Boosting natural marijuana-like brain chemicals treats fragile X syndrome symptoms

September 25, 2012

Science Daily/University of California - Irvine

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.

https://www.sciencedaily.com/releases/2012/09/120925121349.htm

Marijuana use implicated in pregnancy problems

September 12, 2012

Science Daily/Cincinnati Children's Hospital Medical Center

New research indicates marijuana-like compounds called endocannabinoids alter genes and biological signals critical to the formation of a normal placenta during pregnancy and may contribute to pregnancy complications like preeclampsia.

A study in the Sept. 14 edition of the Journal of Biological Chemistry offers new evidence that abnormal biological signaling by endocannabinoid lipid molecules produced by the body disrupts the movement of early embryonic cells important to a healthy pregnancy, in particular trophoblast cells that form the placenta. Abnormal placental function is common in preeclampsia -- a medical condition of unknown cause that is a danger to mother and child.

The research -- from scientists in the Division of Reproductive Sciences at Cincinnati Children's Hospital Medical Center -- analyzed mouse preimplantation embryos mutated to alter endocannabinoid signaling. They found that either silencing or enhancing endocannabinoid signaling adversely affects trophoblast stem cell migration.

"The findings or our investigation raise concerns that exposure to cannabis products may adversely affect early embryo development that is then perpetuated later in pregnancy," said Sudhansu K. Dey, PhD., principal investigator on the study and division director. "Also, given that endocannabinoid signaling plays a key role in the central nervous system, it would be interesting in future studies to examine whether affected cell migration-related genes in early embryos also participate in neuronal cell migration during brain development."

Along with co-first authors Huirong Xie and Xiaofei Sun, Dey and other members of the research team studied mouse embryos that had not yet implanted inside the uterus of the mother. Previous research by Dey's laboratory has shown the timing of critical events in early pregnancy, including when and how well an embryo implants in the uterus, is vital to a healthy pregnancy and birth.

In the current study, researchers conducted DNA microarray analyses to determine how the expression levels of genes important to healthy embryo development were affected in embryos with abnormal endocannabinoid signaling.

In one group of embryos endocannabinoid signaling was silenced by deleting the gene Cnr1, which activates endocannabinoid signaling processes. A second group of mice was mutated to produce elevated endocannabinoid levels similar to that observed in wild type mice treated with tetrahydrocannabinol (THC), the active psychotropic agent in cannabis. This was done by deleting the gene Faah, which breaks down molecules that activate endocannabinoid signaling.

In both groups, the expression of numerous genes known to be important to cell movement and embryo development was lower than in normal wild type mice. This included the development and migration of trophoblast stem cells. Trophoblast cells help anchor the conceptus with the uterus and also form much of the placenta, critical to establishment of maternal-fetal circulation and exchange of nutrients.

Researchers said mouse models developed for the current study (with silenced and elevated endocannabinoid signaling) may help advance more extensive studies on the causes of preeclampsia.

https://www.sciencedaily.com/releases/2012/09/120912101806.htm

Marijuana use may increase risk of testicular cancer

September 10, 2012

Science Daily/Wiley

A new study from the University of Southern California (USC) has found a link between recreational marijuana use and an increased risk of developing subtypes of testicular cancer that tend to carry a somewhat worse prognosis. Published early online in Cancer, a peer-reviewed journal of the American Cancer Society, the findings suggest that the potential cancer-causing effects of marijuana on testicular cells should be considered not only in personal decisions regarding recreational drug use, but also when marijuana and its derivatives are used for therapeutic purposes in young male patients.

Testicular cancer is the most common cancer diagnosed in young men ages 15 to 45 years. The malignancy is becoming more common, and researchers suspect this is due to increasing exposure to unrecognized environmental causes.

To see if recreational drug use might play a role, Victoria Cortessis, MSPH, PhD, assistant professor of preventive medicine at the Keck School of Medicine of USC in Los Angeles, and her colleagues looked at the self-reported history of recreational drug use in 163 young men diagnosed with testicular cancer and compared it with that of 292 healthy men of the same age and race/ethnicity.

The investigators found that men with a history of using marijuana were twice as likely to have subtypes of testicular cancer called non-seminoma and mixed germ cell tumors. These tumors usually occur in younger men and carry a somewhat worse prognosis than the seminoma subtype. The study's findings confirm those from two previous reports in CANCER on a potential link between marijuana use and testicular cancer.

"We do not know what marijuana triggers in the testis that may lead to carcinogenesis, although we speculate that it may be acting through the endocannabinoid system -- the cellular network that responds to the active ingredient in marijuana -- since this system has been shown to be important in the formation of sperm," said Cortessis.

The researchers also discovered that men with a history of using cocaine had a reduced risk of both subtypes of testicular cancer. This finding suggests that men with testicular cancer are not simply more willing to report a history of using recreational drugs. While it is unknown how cocaine may influence testicular cancer risk, the authors suspect that the drug may kill sperm-producing germ cells since it has this effect on experimental animals.

"If this is correct, then 'prevention' would come at a high price," Cortessis said. "Although germ cells can not develop cancer if they are first destroyed, fertility would also be impaired. Since this is the first study in which an association between cocaine use and lower testis cancer risk is noted, additional epidemiological studies are needed to validate the results."

https://www.sciencedaily.com/releases/2012/09/120910082534.htm

Potential drug for treatment of Alzheimer's disease investigated

August 31, 2012

Science Daily/Cleveland Clinic

A compound developed to treat neuropathic pain has shown potential as an innovative treatment for Alzheimer's disease, according to a study by researchers at Cleveland Clinic's Lerner Research Institute and Anesthesiology Institute.

"Cleveland Clinic dedicated two years of research into the examination of this compound and our findings show it could represent a novel therapeutic target in the treatment of Alzheimer's disease," said Mohamed Naguib, M.D., Professor of Anesthesiology, Cleveland Clinic Lerner College of Medicine. "Development of this compound as a potential drug for Alzheimer's would take many more years, but this is a promising finding worthy of further investigation."

