Researchers find new role for cannabinoids in vision

Chemicals shown to improve low-light vision of tadpoles by sensitizing retinal cells

August 25, 2016

Science Daily/McGill University

A multidisciplinary team including researchers from the Montreal Neurological Institute has improved our understanding of how cannabinoids, the active agent in marijuana, affect vision in vertebrates.

Scientists used a variety of methods to test how tadpoles react to visual stimuli when they've been exposed to increased levels of exogenous or endogenous cannabinoids. Exogenous cannabinoids are artificially introduced drugs, whereas endogenous cannabinoids occur naturally in the body.

They found that, contrary to what they expected, activating cannabinoid signaling in tadpoles actually increased the activity in their retinal ganglion cells (RGCs), which are responsible for transmitting information about light detection from the eye to the brain. Previous studies found that cannabinoids typically work to reduce neurotransmission, not increase it.

"Initially you distrust yourself when you see something that goes against widely held ideas, but we tried the experiment so many times, using diverse techniques, and it was a consistent result," says Ed Ruthazer, a professor of neurology and neurosurgery at the Montreal Neurological Institute of McGill University, and the paper's senior author. "So then we knew we had to figure out what was going on. The first tendency is to want to ignore it. But it was such a strong effect, we knew there was something important here."

What the researchers found is that one class of cannabinoid receptor, known as CB1R, plays a role in the suppression of chloride transport into the RGCs. When the receptor is activated, chloride levels are reduced, which hyperpolarizes the cell, making it able to fire at higher frequencies when stimulated.

For the tadpoles, this meant they were able to detect dimmer objects in low light than when they had not been exposed to increased levels of cannabinoids. The team used software developed with McGill physics and chemistry professor Paul Wiseman to detect behavior changes in the tadpoles.

It is too early to say if cannabinoids have the same effect on human vision, but there is anecdotal evidence in scientific literature of cannabis ingestion improving night vision of Jamaican and Moroccan fishermen.

What's more interesting however, according to Ruthazer, is that they have discovered a previously unknown role for cannabinoids in brain signaling. Therapeutic use of cannabinoids is becoming increasingly accepted by the medical community, and the need for an accurate and thorough understanding of these chemicals' role in the brain is greater than ever.

"Our work provides an exciting potential mechanism for cannabinoid regulation of neuronal firing, but it will obviously be important to confirm that similar mechanisms are also at play in the eyes of mammals," says Ruthazer. "Though technically more challenging, a similar study should now be performed in the mouse retina or even in cultures of human retinal cells."

https://www.sciencedaily.com/releases/2016/08/160825130616.htm

Drunk or stoned: Comparing sexual experiences related to alcohol and marijuana use among adults

August 4, 2016

Science Daily/New York University

A new study, published in Archives of Sexual Behavior by researchers affiliated with New York University's Center for Drug Use and HIV Research (CDUHR), compared self-reported sexual experiences related to use of alcohol and marijuana. Since marijuana has increased in popularity in the U.S., the researchers examined if and how marijuana use may influence risk for unsafe sexual behavior.

"With marijuana becoming more accepted in the U.S. along with more liberal state-level policies," notes Joseph J. Palamar, PhD, MPH, an affiliate of CDUHR and an assistant professor of Population Health at NYU Langone Medical Center (NYULMC), "it is important to examine users' sexual experiences and sexual risk behavior associated with use to inform prevention and harm reduction."

In this study, the researchers interviewed 24 adults (12 males and 12 females, all self-identified as heterosexual and HIV-negative) who recently used marijuana before sex. Compared to marijuana, alcohol use was more commonly associated with social outgoingness and use often facilitated connections with potential sexual partners; however, alcohol was more likely than marijuana to lead to atypical partner choice or post-sex regret.

Alcohol was commonly used as a social lubricant to meet sexual partners, and this was related, in part, to alcohol being readily available in social gatherings.

"Interestingly, some users reported that the illegality of marijuana actually facilitated sexual interactions," notes Dr. Palamar. "Since smoking marijuana recreationally is illegal in most states and smoking it tends to produce a strong odor, it usually has to be used in a private setting. Some individuals utilize such private or intimate situations to facilitate sexual encounters."

While users often described favorable sexual effects of each drug, both alcohol and marijuana were reportedly associated with a variety of negative sexual effects including sexual dysfunction. For example, marijuana use was linked to vaginal dryness and alcohol was commonly described as increasing the likelihood of impotence among males.

The researchers noted that the sexual effects tended to be similar across males and females, and both alcohol and marijuana were generally associated with loss of inhibitions. Both drugs appear to be potentially associated with increased feelings of self-attractiveness, but possibly more so for alcohol, and participants reported feelings of increased sociability and boldness while consuming alcohol.

While some participants reported that marijuana use made them more selective in choosing a partner, many participants -- both male and female -- felt that their "standards" for choosing a partner were lowered while under the influence of alcohol.

"It wasn't surprising that alcohol use reportedly led to less post-sex satisfaction than marijuana," said Dr. Palamar. "Participants reported feelings of regret more frequently after sex on alcohol, but compared to alcohol they generally didn't report poor judgment after using marijuana."

When smoking marijuana, participants tended to reported increased feelings of anxiety or a sense of wariness in unfamiliar situations that they did not generally seem to experience after using alcohol. Therefore, these drugs appear to have different effects with regard to socialization that may precede a sexual encounter.

"Sexual encounters on marijuana tended to be with someone the individual knew," comments Dr. Palamar. "Sex on alcohol was often with a stranger so the situation before sex may be much more important than the drug used."

Marijuana and alcohol are associated with unique sexual effects, with alcohol use reportedly leading to riskier sexual behavior. Both drugs appear to potentially increase risk for unsafe sex.

"Research is needed continue to study sexual effects of recreational drugs to inform prevention to ensure that users and potential users of these drugs are aware of sexual effects associated with use," emphasizes Dr. Palamar. "Our results can inform prevention and harm reduction education especially with regard to marijuana, since people who smoke marijuana generally don't receive any harm reduction information at all. They're pretty much just told not to use it."

https://www.sciencedaily.com/releases/2016/08/160804141034.htm

Cannabinoids remove plaque-forming Alzheimer's proteins from brain cells

June 29, 2016

Science Daily/Salk Institute

Salk Institute scientists have found preliminary evidence that tetrahydrocannabinol (THC) and other compounds found in marijuana can promote the cellular removal of amyloid beta, a toxic protein associated with Alzheimer's disease.

