 |
|
The endocannabinoids: Functional roles and therapeutic opportunities
October 15, 2007Cannabis (marijuana) is the most widely produced plant-based illicit drug worldwide and the illegal drug most frequently used in Europe. Its use increased in almost all EU countries during the 1990s, in particular among young people, including school students. Cannabis use is highest among 15- to 24-year-olds, with lifetime prevalence ranging for most countries from 20-40% (EMCDDA 2006).
Recently there has been a new surge in the level of concern about potential social and health outcomes of cannabis use, although the available evidence still does not provide a clear-cut understanding of the issues. Intensive cannabis use is correlated with non-drug-specific mental problems, but the question of co-morbidity is intertwined with the questions of cause and effect (EMCDDA 2006). Prevention is of importance in adolescents, which is underlined by evidence that early-onset cannabis-users (pre- to mid-adolescence) have a significantly higher risk of developing drug problems, including dependence (Von Sydow et al., 2002; Chen et al., 2005).
The illegal status and wide-spread use of cannabis made basic and clinical cannabis research difficult in the past decades; on the other hand, it has stimulated efforts to identify the psychoactive constituents of cannabis. As a consequence, the endocannabinoid system was discovered, which was shown to be involved in most physiological systems - the nervous, the cardiovascular, the reproductive, the immune system, to mention a few.
One of the main roles of endocannabinoids is neuroprotection, but over the last decade they have been found to affect a long list of processes, from anxiety, depression, cancer development, vasodilatation to bone formation and even pregnancy (Panikashvili et al., 2001; Pachter et al., 2006).
Cannabinoids and endocannabinoids are supposed to represent a medicinal treasure trove which waits to be discovered.
What is the endocannabinoid system?
In the 1960s the constituent of the cannabis plant was discovered - named tetrahydrocannabinol, or THC - which causes the 'high' produced by it (Gaoni & Mechoulam, 1964). Thousands of publications have since appeared on THC. Today it is even used as a therapeutic drug against nausea and for enhancing appetite, and, surprisingly, has not become an illicit drug - apparently cannabis users prefer the plant-based marijuana and hashish.
Two decades later it was found that THC binds to specific receptors in the brain and the periphery and this interaction initiates a cascade of biological processes leading to the well known marijuana effects. It was assumed that a cannabinoid receptor is not formed for the sake of a plant constituent (that by a strange quirk of nature binds to it), but for endogenous brain constituents and that these putative 'signaling' constituents together with the cannabinoid receptors are part of a new biochemical system in the human body, which may affect various physiological actions. In trying to identify these unknown putative signaling molecules, our research group in the 1990s was successful in isolating 2 such endogenous 'cannabinoid' components - one from the brain, named anandamide (from the word 'ananda, meaning 'supreme joy' in Sanscrit), and another one from the intestines named 2-arachidonoyl glycerol (2-AG) (Devane et al., 1992; Mechoulam et al., 1995).
Neuroprotection
The major endocannabinoid (2-AG) has been identified both in the central nervous system and in the periphery. Stressful stimuli - traumatic brain injury (TBI) for example - enhance brain 2-AG levels in mice. 2-AG, both of endogenous and exogenous origin, has been shown to be neuroprotective in closed head injury, ischemia and excitotoxicity in mice. These effects may derive from the ability of cannabinoids to act through a variety of biochemical mechanisms. 2-AG also helps repair the blood brain barrier after TBI. The endocannabinoids act via specific cannabinoid receptors, of which the CB1 receptors are most abundant in the central nervous system. Mice whose CB1 receptors are knocked out display slower functional recovery after TBI and do not respond to treatment with 2-AG. Over the last few years several groups have noted that CB2 receptors are also formed in the brain, particularly as a reaction to numerous neurological diseases, and are apparently activated by the endocannabinoids as a protective mechanism.
Through evolution the mammalian body has developed various systems to guard against damage that may be caused by external attacks. Thus, it has an immune system, whose main role is to protect against protein attacks (microbes, parasites for example) and to reduce the damage caused by them. Analogous biological protective systems have also been developed against non-protein attacks, although they are much less well known than the immune system. Over the last few years the research group of Esther Shohami in collaboration with our group showed that the endocannabinoid system, through various biological routes, lowers the damage caused by brain trauma. Thus, it helps to attenuate the brain edema and the neurological injuries caused by it (Panikashvili et al., 2001; Panikashvili et al., 2006).
