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Cannabis is a well-known drug widely used across the world for his relaxing effect. It is also used as medicine in some countries like USA to ease the pain. In the 90’s, investigators find out that humans have a system called ‘endocannabinoid system” which is mediated by lipophilic compounds such anandamide (naturally found in human body) or plant compounds Δ9-THC which modulate CB1 and CB2 receptors. Highlighting this has paved the way to various researches to modulate this system which had previously shown its importance in various diseases such as metabolic syndrome, which comprises four pathologies (diabetes, hypertension, obesity and hypertriglyceridemia). After various stages of study where it a showed his effectiveness in both animals and humans, rimonabant, the first compound indicated for his multiple effects on several components of metabolic syndrome, was put on the market. But it soon became clear that psychiatric side effects were “hidden” in previous studies and the drug was quickly removed from the European market (FDA never granted its AMM for USA). The withdrawal seemed to sound the death for the CB1 receptor antagonists. But another possibility is the development of compounds that does not cross the blood-brain barrier, but affects peripheral CB1 receptors located in various tissues such liver, intestines or muscles. Finally, it worth to mention that CB1 receptor antagonists are a hope in the management of drug addiction (although it would involve a central mode of action), acute pancreatitis and prevention of post-traumatic epilepsy Le cannabis est une drogue bien connue et largement utilisée à travers le monde pour ses effets relaxants et psychotropes. Il est§ également utilisé dans certains pays comme les USA pour diminuer la douleur. Au début des années 90, les chercheurs ont découvert que l’homme possédait un système appelé endocannabinoïde qui est modulé par des composés lipophiles naturellement présents dans le corps comme l’anandamide ou des dérivés naturels comme le Δ9-THC qui agissent sur les récepteurs CB1 et CB2. La mise en évidence de ce système a ouvert la voie a diverses recherches afin de moduler ce système qui avait montré son importance dans diverses pathologies, dont la principale est le syndrome métabolique, nom sous lequel est regroupés l’hypertension, le diabète, l’hypercholestérolémie et l’obésité. Après avoir passé les différents stades d’étude t ayant montré son efficacité tant chez l’animal que chez l’homme, le rimonabant, premier composé ayant cette indication thérapeutique, fut mis sur le marché pour ses effets sur les différentes composantes du syndrome métabolique. Mais il apparut rapidement que les risques psychiatriques associés étaient non-négligeables et il fut donc retiré du marché en Europe (le FDA luis ayant refusé son AMM). Ce retrait sembla sonner le glas des antagonistes des récepteurs CB1. Une autre possibilité est la mise au point de composés ne passant pas au niveau du système nerveux central mais agissant sur les récepteurs CB1 périphériques des muscles intestins et du foie. Enfin, notons également que les antagonistes des récepteurs CB1 présentent un espoir dans le cadre de la prise en charge de la dépendance aux drogues (mais cela impliquerait un mode d’action central), la pancréatite aigüe et la prévention de l’épilepsie post-trauma

Cannabis --- Receptors, Cannabinoid, CB1

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The past two decades have seen a tremendous growth in knowledge related to cannabinoid receptor signaling in brain.  In addition, the impact and consequences of cannabinoid modulation of monoaminergic circuits is steadily emerging demonstrating a significant interaction between these two systems in a variety of psychiatric (affective disorders) and neurological disorders (multiple sclerosis, pain). Despite increasing evidence from preclinical data suggesting that therapeutic use of cannabinoid-based drugs may outweigh any potential risks in certain serious medical conditions, the debate surrounding its widespread utility continues as regulatory concerns preclude a smooth transition of promising preclinical studies into clinical trial testing. This may persist in the near future as state and federal governments debate over regulation of medicinal applications of cannabis. Applications for medicinal cannabinoids that are already under investigation include the treatment of nausea, anorexia, neurodegeneration, inflammation, excitotoxicity and pain. The appetitive and anti-emetic properties of cannabinoids have led to the approval of their use in chemotherapy and AIDS patients.  There is growing evidence for therapeutic cannabinoid effects on inflammatory and excitotoxic cellular processes that are linked to epilepsy, Parkinson’s disease, amyotrophic lateral sclerosis, spasticity, and central nervous system injury. The chapters, herein, review and discuss current insights into the brain endocannabinoid system, cannabinoid receptor signaling on synaptic plasticity, potential therapeutic applications with a particular focus on endocannabinoid modulation of dopaminergic, noradrenergic and serotonergic circuitry. The potential for establishing cannabinoid-monoaminergic interactions as a novel target in the development of improved treatment strategies for psychiatric and neurological disorders is promising and will require future clinical studies to determine whether promising pre-clinical findings translate into new therapies.

Cannabinoids -- Therapeutic use. --- Medicine. --- Mental illness -- Treatment. --- Nervous system -- Diseases -- Treatment. --- Neurochemistry. --- Neurology. --- Neurosciences. --- Psychiatry. --- Cannabinoids --- Cannabis --- Diseases --- Receptors, G-Protein-Coupled --- Psychiatry and Psychology --- Therapeutics --- Neurotransmitter Agents --- Receptors, Cell Surface --- Molecular Mechanisms of Pharmacological Action --- Analytical, Diagnostic and Therapeutic Techniques and Equipment --- Pharmacologic Actions --- Membrane Proteins --- Chemical Actions and Uses --- Proteins --- Chemicals and Drugs --- Amino Acids, Peptides, and Proteins --- Mental Disorders --- Drug Therapy --- Endocannabinoids --- Nervous System Diseases --- Receptors, Cannabinoid --- Medicine --- Health & Biological Sciences --- Neurology --- Therapeutic use --- Psychopharmacology. --- Nervous system --- Therapeutic use. --- Treatment. --- Behavioral pharmacology --- Drugs --- Psychotropic effects --- Biomedicine. --- Chemotherapy --- Pharmacology --- Psychotropic drugs --- Hallucinogenic drugs --- Terpenes --- Biochemistry --- Neurosciences --- Neuropsychiatry --- Neural sciences --- Neurological sciences --- Neuroscience --- Medical sciences --- Medicine and psychology --- Mental health --- Psychology, Pathological --- Neurology .