain chemical dopamine is important for the proper working of the brain and also plays a role in learning performance.
Less good at brainstorming
Kowal's research showed that cannabis users were less able to brainstorm, a mental process that is crucial for creative performance: 'There is a widespread belief among users that these drugs enhance creativity. This experiment disproves that belief.'
Poor at recognising mistakes
Kowal also demonstrated that for chronic users the brain processes involved in monitoring mistakes also work less effectively. A high dose of cannabis seems to influence both the unconscious processing of mistakes and also the later and more conscious stages of error processing. Kowal: 'It is important that we gather more knowledge about the effects of cannabis on a person's ability to detect mistakes. This can help with putting together a treatment programme for drug addiction.'
Lower dopamine production
The research also indicated clear long-term effects: cannabis disrupts the activity of dopamine in the brain. With chronic users a significant reduction was seen in the frequency of spontaneous eye blinking, an indication of a reduction in dopamine production.
More research needed
The conclusion from other scientific research is that regular cannabis use does not necessarily have disastrous effects for the take-up of dopamine. It may well be that the age at which cannabis is first used is a crucial factor, Kowal suggests. The type of cannabis and the way neurobiological processes interact with one another can also result in individual differences. Kowal: 'More research is needed on the effects of cannabis and on the individual consequences it can have on mental functions.'
https://www.sciencedaily.com/releases/2016/10/161004125829.htm
With worrisome animal research, more focus needed on effects of cannabis on human development
September 30, 2016
Science Daily/Georgetown University Medical Center
In this new era of legalized marijuana, far too little research has been conducted on the effect of cannabis on the development of human embryos, say researchers at Georgetown University Medical Center who scoured medical literature on the topic and found what they say is worrisome animal research.
Their study, in the journal BioMed Central (BMC) Pharmacology and Toxicology, suggests an urgent need for human epidemiological and basic research that examines the link between maternal cannabinoid use, either smoked or eaten in candy bars, and the health of newborns. Cannabinoids are chemicals like THC, the primary psychoactive compound in marijuana, that act on cannabinoid receptors in neurons, repressing the normal release of neurotransmitters.
"We know from limited human studies that use of marijuana in early pregnancy is associated with many of the same risks as tobacco, including miscarriage, birth defects, developmental delays and learning disabilities, but animal research suggests the potential for many more developmental issues linked with the drug," says the study's senior investigator, G. Ian Gallicano, PhD, associate professor of biochemistry and molecular & cellular biology at Georgetown.
Gallicano says one reason for limited research is that the classification of marijuana as a Schedule I drug creates challenges to conducting research.
"All of the model systems point to the notion that cannabinoids affects many aspects of human development because THC and other chemicals alter molecular pathways that shouldn't be disrupted during development of a fetus," he says.
"We also know that THC is a promising agent for treating cancer, because it negatively affects tumor growth and can cause the death of cancer cells. Embryo development has similarities to tumor formation -- it turns on growth pathways that are necessary for development," Gallicano says. "The fact that THC seems to stop cancer growth suggests how damaging the chemical could be for a fetus."
The study grew from a project of four current Georgetown medical students (Joseph Friedrich, Dara Khatib, Keon Parsa, and Ariana Santopietro) for a course, Sexual Development and Reproduction, taught by Gallicano. They undertook the analysis given that although four states have legal recreational marijuana use and 24 allow use of medical marijuana, little research has been conducted on outcomes from use of the drug in pregnancy and biological mechanisms that cause these issues.
The students reviewed the scientific literature for studies on cannabinoids and embryonic development published between 1975 and 2015. They cite the following findings:
• THC lasts in the body for weeks, especially in maternal tissues that act as reservoirs for THC and other cannabinoids, according to studies of pregnant dogs. Human cells studies have shown that THC has a half-life of eight days in fat deposits and can be detected in blood for up to 30 days;
• THC readily crosses the human placenta, which can slow clearance of the drugs while prolonging fetal exposure;
• THC levels in smoked marijuana have increased nearly 25-fold since 1970, and can be substantially stronger in edible preparations of cannabis;
• THC and other cannabinoids interfere with use of folic acid (vitamin B9), which has long been known to be essential for normal development and growth of the human placenta and embryo. Deficiencies in folic acid are linked to low human birth weight, increased risk of spontaneous abortion, and neural tube defects such as spina bifida.
• Cannabinoid signaling plays important roles in development of a mouse embryo. It is required for proper pre-implantation development, embryo transport to the uterus, and implantation.