Clinical importance
Furthermore it is assumed that the endocannabinoid system may be involved in the pathogenesis of hepatic encephalopathy, a neuropsychiatric syndrome induced by fulminant hepatic failure. Indeed in an animal model the brain levels of 2-AG were found to be elevated. Administration of 2-AG improved a neurological score, activity and cognitive function (Avraham et al., 2006). Activation of the CB2 receptor by a selective agonist also improved the neurological score. The authors concluded that the endocannabinoid system may play an important role in the pathogenesis of hepatic encephalopathy. Modulation of this system either by exogenous agonists specific for the CB2 receptors or possibly also by antagonists to the CB1 receptors may have therapeutic potential. The endocannabinoid system generally is involved in the protective reaction of the mammalian body to a long list of neurological diseases such as multiple sclerosis, Alzheimer's and Parkinson's disease. Thus, there is hope for novel therapeutic opportunities.
Numerous additional endocannabinoids - especially various fatty acid ethanolamides and glycerol esters - are known today and regarded as members of a large 'endocannabinoid family'. Endogenous cannabinoids, the cannabinoid receptors and various enzymes that are involved in their syntheses and degradations comprise the endocannabinoid system.
The endocannabinoid system acts as a guardian against various attacks on the mammalian body.
Conclusion
The above described research concerning the endocannabinoid-system is of importance in both basic science and in therapeutics:
* The discovery of the cannabis plant active constituent has helped advance our understanding of cannabis use and its effects.
* The discovery of the endocannabinoids has been of central importance in establishing the existence of a new biochemical system and its physiological roles - in particular in neuroprotection.
* These discoveries have opened the door for the development of novel types of drugs, such as THC for the treatment of nausea and for enhancing appetite in cachectic patients.
* The endocannabinoid system is involved in the protective reaction of the mammalian body to a long list of neurological diseases such as multiple sclerosis, Alzheimer's and Parkinson's disease which raises hope for novel therapeutic opportunities for these diseases.
European College of Neuropsychopharmacology
One of the main roles of endocannabinoids is neuroprotection, but over the last decade they have been found to affect a long list of processes, from anxiety, depression, cancer development, vasodilatation to bone formation and even pregnancy (Panikashvili et al., 2001; Pachter et al., 2006).
Cannabinoids and endocannabinoids are supposed to represent a medicinal treasure trove which waits to be discovered.
What is the endocannabinoid system?
In the 1960s the constituent of the cannabis plant was discovered - named tetrahydrocannabinol, or THC - which causes the 'high' produced by it (Gaoni & Mechoulam, 1964). Thousands of publications have since appeared on THC. Today it is even used as a therapeutic drug against nausea and for enhancing appetite, and, surprisingly, has not become an illicit drug - apparently cannabis users prefer the plant-based marijuana and hashish.
Two decades later it was found that THC binds to specific receptors in the brain and the periphery and this interaction initiates a cascade of biological processes leading to the well known marijuana effects. It was assumed that a cannabinoid receptor is not formed for the sake of a plant constituent (that by a strange quirk of nature binds to it), but for endogenous brain constituents and that these putative 'signaling' constituents together with the cannabinoid receptors are part of a new biochemical system in the human body, which may affect various physiological actions. In trying to identify these unknown putative signaling molecules, our research group in the 1990s was successful in isolating 2 such endogenous 'cannabinoid' components - one from the brain, named anandamide (from the word 'ananda, meaning 'supreme joy' in Sanscrit), and another one from the intestines named 2-arachidonoyl glycerol (2-AG) (Devane et al., 1992; Mechoulam et al., 1995).
Neuroprotection
The major endocannabinoid (2-AG) has been identified both in the central nervous system and in the periphery. Stressful stimuli - traumatic brain injury (TBI) for example - enhance brain 2-AG levels in mice. 2-AG, both of endogenous and exogenous origin, has been shown to be neuroprotective in closed head injury, ischemia and excitotoxicity in mice. These effects may derive from the ability of cannabinoids to act through a variety of biochemical mechanisms. 2-AG also helps repair the blood brain barrier after TBI. The endocannabinoids act via specific cannabinoid receptors, of which the CB1 receptors are most abundant in the central nervous system. Mice whose CB1 receptors are knocked out display slower functional recovery after TBI and do not respond to treatment with 2-AG. Over the last few years several groups have noted that CB2 receptors are also formed in the brain, particularly as a reaction to numerous neurological diseases, and are apparently activated by the endocannabinoids as a protective mechanism.
