Posts tagged marijuana
Articles and news from the latest research reports.
(Image caption: Whole brain functional connectivity between the nucleus accumbens (NAc) and other brain areas in response to cannabis cues (vs. neutral cues) in all participants)
Dependence Alters the Brain’s Response to Pot Paraphernalia
New research from The University of Texas at Dallas demonstrates that drug paraphernalia triggers the reward areas of the brain differently in dependent and non-dependent marijuana users.
The study, published July 1 in Drug and Alcohol Dependence, demonstrated that different areas of the brain activated when dependent and non-dependent users were exposed to drug-related cues.
The 2012 National Survey on Drug Use and Health shows marijuana is the most widely used illicit drug in the United States. According to a 2013 survey from the Pew Research Center, 48 percent of Americans ages 18 and older have tried marijuana. The National Institute on Drug Abuse says that 9 percent of daily users will become dependent on marijuana.
“We know that people have a hard time staying abstinent because seeing cues for the drug use triggers this intense desire to seek out the drugs,” said Dr. Francesca Filbey, lead author of the study and professor at the Center for BrainHealth in the School of Behavioral and Brain Sciences. “That’s a clinically validated phenomenon and behavioral studies have also shown this to be the case. What we didn’t know was what was driving those effects in the brain.”
To find this effect, Filbey and colleagues conducted brain-imaging scans, called functional magnetic resonance imaging (fMRI), on 71 participants who regularly used marijuana. Just more than half of those were classified as dependent users. While being scanned, the participants were given either a used marijuana pipe or a pencil of approximately the same size that they could see and feel.
A comparison of the images revealed that the nucleus accumbens, the reward region in the brain, was activated in all users in response to the pipe. However, the strengths of the connections with other areas differed between dependent and non-dependent users.
“We found that the reward network is actually being driven by other areas unrelated to reward, like the areas in memory and attention or emotion,” Filbey said.
Non-dependent users showed greater activations in the orbital frontal cortex and hippocampus, suggesting that memory and attention were connected to the activation of the reward network. Dependent users had greater activations in the amygdala and anterior cingulate gyrus, suggesting a more emotional connection.
Additionally, the areas of the brain activated resemble areas activated for other addictions, such as nicotine or cocaine, lending greater support to the addictiveness of marijuana.
These findings suggest that marijuana abuse intervention needs to cater more specifically to a user’s level of addiction.
"Clinicians treating people with problems with marijuana dependence should consider the different processes that trigger the reward response when determining possible pharmacological or behavioral interventions,” Filbey said.
Marijuana shows potential in treating autoimmune disease
A team of University of South Carolina researchers led by Mitzi Nagarkatti, Prakash Nagarkatti and Xiaoming Yang have discovered a novel pathway through which marijuana can suppress the body’s immune functions. Their research has been published online in the Journal of Biological Chemistry.
Marijuana is the most frequently used illicit drug in the United States, but as more states legalize the drug for medical and even recreational purposes, research studies like this one are discovering new and innovative potential health applications for the federal Schedule I drug.
Marijuana is now regularly and successfully used to alleviate the nausea and vomiting many cancer patients experience as side effects to chemotherapy, combat the wasting syndrome that causes some AIDS patients to lose significant amounts of weight and muscle mass and ease chronic pain that is unresponsive to opioids, among other applications.
The university study has uncovered yet another potential application for marijuana, in the suppression of immune response to treat autoimmune diseases. The work builds on recent scientific discoveries that the environment in which humans live can actually trigger changes that occur outside of human DNA, but nevertheless can cause alterations to the function of genes controlled by DNA. These outside molecules that have the ability to alter DNA function are known collectively as the epigenome. In this study, the investigators wanted to find out if the tetrahydrocannabinol found in marijuana has the capacity to affect DNA expression through epigenetic pathways outside of the DNA itself.