• In post-implantation development, cannabinoid signaling functions in a multitude of pathways, including, but not limited to blood vessel growth, fate of embryonic stem cells, and normal cognitive development. For example, disruption of one key neural pathway, BDNF, has been linked to increased risk of congenital malformations and impaired cognition, including autism and low IQ in humans.
The authors also say the harms found in animal studies cited in this study do not include the damaged induced from the act of smoking marijuana.
https://www.sciencedaily.com/releases/2016/09/160930080859.htm
Exercise can increase levels of hunger-promoting endocannabinoids even if you are sleep-deprived
September 26, 2016
Science Daily/Uppsala Universitet
A research group at Uppsala University has investigated how levels of endocannabinoids -- which target the same receptors as cannabis -- are affected by short sleep duration, and whether acute exercise can modulate this effect.
Chronic lack of sleep has been linked to an increased risk of overweight and obesity and previous studies have demonstrated that healthy participants who are sleep deprived eat more, make unfavorable food choices and crave more high-calorie foods. Now, a research group at Uppsala University has investigated how levels of endocannabinoids -- which target the same receptors as cannabis -- are affected by short sleep duration, and whether acute exercise can modulate this effect.
'Previous studies have shown alterations in the levels of some hunger hormones after sleep loss, but the results have been mixed and hormones that drive hedonic food intake have been less investigated. Furthermore, whereas exercise has many beneficial effects, whether exercise can modulate the effects of sleep loss on various hormonal pathways is currently unknown,' says lead author of the new study Jonathan Cedernaes, M.D., Ph.D, at Uppsala University.
In the new study, published in the journal Psychoneuroendocrinology, the researchers invited healthy normal-weight participants to a sleep laboratory on two separate occasions, to be studied after three consecutive nights of normal sleep, and after three nights of only sleeping four hours each night. Meals and activity patterns were kept standardized while participants were in the lab, and blood was drawn repeatedly to assess endocannabinoid levels in blood. This was also done on the last day both before and after a short bout of intensive exercise.
The researchers found that the levels of 2-arachidonoylglycerol -- the most abundant endocannabinoid in the brain -- was about 80 percent higher after the nights of short sleep compared with after the normal sleep session. When the participants exercised, the levels of 2AG still went up almost by half, regardless of whether participants had been allowed to sleep for three normal nights, or to only sleep four hours each night.
'As previously shown by us and others, sleep loss increased subjective hunger compared with the well-rested state. Given the role of endocannabinoids for promoting hunger and hedonic eating, this could offer an explanation as to why. Meanwhile, we instead saw lower stress ratings after exercise in the sleep deprivation condition, which could also possibly be attributed to the observed endocannabinoid levels following our exercise intervention,' says senior author associate professor Christian Benedict.
'It is noteworthy that when sleep-deprived, the participants saw the same amount of increase in endocannabinoid levels following the acute exercise. Endocannabinoids are thought to confer both the "runner's high" as well as at least some of the neuroprotective effects of exercise. Therefore, this may suggest that even under conditions of chronic sleep loss, exercise may exert similar centrally active, and possibly neuroprotective, properties as under conditions of sufficient sleep. This is an important area for future research as we and others have found that short sleep duration by itself may be harmful to the brain, and in the long run increase the risk of e.g. Alzheimer's disease', says Jonathan Cedernaes.
https://www.sciencedaily.com/releases/2016/09/160926105542.htm
Cannabis reduces short-term motivation to work for money
Smoking the equivalent of a single 'spliff' of cannabis makes people less willing to work for money while 'high'
September 1, 2016
Science Daily/University College London
Smoking the equivalent of a single 'spliff' of cannabis makes people less willing to work for money while 'high', finds a new UCL study.
The research, published in Psychopharmacology, is the first to reliably demonstrate the short-term effects of cannabis on motivation in humans. The researchers also tested motivation in people who were addicted to cannabis but not high during the test, and found that their motivation levels were no different to volunteers in the control group.
"Although cannabis is commonly thought to reduce motivation, this is the first time it has been reliably tested and quantified using an appropriate sample size and methodology," says lead author Dr Will Lawn (UCL Clinical Psychopharmacology). "It has also been proposed that long-term cannabis users might also have problems with motivation even when they are not high. However, we compared people dependent on cannabis to similar controls, when neither group was intoxicated, and did not find a difference in motivation. This tentatively suggests that long-term cannabis use may not result in residual motivation problems when people stop using it. However, longitudinal research is needed to provide more conclusive evidence."