Through evolution the mammalian body has developed various systems to guard against damage that may be caused by external attacks. Thus, it has an immune system, whose main role is to protect against protein attacks (microbes, parasites for example) and to reduce the damage caused by them. Analogous biological protective systems have also been developed against non-protein attacks, although they are much less well known than the immune system. Over the last few years the research group of Esther Shohami in collaboration with our group showed that the endocannabinoid system, through various biological routes, lowers the damage caused by brain trauma. Thus, it helps to attenuate the brain edema and the neurological injuries caused by it (Panikashvili et al., 2001; Panikashvili et al., 2006).
Clinical importance
Furthermore it is assumed that the endocannabinoid system may be involved in the pathogenesis of hepatic encephalopathy, a neuropsychiatric syndrome induced by fulminant hepatic failure. Indeed in an animal model the brain levels of 2-AG were found to be elevated. Administration of 2-AG improved a neurological score, activity and cognitive function (Avraham et al., 2006). Activation of the CB2 receptor by a selective agonist also improved the neurological score. The authors concluded that the endocannabinoid system may play an important role in the pathogenesis of hepatic encephalopathy. Modulation of this system either by exogenous agonists specific for the CB2 receptors or possibly also by antagonists to the CB1 receptors may have therapeutic potential. The endocannabinoid system generally is involved in the protective reaction of the mammalian body to a long list of neurological diseases such as multiple sclerosis, Alzheimer's and Parkinson's disease. Thus, there is hope for novel therapeutic opportunities.
Numerous additional endocannabinoids - especially various fatty acid ethanolamides and glycerol esters - are known today and regarded as members of a large 'endocannabinoid family'. Endogenous cannabinoids, the cannabinoid receptors and various enzymes that are involved in their syntheses and degradations comprise the endocannabinoid system.
The endocannabinoid system acts as a guardian against various attacks on the mammalian body.
Conclusion
The above described research concerning the endocannabinoid-system is of importance in both basic science and in therapeutics:
* The discovery of the cannabis plant active constituent has helped advance our understanding of cannabis use and its effects.
* The discovery of the endocannabinoids has been of central importance in establishing the existence of a new biochemical system and its physiological roles - in particular in neuroprotection.
* These discoveries have opened the door for the development of novel types of drugs, such as THC for the treatment of nausea and for enhancing appetite in cachectic patients.
* The endocannabinoid system is involved in the protective reaction of the mammalian body to a long list of neurological diseases such as multiple sclerosis, Alzheimer's and Parkinson's disease which raises hope for novel therapeutic opportunities for these diseases.
European College of Neuropsychopharmacology
Endocannabinoid News and Current Endocannabinoid Events RSSNew brain cells implicated in machinery of cannabinoid signaling
The brain cells called astrocytes, and not just neurons, are sensitive to the substances called cannabinoids-the active chemicals in marijuana.
Leicester medical team announces 'predictor' for pregnant women who may have miscarriages
A medical team from the University of Leicester has been able to establish for the first time a predictor for pregnant women who may have miscarriages and those who won't. Their research is published in the highly prestigious Journal of the American Medical Association.
Curing addiction with cannabis medicines
Smokers trying to quit in the future could do it with the help of cannabis based medicines, according to research from The University of Nottingham.
Marijuana-like brain chemicals work as antidepressant
American and Italian researchers have found that boosting the amounts of a marijuana-like brain transmitter called anandamide produces antidepressant effects in test rats.
Role seen for cannabis in helping to alleviate allergic skin disease
Administering a substance found in the cannabis plant can help the body's natural protective system alleviate an allergic skin disease (allergic contact dermatitis), an international group of researchers from Germany, Israel, Italy, Switzerland and the U.S. has found.
Discovery of novel nerve cell modulator offers potential for mood disorders, epilepsy treatments
The discovery of a novel molecular switch that powerfully modulates nerve cell activity offers the potential for new mood disorder and epilepsy treatments, University of California, Irvine researchers report.