In a study published online in the Neurobiology of Aging, the compound MDA7 induced beneficial immune responses that limited the development of Alzheimer's disease. Treatment with the compound restored cognition, memory and synaptic plasticity -- a key neurological foundation of learning and memory -- in an animal model.

Neuroinflammation is an important mechanism involved in the progression of Alzheimer's disease. The MDA7 compound has anti-inflammatory properties that act on the CB2 receptor -- one of the two cannabinoid receptors in the body -- but without the negative side effects normally seen with cannabinoid compounds.

Alzheimer's disease is an irreversible, fatal brain disease that slowly destroys memory and thinking skills. About 5 million people in the United States have Alzheimer's disease. With the aging of the population, and without successful treatment, there will be 16 million Americans and 106 million people worldwide with Alzheimer's by 2050, according to the 2011 Alzheimer's Disease Facts and Figures report from the Alzheimer's Association.

https://www.sciencedaily.com/releases/2012/08/120831123750.htm

Cannabis as painkiller

August 7, 2012

Science Daily/Deutsches Aerzteblatt International

Cannabis-based medications have been demonstrated to relieve pain. Cannabis medications can be used in patients whose symptoms are not adequately alleviated by conventional treatment. The indications are muscle spasms, nausea and vomiting as a result of chemotherapy, loss of appetite in HIV/Aids, and neuropathic pain.

This is the conclusion drawn by Franjo Grotenhermen and Kirsten Müller-Vahl in issue 29-30 of Deutsches Ärzteblatt International.

The clinical effect of the various cannabis-based medications rests primarily on activation of endogenous cannabinoid receptors. Consumption of therapeutic amounts by adults does not lead to irreversible cognitive impairment. The risk is much greater, however, in children and adolescents (particularly before puberty), even at therapeutic doses.

Over 100 controlled trials of the effects of cannabinoids in various indications have been carried out since 1975. The positive results have led to official licensing of cannabis-based medications in many countries. In Germany, a cannabis extract was approved in 2011 for treatment of spasticity in multiple sclerosis. In June 2012 the Federal Joint Committee (the highest decision-making body for the joint self-government of physicians, dentists, hospitals and health insurance funds in Germany) pronounced that the cannabis extract showed a slight additional benefitfor this indication and granted a temporary license until 2015.

https://www.sciencedaily.com/releases/2012/08/120807101232.htm

Mothers' teen cannabinoid exposure may increase response of offspring to opiate drugs

Science Daily/June 5, 2012

Tufts University, Health Sciences Campus

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.

https://www.sciencedaily.com/releases/2012/06/120605155944.htm

Marijuana-like chemicals inhibit human immunodeficiency virus (HIV) in late-state AIDS

March 20, 2012

Science Daily/Mount Sinai Medical Center

Mount Sinai School of Medicine researchers have discovered that marijuana-like chemicals trigger receptors on human immune cells that can directly inhibit a type of human immunodeficiency virus (HIV) found in late-stage AIDS, according to new findings published online in the journal PLoS ONE.

Medical marijuana is prescribed to treat pain, debilitating weight loss and appetite suppression, side effects that are common in advanced AIDS. This is the first study to reveal how the marijuana receptors found on immune cells -- called cannabinoid receptors CB1 and CB2 -- can influence the spread of the virus. Understanding the effect of these receptors on the virus could help scientists develop new drugs to slow the progression of AIDS.

"We knew that cannabinoid drugs like marijuana can have a therapeutic effect in AIDS patients, but did not understand how they influence the spread of the virus itself," said study author Cristina Costantino, PhD, Postdoctoral Fellow in the Department of Pharmacology and Systems Therapeutics at Mount Sinai School of Medicine. "We wanted to explore cannabinoid receptors as a target for pharmaceutical interventions that treat the symptoms of late-stage AIDS and prevent further progression of the disease without the undesirable side effects of medical marijuana."

HIV infects active immune cells that carry the viral receptor CD4, which makes these cells unable to fight off the infection. In order to spread, the virus requires that "resting" immune cells be activated. In advanced AIDS, HIV mutates so it can infect these resting cells, gaining entry into the cell by using a signaling receptor called CXCR4. By treating the cells with a cannabinoid agonist that triggers CB2, Dr. Costantino and the Mount Sinai team found that CB2 blocked the signaling process, and suppressed infection in resting immune cells.

Triggering CB1 causes the drug high associated with marijuana, making it undesirable for physicians to prescribe. The researchers wanted to explore therapies that would target CB2 only. The Mount Sinai team infected healthy immune cells with HIV, then treated them with a chemical that triggers CB2 called an agonist. They found that the drug reduced the infection of the remaining cells.

"Developing a drug that triggers only CB2 as an adjunctive treatment to standard antiviral medication may help alleviate the symptoms of late-stage AIDS and prevent the virus from spreading," said Dr. Costantino. Because HIV does not use CXCR4 to enhance immune cell infection in the early stages of infection, CB2 agonists appear to be an effective antiviral drug only in late-stage disease.

As a result of this discovery, the research team led by Benjamin Chen, MD, PhD, Associate Professor of Infectious Diseases, and Lakshmi Devi, PhD, Professor of Pharmacology and Systems Therapeutics at Mount Sinai School of Medicine, plans to develop a mouse model of late-stage AIDS in order to test the efficacy of a drug that triggers CB2 in vivo. In 2009 Dr. Chen was part of a team that captured on video for the first time the transfer of HIV from infected T-cells to uninfected T-cells.

