Cannabinoids: possible role in patho-physiology and therapy of Gilles de la Tourette syndrome.

Abstract

“High densities of cannabinoid receptors were found in the basal ganglia and hippocampus, indicating a putative functional role of cannabinoids in movement and behaviour. Anecdotal reports suggested beneficial effects of marijuana in Tourette’s syndrome (TS). We therefore interviewed 64 TS patients with regard to use of marijuana and its influence on TS symptomatology. Of 17 patients (27%) who reported prior use of marijuana, 14 subjects (82%) experienced a reduction or complete remission of motor and vocal tics and an amelioration of premonitory urges and obsessive-compulsive symptoms. Our results provide more evidence that marijuana improves tics and behavioural disorders in TS. It can be speculated that cannabinoids might act through specific receptors, and that the cannabinoid system might play a major role in TS pathology.”

http://www.ncbi.nlm.nih.gov/pubmed/9879795

Phytocannabinoids and endocannabinoids.

“Progress in understanding the molecular mechanisms of cannabis action was made after discovery of cannabinoid receptors in the brain and the finding of endogenous metabolites with affinity to them. Activation of cannabinoid receptors on synaptic terminals results in regulation of ion channels, neurotransmitter release and synaptic plasticity

. Neuromodulation of synapses by the cannabinoids is proving to have a wide range of functional effects, making them potential targets as medical preparations in a variety of illnesses, including some mental disorders and neurodegenerative illnesses. Cannabis contains a large amount of substances with affinity for the cannabinoid receptors. The endocannabinoids are a family of lipid neurotransmitters that engage the same membrane receptors targeted by tetrahydrocannabinol and that mediate retrograde signal from postsynaptic neurons to presynaptic ones.

 Discovery of endogenous cannabinoids and studies of the physiological functions of the cannabinoid system in the brain and body are producing a number of important findings about the role of membrane lipids and fatty acids in nerve signal transduction. Plant, endogenous and synthetic cannabinoids are using in these studies. The role of lipid membranes in the cannabinoid system follows from the fact that the source and supply of endogenous cannabinoids are derived from arachidonic acid, an important membrane constituent

. The study of structure-activity relationships of molecules which influence the cannabinoid system in the brain and body is crucial in search of medical preparations with the therapeutic effects of the phytocannabinoids without the negative effects on cognitive function attributed to cannabis.”

http://www.ncbi.nlm.nih.gov/pubmed/19630737

Molecular biology of cannabinoid receptors.

Abstract

“During the last decade, research on the molecular biology and genetics of cannabinoid receptors has led to a remarkable progress in understanding of the endogenous cannabinoid system, which functions in a plethora of physiological processes in the animal. At present, two types of cannabinoid receptors have been cloned from many vertebrates, and three endogenous ligands (the endocannabinoids arachidonoyl ethanolamide, 2-arachidonoyl glycerol and 2-arachidonoyl-glycerol ether) have been characterized. Cannabinoid receptor type 1 (CB(1)) is expressed predominantly in the central and peripheral nervous system, while cannabinoid receptor type 2 (CB(2)) is present almost exclusively in immune cells. Cannabinoid receptors have not yet been cloned from invertebrates, but binding proteins for endocannabinoids, endocannabinoids and metabolic enzyme activity have been described in a variety of invertebrates except for molting invertebrates such as Caenorhabditis elegans and Drosophila. In the central nervous system of mammals, there is strong evidence emerging that the CB(1) and its ligands comprise a neuromodulatory system functionally interacting with other neurotransmitter systems. Furthermore, the presynaptic localization of CB(1) together with the results obtained from electrophysiological experiments strengthen the notion that in cerebellum and hippocampus and possibly in other regions of the central nervous system, endocannabinoids may act as retrograde messengers to suppress neurotransmitter release at the presynaptic site. Many recent studies using genetically modified mouse lines which lack CB(1) and/or CB(2) finally could show the importance of cannabinoid receptors in animal physiology and will contribute to unravel the full complexity of the cannabinoid system.”

http://www.ncbi.nlm.nih.gov/pubmed/12052031

Marijuana May Fight Lung Tumors WebMD

WebMD: Better information. Better health.
 
 
 
“Cannabis Compound Slows Cancer Spread in Mice, Researchers Say.
 
… the active ingredient in marijuana may help combat lung cancer, new research suggests. In lab and mouse studies, the compound, known as THC, cut lung tumor growth in half and helped prevent the cancer from spreading, says Anju Preet, PhD, a Harvard University researcher in Boston who tested the chemical.While a lot more work needs to be done, “the results suggest THC has therapeutic potential,” she tells WebMD.Moreover, other early research suggests the cannabis compound could help fight brain, prostate, and skin cancers as well, Preet says.

The findings were presented at the annual meeting of the American Association for Cancer Research.

The finding builds on the recent discovery of the body’s own cannabinoid system, Preet says. Known as endocannabinoids, the natural cannabinoids stimulate appetite and control pain and inflammation.

THC seeks out, attaches to, and activates two specific endocannabinoids that are present in high amounts on lung cancer cells, Preet says. This revs up their natural anti-inflammatory properties. Inflammation can promote the growth and spread of cancer.

In the new study, the researchers first demonstrated that THC inhibited the growth and spread of cells from two different lung cancer cell lines and from patient lung tumors. Then, they injected THC into mice that had been implanted with human lung cancer cells. After three weeks, tumors shrank by about 50%, compared with tumors in untreated mice.

Paul B. Fisher, PhD, a professor of clinical pathology at Columbia University, says that though the work is “interesting,” it’s still very early.

“The issue with using a drug of this type becomes the window of concentration that will be effective. Can you physiologically achieve what you want without causing unwanted effects?” he tells WebMD.”