While these exploratory studies were conducted in neurons grown in the laboratory, they may offer insight into the role of inflammation in Alzheimer's disease and could provide clues to developing novel therapeutics for the disorder.

"Although other studies have offered evidence that cannabinoids might be neuroprotective against the symptoms of Alzheimer's, we believe our study is the first to demonstrate that cannabinoids affect both inflammation and amyloid beta accumulation in nerve cells," says Salk Professor David Schubert, the senior author of the paper.

Alzheimer's disease is a progressive brain disorder that leads to memory loss and can seriously impair a person's ability to carry out daily tasks. It affects more than five million Americans according to the National Institutes of Health, and is a leading cause of death. It is also the most common cause of dementia and its incidence is expected to triple during the next 50 years.

It has long been known that amyloid beta accumulates within the nerve cells of the aging brain well before the appearance of Alzheimer's disease symptoms and plaques. Amyloid beta is a major component of the plaque deposits that are a hallmark of the disease. But the precise role of amyloid beta and the plaques it forms in the disease process remains unclear.

In a manuscript published in June 2016's Aging and Mechanisms of Disease, Salk team studied nerve cells altered to produce high levels of amyloid beta to mimic aspects of Alzheimer's disease.

The researchers found that high levels of amyloid beta were associated with cellular inflammation and higher rates of neuron death. They demonstrated that exposing the cells to THC reduced amyloid beta protein levels and eliminated the inflammatory response from the nerve cells caused by the protein, thereby allowing the nerve cells to survive.

"Inflammation within the brain is a major component of the damage associated with Alzheimer's disease, but it has always been assumed that this response was coming from immune-like cells in the brain, not the nerve cells themselves," says Antonio Currais, a postdoctoral researcher in Schubert's laboratory and first author of the paper. "When we were able to identify the molecular basis of the inflammatory response to amyloid beta, it became clear that THC-like compounds that the nerve cells make themselves may be involved in protecting the cells from dying."

Brain cells have switches known as receptors that can be activated by endocannabinoids, a class of lipid molecules made by the body that are used for intercellular signaling in the brain. The psychoactive effects of marijuana are caused by THC, a molecule similar in activity to endocannabinoids that can activate the same receptors. Physical activity results in the production of endocannabinoids and some studies have shown that exercise may slow the progression of Alzheimer's disease.

Schubert emphasized that his team's findings were conducted in exploratory laboratory models, and that the use of THC-like compounds as a therapy would need to be tested in clinical trials.

In separate but related research, his lab found an Alzheimer's drug candidate called J147 that also removes amyloid beta from nerve cells and reduces the inflammatory response in both nerve cells and the brain. It was the study of J147 that led the scientists to discover that endocannabinoids are involved in the removal of amyloid beta and the reduction of inflammation.

Other authors on the paper include Oswald Quehenberger and Aaron Armando at the University of California, San Diego; and Pamela Maher and Daniel Daughtery at the Salk Institute.

The study was supported by the National Institutes of Health, The Burns Foundation and The Bundy Foundation.

https://www.sciencedaily.com/releases/2016/06/160629095609.htm

Long-term marijuana use changes brain's reward circuit

June 7, 2016

Science Daily/Center for BrainHealth

Chronic marijuana use disrupts the brain's natural reward processes, according to researchers at the Center for BrainHealth at The University of Texas at Dallas.

In a paper published in Human Brain Mapping, researchers demonstrated for the first time with functional magnetic resonance imaging that long-term marijuana users had more brain activity in the mesocorticolimbic-reward system when presented with cannabis cues than with natural reward cues.

"This study shows that marijuana disrupts the natural reward circuitry of the brain, making marijuana highly salient to those who use it heavily. In essence, these brain alterations could be a marker of transition from recreational marijuana use to problematic use," said Dr. Francesca Filbey, director of Cognitive Neuroscience Research in Addictive Disorders at the Center for BrainHealth and associate professor in the School of Behavioral and Brain Sciences.

Researchers studied 59 adult marijuana users and 70 nonusers, accounting for potential biases such as traumatic brain injury and other drug use. Study participants rated their urge to use marijuana after looking at various visual cannabis cues, such as a pipe, bong, joint or blunt, and self-selected images of preferred fruit, such as a banana, an apple, grapes or an orange.

Researchers also collected self-reports from study participants to measure problems associated with marijuana use. On average, marijuana participants had used the drug for 12 years.

When presented with marijuana cues compared to fruit, marijuana users showed enhanced response in the brain regions associated with reward, such as the orbitofrontal cortex, striatum, anterior cingulate gyrus, precuneus and the ventral tegmental area.

"We found that this disruption of the reward system correlates with the number of problems, such as family issues, individuals have because of their marijuana use," Filbey said. "Continued marijuana use despite these problems is an indicator of marijuana dependence."

The research was funded by the National Institute on Drug Abuse.

https://www.sciencedaily.com/releases/2016/06/160607151239.htm

How the brain makes, and breaks, a habit

Neuroscience study identifies brain chemicals, neural pathway involved in switching between habitual behavior, deliberate decision-making

May 26, 2016

Science Daily/University of California - San Diego

Not all habits are bad. Some are even necessary. It's a good thing, for example, that we can find our way home on "autopilot" or wash our hands without having to ponder every step. But inability to switch from acting habitually to acting in a deliberate way can underlie addiction and obsessive compulsive disorders.

Working with a mouse model, an international team of researchers demonstrates what happens in the brain for habits to control behavior.

The study is published in Neuron and was led by Christina Gremel, assistant professor of psychology at the University of California San Diego, who began the work as a postdoctoral researcher at the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health. Senior authors on the study are Rui Costa, of the Champalimaud Centre for the Unknown in Lisbon, and David Lovinger of the NIAAA/NIH.

The study provides the strongest evidence to date, Gremel said, that the brain's circuits for habitual and goal-directed action compete for control -- in the orbitofrontal cortex, a decision-making area of the brain -- and that neurochemicals called endocannabinoids allow for habit to take over, by acting as a sort of brake on the goal-directed circuit.

Endocannabinoids are a class of chemicals produced naturally by humans and other animals. Receptors for endocannabinoids are found throughout the body and brain, and the endocannabinoid system is implicated in a variety of physiological processes -- including appetite, pain sensation, mood and memory. It is also the system that mediates the psychoactive effects of cannabis.