Funding for this study was provided to Drs. Chen and Devi by the National Institutes of Health in Bethesda, Maryland. Dr. Costantino is supported by a National Institutes of Health Clinical and Translational Science Award grant awarded to Mount Sinai School of Medicine.

https://www.sciencedaily.com/releases/2012/03/120320195252.htm

How marijuana impairs memory

March 1, 2012

Science Daily/Cell Press

A major downside of the medical use of marijuana is the drug's ill effects on working memory, the ability to transiently hold and process information for reasoning, comprehension and learning. Researchers provide new insight into the source of those memory lapses. The answer comes as quite a surprise: Marijuana's major psychoactive ingredient (THC) impairs memory independently of its direct effects on neurons.

The findings offer important new insight into the brain and raise the possibility that marijuana's benefits for the treatment of pain, seizures and other ailments might some day be attained without hurting memory, the researchers say.

With these experiments in mice, "we have found that the starting point for this phenomenon -- the effect of marijuana on working memory -- is the astroglial cells," said Giovanni Marsicano of INSERM in France.

"This is the first direct evidence that astrocytes modulate working memory," added Xia Zhang of the University of Ottawa in Canada.

The new findings aren't the first to suggest astroglia had been given short shrift. Astroglial cells (also known as astrocytes) have been viewed as cells that support, protect and feed neurons for the last 100 to 150 years, Marsicano explained. Over the last decade, evidence has accumulated that these cells play a more active role in forging the connections from one neuron to another.

The researchers didn't set out to discover how marijuana causes its cognitive side effects. Rather, they wanted to learn why receptors that respond to both THC and signals naturally produced in the brain are found on astroglial cells. These cannabinoid type-1 (CB1R) receptors are very abundant in the brain, primarily on neurons of various types.

Zhang and Marsicano now show that mice lacking CB1Rs only on astroglial cells of the brain are protected from the impairments to spatial working memory that usually follow a dose of THC. In contrast, animals lacking CB1Rs in neurons still suffer the usual lapses. Given that different cell types express different variants of CB1Rs, there might be a way to therapeutically activate the receptors on neurons while leaving the astroglial cells out, Marsicano said.

"The study shows that one of the most common effects of cannabinoid intoxication is due to activation of astroglial CB1Rs," the researchers wrote.

The findings further suggest that astrocytes might be playing unexpected roles in other forms of memory in addition to spatial working memory, Zhang said.

The researchers hope to explore the activities of endogenous endocannabinoids, which naturally trigger CB1Rs, on astroglial and other cells. The endocannabinoid system is involved in appetite, pain, mood, memory and many other functions. "Just about any physiological function you can think of in the body, it's likely at some point endocannabinoids are involved," Marsicano said.

And that means an understanding of how those natural signaling molecules act on astroglial and other cells could have a real impact. For instance, Zhang said, "we may find a way to deal with working memory problems in Alzheimer's."

https://www.sciencedaily.com/releases/2012/03/120301143424.htm

Cannabis: The good, the evil, the ugly

February 28, 2012

Science Daily/Umeå University

Cannabis-like substances that are produced by the body have both therapeutic and harmful properties, besides their well-known intoxicating effects, and the body's cannabinoid system may be a target for new strategies in cancer treatment. This is what Sofia Gustafsson finds in the dissertation she recently defended at Umeå University in Sweden.

Abuse of cannabis and preparations containing synthetic cannabis-like substances (cannabinoids) is on the rise all over Europe. At the same time, cannabis-based drugs have been approved for certain medical purposes, and in Sweden a compound was approved for symptom alleviation in multiple sclerosis (MS) just the other day. Intensive research is underway about whether new substances that affect the body's own cannabinoids can be exploited for medical purposes, for instance, to relieve pain and to inhibit the growth of tumors. These are the reasons why Sofia Gustafsson studied the impact of cannabinoids on both the nervous system and tumor cells.

The body's own cannabinoids, so-called endocannabinoids, mediate a number of different functions in the central nervous system and in the immune system and are involved in motor movement, reward effects, and learning and memory processes. Cannabinoids from the plant kingdom and synthetically produced cannabinoids affect both of these functions, all of which are mediated via cannabinoid receptors.

Cannabinoids have moreover been shown to affect the fate of cells. Cannabinoids protect some brain cells, whereas cells in certain types of brain tumors, such as glioma, are stimulated to commit controlled cell suicide (apoptosis). Most research on the effects of cannaboids on the nervous system has focused on the adult, fully developed nervous system, while we have relatively little knowledge about the effects on a nervous system that is still developing.

In summary, the findings of Sofia Gustafsson's studies show that cannabinoids can be toxic for cancer cells as well as for nerve cells, and that they decrease emryonal survival. These findings are important for our knowledge both of the potential of the cannabinoid system as a target system for new strategies in cancer treatment and of the risks of new drugs, such as Spice, on nerve development.

https://www.sciencedaily.com/releases/2012/02/120228114159.htm

New way to boost potency of natural pain relief chemical in body

November 21, 2011

Science Daily/University of California - Irvine

UC Irvine and Italian researchers have discovered a new means of enhancing the effects of anandamide -- a natural, marijuana-like chemical in the body that provides pain relief.

Led by Daniele Piomelli, UCI's Louise Turner Arnold Chair in the Neurosciences, the team identified an "escort" protein in brain cells that transports anandamide to sites within the cell where enzymes break it down. They found that blocking this protein -- called FLAT -- increases anandamide's potency.

Previous work by the researchers indicates that compounds boosting anandamide's natural abilities could form the basis of pain medications that don't produce sedation, addiction or other central nervous system side effects common with existing painkillers, such as opiates.

"These findings raise hope that the analgesic properties of marijuana can be harnessed for new, safe drugs," said Piomelli, a professor of pharmacology. "Specific drug compounds we are creating that amplify the actions of natural, marijuana-like chemicals are showing great promise."

For the study, which appears in the Nov. 20 online version of Nature Neuroscience, he and his colleagues used computational methods to understand how FLAT binds with anandamide and escorts it to cell sites to be degraded by fatty acid amide hydrolase (FAAH) enzymes.