More:http://www.webmd.com/lung-cancer/news/20070417/marijuana-may-fight-lung-tumors

{Delta}-9 Tetrahydrocannabinol inhibits growth and metastasis of lung cancer.”  http://www.aacrmeetingabstracts.org/cgi/content/meeting_abstract/2007/1_Annual_Meeting/4749%20?maxtoshow&hits=80&RESULTFORMAT&fulltext=cannabinoid&searchid=1&FIRSTINDEX=1760&resourcetype=HWCIT

“Delta9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo.” http://www.ncbi.nlm.nih.gov/pubmed/17621270

The role of cannabinoid system on immune modulation: therapeutic implications on CNS inflammation.

Abstract

“There is a growing amount of evidence suggesting that cannabinoids may be neuroprotective in CNS inflammatory conditions. Advances in the understanding of the physiology and pharmacology of the cannabinoid system have increased the interest of cannabinoids as potential therapeutic targets. Cannabinoid receptors and their endogenous ligands, the endocannabinoids, have been detected in cells of the immune system, as well as in brain glial cells. In the present review it is summarized the effects of cannabinoids on immune reactivity and on the regulation of neuroinflammatory processes associated with brain disorders with special attention to chronic inflammatory demyelinating diseases such as multiple sclerosis.”

http://www.ncbi.nlm.nih.gov/pubmed/16026313

The cannabinoid system and immune modulation

Figure 1.

“Studies on the effects of marijuana smoking have evolved into the discovery and description of the endocannabinoid system. To date, this system is composed of two receptors, CB1 and CB2, and endogenous ligands including anandamide, 2-arachidonoyl glycerol, and others. CB1 receptors and ligands are found in the brain as well as immune and other peripheral tissues. Conversely, CB2 receptors and ligands are found primarily in the periphery, especially in immune cells. Cannabinoid receptors are G protein-coupled receptors, and they have been linked to signaling pathways and gene activities in common with this receptor family. In addition, cannabinoids have been shown to modulate a variety of immune cell functions in humans and animals and more recently, have been shown to modulate T helper cell development, chemotaxis, and tumor development. Many of these drug effects occur through cannabinoid receptor signaling mechanisms and the modulation of cytokines and other gene products.

It appears the immunocannabinoid system is involved in regulating the brain-immune axis and might be exploited in future therapies for chronic diseases and immune deficiency.”

“The medicinal uses of marijuana were described centuries ago for diseases such as asthma, migraine, pain, convulsions, and anxiety (reviewed in ref.). More recently, emphasis has been placed on marijuana’s putative, beneficial effects on appetite, glaucoma, spasticity in multiple sclerosis, pain, and inflammation.

Recent experimental evidence supports marijuana’s therapeutic potential in some of these maladies.

The active plant ingredients in marijuana belong to the C21-cannabinoid compounds including the primary psychoactive compound, Δ9-tetrahydrocannabinol (THC). This cannabinoid along with others such as Δ8-THC, cannabidiol, and cannabinol, as well as chemical analogs, have been extensively studied over the years for their biological and therapeutic properties. Some of the properties of these agents have included effects on immunity ranging from suppression of resistance to infection to enhancement of IL-1 production by macrophages. These early studies about the immunomodulating effects of these drugs have been the subject of previous overviews and will not be reviewed here. Instead, we will briefly summarize the general features of the cannabinoid system and review recent findings on the structure and function of the cannabinoid system components in the immune system. For convenience, we will refer to this as the “immunocannabinoid” system.

CANNABINOID SYSTEM

Marijuana cannabinoids, analogs, and endocannabinoids”

https://jlb.onlinelibrary.wiley.com/doi/full/10.1189/jlb.0303101?sid=nlm%3Apubmed

Cannabinoids and the immune system.

“The effect of cannabimimetic agents on the function of immune cells such as T and B lymphocytes, natural killer cells and macrophages has been extensively studied over the past several decades using human and animal paradigms involving whole animal models as well as tissue culture systems.

From this work, it can be concluded that these drugs have subtle yet complex effects on immune cell function and that some of the drug activity is mediated by cannabinoid receptors expressed on the various immune cell subtypes.

However, the overall role of the cannabinoid system of receptors and ligands in human health and disease is still unclear and requires extensive elucidation.

Further studies will define the precise structure and function of the putative immunocannabinoid system, the potential therapeutic usefulness of these drugs in chronic diseases such as acquired immune deficiency syndrome and multiple sclerosis, the effects of these agents on tumour growth and induction of apoptosis, and the potential anti-inflammatory and proinflammatory properties of cannabimimetic compounds.

It is likely that the cannabinoid system, along with other neuroimmune systems, has a subtle but significant role in the regulation of immunity and that this role can eventually be exploited in the management of human disease.”

The endocannabinoid system: a revolving plate in neuro-immune interaction in health and disease.

Abstract

“Studies of the last 40 years have brought to light an important physiological network, the endocannabinoid system. Endogenous and exogenous cannabinoids mediate their effects through activation of specific cannabinoid receptors. This modulatory homoeostatic system operates in the regulation of brain function and also in the periphery. The cannabinoid system has been shown to be involved in regulating the immune system. Studies examining the effect of cannabinoid-based drugs on immunity have shown that many cellular and cytokine mechanisms are modulated by these agents, thus raising the hypothesis that these compounds may be of value in the management of chronic inflammatory diseases. The special properties of endocannabinoids as neurotransmitters, their pleiotropic effects and the impact on immune function show that the endocannabinoid system represents a revolving plate of neural and immune interactions. In this paper, we outline current information on immune effects of cannabinoids in health and disease.”

http://www.ncbi.nlm.nih.gov/pubmed/22367605