Earlier work by Gremel and Costa had shown that the orbitofrontal cortex, or OFC, is an important brain area for relaying information on goal-directed action. They found that by increasing the output of neurons in the OFC with a technique called optogenetics -- precisely turning neurons on and off with flashes of light -- they increased goal-directed actions. In contrast, when they decreased activity in the same area with a chemical approach, they disrupted goal-directed actions and the mice relied on habit instead.

"Habit takes over when the OFC is quieted," Gremel said.

In the current study, since endocannabinoids are known to reduce the activity of neurons in general, the researchers hypothesized that endocannabinoids may be quieting or reducing activity in the OFC and, with it, the ability to shift to goal-directed action. They focused particularly on neurons projecting from the OFC into the dorsomedial striatum.

They trained mice to perform the same lever-pressing action for the same food reward but in two different environments that differentially bias the development of goal-directed versus habitual actions. Like humans who don't suffer from neuropsychiatric disorders, healthy mice will readily shift between performing the same action using a goal-directed versus habitual action strategy. To stick with the earlier example of getting home, we can switch the homing autopilot off and shift to goal-directed behavior when we need to get to a new or different location.

To test their hypothesis on the role played by endocannabinoids, the researchers then deleted a particular endocannabinoid receptor, called cannabinoid type 1, or CB1, in the OFC-to-striatum pathway. Mice missing these receptors did not form habits -- showing the critical role played by the neurochemicals as well as that particular pathway.

"We need a balance between habitual and goal-directed actions. For everyday function, we need to be able to make routine actions quickly and efficiently, and habits serve this purpose," Gremel said. "However, we also encounter changing circumstances, and need the capacity to 'break habits' and perform a goal-directed action based on updated information. When we can't, there can be devastating consequences."

The findings may suggest, the authors say, a new therapeutic target for people suffering from OCD or addictions: To stop overreliance on habit and restore the ability to shift from habit to goal-directed action, it may be helpful to treat the brain's endocannabinoid system and so reduce habitual control over behavior. Treatment could be pharmaceutical or might involve behavioral therapy. Further research is needed.

https://www.sciencedaily.com/releases/2016/05/160526185419.htm

Neuroscientists discover previously unknown function of cannabinoid receptor

Study could improve our insights into brain diseases

May 2, 2016

Science Daily/DZNE - German Center for Neurodegenerative Diseases

In the brain, there is a delicate interplay of signaling substances and cellular activity. Scientists have now identified another key player within this ensemble. In a laboratory study they found that the 'cannabinoid type 2 receptor' influences information processing inside the hippocampus. The research results might help advance our understanding of schizophrenia and Alzheimer's, say the authors.

The cannabinoid type 2 receptor -- also called "CB2 receptor" -- is a special membrane protein. Its function is to receive chemical signals that control cellular activity. "Until now, this receptor was considered part of the immune system without function in nerve cells. However, our study shows that it also plays an important role in the signal processing of the brain," explains Professor Dietmar Schmitz, Speaker for the DZNE-Site Berlin and Director of the Neuroscience Research Center of the Charité (NWFZ/NeuroCure). Schmitz coordinated the current study, which involved Berlin colleagues and also scientists from the University of Bonn and from the "National Institute on Drug Abuse" of the US.

As the researchers demonstrated in an animal model, the CB2 receptor raises the excitation threshold of nerve cells in the hippocampus. "Operation of the brain critically depends on the fact that nerve impulses sometimes have an exciting impact on downstream cells and in other cases they have a suppressing effect," says Dr Vanessa Stempel, lead author of the current publication, who is now doing research in Cambridge, UK. "The CB2 receptor works like a set screw by which such communication processes can be adjusted."

Component of the "endocannabinoid system"

The CB2 receptor is part of the endocannabinoid system (ECS). This family of receptors and signaling substances exists in many organisms including humans. It is a biochemical control system which is involved in the regulation of numerous physiological processes. Its name refers to the fact that chemicals derived from the cannabis plant bind to receptors of the ECS. So far, there are two known types of these receptors: The CB2 receptor has no psychoactive effect. Hence, the mind-altering effects triggered by the consumption of cannabis are ascribed to the "cannabinoid type 1 receptor."

Potential therapeutic applications

The results of the current study could contribute to a better understanding of disease mechanisms and provide a starting point for novel medications. "Brain activity is disturbed in schizophrenia, depression, Alzheimer's disease and other neuropsychiatric disorders. Pharmaceuticals that bind to the CB2 receptor could possibly influence the activity of brain cells and thus become part of a therapy," Professor Schmitz concludes.

https://www.sciencedaily.com/releases/2016/05/160502111228.htm

Heavy cannabis use associated with reduced dopamine release in brain

Effect similar to other addictions

April 14, 2016

Science Daily/Columbia University Medical Center

In a recent study, researchers found evidence of a compromised dopamine system in heavy users of marijuana. Lower dopamine release was found in the striatum -- a region of the brain that is involved in working memory, impulsive behavior, and attention. Previous studies have shown that addiction to other drugs of abuse, such as cocaine and heroin, have similar effects on dopamine release, but such evidence for cannabis was missing until now.

"In light of the more widespread acceptance and use of marijuana, especially by young people, we believe it is important to look more closely at the potentially addictive effects of cannabis on key regions of the brain," said Anissa Abi-Dargham, MD, professor of psychiatry (in radiology) at Columbia University Medical Center (CUMC) and a lead author of the paper.

The study included 11 adults between the ages of 21 and 40 who were severely dependent on cannabis and 12 matched healthy controls. On average, the cannabis group started using at age 16, became dependent on cannabis by age 20, and have been dependent for the past 7 years. In the month prior to the study, nearly all users in this study smoked marijuana daily.

Using positron emission tomography (PET) to track a radiolabelled molecule that binds to dopamine receptors in the brain, the scientists measured dopamine release in the striatum and its subregions, as well as in several brain regions outside the striatum, including the thalamus, midbrain, and globus pallidus. The cannabis users in this study stayed in the hospital for a week of abstinence to ensure that the PET scans were not measuring the acute effects of the drug. Participants were scanned before and after being given oral amphetamine to elicit dopamine release. The percent change in the binding of the radiotracer was taken as an indicator of capacity for dopamine release.

Compared with the controls, the cannabis users had significantly lower dopamine release in the striatum, including subregions involved in associative and sensorimotor learning, and in the globus pallidus.

The investigators also explored the relationship between dopamine release in a key area of the striatum and cognitive performance on learning and working memory tasks. Although there was no difference between groups in task performance, in all participants lower dopamine release was associated with worse performance on both tasks.