57 volunteers were involved in the research, which consisted of two separate studies. The first involved 17 adult volunteers who all used cannabis occasionally. Through a balloon, they inhaled cannabis vapour on one occasion and cannabis-placebo vapour on separate occasion. Straight after, they completed a task designed to measure their motivation for earning money. This was a real-life task as the volunteers were given money they had earned at the end of the experiment.
In each trial of the task, volunteers could choose whether to complete low- or high-effort tasks to win varying sums of money. The low-effort option involved pressing the spacebar key with the little finger of their non-dominant hand 30 times in 7 seconds to win 50p. The high-effort option involved 100 space bar presses in 21 seconds, for rewards varying from 80p to £2.
"Repeatedly pressing keys with a single finger isn't difficult but it takes a reasonable amount of effort, making it a useful test of motivation," explains senior author Professor Val Curran (UCL Clinical Psychopharmacology). "We found that people on cannabis were significantly less likely to choose the high-effort option. On average, volunteers on placebo chose the high-effort option 50% of the time for a £2 reward, whereas volunteers on cannabis only chose the high-effort option 42% of the time."
In the second study, 20 people addicted to cannabis were matched with 20 control participants who reported the same levels of non-cannabis drug use. Participants were not allowed to consume alcohol or drugs, other than tobacco or coffee, for 12 hours before the study. They were then asked to perform the same motivation task as participants in the first study. The results showed that cannabis-dependent volunteers were no less motivated than the control group. However, much more research is needed to fully understand the relationship between long-term cannabis use and possible amotivational deficits.
https://www.sciencedaily.com/releases/2016/09/160901211303.htm
Cannabinoid receptor activates spermatozoa
August 30, 2016
Science Daily/Ruhr-University Bochum
Biologists have detected a cannabinoid receptor in spermatozoa. Endogenous cannabinoids that occur in both the male and the female genital tract activate the spermatozoa: they trigger the so-called acrosome reaction, during which the spermatozoon releases digestive enzymes and loses the cap on the anterior half of its head. Without this reaction, spermatozoa cannot penetrate the ovum.
During fertilization, a sperm must first fuse with the plasma membrane and then penetrate the female egg in order to penetrate it. To this end, sperm cells go through a process known as the acrosome reaction which is the reaction that occurs in the acrosome of the sperm as it approaches the egg. In the lab, this so-called acrosome reaction is considered a test for analysing the ability of semen to accomplish fertilisation. A receptor for an endogenous cannabinoid plays a crucial role in this process. A team of biologists from Bochum and Bonn, headed by Prof Dr Dr Dr Hanns Hatt, have been the first one to provide a proof of the so-called G protein-coupled receptors 18 (GPR18) in spermatozoa, following a comprehensive analysis. They published their findings in Scientific Reports.
Researchers find 223 additional receptors
Specialised in olfaction research, the team from Bochum had detected as many as 60 olfactory receptors in spermatozoa early this year, and has activated and localised ten of them. "In the current study, we have focused on the remaining G protein-coupled receptors, which, rather than being olfactory receptors, bind other substances," explains Hanns Hatt. Analysing samples by numerous donors, the researchers investigated which genes are expressed in spermatozoa; their conclusion was that the number of receptors totalled 223. The three most common ones include receptor GPR18, a cannabinoid receptor that has recently been described for the first time.
New receptor is more sensitive to NAGly than classical ones
"The receptor reacts to the herbal cannabis agent THC as well as to the endogenous fatty acid NAGly, which is associated with the cannabinoid system," says Hatt. "It is much more sensitive to NAGly than the classical, long-known cannabinoid receptors." Activating the receptor, which is situated in the centre of spermatozoa, can trigger the so-called acrosome reaction. In the course of this process, the spermatozoon's surface is altered as it approaches the egg. Without this reaction, the spermatozoon cannot penetrate the egg cell.
Cannabinoids in female reproductive tract
Scientists know that endocannabinoids occur in both the male and the female genital tract. Studies suggest that in women their concentration increases during the fertile days. "The endocannabinoid activates the spermatozoa for fertilization" concludes Hanns Hatt. The GPR18 receptor also occurs in other tissues in the human body, for example in the brain and in the heart. However, its function was not known until now.
https://www.sciencedaily.com/releases/2016/08/160830121726.htm