Anandamide has been dubbed "the bliss molecule" for its similarities to the active ingredient in marijuana. A neurotransmitter that's part of the body's endocannabinoid system, it's been shown in studies by Piomelli and others to play analgesic, antianxiety and antidepressant roles. It's also important in regulating food consumption. Blocking FAAH activity enhances several effects of anandamide without generating the "high" seen with marijuana.

Piomelli and his collaborators speculate that inhibiting FLAT (FAAH-like anandamide transporters) might be particularly useful in controlling certain forms of pain -- that caused by damage to the central nervous system, for example -- and curbing addiction to such drugs as nicotine and cocaine.

Researchers from UCI, Italy's University of Parma and University of Bologna, and the Italian Institute of Technology participated in the study, which was supported by grants from the U.S. National Institute on Drug Abuse, the U.S. National Institute on Alcohol Abuse & Alcoholism, and the U.S. National Institute of General Medical Sciences.

https://www.sciencedaily.com/releases/2011/11/111121142501.htm

Do deficits in brain cannabinoids contribute to eating disorders?

October 31, 2011

Science Daily/Elsevier

A new report in Biological Psychiatry suggests that deficits in endocannabinoid function may contribute to anorexia nervosa and bulimia. Endocannabinoids are substances made by the brain that affect brain function and chemistry in ways that resemble the effects of cannabis derivatives, including marijuana and hashish. These commonly abused drugs are well known to increase appetite, i.e. to cause the "munchies." Thus, it makes sense that deficits in this brain system would be associated with reduced appetite.

Researchers measured the status of the endocannabinoid system indirectly by determining whether there was an increase or decrease in the density of endocannabinoid receptors, called the CB1 receptor, in several brain regions using positron emission tomography, or PET, imaging. They compared these densities in women with anorexia or bulimia with those of healthy women.

They found global increases in ligand binding to CB1 receptors in the brains of women with anorexia nervosa. This finding is consistent with a compensatory process engaged by deficits in endocannabinoid levels or reduced CB1 receptor function.

CB1R availability was also increased in the insula in both anorexia and bulimia patients. The insula "is a region that integrates body perception, gustatory information, reward and emotion, functions known to be disturbed in these patients," explained Dr. Koen Van Laere, the study's lead author.

"The role of endocannabinoids in appetite control is clearly important. These new data point to important connections between this system and eating disorders," added Dr. John Krystal, Editor of Biological Psychiatry.

Additional research is now needed to establish whether the observed changes are caused by the disease or whether these are neurochemical alterations that serve as risk factors for developing an eating disorder.

Furthermore, since very few effective treatments exist for these disorders, these data indicate that the endocannabinoid system may be a potential new target for developing drugs to treat eating disorders. Such new therapies are currently being investigated in animal models.

https://www.sciencedaily.com/releases/2011/10/111031115226.htm

How cannabis causes 'cognitive chaos' in the brain

October 28, 2011

Science Daily/University of Bristol

Cannabis use is associated with disturbances in concentration and memory. New research by neuroscientists at the University of Bristol, published in the Journal of Neuroscience, has found that brain activity becomes uncoordinated and inaccurate during these altered states of mind, leading to neurophysiological and behavioural impairments reminiscent of those seen in schizophrenia.

The collaborative study, led by Dr Matt Jones from the University's School of Physiology and Pharmacology, tested whether the detrimental effects of cannabis on memory and cognition could be the result of 'disorchestrated' brain networks.

Brain activity can be compared to performance of a philharmonic orchestra in which string, brass, woodwind and percussion sections are coupled together in rhythms dictated by the conductor. Similarly, specific structures in the brain tune in to one another at defined frequencies: their rhythmic activity gives rise to brain waves, and the tuning of these brain waves normally allows processing of information used to guide our behaviour.

Using state-of-the-art technology, the researchers measured electrical activity from hundreds of neurons in rats that were given a drug that mimics the psychoactive ingredient of marijuana. While the effects of the drug on individual brain regions were subtle, the drug completely disrupted co-ordinated brain waves across the hippocampus and prefrontal cortex, as though two sections of the orchestra were playing out of synch. Both these brain structures are essential for memory and decision-making and heavily implicated in the pathology of schizophrenia.

The results from the study show that as a consequence of this decoupling of hippocampus and prefrontal cortex, the rats became unable to make accurate decisions when navigating around a maze.

Dr Jones, lead author and MRC Senior Non-clinical Fellow at the University, said: "Marijuana abuse is common among sufferers of schizophrenia and recent studies have shown that the psychoactive ingredient of marijuana can induce some symptoms of schizophrenia in healthy volunteers. These findings are therefore important for our understanding of psychiatric diseases, which may arise as a consequence of 'disorchestrated brains' and could be treated by re-tuning brain activity."

Michal Kucewicz, first author on the study, added: "These results are an important step forward in our understanding of how rhythmic activity in the brain underlies thought processes in health and disease."

The research is part of a Medical Research Council (MRC)-supported collaboration between the University and the Eli Lilly & Co. Centre for Cognitive Neuroscience that aims to develop new tools and targets for treatment of brain diseases like schizophrenia and Alzheimer's disease.

https://www.sciencedaily.com/releases/2011/10/111025172633.htm

The cannabis genome: How hemp got high

October 20, 2011

Science Daily/BioMed Central

Throughout history, Cannabis sativa has been exploited by humanity. Hemp seed oil is rich in omega 6, an essential fatty acid, and its fibre is used in the production of fabrics. Marijuana is known for its mind-altering properties and has been used medicinally for over 2700 years. The changes to the genome that led to drug-producing plants is a mystery of cannabis evolution, but one that has now been solved, thanks to an article published in BioMed Central's open access journal Genome Biology.

A team of researchers led by Drs Jon Page and Tim Hughes from Canada sequenced DNA from the potent Purple Kush (PK) marijuana strain, which is widely used for medicinal purposes. The PK genome and transcriptome (genes that are switched on) were then compared to those of 'Finola' hemp, and scanned for differences which might explain why marijuana produces tetrahydrocannabinolic acid (THCA), the active ingredient of cannabis, while hemp strains lack THCA but contain the non-psychoactive cannabinoid, cannabidiolic acid (CBDA).