"We don't know whether decreased dopamine was a preexisting condition or the result of heavy cannabis use," said Dr. Abi-Dargham. "But the bottom line is that long-term, heavy cannabis use may impair the dopaminergic system, which could have a variety of negative effects on learning and behavior."

Jeffrey Lieberman, MD, Chair of Psychiatry at CUMC and past president of the American Psychiatric Association, noted that "these findings add to the growing body of research demonstrating the potentially adverse effects of cannabis, particularly in youth, at the same time that government policies and laws are increasing access and use."

https://www.sciencedaily.com/releases/2016/04/160414214826.htm

'Marijuana receptor' might hold the key to new fertility treatments for men

Research suggests that cannabis exposure may affect DNA-bound proteins, sperm chromatin and have an impact on fertility, embryo development and offspring health

April 8, 2016

Science Daily/Federation of American Societies for Experimental Biology

In a research report appearing in the April 2016 issue of The FASEB Journal, scientists show that a cannabinoid receptor, called "CB2," helps regulate the creation of sperm. Not only does this provide more evidence that marijuana can disrupt fertility in males, but it also suggests a therapeutic strategy for treating male infertility.

"The possibility to improve male fertility is one of the main focuses of this study, since infertility is a worldwide problem that affect up to 15% of couples in which male factors account for almost 20-70%," said Paola Grimaldi, Ph.D., a researcher involved in the work from the Department of Biomedicine and Prevention, School of Medicine at the University of Rome Tor Vergata in Rome, Italy.

To make their discovery, Grimaldi and colleagues treated three groups of mice with different agents for 14 to 21 days. The first group was treated with a specific activator of the CB2 receptor. The second group was treated with a specific inhibitor of the CB2 receptor. The third group received only a saline solution and served as the control group. The group treated with the CB2 activator showed an acceleration of spermatogenesis, while the group treated with the inhibitor displayed a slower rate of the process. This suggests that a tight balance of CB2 activation is required for the proper progression of spermatogenesis.

"That the normal beneficial effects of endogenous cannabinoids on spermatogenesis can be stimulated further by a chemical mimic, an agonist, is a potentially promising new idea for treating male infertility," said Thoru Pederson, Ph.D., Editor-in-Chief of The FASEB Journal.

https://www.sciencedaily.com/releases/2016/04/160408163828.htm

Cells chat via cannabinoids, about your future diabetes

February 1, 2016

Science Daily/Nencki Institute of Experimental Biology

The level of glucose in human blood depends on the continuous cooperation between two types of cells in the pancreas. Alpha cells secrete glucagon hormone that increases glucose in blood, while the beta cells secrete insulin, the hormone decreasing glucose concentration. Scientists from the Nencki Institute of Experimental Biology of the Polish Academy of Sciences in Warsaw have recently discovered that the alpha and beta cells communicate with each other, and the central role in this communication is played by cannabinoids -- organic compounds that occur in nature also in inflorescences of cannabis. In recent studies, carried out in cooperation with institutes from Sweden, Austria, Italy and the United States, it has also been shown that cannabinoids have an impact on the identity of the beta cells, and in human embryos they may lead to significant changes in the architecture of a forming pancreatic islets.

"Our discovery is essential to understand the mechanisms responsible for the development of type 2 diabetes, which occurs generally in adults and is often associated with weight gain. If our further research brings expected results, perhaps in the near future we will be able to use them to free up at least some patients from the nightmare of continuous insulin injections," says Prof. Agnieszka Dobrzyn from the Nencki Institute.

In the latest publication in the journal Proceedings of the National Academy of Sciences (PNAS), the researchers from the Nencki Institute showed that the pathway of chemical signals involving cannabinoids not only plays an important role in communication between alpha and beta cells, but also is involved in keeping the identity of the latter. Cannabinoids produced by the alpha cells may in fact activate cannabinoid CB1 receptors located in the pancreatic islets. These receptors determine the differentiation of cell function and may increase the ability to produce insulin in response to glucose by beta cells.

"Observing the changes in the architecture of islets during embryonic development in mice and in pseudoislets -- a model we generated in our lab -- was also very interesting. Depending on the concentration of cannabinoids and the activity of two different receptors, the islets became larger or smaller, while the alpha cells, usually located outside the islets, were able to migrate inside," explains Dr. Katarzyna Malenczyk fom the Nencki Institute, the first author of the publication.

The studies already have their practical application. They suggest that future mothers consuming substances containing cannabinoids in the pregnancy period are more likely to deliver children with impaired pancreatic islet architecture, and therefore prone to type 2 diabetes.

"Under no circumstances should it be concluded from our work that consumption of marijuana can be a way to cure diabetes," Prof. Dobrzyn warns and explains: "The concentration of glucose in the blood is determined by the balance between the activities of alpha and beta cells of the pancreas and insulin target tissues such as skeletal muscle and adipose tissue. In adults, more cannabinoids will force one group of cells to more intensive work, but at the same time it will weaken the efficiency of the other, and in consequence blood glucose level will not change or may even increase significantly."

The discovery of the role of cannabinoids in the communication between alpha and beta cells gives hope for more effective treatment of diabetes by islet transplantation. Such allografts have already been performed: a portion of respective tissue is being recovered from a dead donor and placed under the mucosa of the recipient's stomach. Yet, the effects are not fully rewarding as beta cells of the implant often lose their identity: they are still alive, but can no longer produce insulin. After implantation of a foreign tissue a patient must take immunosuppressive drugs and the damage caused by such therapy often outweighs its gains. Scientists from the Nencki Institute hope that understanding the cannabinoid pathway will enable to significantly extend beta cells working time. If further studies validate these assumptions, the islet transplants could become a full-fledged method of diabetes treatment. Moreover, nowadays beta cells can be grown from stem cells derived from a patient's adipose tissue. Therefore, in future patients would not need to take drugs to prevent rejection of transplanted pancreatic islets.

This research was supported by National Science Centre, Poland, grant no UMO-2013/10/E/NZ3/00670.

https://www.sciencedaily.com/releases/2016/02/160201085000.htm

Can marijuana help transplant patients?

Mice receiving THC, the active ingredient in marijuana, had a delay in the rejection of an incompatible organ

September 1, 2015

Science Daily/Federation of American Societies for Experimental Biology

Here's another discovery to bolster the case for medical marijuana: New research in mice suggests that THC, the active ingredient in marijuana, may delay the rejection of incompatible organs. Although more research is necessary to determine if there are benefits to humans, this suggests that THC, or a derivative, might prove to be a useful antirejection therapy, particularly in situations where transplanted organs may not be a perfect match. These findings were published in the September 2015 issue of The Journal of Leukocyte Biology.