The recent findings show that marijuana THC can change critical molecules of epigenome called histones, leading to suppression of inflammation. These results suggest that one potential negative impact of marijuana smoking could be suppression of beneficial inflammation in the body. But they also suggest that, because of its epigenetic influence toward inflammation suppression, marijuana use could be efficacious in the treatment of autoimmune diseases such as arthritis, lupus, colitis, multiple sclerosis and the like, in which chronic inflammation plays a central role.
(Source: eurekalert.org)
Casual marijuana use linked to brain abnormalities in students
Young adults who used marijuana only recreationally showed significant abnormalities in two key brain regions that are important in emotion and motivation, scientists report. The study was a collaboration between Northwestern Medicine® and Massachusetts General Hospital/Harvard Medical School.
This is the first study to show casual use of marijuana is related to major brain changes. It showed the degree of brain abnormalities in these regions is directly related to the number of joints a person smoked per week. The more joints a person smoked, the more abnormal the shape, volume and density of the brain regions.
"This study raises a strong challenge to the idea that casual marijuana use isn’t associated with bad consequences," said corresponding and co-senior study author Hans Breiter, M.D. He is a professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine and a psychiatrist at Northwestern Memorial Hospital.
"Some of these people only used marijuana to get high once or twice a week," Breiter said. "People think a little recreational use shouldn’t cause a problem, if someone is doing OK with work or school. Our data directly says this is not the case."
The study will be published April 16 in the Journal of Neuroscience.
Scientists examined the nucleus accumbens and the amygdala — key regions for emotion and motivation, and associated with addiction — in the brains of casual marijuana users and non-users. Researchers analyzed three measures: volume, shape and density of grey matter (i.e., where most cells are located in brain tissue) to obtain a comprehensive view of how each region was affected.
Both these regions in recreational pot users were abnormally altered for at least two of these structural measures. The degree of those alterations was directly related to how much marijuana the subjects used.
Of particular note, the nucleus acccumbens was abnormally large, and its alteration in size, shape and density was directly related to how many joints an individual smoked.
"One unique strength of this study is that we looked at the nucleus accumbens in three different ways to get a detailed and consistent picture of the problem," said lead author Jodi Gilman, a researcher in the Massachusetts General Center for Addiction Medicine and an instructor in psychology at Harvard Medical School. "It allows a more nuanced picture of the results."
Examining the three different measures also was important because no single measure is the gold standard. Some abnormalities may be more detectable using one type of neuroimaging analysis method than another. Breiter said the three measures provide a multidimensional view when integrated together for evaluating the effects of marijuana on the brain.
"These are core, fundamental structures of the brain," said co-senior study author Anne Blood, director of the Mood and Motor Control Laboratory at Massachusetts General and assistant professor of psychiatry at Harvard Medical School. "They form the basis for how you assess positive and negative features about things in the environment and make decisions about them."
Through different methods of neuroimaging, scientists examined the brains of young adults, ages 18 to 25, from Boston-area colleges; 20 who smoked marijuana and 20 who didn’t. Each group had nine males and 11 females. The users underwent a psychiatric interview to confirm they were not dependent on marijuana. They did not meet criteria for abuse of any other illegal drugs during their lifetime.
The changes in brain structures indicate the marijuana users’ brains are adapting to low-level exposure to marijuana, the scientists said.
The study results fit with animal studies that show when rats are given tetrahydrocannabinol (THC) their brains rewire and form many new connections. THC is the mind-altering ingredient found in marijuana.
"It may be that we’re seeing a type of drug learning in the brain," Gilman said. "We think when people are in the process of becoming addicted, their brains form these new connections."
In animals, these new connections indicate the brain is adapting to the unnatural level of reward and stimulation from marijuana. These connections make other natural rewards less satisfying.
"Drugs of abuse can cause more dopamine release than natural rewards like food, sex and social interaction," Gilman said. "In those you also get a burst of dopamine but not as much as in many drugs of abuse. That is why drugs take on so much salience, and everything else loses its importance."