The transcriptome held the clues to solving this genomic puzzle. Dr Page explained, "The transcriptome analysis showed that the THCA synthase gene, an essential enzyme in THCA production, is turned on in marijuana, but switched off in hemp." Dr Hughes continued, "Detailed analysis of the two genomes suggests that domestication, cultivation, and breeding of marijuana strains has caused the loss of the enzyme (CBDA synthase) which would otherwise compete for the metabolites used as starting material in THCA production."

Dr Page added: "Plants continue to be a major source of medicines, both as herbal drugs and as pharmaceutical compounds. Although more than twenty plant genomes have been published, ranging from major food crops such as rice and corn, to laboratory models like Arabidopsis, this is the first genome of a medicinal plant. Decoding the cannabis genome will help answer basic questions about the biology of Cannabis sativa and further the development of its myriad applications including strains for pharmaceutical production, and hemp plants with improved productivity and fatty acid profiles."

https://www.sciencedaily.com/releases/2011/10/111020024443.htm

How hemp got high: Cannabis genome mapped

October 24, 2011

Science Daily/University of Saskatchewan

A team of Canadian researchers has sequenced the genome of Cannabis sativa, the plant that produces both industrial hemp and marijuana, and in the process revealed the genetic changes that led to the plant's drug-producing properties.

Jon Page is a plant biochemist and adjunct professor of biology at the University of Saskatchewan. He explains that a simple genetic switch is likely responsible for the production of THCA, or tetrahydrocannabinolic acid, the precursor of the active ingredient in marijuana.

"The transcriptome analysis showed that the THCA synthase gene, an essential enzyme in THCA production, is turned on in marijuana, but switched off in hemp," Page says.

Tim Hughes, co-leader of the project, is a professor at the Terrence Donnelly Centre for Cellular and Biomolecular Research and the Department of Molecular Genetics at the University of Toronto. He explains the team compared the potent Purple Kush marijuana variety with 'Finola' hemp, which is grown for seed production. Hemp lacks THCA, but does contain another, non-psychoactive substance called CBDA, or cannabidiolic acid.

"Detailed analysis of the two genomes suggests that domestication, cultivation, and breeding of marijuana strains has caused the loss of the enzyme (CBDA synthase), which would otherwise compete for the metabolites used as starting material in THCA production," Hughes says.

Essentially, this means that over thousands of years of cultivation, hemp farmers selectively bred Cannabis sativa into two distinct strains -- one for fibre and seed, and one for medicine. Marijuana has been used medicinally for more than 2,700 years, and continues to be explored for its pharmaceutical potential.

"Plants continue to be a major source of medicines, both as herbal drugs and as pharmaceutical compounds," Page says. "Although more than 20 plant genomes have been published, ranging from major food crops such as rice and corn, to laboratory models like Arabidopsis, this is the first genome of a medicinal plant."

The researchers expect that sequencing the Cannabis sativa genome will help answer basic questions about the biology of the plant as well as furthering development of its myriad applications. These include strains for pharmaceutical production, high-producing industrial hemp plants, and hemp seed varieties to produce high-quality edible oil. Hemp seed oil is rich in omega 6, an essential fatty acid, and its fibre is used in the production of textiles.

According to the Canadian Hemp Trade Alliance, about 25,000 acres of the crop were sown in Canada in 2010, much of this in Manitoba. Due to hemp's association with marijuana, farmers need to be licensed through Health Canada to grow the crop. Canadian medicinal marijuana is currently produced under Health Canada contract with Prairie Plant Systems, a biotechnology company based in Saskatoon.

https://www.sciencedaily.com/releases/2011/10/111020025752.htm

How the brain’s own marijuana-like chemicals suppress pain

October 12, 2011

Science Daily/National University of Ireland, Galway

New findings about how the brain functions to suppress pain have been published in the journal Pain, by NUI Galway researchers. For the first time, it has been shown that the hippocampus of the brain, which is usually associated with memory, has an active role to play in suppressing pain during times of stress.

The work was carried out by researchers in Pharmacology and Therapeutics, and the Centre for Pain Research at the National Centre for Biomedical Engineering Science, NUI Galway.

In times of immense stress or fear, pain transmission and perception can be suppressed potently in humans and other animals. This important survival response can help us cope with, or escape from, potentially life-threatening situations. An increased understanding of the biological mechanisms involved in this so-called fear-induced analgesia is important from a fundamental physiological perspective and may also advance the search for new therapeutic approaches to the treatment of pain.

Dr David Finn, Co-Director of the Centre for Pain Research at NUI Galway, and study leader, says: "The body can suppress pain when under extreme stress, in part through the action of marijuana-like substances produced in the brain. What we have now identified for the first time, is that the brain's hippocampus is an important site of action of these endocannabinoids during the potent suppression of pain by fear. This research, which was funded by a grant from Science Foundation Ireland, advances our fundamental understanding of the neurobiology of pain and may facilitate the identification of new therapeutic targets for the treatment of pain and anxiety disorders."

Working with Dr Finn, first author Dr Gemma Ford was able to demonstrate that inhibition of the enzyme that breaks down one of these endogenous marijuana-like substances in the hippocampus, had the effect of enhancing stress-induced pain suppression. Further experimentation revealed that these effects were mediated by the cannabinoid CB1 receptor and were likely to be mediated by stress-induced increases in levels of endocannabinoids in the hippocampus.

https://www.sciencedaily.com/releases/2011/10/111012083619.htm

Marijuana component could ease pain from chemotherapy drugs

October 6, 2011

Science Daily/Temple University

A chemical component of the marijuana plant could prevent the onset of pain associated with drugs used in chemo therapy, particularly in breast cancer patients, according to researchers at Temple University's School of Pharmacy.