"We are excited to demonstrate for the first time that cannabinoid receptors play an important role in the prolongation of rejection of a foreign graft by suppressing immune response in the recipient, said Mitzi Nagarkatti, Ph.D., a researcher involved in the work from the University of South Carolina School of Medicine. "This opens up a new area of research that would lead to better approaches to prevent transplant rejection as well as to treat other inflammatory diseases."

To make this discovery, Nagarkatti and colleagues used two groups of mice that were genetically different, and transplanted skin from one group to the other. All of the mice received incompatible skin, but one group was treated with vehicle (placebo) and the other was treated with THC. The scientists observed that the rejection of the skin graft in mice that received THC was delayed when compared to the control group that only received a placebo.

Please note: Transplant patients should not use marijuana as a therapy without the consent of their physician and should only do so in compliance with any and all local, state and federal laws.

"More and more research is identifying potential beneficial effects of substances contained in marijuana, but a major challenge has been identifying the molecular pathways involved," said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology. "These new studies point to important roles for the cannabinoid receptors as targets that might be exploited using approaches that refine how we think about substances derived from marijuana."

https://www.sciencedaily.com/releases/2015/09/150901113535.htm

Botanists conduct first large-scale genetic study of marijuana, hemp

August 26, 2015

Science Daily/University of British Columbia

A study by Canadian researchers is providing a clearer picture of the evolutionary history and genetic organization of cannabis, a step that could have agricultural, medical and legal implications for this valuable crop.

"Even though hemp and marijuana are important crops, knowledge about cannabis is lacking because of its status as a controlled drug," said Jonathan Page, a University of British Columbia botanist who co-led the first large-scale study of the genetic diversity of cannabis. The research was conducted together with Sean Myles, a population geneticist at Dalhousie University.

Researchers looked at the genotypes of 81 marijuana and 43 hemp samples. Using the DNA variants in the cannabis genome, they were able to search for relationships between different plants. They found that cannabis plants, which consist of three species (C. sativa, C. indica and C. ruderalis), are often incorrectly labeled.

Popular lore assigns different characteristics to marijuana plants. For example, Indica-type plants are believed to produce relaxing and sedative effects as opposed to more stimulating Sativa-type plants. The researchers found only a moderate correlation between the ancestry of marijuana strains reported by breeders and the ancestry inferred from their DNA. For example, a sample of Jamaican Lambs Bread, which is classified as C. sativa, was almost identical at a genetic level to a C. indica strain from Afghanistan.

"Cannabis breeders and growers often indicate the percentage of Sativa or Indica in a cannabis strain, but they are not very accurate," Page explained.

While hemp plants also go by the latin name C. sativa, researchers discovered that hemp showed a high amount of genetic separation from marijuana, likely due to the breeding of the plants for radically different uses.

Canada is a global leader in hemp production, with more than 80,000 acres devoted to seed and fibre production. A licence from Health Canada is required to grow marijuana for medical purposes, and there are now 25 licensed producers supplying about 21,000 Canadian patients. Understanding cannabis genetics and evolution could assist in better breeding efforts for both crops.

"The genetic difference between marijuana and hemp has legal implications in many countries," said Page. "Right now, the genetic identity of a marijuana strain cannot be accurately determined by its name or reported ancestry. Ultimately we require a practical, accurate and more reliable classification system of this plant."

https://www.sciencedaily.com/releases/2015/08/150826144110.htm

Mixed findings regarding quality of evidence supporting benefit of medical marijuana

June 23, 2015

Science Daily/JAMA - Journal of the American Medical Association

In an analysis of the findings of nearly 80 randomized trials that included about 6,500 participants, there was moderate-quality evidence to support the use of cannabinoids (chemical compounds that are the active principles in cannabis or marijuana) for the treatment of chronic pain and lower-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, sleep disorders, and Tourette syndrome, according to a study in the June 23/30 issue of JAMA.

Medical cannabis refers to the use of cannabis or cannabinoids as medical therapy to treat disease or alleviate symptoms. In the United States, 23 states and Washington, D.C., have introduced laws to permit the medical use of cannabis; many other countries have similar laws. Despite the wide us of cannabis and cannabinoid drugs for medical purposes, their efficacy for specific indications is not clear, according to background information in the article.

Penny F. Whiting, Ph.D., of the University of Bristol, Bristol, United Kingdom, and colleagues evaluated the evidence for the benefits and adverse events (AEs) of medical cannabinoids by searching various databases for randomized clinical trials of cannabinoids for a variety of indications. The researchers identified 79 trials (6,462 participants) that met criteria for inclusion in the review and meta-analysis.

The researchers found that most studies suggested that cannabinoids were associated with improvements in symptoms, but these associations did not reach statistical significance in all studies. There was moderate-quality evidence to suggest that cannabinoids may be beneficial for the treatment of chronic neuropathic or cancer pain and spasticity due to multiple sclerosis (sustained muscle contractions or sudden involuntary movements). There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV, sleep disorders, and Tourette syndrome; and very low-quality evidence for an improvement in anxiety. There was low-quality evidence for no effect on psychosis and very low-level evidence for no effect on depression.

There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination. There was no clear evidence for a difference in association (either beneficial or harmful) based on type of cannabinoids or mode of administration. Only 2 studies evaluated cannabis. There was no evidence that the effects of cannabis differed from other cannabinoids.

"Further large, robust, randomized clinical trials are needed to confirm the effects of cannabinoids, particularly on weight gain in patients with HIV/AIDS, depression, sleep disorders, anxiety disorders, psychosis, glaucoma, and Tourette syndrome are required. Further studies evaluating cannabis itself are also required because there is very little evidence on the effects and AEs of cannabis," the authors write.

Editorial: Medical Marijuana

"If the states' initiative to legalize medical marijuana is merely a veiled step toward allowing access to recreational marijuana, then the medical community should be left out of the process, and instead marijuana should be decriminalized," write Deepak Cyril D'Souza, M.B.B.S., M.D., and Mohini Ranganathan, M.D., of the Yale University School of Medicine, New Haven, Conn., in an accompanying editorial.