The brain changes suggest that structural changes to the brain are an important early result of casual drug use, Breiter said. “Further work, including longitudinal studies, is needed to determine if these findings can be linked to animal studies showing marijuana can be a gateway drug for stronger substances,” he noted.
Because the study was retrospective, researchers did not know the THC content of the marijuana, which can range from 5 to 9 percent or even higher in the currently available drug. The THC content is much higher today than the marijuana during the 1960s and 1970s, which was often about 1 to 3 percent, Gilman said.
Marijuana is the most commonly used illicit drug in the U.S. with an estimated 15.2 million users, the study reports, based on the National Survey on Drug Use and Health in 2008. The drug’s use is increasing among adolescents and young adults, partially due to society’s changing beliefs about cannabis use and its legal status.
A recent Northwestern study showed chronic use of marijuana was linked to brain abnormalities. “With the findings of these two papers,” Breiter said, “I’ve developed a severe worry about whether we should be allowing anybody under age 30 to use pot unless they have a terminal illness and need it for pain.”
(Source: eurekalert.org)
Perception of Marijuana as a “Safe Drug” Is Scientifically Inaccurate
The nature of the teenage brain makes users of cannabis amongst this population particularly at risk of developing addictive behaviors and suffering other long-term negative effects, according to researchers at the University of Montreal and New York’s Icahn School of Medicine at Mount Sinai.
“Of the illicit drugs, cannabis is most used by teenagers since it is perceived by many to be of little harm. This perception has led to a growing number of states approving its legalization and increased accessibility. Most of the debates and ensuing policies regarding cannabis were done without consideration of its impact on one of the most vulnerable population, namely teens, or without consideration of scientific data,” wrote Professor Didier Jutras-Aswad of the University of Montreal and Yasmin Hurd, MD, PhD, of Mount Sinai. “While it is clear that more systematic scientific studies are needed to understand the long-term impact of adolescent cannabis exposure on brain and behavior, the current evidence suggests that it has a far-reaching influence on adult addictive behaviors particularly for certain subsets of vulnerable individuals.”
The researchers reviewed over 120 studies that looked at different aspects of the relationship between cannabis and the adolescent brain, including the biology of the brain, chemical reaction that occurs in the brain when the drug is used, the influence of genetics and environmental factors, in addition to studies into the “gateway drug” phenomenon. “Data from epidemiological studies have repeatedly shown an association between cannabis use and subsequent addiction to heavy drugs and psychosis (i.e. schizophrenia). Interestingly, the risk to develop such disorders after cannabis exposure is not the same for all individuals and is correlated with genetic factors, the intensity of cannabis use and the age at which it occurs. When the first exposure occurs in younger versus older adolescents, the impact of cannabis seems to be worse in regard to many outcomes such as mental health, education attainment, delinquency and ability to conform to adult role,” Dr Jutras-Aswad said.
Although it is difficult to confirm in all certainty a causal link between drug consumption and the resulting behavior, the researchers note that rat models enable scientists to explore and directly observe the same chemical reactions that happen in human brains. Cannabis interacts with our brain through chemical receptors (namely cannabinoid receptors such as CB1 and CB2.) These receptors are situated in the areas of our brain that govern our learning and management of rewards, motivated behavior, decision-making, habit formation and motor function. As the structure of the brain changes rapidly during adolescence (before settling in adulthood), scientists believe that the cannabis consumption at this time greatly influences the way these parts of the user’s personality develop. In adolescent rat models, scientists have been able to observe differences in the chemical pathways that govern addiction and vulnerability – a receptor in the brain known as the dopamine D2 receptor is well known to be less present in cases of substance abuse.