The researchers published their findings in the journal Anesthesia and Analgesia.

The researchers developed animal models and tested the ability of the compound cannabidiol, which is the second most abundant chemical found in the marijuana plant, to relieve chemo-induced neuropathic pain, said Sara Jane Ward, research assistant professor of pharmaceutical sciences in Temple's School of Pharmacy and the study's lead author.

"We found that cannabidiol completely prevented the onset of the neuropathic, or nerve pain caused by the chemo drug Paclitaxel, which is used to treat breast cancer," said Ward, who is also a research associate professor in Temple's Center for Substance Abuse Research.

Ward said that one of cannabidiol's major benefits is that, unlike other chemicals found in marijuana such as THC, it does not produce psycho-active effects such as euphoria, increased appetite or cognitive deficits. "Cannabidiol has the therapeutic qualities of marijuana but not the side effects," she said.

Ward's research has long focused on systems in the brain that are impacted by marijuana and whether those systems could be targeted in the treatment of various disorders. "Marijuana binds to the cannabinoid receptors in the body and researchers have long been interested in whether there is therapeutic potential for targeting this receptor system," she said.

Ward became interested in this current study after attending a conference in which she learned about a pain state that is induced by chemo-therapeutic agents, especially those used to treat breast cancer, which can produce really debilitating neuropathic pain.

Cannabidiol has also demonstrated the ability to decrease tumor activity in animal models, said Ward, which could make it an effective therapeutic for breast cancer, especially if you "combined it with a chemo agent like Paclitaxel, which we already know works well."

According to Ward, there are currently about 10 clinical trials underway in the United States for cannabidiol on a range of different disorders, including cannabis dependence, eating disorders and schizophrenia. Because of this, she believes it will be easier to establish a clinical trial for cannabidiol as a therapeutic against neuropathic pain associated with chemo drugs.

In addition to Ward, Temple researchers involved in the study included Michael David Ramirez, Harshini Neelakantan and Ellen Ann Walker. The study was supported by grants from the National Institutes of Health and the Peter F. McManus Charitable Trust.

https://www.sciencedaily.com/releases/2011/10/111006125418.htm

Bodyguard for the brain: Researchers identify mechanism that seems to protect brain from aging

July 13, 2011

Science Daily/University of Bonn

Researchers from the Universities of Bonn and Mainz have discovered a mechanism that seems to protect the brain from aging. In experiments with mice, they switched off the cannabinoid-1 receptor. As a consequence, the animals showed signs of degeneration -- as seen in people with dementia -- much faster.

The research results are presented in a current issue of the Proceedings of the National Academy of Sciences (PNAS).

Humans are getting older and older, and the number of people with dementia is increasing. The factors controlling degeneration of the brain are still mostly unknown. However, researchers assume that factors such as stress, accumulation of toxic waste products as well as inflammation accelerate aging. But, vice versa, there are also mechanisms that can -- like a bodyguard -- protect the brain from degenerating, or repair defective structures.

Researchers from the Universities of Bonn and Mainz have now discovered a hitherto unknown function of the cannabinoid-1 receptor (CB1). A receptor is a protein that can bind to other substances, triggering a chain of signals. Cannabinoids such as THC -- the active agent in cannabis sativa -- and endocannabinoids formed by the body bind to the CB1 receptors. The existence of this receptor is also the reason for the intoxicating effect of hashish and marijuana.

Not only does the CB1 receptor have an addictive potential, but it also plays a role in the degeneration of the brain. "If we switch off the receptor using gene technology, mouse brains age much faster," said Önder Albayram, principal author of the publication and a doctoral student on the team of Professor Dr. Andreas Zimmer from the Institut für Molekulare Psychiatrie at the University of Bonn. "This means that the CB1 signal system has a protective effect for nerve cells."

Mice prove their brain power in a pool

The researchers studied mice in different age categories -- young six week old animals, middle-aged ones at five months, and those of an advanced age at 12 months. The animals had to master various tasks -- first, they had to find a submerged platform in the pool. Once the mice knew its location, the platform was moved, and the animals had to find it again. This was how the researchers tested how well the rodents learned and remembered.

The animals in which the CB1 receptor had been switched off (the knock-out mice) clearly differed from their kind. "The knock-out mice showed clearly diminished learning and memory capacity," said Privatdozent Dr. Andras Bilkei-Gorzo from Professor Zimmer's team, who led the study. So, animals that did not have the receptor were less successful in their search for the platform. "In addition, they showed a clear loss of nerve cells in the hippocampus," he explained further. This part of the brain is the central area for forming and storing information. In addition, the researchers found inflammation processes in the brain. As the mice advanced in age, the degenerative processes became increasingly noticeable.

Amazing parallels with the human brain

The animals with the intact CB1 receptor, to the contrary, did clearly better with regard to their learning and memory capabilities, as well as the health of their nerve cells. "The root cause of aging is one of the secrets of life," commented Albayram. This study has begun to open the door to solving this enigma. The processes in the mouse brains have a surprising number of parallels with age-related changes in human brains. So, the endocannabinoid system may also present a protective mechanism in the aging of the human brain.

The principal author cautioned, "This will require additional research." The scientists would like to better understand the mechanism by which CB1 receptors protect the brain from inflammation processes. And based on these signal chains, it might then be possible to develop substances for new therapies.

https://www.sciencedaily.com/releases/2011/07/110712093856.htm

Chronic marijuana smoking affects brain chemistry, molecular imaging shows

June 13, 2011

Science Daily/Society of Nuclear Medicine

Definitive proof of an adverse effect of chronic marijuana use revealed at SNM's 58th Annual Meeting could lead to potential drug treatments and aid other research involved in cannabinoid receptors, a neurotransmission system receiving a lot of attention. Scientists used molecular imaging to visualize changes in the brains of heavy marijuana smokers versus non-smokers and found that abuse of the drug led to a decreased number of cannabinoid CB1 receptors, which are involved in not just pleasure, appetite and pain tolerance but a host of other psychological and physiological functions of the body.