"Conversely, if the goal is to make marijuana available for medical purposes, then it is unclear why the approval process should be different from that used for other medications. Evidence justifying marijuana use for various medical conditions will require the conduct of adequately powered, double-blind, randomized, placebo/active controlled clinical trials to test its short- and long-term efficacy and safety. The federal government and states should support medical marijuana research. Since medical marijuana is not a life-saving intervention, it may be prudent to wait before widely adopting its use until high-quality evidence is available to guide the development of a rational approval process."

https://www.sciencedaily.com/releases/2015/06/150623113152.htm

Any dose of alcohol combined with cannabis significantly increases levels of THC in blood

May 27, 2015

Science Daily/American Association for Clinical Chemistry (AACC)

Cannabis plus alcohol is one of the most frequently detected drug combinations in car accidents, yet the interaction of these two compounds is still poorly understood. A study appearing online in Clinical Chemistry, the journal of AACC, shows for the first time that the simultaneous use of alcohol and cannabis produces significantly higher blood concentrations of cannabis's main psychoactive constituent, Δ9-tetrahydrocannabinol (THC), as well as THC's primary active metabolite, 11-hydroxy-THC (11-OH-THC), than cannabis use alone.

Currently, 23 states and the District of Columbia have legalized medical cannabis, and Colorado, Washington, Oregon, and Alaska have decriminalized recreational cannabis use. As cannabis becomes more widely accessible, the verdict remains out on whether cannabis intoxication increases the risk of car accidents. Experts agree, however, that the combination of cannabis and alcohol raises the chance of crashing more than either substance by itself. In a study of 1,882 motor vehicle deaths, the U.S. Department of Transportation found an increased accident risk of 0.7 for cannabis use, 7.4 for alcohol use, and 8.4 for cannabis and alcohol use combined.

To shed light on the ways in which cannabis and alcohol interact to negatively impact driving, a group of researchers studied 19 adult participants who drank placebo or low-dose alcohol (with a target peak breath-alcohol concentration of approximately 0.065%) 10 minutes prior to inhaling 500 mg of placebo, low-dose (2.9% THC), or high-dose (6.7% THC) vaporized cannabis. The researchers found that with no alcohol, the median maximum blood concentrations for low and high THC doses were 32.7 and 42.2 µg/L THC, respectively, and 2.8 and 5.0 µg/L 11-OH-THC. With alcohol, the median maximum blood concentrations for low and high THC doses were 35.3 and 67.5 µg/L THC and 3.7 and 6.0 µg/L 11-OH-THC -- which is significantly higher than without alcohol.

"The significantly higher blood THC and 11-OH-THC [median maximum concentration] values with alcohol possibly explain increased performance impairment observed from cannabis-alcohol combinations," said lead study author Marilyn A. Huestis, PhD, of the National Institute on Drug Abuse, Baltimore, Maryland. "Our results will help facilitate forensic interpretation and inform the debate on drugged driving legislation."

https://www.sciencedaily.com/releases/2015/05/150527112728.htm

'Extreme' exposure to secondhand cannabis smoke causes mild intoxication

May 13, 2015

Science Daily/Johns Hopkins Medicine

Secondhand exposure to cannabis smoke under "extreme conditions," such as an unventilated room or enclosed vehicle, can cause nonsmokers to feel the effects of the drug, have minor problems with memory and coordination, and in some cases test positive for the drug in a urinalysis. Those are the findings of a Johns Hopkins University School of Medicine study, reported online this month in the journal Drug and Alcohol Dependence.

Cannabis is the most widely used illicit drug in the world. "Many people are exposed to secondhand cannabis smoke," says lead author Evan S. Herrmann, Ph.D., a postdoctoral fellow in psychiatry and behavioral sciences at Johns Hopkins. "The scenario we looked at was almost a worst-case scenario. It could happen in the real world, but it couldn't happen to someone without him or her being aware of it."

"We found positive drug effects in the first few hours, a mild sense of intoxication and mild impairment on measures of cognitive performance," says senior author Ryan Vandrey, Ph.D. , an associate professor of psychiatry and behavioral sciences at Johns Hopkins. "These were relatively slight effects, but even so, some participants did not pass the equivalent of a workplace drug test."

The new research is the most comprehensive study of secondhand cannabis smoke and its effects since the 1980s, when researchers found the drug's active ingredient, tetrahydrocannabinol, or THC, and other cannabis byproducts could turn up in nonsmokers' bodies after an hour or more spent in extreme conditions with heavy smokers in an enclosed space. That finding needed updating, since the average potency of street cannabis has tripled since the 1980s, the Johns Hopkins researchers wrote. Additionally, many earlier studies did not look at whether the nonsmokers reported feeling the drug's effects, or whether their behavior and thinking were affected by secondhand smoke, as the new study did.

Researchers recruited seven people ages 18 to 45 who said they smoked cannabis at least twice per week and tested positive for THC, but who tested negative for other drugs, and 12 others in the same age range who said they had not used cannabis in the past six months and tested negative for cannabis, other drugs, and alcohol. None of the participants were pregnant, and none of the nonsmokers took part in more than one session.

Six smokers and six nonsmokers spent an hour sitting side by side in a 10-by-13-foot, acrylic-walled room in two different experimental sessions. Each smoker was given 10 high-potency cannabis cigarettes to smoke. In one session, the room's ventilation fans were turned on. In another session, the fans were turned off, and the room became smoke-filled. This was a realistic simulation of home ventilation conditions. At the end of the exposures, smokers' and nonsmokers' blood, urine, saliva and hair were tested at regular intervals for THC.

All six nonsmokers who spent an hour exposed to secondhand smoke in the unventilated room under extreme conditions had detectable amounts of THC in their urine and blood. THC in blood was observed immediately after exposure and for up to three hours afterwards. Four hours after the experiment ended, one nonsmoker tested positive for THC on a urine test with the same cutoff (50 nanograms per milliliter) used in the Federal Workplace Drug Testing Program. At intervals between two and 22 hours after the experiment, four of the six nonsmokers tested positive for THC in their urine at a lower cutoff (20 nanograms per milliliter) sometimes used in commercial drug testing programs.

None of the nonsmokers exposed to secondhand smoke in the ventilated room tested positive for THC on either the more sensitive or the less sensitive urinalysis. (All the cannabis smokers tested positive for THC afterward.)

Nonsmokers exposed to secondhand smoke with fans running reported no effects other than being hungry. Those who were exposed in the unventilated experiment reported feeling "pleasant," more tired and less alert. When the nonsmokers were asked to duplicate grid patterns they saw on a computer monitor or perform a basic numbers drill, those in the unventilated study responded faster but made more mistakes than they did before they were exposed to the cannabis smoke, the researchers found.