Only a minority (approximately one in four) of teenage users of cannabis will develop an abusive or dependant relationship with the drug. This suggests to the researchers that specific genetic and behavioral factors influence the likelihood that the drug use will continue. Studies have also shown that cannabis dependence can be inherited through the genes that produce the cannabinoid receptors and an enzyme involved in the processing of THC. Other psychological factors are also likely involved. “Individuals who will develop cannabis dependence generally report a temperament characterized by negative affect, aggressivity and impulsivity, from an early age. Some of these traits are often exacerbated with years of cannabis use, which suggests that users become trapped in a vicious cycle of self-medication, which in turn becomes a dependence” Jutras-Aswad said.
The researchers stress that while a lot remains unknown about the mechanics of cannabis abuse, the body of existing research has clear implications for society. “It is now clear from the scientific data that cannabis is not harmless to the adolescent brain, specifically those who are most vulnerable from a genetic or psychological standpoint. Identifying these vulnerable adolescents, including through genetic or psychological screening, may be critical for prevention and early intervention of addiction and psychiatric disorders related to cannabis use. The objective is not to fuel the debate about whether cannabis is good or bad, but instead to identify those individuals who might most suffer from its deleterious effects and provide adequate measures to prevent this risk” Jutras-Aswad said. “Continuing research should be performed to inform public policy in this area. Without such systematic, evidenced-based research to understand the long-term effects of cannabis on the developing brain, not only the legal status of cannabis will be determined on uncertain ground, but we will not be able to innovate effective treatments such as the medicinal use of cannabis plant components that might be beneficial for treating specific disorders,” Dr Hurd said.
(Image: AP)
Marijuana use in adolescence may cause permanent brain abnormalities
Regular marijuana use in adolescence, but not adulthood, may permanently impair brain function and cognition, and may increase the risk of developing serious psychiatric disorders such as schizophrenia, according to a recent study from the University of Maryland School of Medicine. Researchers hope that the study, published in Neuropsychopharmacology — a publication of the journal Nature – will help to shed light on the potential long-term effects of marijuana use, particularly as lawmakers in Maryland and elsewhere contemplate legalizing the drug.
"Over the past 20 years, there has been a major controversy about the long-term effects of marijuana, with some evidence that use in adolescence could be damaging," says the study’s senior author Asaf Keller, Ph.D., Professor of Anatomy and Neurobiology at the University of Maryland School of Medicine. "Previous research has shown that children who started using marijuana before the age of 16 are at greater risk of permanent cognitive deficits, and have a significantly higher incidence of psychiatric disorders such as schizophrenia. There likely is a genetic susceptibility, and then you add marijuana during adolescence and it becomes the trigger."
"Adolescence is the critical period during which marijuana use can be damaging," says the study’s lead author, Sylvina Mullins Raver, a Ph.D. candidate in the Program in Neuroscience in the Department of Anatomy and Neurobiology at the University of Maryland School of Medicine. "We wanted to identify the biological underpinnings and determine whether there is a real, permanent health risk to marijuana use."
The scientists — including co-author Sarah Paige Haughwout, a research technician in Dr. Keller’s laboratory — began by examining cortical oscillations in mice. Cortical oscillations are patterns of the activity of neurons in the brain and are believed to underlie the brain’s various functions. These oscillations are very abnormal in schizophrenia and in other psychiatric disorders. The scientists exposed young mice to very low doses of the active ingredient in marijuana for 20 days, and then allowed them to return to their siblings and develop normally.
"In the adult mice exposed to marijuana ingredients in adolescence, we found that cortical oscillations were grossly altered, and they exhibited impaired cognitive abilities," says Ms. Raver. "We also found impaired cognitive behavioral performance in those mice. The striking finding is that, even though the mice were exposed to very low drug doses, and only for a brief period during adolescence, their brain abnormalities persisted into adulthood."
The scientists repeated the experiment, this time administering marijuana ingredients to adult mice that had never been exposed to the drug before. Their cortical oscillations and ability to perform cognitive behavioral tasks remained normal, indicating that it was only drug exposure during the critical period of adolescence that impaired cognition through this mechanism. The researchers took the next step in their studies, trying to pinpoint the mechanisms underlying these changes and the time period in which they occur.