"Addictions are a major medical and socioeconomic problem," says Jussi Hirvonen, MD, PhD, lead author of the collaborative study between the National Institute of Mental Health and National Institute on Drug Abuse, Bethesda, Md. "Unfortunately, we do not fully understand the neurobiological mechanisms involved in addiction. With this study, we were able to show for the first time that people who abuse cannabis have abnormalities of the cannabinoid receptors in the brain. This information may prove critical for the development of novel treatments for cannabis abuse. Furthermore, this research shows that the decreased receptors in people who abuse cannabis return to normal when they stop smoking the drug."

According to the National Institute on Drug Abuse, marijuana is the number-one illicit drug of choice in America. The psychoactive chemical in marijuana, or cannabis, is delta-9-tetrahydrocannabinol (THC), which binds to numerous cannabinoid receptors in the brain and throughout the body when smoked or ingested, producing a distinctive high. Cannabinoid receptors in the brain influence a range of mental states and actions, including pleasure, concentration, perception of time and memory, sensory perception, and coordination of movement. There are also cannabinoid receptors throughout the body involved in a wide range of functions of the digestive, cardiovascular, respiratory and other systems of the body. Currently two subtypes of cannabinoid receptors are known, CB1 and CB2, the former being involved mostly in functions of the central nervous system and the latter more in functions of the immune system and in stem cells of the circulatory system.

For this study, researchers recruited 30 chronic daily cannabis smokers who were then monitored at a closed inpatient facility for approximately four weeks. The subjects were imaged using positron emission tomography (PET), which provides information about physiological processes in the body. Subjects were injected with a radioligand, 18F-FMPEP-d2, which is a combination of a radioactive fluorine isotope and a neurotransmitter analog that binds with CB1 brain receptors.

Results of the study show that receptor number was decreased about 20 percent in brains of cannabis smokers when compared to healthy control subjects with limited exposure to cannabis during their lifetime. These changes were found to have a correlation with the number of years subjects had smoked. Of the original 30 cannabis smokers, 14 of the subjects underwent a second PET scan after about a month of abstinence. There was a marked increase in receptor activity in those areas that had been decreased at the outset of the study, an indication that while chronic cannabis smoking causes downregulation of CB1 receptors, the damage is reversible with abstinence.

Information gleaned from this and future studies may help other research exploring the role of PET imaging of CB1 receptors -- not just for drug use, but also for a range of human diseases, including metabolic disease and cancer.

https://www.sciencedaily.com/releases/2011/06/110606131705.htm

How marijuana affects the way the brain processes emotional information

April 11, 2011

Science Daily/University of Western Ontario

Drugs like marijuana act on naturally occurring receptors in the brain called cannabinoid receptors. However, the mechanisms by which these drugs produce their sensory and mood altering effects within the brain are largely unknown. Research led by Steven Laviolette at The University of Western Ontario has now identified a critical brain pathway responsible for the effects of cannabinoid drugs on how the brain processes emotional information.

The findings, published in The Journal of Neuroscience, also help to explain the possible link between marijuana use and schizophrenia.

Laviolette and his team at the Schulich School of Medicine & Dentistry discovered that activating cannabinoid receptors directly in a region of the brain called the amygdala, can strongly influence the significance of emotional information and memory processes. It also dramatically increased the activity patterns of neurons in a connected region of the brain called the prefrontal cortex, controlling both how the brain perceived the emotional significance of incoming sensory information, and the strength of memories associated with these emotional experiences.

"These findings are of great clinical relevance given recent evidence suggesting that exposure to marijuana during adolescence can increase the likelihood of developing schizophrenia later in life," says Laviolette, an associate professor in the Department of Anatomy and Cell Biology. "We know there are abnormalities in both the amygdala and prefrontal cortex in patients who have schizophrenia, and we now know these same brain areas are critical to the effects of marijuana and other cannabinoid drugs on emotional processing."

Furthermore, the findings by Laviolette's laboratory identify a novel new brain pathway by which drugs acting on the cannabinoid system can distort the emotional relevance of incoming sensory information which in turn may lead to psychotic side-effects, such as paranoia, associated with heavy marijuana use. Developing pharmacological compounds, and there already are some, that block or modify this pathway could help control psychotic episodes. It could also be used to help patients with Post Traumatic Stress Disorder who have difficulty controlling the resurgence of highly emotional events into their memory.

Laviolette's research was funded by the Ontario Mental Health Foundation and the Natural Sciences and Engineering Research Council of Canada (NSERC).

https://www.sciencedaily.com/releases/2011/04/110405174833.htm

Cannabis ingredient can help cancer patients regain their appetites and sense of taste

February 25, 2011

Science Daily/Oxford University Press (OUP)

The active ingredient in cannabis can improve the appetites and sense of taste in cancer patients, according to a new study published online in the cancer journal, Annals of Oncology.

Loss of appetite is common among cancer patients, either because the cancer itself or its treatment affects the sense of taste and smell, leading to decreased enjoyment of food. This, in turn, can lead to weight loss, anorexia, a worse quality of life and decreased survival; therefore, finding effective ways of helping patients to maintain a good diet and consume enough calories is an important aspect of their treatment.

Researchers in Canada ran a small pilot study from May 2006 to December 2008in 21 adult patients with any advanced cancer (except brain cancer) who had been eating less as a result of their illness for two weeks or more. All were either being treated with chemotherapy or had been in the past. The patients were randomly assigned to receive medication from a pharmacist in a double-blind manner, which meant that neither the patients nor the doctors knew which treatment they were receiving. Eleven patients received oral capsules containing delta-9-tetrahydrocannabinol (THC) -- the main psychoactive ingredient in cannabis -- and eight patients were assigned to the control group to receive placebo capsules. The active capsules contained 2.5mg of THC and the patients took them once a day for the first three days, twice a day thereafter, and they had the option to increase their dose up to a maximum of 20mg a day if they wished; however, most followed the dosing protocol, with three patients in both groups increasing their dose to three times a day. The treatment ran for 18 days.