"The behavioral and cognitive effects were minor and consistent with a mild cannabis effect," Herrmann says.

"This study is a significant update in our knowledge of cannabis smoke effect on nonsmokers and has implications in many arenas, including drugs and driving," says co-author Edward J. Cone, Ph.D., a Johns Hopkins adjunct professor of psychiatry and behavioral sciences who performed the early passive inhalation studies in the 1980s.

The study's limitations included its small size and the lack of a placebo trial using cannabis that contained no THC. The study was supported by the Substance Abuse and Mental Health Services Administration (SAMHSA), an agency in the U.S. Department of Health and Human Services that sets standards for federal workplace drug testing. Information about the effects of secondhand smoke on drug test results were being sought to support different ways of measuring drug use or drug exposure, Vandrey says. Funding came from SAMHSA and the National Center for Research Resources of the National Institutes of Health. The cannabis used in the experiment was provided by the National Institute on Drug Abuse.

https://www.sciencedaily.com/releases/2015/05/150513102904.htm

The dark side of cannabis: Panic attacks, nausea

May 5, 2015

Science Daily/Deutsches Aerzteblatt International

Although the use of cannabis as a medical drug is currently booming, we should not forget that leisure time consumption -- for example, smoking weed -- can cause acute and chronic harms. These include panic attacks, impaired coordination of movement, and nausea, as Eva Hoch and colleagues show in a topical review article in Deutsches Ärzteblatt International.

The symptoms depend on a patient's age, the amount of the drug consumed, and the frequency of drug use. It also matters in which form the cannabis is consumed -- for example, as a joint, bong, or hash cake.

Cannabis is the most popular illegal drug in Germany and was consumed by almost one in 20 adults in Germany last year. An estimated one in 10 consumers will become dependent. This is critical especially for adolescents, because they are more prone to becoming dependent than adults. Addiction treatment is mostly provided on an outpatient basis.

Currently, combination therapy -- consisting of motivational support, cognitive behavioral therapy, and contingency management (learning via systematic rewards) -- is the most promising approach, as the authors emphasize.

They recommend combination therapy, together with a family therapeutic intervention, especially for adolescents with dependency problems.

https://www.sciencedaily.com/releases/2015/05/150505102117.htm

Synthetic drugs: evidence that they can cause cancer

April 16, 2015

Science Daily/Medical University of Vienna

Almost weekly, a new synthetic psychoactive drug comes onto the market somewhere in Europe that can be ordered legally and easily, for example as an incense blend, via the Internet. Synthetic cannabinoids are difficult to identify chemically and the possible unwanted toxic effects that can occur following their consumption have so far barely been investigated. As part of the international EU project "SPICE II Plus," which is now coming to an end, scientists from the MedUni Vienna's Institute for Cancer Research have now also found evidence that synthetic substances damage the DNA of human cells and can therefore possibly have cancer-causing effects.

Synthetic cannabinoids, similar to tetrahydrocannabinol (the psychoactive ingredient of marijuana), bind to cannabinoid receptors in the human brain, triggering similar neurophysiological effects. These synthetic cannabinoids are marketed in incense mixtures as "legal highs" via the Internet and are "flooding the market," as Siegfried Knasmüller from the Institute for Cancer Research at the MedUni Vienna warns.

"The substances are directly active, in other words they are not activated via enzymes that metabolise foreign substances," explains Knasmüller. "The respiratory organs and the digestive tract especially are subjected to increased concentrations of these drugs. Our investigations on human cell lines in the laboratory have shown that synthetic cannabinoids, in the high concentrations found in cells in the oral cavity or in the lungs, for example, are likely to trigger damage to the DNA that may have significant consequences for the consumers of such substances. They damage chromosomes, and this is directly associated with cancer."

Effects on consumers cannot be quantified

Synthetic cannabinoids bind very differently and some have an effect even in very small quantities. Consumers have absolutely no information about the varying levels of effect, since they are unaware of the detailed composition of synthetically manufactured drugs. Even with "known" products, the type and quantity of ingredients added change constantly. The risk of an unwanted overdose is correspondingly great. As a result, there have been repeated cases of damage to users' health or poisoning, and in some cases users have even died.

Between 2005 and 2012, the European Union's early warning system registered just under 240 new psychoactive substances that were disguised as incense blends, bath salts or plant fertiliser, and around 140 of them contained synthetic cannabinoids.

SPICE I and SPICE II Plus are international cooperation projects at EU level that have been led by the Institute of Medical Jurisprudence at the University Hospital of Freiburg (Prof. Volker Auwärter) and which have also involved the MedUni Vienna and the Goethe University of Frankfurt, the University of Helsinki, the Institute of Therapy Research in Munich, as well as input from partners such as the Federal Criminal Office of Wiesbaden.

https://www.sciencedaily.com/releases/2015/04/150416083746.htm

Common cholesterol drug stimulates the same receptors as marijuana

April 1, 2015

Science Daily/Federation of American Societies for Experimental Biology

If you want the benefits of medical marijuana without the "unwanted side effects" of cannabis, new research should leave you on a high note. According to a research report appearing in the April 2015 issue of The FASEB Journal, fenofibrate, also known by the brand name Tricor®, may benefit a wide range of health issues, such as pain, appetite stimulation, nausea, as well as immune and various psychiatric and neurological conditions. This suggests that fenofibrate may be the starting point for a new class of cannabis-like drugs to treat these types of conditions.

"By illustrating the relationship between fenofibrate and the cannabinoid system, we aim to improve our understanding of this clinically important drug," said Richard S. Priestley, Ph.D., a researcher involved in the work from the School of Life Sciences at the University of Nottingham Medical School in Nottingham, United Kingdom. "Our study provides the basis for the investigation of new drugs targeting these important receptors."

To make this discovery Priestly and colleagues cultured cells containing cannabinoid receptors and exposed them to a tracer compound, which binds to cannabinoid receptors. They found that fenofibrate was able to displace the tracer, suggesting that it also binds to the receptors. Furthermore, they discovered that fenofibrate actually switched the cannabinoid receptors "on," not only in these cells, but also in sections of intestine. This led to the relaxation of the tissue in a way that mimicked what marijuana does. Despite the fact that fenofibrate has been used for many years, and its mechanism of action was presumed to be through a completely different family of receptors, this suggests that at least some of the effects of fenofibrate may be controlled by cannabinoid receptors. Furthermore, these cannabinoid receptors may be a future target for drugs used to treat pain and a variety of immune and psychiatric diseases.