"We looked at the different regions of the brain," says Dr. Keller. "The back of the brain develops first, and the frontal parts of the brain develop during adolescence. We found that the frontal cortex is much more affected by the drugs during adolescence. This is the area of the brain controls executive functions such as planning and impulse control. It is also the area most affected in schizophrenia."
Dr. Keller’s team believes that the results have indications for humans as well. They will continue to study the underlying mechanisms that cause these changes in cortical oscillations. “The purpose of studying these mechanisms is to see whether we can reverse these effects,” says Dr. Keller. “We are hoping we will learn more about schizophrenia and other psychiatric disorders, which are complicated conditions. These cognitive symptoms are not affected by medication, but they might be affected by controlling these cortical oscillations.”
Mutations found in individuals with autism interfere with endocannabinoid signaling in the brain
Mutations found in individuals with autism block the action of molecules made by the brain that act on the same receptors that marijuana’s active chemical acts on, according to new research reported online April 11 in the Cell Press journal Neuron. The findings implicate specific molecules, called endocannabinoids, in the development of some autism cases and point to potential treatment strategies.
"Endocannabinoids are molecules that are critical regulators of normal neuronal activity and are important for many brain functions," says first author Dr. Csaba Földy, of Stanford University Medical School. "By conducting studies in mice, we found that neuroligin-3, a protein that is mutated in some individuals with autism, is important for relaying endocannabinoid signals that tone down communication between neurons."
When the researchers introduced different autism-associated mutations in neuroligin-3 into mice, this signaling was blocked and the overall excitability of the brain was changed.
"These findings point out an unexpected link between a protein implicated in autism and a signaling system that previously had not been considered to be particularly important for autism," says senior author Dr. Thomas Südhof, also of Stanford. "Thus, the findings open up a new area of research and may suggest novel strategies for understanding the underlying causes of complex brain disorders."
The results also indicate that targeting components of the endocannabinoid signaling system may help reverse autism symptoms.
The study’s findings resulted from a research collaboration between the Stanford laboratories of Dr. Südhof and Dr. Robert Malenka, who is also an author on the paper.
Study Confirms AKT1 Genotype Contributes to Risk of Cannabis Psychosis
The ability of cannabis to produce psychosis is an important public health concern. Some studies have suggested that cannabis exposure during adolescence may increase the risk of developing schizophrenia.
For these reasons, it would be valuable if a biological test could be developed that predicted the risk of developing psychosis in people who abuse cannabis or use marijuana as a medication.
A recent study has implicated a variation in the gene that codes for a protein called RAC-alpha serine/threonine-protein kinase in the risk for cannabis psychosis. However, independent verification of these finding is critical for genetic associations with complex genetic traits, like cannabis-related psychosis, because these findings are difficult to replicate.
Dr Forti’s team carried out a case control study to investigate variation in the AKT1 gene and cannabis use in increasing the risk of psychosis.
“We studied the AKT1 gene as this is involved in dopamine signaling which is known to be abnormal in psychosis. Our sample comprised 489 patients with their first episode of psychosis and 278 healthy controls,” explained Dr Forti, who, with colleagues, reports on the results in the journal Biological Psychiatry.
Boosting natural marijuana-like brain chemicals treats fragile X syndrome symptoms
UCI study points to role endocannabinoids play in common genetic cause of autism
American and European scientists have found that increasing natural marijuana-like chemicals in the brain can help correct behavioral issues related to fragile X syndrome, the most common known genetic cause of autism.
The work indicates potential treatments for anxiety and cognitive defects in people with this condition. Results appear online in Nature Communications.
Daniele Piomelli of UC Irvine and Olivier Manzoni of INSERM, the French national research agency, led the study, which identified compounds that inhibit enzymes blocking endocannabinoid transmitters called 2-AG in the striatum and cortex regions of the brain.