Cannabinoids produced in the human body have an anti-inflammatory effect
Endocannabinoids seem to play an important role in regulating inflammation processes. Scientists from the University of Bonn have discovered this in experiments on mice.
Study shows enzyme builds neurotransmitters via newly discovered pathway
The new study describes a pathway-different than the one previously suggested-for the biosynthesis of neurotransmitter lipids, N-acyl ethanolamines (NAEs), which include the endogenous cannabinoid ("endocannabinoid") anandamide.
Brain's cannabinoid system 'mellows' seizures
The same brain machinery that responds to the active substance in marijuana provides a central "on-demand" protection against seizures, researchers have found. They said their discoveries suggest that the "endocannabinoid" system might constitute a prime target for drugs against seizures of epilepsy and other neurodegenerative diseases.
Researcher predicts paradigm shift in heart disease treatment
As the obesity epidemic grows in the United States, the medical community is faced with the significant challenge of properly treating patients before complications such as heart disease arise.
More Endocannabinoid News Articles
 | Cannabinoids and the Brain Endocannabinoids control most of the body functions, and in the brain, they modulate neurotransmission, synaptic plasticity, confer neuroprotection, control metabolism, neuro- and neuritogenesis, survival, cognitive and motor functions as well as a plethora of other higher-order brain functions. Their fruitful therapeutic potential is recognized by cannabinoid researchers and pharmaceutical... |
 | Cannabinoids as Therapeutics (Milestones in Drug Therapy) In recent years, cannabis research has concentrated on the potential of cannabinoids as therapeutic substances, particularly in serious chronic illnesses such as multiple sclerosis. Most volumes published on cannabinoids so far concentrate on the biological activity, biochemistry and pharmacology, whereas this volume concentrates on the diseases, the physiological effects and therapeutic use of... |
| Rimonabant cuts rate of metabolic syndrome by 53%: selective endocannabinoid type 1 receptor blocker improves weight loss, lipid profile.(News)(selective ... An article from: Internal Medicine News by Bruce Jancin This digital document is an article from Internal Medicine News, published by International Medical News Group on October 1, 2004. The length of the article is 1489 words. The page length shown above is based on a typical 300-word page. The article is delivered in HTML format and is available in your Amazon.com Digital Locker immediately after purchase. You can view it with any web... | |
 | Endocannabinoids: The Brain and Body's Marijuana and Beyond This volume explores research on marijuana-like substances produced naturally by the human body and brain. These endogenous lipid molecules, or endocannabinoids, constitute a uniquely conserved and ubiquitous physiological control system in a variety of species and plays fundamental roles in development and cell death. The authors discuss this remarkable progress in marijuana research including... |
| Abdominal Obesity and the Endocannabinoid System: From Basic Aspects to Clinical Management of Related Cardiometabolic Risk This internationally renowned author team provides a unique and thorough analysis and distillation of the endocannabinoid system and its relationship to abdominal obesity, diabetes, and cardiovascular disease. The endocannabinoid system (ECS) plays an important role in cardiometabolic risk, as well as modulating energy balance, feeding behavior, hepatic lipogenesis, and perhaps glucose... | |
| ENDOCANNABINOIDS by Takayuki Sugiura | |
 | Reviews of Physiology, Biochemistry and Pharmacology / Volume 160 (Reviews of Physiology, Biochemistry and Pharmacology) (Reviews of Physiology, Biochemistry and Pharmacology) Reviews of Physiology, Biochemistry and Pharmacology Volume 160 2008 V. di Marzo: Endocannabinoids: Synthesis and Degradation R. Rivera and J. Chun: Biological Effects of Lysophospholipids S. J. O Meara, K. Rodgers, and C. Godson: Lipoxins: Update and Impact of Endogenous Pro-Resolution Lipid Mediators R.K.P. Benninger, M. Hao, and D. Piston: Multi-photon Excitation Imaging of... |
 | Cannabinoids |
| The Cannabinoid Receptors (The Receptors) As research has progressed, the cannabinoid CB 1 and CB 2 receptors have expanded significantly in importance within the neuroscience mainstream. In The Cannabinoid Receptors, leading experts introduce newcomers to the cannabinoid field with chapters covering cannabinoid ligand synthesis and structure activity relationships, the molecular pharmacology of the cannabinoid receptors and the... |
| © 2008 BrightSurf.com |