"It may be difficult to persuade people in Colorado, Washington, and the District of Columbia that there are people who want the beneficial effects of marijuana without actually getting high," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal, "but there are people who do not want to get stoned just to get the relief that marijuana brings. This new work suggests that possibility."

https://www.sciencedaily.com/releases/2015/04/150401161640.htm

How cannabis use affects people with Bipolar Disorder

Science Daily/March 13, 2015

Lancaster University

The first study to examine the use of cannabis in the context of daily life among people with Bipolar Disorder has shown how the drug is linked to increases in both manic and depressive symptoms.

Around 2% of the UK population has Bipolar Disorder, with up to 60% using cannabis at some point in their lives, but research in this area is limited and reasons for high levels of use are unclear.

Dr Elizabeth Tyler of the Spectrum Centre for Mental Health Research at Lancaster University led the study published in PLOS ONE with Professor Steven Jones and colleagues from the University of Manchester, Professor Christine Barrowclough, Nancy Black and Lesley-Anne Carter.

She said: "One theory that is used to explain high levels of drug use is that people use cannabis to self-medicate their symptoms of bipolar disorder. " The study looked at people diagnosed with bipolar disorder but who were not experiencing a depressive or manic episode during the six days the research was carried out.

Each participant completed a paper diary about their emotional state and drug use at several random points daily over a period of week. This enabled people to log their daily experiences in the moment before they forgot how they were feeling.

An individual with experience of bipolar disorder and cannabis use commented: "I do smoke a small amount to lift my mood and make myself slightly manic but it also lifts my mood and switches me into a different mind-set."

"I do not use weed to manage depression as it can make it worse, making me anxious and paranoid."

"I have found though that if I have smoked more excessively it can make me feel depressed for days afterwards."

The study found that the odds of using cannabis increased when individuals were in a good mood. Cannabis use was also associated with an increase in positive mood, manic symptoms and paradoxically an increase in depressive symptoms, but not in the same individuals.

Dr Tyler said: "The findings suggest that cannabis is not being used to self-medicate small changes in symptoms within the context of daily life. However, cannabis use itself may be associated with both positive and negative emotional states. We need to find out whether these relationships play out in the longer term as this may have an impact on a person's course of bipolar disorder."

https://www.sciencedaily.com/releases/2015/03/150313130855.htm

Mulling the marijuana munchies: How the brain flips the hunger switch

February 18, 2015

Science Daily/Yale University

The "munchies," or that uncontrollable urge to eat after using marijuana, appear to be driven by neurons in the brain that are normally involved in suppressing appetite, according to a new study by Yale School of Medicine researchers in the Feb. 18 issue of the journal Nature.

Lead author Tamas Horvath and his colleagues set out to monitor the brain circuitry that promotes eating by selectively manipulating the cellular pathway that mediates marijuana's action on the brain, using transgenic mice.

"By observing how the appetite center of the brain responds to marijuana, we were able to see what drives the hunger brought about by cannabis and how that same mechanism that normally turns off feeding becomes a driver of eating," said Horvath, the Jean and David W. Wallace Professor of Neurobiology and of Obstetrics, Gynecology, and Reproductive Sciences, director of the Yale Program in Cell Signaling and Neurobiology of Metabolism, and chair of the Section of Comparative Medicine.

"It's like pressing a car's brakes and accelerating instead," he said. "We were surprised to find that the neurons we thought were responsible for shutting down eating, were suddenly being activated and promoting hunger, even when you are full. It fools the brain's central feeding system."

In addition to helping explain why you become extremely hungry when you shouldn't be, Horvath said, the new findings could provide other benefits, like helping cancer patients who often lose their appetite during treatment.

Researchers have long known that using cannabis is associated with increased appetite even when you are full. It is also well known that activating the cannabinoid receptor 1 (CB1R) can contribute to overeating. A group of nerve cells called pro-opiomelanocortin (POMC) neurons are considered as key drivers of reducing eating when full.

"This event is key to cannabinoid-receptor-driven eating," said Horvath, who points out that the feeding behavior driven by these neurons is just one mode of action that involves CB1R signaling. "More research is needed to validate the findings." Whether this primitive mechanism is also key to getting "high" on cannabis is another question the Horvath lab is aiming to address.

https://www.sciencedaily.com/releases/2015/02/150218072757.htm

Significant link between cannabis use and onset of mania symptoms

February 10, 2015

Science Daily/University of Warwick

Researchers from the University of Warwick have found evidence to suggest a significant relationship between cannabis use and the onset and exacerbation of mania symptoms.

In a paper published in the Journal of Affective Disorders, mental health researchers from Warwick Medical School carried out a review of scientific literature examining the effect of cannabis use. The literature sampled 2,391 individuals who had experienced mania symptoms.

Mania symptoms are part of bipolar disorder and can include feelings of persistent elation, heightened energy and hyperactivity and a reduced need for sleep. Mania can also make people feel angry and aggressive with extreme symptoms including becoming delusional or hearing voices.

Lead author Dr Steven Marwaha said: "Previously it has been unclear whether cannabis use predates manic episodes. We wanted to answer two questions -- does cannabis use lead to increased occurrence of mania symptoms or manic episodes in individuals with pre-existing bipolar disorder? But also, does cannabis use increase the risk of onset of mania symptoms in those without pre-existing bipolar disorder?"

The researchers looked at a number of previous studies and concluded that cannabis use preceded the onset of mania symptoms.

Dr Marwaha said: "The observed tendency for cannabis use to precede or coincide with rather than follow mania symptoms, and the more specific association between cannabis use and new onset manic symptoms, suggests potential causal influences from cannabis use to the development of mania. It is a significant link."

Dr Marwaha also said the review suggested that cannabis use significantly worsened mania symptoms in people who had previously been diagnosed with bipolar disorder.

He added: "There are limited studies addressing the association of cannabis use and manic symptoms, which suggests this is a relatively neglected clinical issue. However our review suggests that cannabis use is a major clinical problem occurring early in the evolving course of bipolar disorder. More research is needed to consider specific pathways from cannabis use to mania and how these may be effected by genetic vulnerability and environmental risk factors.

"Cannabis is the most prevalent drug used by the under-18s and during this critical period of development services should be especially aware of and responsive to the problems that cannabis use can cause for adolescent populations.

https://www.sciencedaily.com/releases/2015/02/150210160101.htm