These transmitters allow for the efficient transport of electrical signals at synapses, structures through which information passes between neurons. In fragile X syndrome, regional synapse communication is severely limited, giving rise to certain cognitive and behavioral problems.
Fragile X syndrome is caused by a mutation of the FMR1 gene on the X chromosome. People born with it are mentally disabled; generally experience crawling, walking and language delays; tend to avoid eye contact; may be hyperactive or impulsive; and have such notable physical characteristics as an elongated face, flat feet and large ears.
The researchers stress that their findings, while promising, do not point to a cure for the condition.
“What we hope is to one day increase the ability of people with fragile X syndrome to socialize and engage in normal cognitive functions,” said Piomelli, a UCI professor of anatomy & neurobiology and the Louise Turner Arnold Chair in the Neurosciences.
The study involved mice genetically altered with FMR1 mutations that exhibited symptoms of fragile X syndrome. Treated with novel compounds that correct 2-AG protein signaling in brain cells, these mice showed dramatic behavioral improvements in maze tests measuring anxiety and open-space acceptance.
While other work has focused on pharmacological treatments for behavioral issues associated with fragile X syndrome, Piomelli noted that this is the first to identify the role endocannabinoids play in the neurobiology of the condition.
About endocannabinoids
Endocannabinoid compounds are created naturally in the body and share a similar chemical structure with THC, the primary psychoactive component of the marijuana plant, Cannabis. Endocannabinoids are distinctive because they link with protein molecule receptors — called cannabinoid receptors — on the surface of cells. For instance, when a person smokes marijuana, the cannabinoid THC activates these receptors. Because the body’s natural cannabinoids control a variety of factors — such as pain, mood and appetite — they’re attractive targets for drug discovery and development. Piomelli is one of the world’s leading endocannabinoid researchers. His groundbreaking work is showing that this system can be exploited by new treatments to combat anxiety, pain, depression and obesity.
(Source: today.uci.edu)
Mothers’ Teen Cannabinoid Exposure May Increase Response of Offspring to Opiate Drugs
ScienceDaily (June 5, 2012) — Mothers who use marijuana as teens — long before having children — may put their future children at a higher risk of drug abuse, new research suggests.
Researchers in the Neuroscience and Reproductive Biology section at the Cummings School of Veterinary Medicine conducted a study to determine the transgenerational effects of cannabinoid exposure in adolescent female rats. For three days, adolescent rats were administered the cannabinoid receptor agonist WIN-55, 212-2, a drug that has similar effects in the brain as THC, the active ingredient in marijuana. After this brief exposure, they remained untreated until being mated in adulthood.
The male offspring of the female rats were then measured against a control group for a preference between chambers that were paired with either saline or morphine. The rats with mothers who had adolescent exposure to WIN-55,212-2 were significantly more likely to opt for the morphine-paired chamber than those with mothers who abstained. The results suggest that these animals had an increased preference for opiate drugs.
The study was published in the Journal of Psychopharmocology and funded by the National Institutes of Health.
"Our main interest lies in determining whether substances commonly used during adolescence can induce behavioral and neurochemical changes that may then influence the development of future generations," said Research Assistant Professor John J. Byrnes, the study’s lead author, "We acknowledge that we are using rodent models, which may not fully translate to the human condition. Nevertheless, the results suggest that maternal drug use, even prior to pregnancy, can impact future offspring."
Byrnes added that much research is needed before a definitive connection is made between adolescent drug use and possible effects on future children.
The study builds on earlier findings by the Tufts group, most notably a study published last year in Behavioral Brain Research by Assistant Professor Elizabeth Byrnes that morphine use as adolescent rats induces changes similar to those observed in the present study.
Other investigators in the field have previously reported that cannabinoid exposure during pregnancy (in both rats and humans) can affect offspring development, including impairment of cognitive function, and increased risk of depression and anxiety.
Source: Science Daily