From patient answers to questionnaires conducted before, during and at the end of the trial, the researchers found that the majority (73%) of THC-treated patients reported an increased overall appreciation of food compared with patients receiving placebo (30%) and more often stated that study medication "made food taste better" (55%) compared with placebo (10%).

The majority of THC-treated patients (64%) had increased appetite, three patients (27%) showed no change, and one patient's data was incomplete. No THC-treated patients showed a decrease in appetite. By contrast, the majority of patients receiving placebo had either decreased appetite (50%) or showed no change (20%).

Although there was no difference in the total number of calories consumed by both groups, the THC-treated patients tended to increase the proportion of protein that they ate, and 55% reported that savoury foods tasted better, whereas no patients in the placebo group reported an increased liking for these foods. (Cancer patients often find that meat smells and tastes unpleasant and, therefore, they eat less of it).

In addition, THC-treated patients reported better quality of sleep and relaxation than in the placebo group.

Dr Wendy Wismer (PhD), associate professor at the University of Alberta (Edmonton, Canada), who led the study, said: "This is the first randomised controlled trial to show that THC makes food taste better and improves appetites for patients with advanced cancer, as well as helping them to sleep and to relax better. Our findings are important, as there is no accepted treatment for chemosensory alterations experienced by cancer patients. We are excited about the possibilities that THC could be used to improve patients' enjoyment of food.

"Decreased appetite and chemosensory alterations can be caused by both cancer and its treatment; untreated tumours cause loss of appetite, and by itself, chemotherapy also causes loss of appetite. In any individual patient, some part of both of these effects is usually present.

"It's very important to address these problems as both appetite loss and alterations to taste and smell lead to involuntary weight loss and reduce an individual's ability to tolerate treatment and to stay healthy in general. Additionally, the social enjoyment of eating is greatly reduced and quality of life is affected. For a long time everyone has thought that nothing could be done about this. Indeed, cancer patients are often told to 'cope' with chemosensory problems by eating bland, cold and odourless food. This may well have the result of reducing food intake and food enjoyment."

The researchers say that larger, phase II trials should test their findings further, but, in the meantime Dr Wismer thinks that doctors could consider THC treatment for cancer patients. "It could be investigated for any stage of cancer where taste and smell dysfunction and appetite loss has been indicated by the patient," she said. In addition, treatment would not necessarily have to be limited to the 18 days of the study. "Long term therapy with cannabinoids is possible, however, in each case this would be up to the patient's physician to determine."

Although the study was unable to show that THC treatment could increase total calorie intake, Dr Wismer said this was unsurprising. "In the healthy adult population, we know from personal experience that we usually eat more of something if it tastes better. However, in this advanced cancer population, there is a real struggle with appetite; normal appetitive pathways do not seem to be functioning. We know from our earlier work that individuals with advanced cancer have diminished appetite and have to make a big conscious effort to eat; they are motivated to eat simply to survive. So, although THC did not significantly increase total calorie intake, the fact that it improved appetite and protein intake is important."

This work was supported by the Canadian Institutes of Health Research, the Alberta Cancer Board, Alberta Heritage Foundation for Medical Research, and the Natural Sciences and Engineering Research Council of Canada.

https://www.sciencedaily.com/releases/2011/02/110222192830.htm

How cannabis suppresses immune functions: Cannabis compounds found to trigger unique immune cells which promote cancer growth

November 26, 2010

Science Daily/Wiley-Blackwell

An international team of immunologists studying the effects of cannabis have discovered how smoking marijuana can trigger a suppression of the body's immune functions. The research, published in the European Journal of Immunology, reveals why cannabis users are more susceptible to certain types of cancers and infections.

The team, led by Dr Prakash Nagarkatti from the University of South Carolina, focused their research on cannabinoids, a group of compounds found inside the cannabis plant, including THC (delta-9 tetahydrocannabinol) which is already used for medical purposes such as pain relief.

"Cannabis is one of the most widely used drugs of abuse worldwide and it is already believed to suppress immune functions making the user more susceptible to infections and some types of cancer," said Dr Nagarkatti. "We believe the key to this suppression is a unique type of immune cell, which has only recently been identified by immunologists, called myeloid-derived suppressor cells, MDSCs."

While most immune cells fight against infections and cancers to protect the host, MDSCs actively suppress the immune system. The presence of these cells is known to increase in cancer patients and it is believed that MDSCs may suppress the immune system against cancer therapy, actually promoting cancer growth.

Dr Nagarkatti's team demonstrated that cannabinoids can trigger a massive number of MDSCs through activation of cannabinoid receptors. This research reveals, for the first time, that marijuana cannabinoids may suppress the immune system by activating these unique cells.

"These results raise interesting questions on whether increased susceptibility to certain types of cancers or infections caused from smoking marijuana results from induction of MDSCs," said Nagarkatti. "MDSCs seem to be unique and important cells that may be triggered by inappropriate production of certain growth factors by cancer cells or other chemical agents such as cannabinoids, which lead to a suppression of the immune system's response."

In a related study, also published in the European journal of Immunology, Dr Christian Vosshenrich from the Institut Pasteur in Paris, reveals that when cancer cells grow they produce a molecule called interleukin-1 β (IL-1β), which also triggers MDSCs. This study identifies how MDSCs produced during cancer growth also weaken the ability of immune cells to kill cancer cells.

"Marijuana cannabinoids present us with a double edged sword," concluded Dr Nagarkatti. "On one hand, due to their immunosuppressive nature, they can cause increased susceptibility to cancer and infections. However, further research of these compounds could provide opportunities to treat a large number of clinical disorders where suppressing the immune response is actually beneficial."

https://www.sciencedaily.com/releases/2010/11/101124214728.htm